Pusat Pengajian Sains Kesihatan - Tesis
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- PublicationDevelopment and validation of a quality of life scale for primary caregivers of children with cerebral palsy in Malaysia(2025-09)Wei, Kelvin Ying @ Tang SheeThe quality of life (QoL) among primary caregivers of children with cerebral palsy (CP) is a critical concern, influencing both caregiver well-being and overall family dynamics. Understanding the factors that shape caregivers’ QoL is essential for developing effective support interventions. Yet, there are limited validated tools to assess caregiver QoL in the local context. This study aimed to develop and validate a culturally relevant QoL measure for primary caregivers of children with CP in Malaysia, conducted in three phases. Phase 1 involved a baseline quantitative study assessing primary caregiver QoL, Phase 2 focused on scale development, and Phase 3 validated the scale through exploratory factor analysis (EFA). Participants were recruited using key informant sampling in Phase 1 and purposive sampling in Phases 2 and 3, with a cross-sectional study design applied. In Phase 1, 159 primary caregivers (Mean age = 42.8 years, SD = 8.4) who attended health screening camps in Kelantan, Johor, and Sarawak participated. Their QoL was assessed using the Pediatric Quality of Life Inventory™ Family Impact Module (PEDSQL FIM) and analysed through descriptive analysis, single linear regression, and multiple linear regression. Results indicated that primary caregivers who attending health screening camps generally had good health-related QoL, family functioning, and overall QoL, with maternal education level and family income identified as key factors influencing all three. In Phase 2, a new Malay-language QoL scale was developed through literature review expert input, and in-depth interviews with eighteen local primary caregivers (Mean age = 39.3 years, SD = 7.28), identifying eight key themes: physical constraint, emotional distress, financial hardship, child’s difficult behavior, social support, acceptance, beliefs, and initiative for the child’s development. Items were generated and compiled into a draft scale, which underwent content validation by seven experts and pre-testing with 15 caregivers. In Phase 3, a hundred Malaysian primary caregivers (Mean age = 44.9 years, SD = 11.1) participated in the study. The newly developed scale, named the Primary Caregiver Quality of Life (PCQoL) scale, was tested for construct validity through EFA, concurrent validity through correlations with related constructs, and reliability via Cronbach’s alpha. The final 28-item version, covering eight domains, demonstrated strong validity and reliability in assessing QoL in the Malaysian primary caregiver context. This study provides valuable insights for healthcare providers to improve the QoL of primary caregivers of children with CP
- PublicationDevelopment of dna aptamers against bipd antigen of burkholderia pseudomallei for diagnostic applications(2025-09)Selvam, KasturiMelioidosis is an infectious disease caused by Burkholderia pseudomallei (B. pseudomallei). A major challenge in diagnosing this disease arises from the limitations of the gold standard method, which is often time-consuming and lacks sufficient sensitivity. Therefore, this study aimed to develop DNA aptamers targeting the Burkholderia invasion protein D (BipD) antigen for melioidosis diagnostic applications. The recombinant BipD protein was expressed and purified to serve as the target for DNA aptamer isolation through systematic evolution of ligands by exponential enrichment (SELEX). Three potent aptamers were isolated based on their high frequency. All these selected aptamers were evaluated for their binding affinity to the recombinant BipD protein, followed by specificity testing against lysates from other Gram-negative bacteria, including Salmonella Typhi, Shigella flexneri, Escherichia coli and Klebsiella pneumoniae, through an enzyme-linked oligonucleotide assay (ELONA). AptBipD1 exhibited the highest binding affinity, with a dissociation constant (Kd) of 0.91 ± 0.08 μM, which was lower than AptBipD13 and AptBipD50. All three aptamers demonstrated strong specificity for B. pseudomallei compared to other tested bacteria. Binding analyses were performed through computational methods such as molecular docking and molecular dynamics (MD) simulations. Computational analysis revealed that AptBipD1 exhibited the highest predicted binding free energy of -22.8 kcal/mol and greater stability upon binding with BipD protein, as well as the binding site located away from its 5' and 3' ends. This