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    Anti cancer effect of paddy husk extracts in human salivary gland epidermoid cancer cells in vitro model
    (2024-02)
    Al-Azazi, Entesar Ahmed Abdullah
    Global agriculture produces millions of tons of waste yearly. Paddy husk is an inedible agriculture waste obtained during the process of rice milling. Studies reported that it has chemopreventive potential due to the presence of related phytochemicals. The aim of this study is to elucidate the presence of anti-cancer related phytochemicals from paddy husk extract and evaluate its inhibitory and anti-proliferative effects against human submaxillary salivary gland epidermoid carcinoma cells (HTB-41). Two types of solvent for paddy husk extract have been used; water and aqueous methanol. The phytochemical constituents of paddy husk extracts were identified using GC-MS. The inhibitory activity and cytotoxicity analysis was calculated using Trypan Blue Exclusion Assay (TBEA). Apoptosis and cell cycle analysis were evaluated by flow cytometer, and cell morphology post treatment was analysed ultrastructurally, while Western blot was performed for proteomic analysis. Our results showed presence of vitamin E and other phytochemicals in paddy husk extracts. Both water and aqueous methanol extracts demonstrated inhibitory activity on HTB- 41 cells where IC50 dose of water extract (400 μg/ml) managed to reduce cell viability to 53.0 % and IC50 dose of aqueous methanol extract (200 μg/ml) managed to reduce cell viability to 51.12 % without exhibiting any significant cytotoxic effects. Apoptosis analysis revealed that water and aqueous methanol extracts induce apoptosis effect on HTB-41 as supported with microscopic findings of cell shrinkage, membrane blebbing and apoptotic bodies, meanwhile, Hoechst 33342 staining showed nuclear shrinkage and fragmentation. Flow cytometry analysis demonstrated that paddy husk extracts promote a significant amount of apoptotic cellular population from 76.00% (untreated) to 47.86% (paddy husk water extract) and 43.13% (paddy husk aqueous methanol) and arresting the cells at S-phase from 19.90% (control) to 36.90 % (paddy husk aqueous methanol extract) and 27.86 % (paddy husk water extract). Western blot analysis reveals that apoptosis was induced through caspase 3-mediated intrinsic pathway. Pro-apoptotic and tumour suppressor proteins; Bax, p27kip1 expressed higher (P <0.05), while anti-apoptotic protein, Bcl-2 downregulated after treatment (P <0.01). This leads to increase of caspase 9 expression which in turn activate caspase 3 and 7 leading to cell apoptosis. In conclusion, the presence of phytochemicals in paddy husk especially in aqueous methanol extract successfully showed better