finding suggests that immobilising this aptamer at either end would not affect its binding characteristics. An electrochemical aptasensor was developed by immobilising the most promising aptamer onto screen-printed gold electrodes. AptBipD1-based electrochemical aptasensor demonstrated high specificity for B. pseudomallei over other bacterial strains. This sensor achieved a limit-of-detection (LoD) of 3.4 ± 0.03 ng/mL and limit-of-quantification (LoQ) of 59.2 ± 0.03 ng/mL in buffer, and a LoD of 3.5 ± 0.06 ng/mL and LoQ of 63.2 ± 0.06 ng/mL in spiked serum. The electrochemical aptasensor developed using AptBipD1, which had high binding affinity and specificity, demonstrated low LoD and LoQ in both buffer solution and serum spiked with protein. This indicates its potential for rapid and accurate detection of the BipD protein, making it suitable for diagnostic purposes in melioidosis
- PublicationThe characterisation of mdm2 and cdk4 gene amplification and their association with recurrence in lipomatous tumours(2025-09)James, Jessinntha SptMDM2 and CDK4 are frequently amplified genes in liposarcoma, particularly in atypical lipomatous tumour/well-differentiated liposarcoma (ALT/WDLS) and dedifferentiated liposarcoma (DDLS). Although the individual oncogenic role of MDM2 and CDK4 genes are well established, the prevalence and ratio of their concurrent amplification, as well as their prognostic significance in liposarcoma, remain unclear. The aim of this study was to evaluate MDM2 and CDK4 amplification ratios across lipomatous tumour subtypes, determine their concurrent amplification statuses, and assess associations with patients’ prognosis. Clinicopathological data of cases histologically diagnosed as liposarcoma of any size or benign lipomatous tumours measuring at least 10 cm (≥10 cm), at Hospital Pakar Universiti Sains Malaysia (HPUSM) between January 2014 and May 2021, were retrospectively retrieved from Laboratory Information System of Pathology Department, HPUSM. Formalin-fixed paraffin-embedded tissue samples of eligible cases were subjected to fluorescence in situ hybridisation (FISH) for MDM2 and CDK4 gene amplification detection. Amplification ratio was determined by comparing MDM2 or CDK4 mean copy number with centromere 12 signals, where ratios more than 2.0 indicated amplification, and ratio less than 2.0 indicated no amplification. Recurrence-free and metastasis-free survival across amplification groups were evaluated using Kaplan-Meier survival analysis and compared with log-rank statistics. Prognostic factors of recurrence were analysed using Cox proportional hazard regression. Among 86 cases 23 (27%) were liposarcoma and 63 (73%) were benign lipomatous tumours (≥10 cm) following reclassification by FISH. MDM2 and CDK4 co-amplification (MDM2+/CDK4+; 13%) was observed in all (6/6) DDLS and half (5/10) of ALT/WDLS cases. Five MDM2-amplified cases lacked CDK4 amplification (MDM2+/CDK4-; 6%), all detected in ALT. No amplification of either gene (MDM2-/CDK4-; 81%) was detected in myxoid liposarcoma, pleomorphic liposarcoma, or benign tumours. DDLS showed higher MDM2 and CDK4 amplification ratios (4.4 and 2.8, respectively) than ALT/WDLS (2.9 and 2.6, respectively). In both subtypes, MDM2 amplification ratio exceeded CDK4. MDM2+/CDK4+ group had the shortest recurrence-free (p=0.002; median 34 months) and metastasis-free survival (p=0.003; median 83 months) compared to other groups. Multivariate analysis showed recurrence was significantly associated with surgery combined with chemotherapy (p=0.021), but MDM2 and CDK4 amplification was not an independent prognostic factor. In conclusion, MDM2 amplification was more consistent and quantitatively higher than CDK4, supporting its central role in tumourigenesis. While MDM2/CDK4 co-amplification was associated with poorer outcomes, it lacked independent prognostic value, reflecting the potential influence of other clinical variables. Nevertheless, co-amplification may hold clinical relevance in identifying high-risk liposarcoma subgroups
- PublicationThe effects of psychosocial factors in physical activity promotion among overweight and obese adolescent in Yunnan Province, China using youth physical activity promotion model(2025-08)Mingxue, HanAdolescent obesity is a growing public health issue in China, with insufficient physical activity (PA) as a major contributor. Psychosocial factors play a crucial role in shaping children's PA behaviors, but research focusing on overweight and obese adolescents in this region is limited. This study employs the Youth Physical Activity Promotion Model (YPAP) to explore the influence of psychosocial factors on PA among overweight and obese adolescent in China. An intervention program combining family and school-based PA strategies was designed to assess its effect on PA levels in adolescent in Zhaotong, Yunnan. The study was conducted in two phases. Phase 1 was a cross-sectional study involving 1,500 adolescents aged 12 to 15 who completed several questionnaires on PA and psychosocial factors. Structural equation modelling was used to analyse the relationships between the variables. The final model fit the data well (χ²/df = 2.22, CFI = 0.98, GFI = 0.95, RMSEA = 0.03, SRMR = 0.07, NFI = 0.96, TLI = 0.98). The results revealed significant positive relationships between family influence (FI), peer influence (PI), perceived competence (PC), enjoyment, self-efficacy, and PA levels （p<0.05). However, the path coefficient from FI to PC was non-significant (β = 0.019, p > 0.05), and mediation analysis showed that the pathway from FI to PA through PC was also non-significant (effect = 0.002, p = 0.566). Additionally, psychosocial factors in the YPAP model displayed variations across different BMI and grade-level groups. Phase 2 involved a randomized controlled trial with 96 participants, who were randomly assigned to an intervention or a control group. The intervention lasted eight weeks, with three sessions per week. The interaction effects were significant for FI, PI, enjoyment, self-efficacy, and PA (p< 0.05), with the intervention group showing significantly higher scores than the control group. However, the interaction effect on PC was not significant (p = 0.077). This study highlights significant associations between psychosocial factors and PA among overweight and obese adolescent in China. Self-efficacy, FI, PI, and enjoyment are crucial factors in promoting PA. The YPAP-based intervention is effective in increasing PA levels. Future research should explore mediating or moderating variables and adjust intervention strategies based on BMI and grade-level differences to enhance effectiveness
- PublicationNext generation sequencing based targeted gene mutational profiles of formalin-fixed paraffin embedded specimens from colorectal carcinoma cases in Hospital Pakar Universiti Sains Malaysia(2025-08)Afolabi, Hafeez AbiolaColorectal carcinoma (CRC) is the third most prevailing cancer and the third most common cause of cancer-related deaths worldwide. It is a multistep process involving the accumulation of multiple genetic alterations. Through comprehensive molecular profiling and analysis of CRC using NGS, genetic mutations in colorectal cancer can be accurately identified for potential CRC screening. The present study carried out molecular analysis of formalin-fixed, paraffin-embedded (FFPE) specimens from 30 CRC cases in Hospital Pakar Universiti Sains Malaysia using NGS. Extracted gDNA from FFPE samples using a QIAgen FFPE extraction kit was used for library preparation, then sequenced in an Illumina MiniSeq machine. From a total of 30 FFPE samples [60% male and 40% female] sequenced, 22 completed the sequencing run, representing 73.3% of the samples: 20 CRC samples and 2 normal tissues. From demographics results, the highest data was recorded for “less than 65 years old” at 66.7%, “Retired group” at 70%, “Stage-3” at 53.3%, “Moderately differentiated grade” at 76.7%, and lastly, patients with “More than 2 comorbid” at 36.7%. Overall, 552 mutations involving 29 genes and 11 chromosomes were detected. The most upregulated were KIT:68(12.3%), FGFR4:61(11.1%), EGFR:60(10.9%), ALK:53(9.6%), DCUN1D1:41(7.4%), PDGFR:40(7.2%), KRAS:33(6.0%), CDK4:27(4.9%), and FGFR3:26(4.7%). Most downregulated gene mutations were ESR1, FGFR1, CCND1, HRAS, AR. The five most involved chromosome were chr4:(24.3%), chr7:(15.2%), chr12:(12.2%), chr5:(11.6%), and chr2:(11.1%) respectively. After applying filter criteria, 105 mutations involving 15 genes passed the filter. In-Silico Prediction model of clinical consequences of filtered mutations identified 21 pathogenic mutations (from 9 genes), 57 tolerated benign mutations (from 5 genes), and 17 variants unspecified (from 4 genes). Identified pathogenic gene mutations are APC, NRAS, ALK, PIK3CA, KRAS, IDH1, FGFR1, ERBB2, and ESR1. Validation of the pathogenic mutations on dbSNP, Ensembl, and Franklin by Genoox online databases also identified them as pathogenic genes. This is the first comprehensive NGS genetic profiling of CRC cases in Malaysia and HPUSM. The study’s novelty is based on the successful identification of pathogenic gene mutations in colorectal cancer cases in Malaysia and HPUSM. These findings will serve as a leadway for potential targeted therapy for CRC cases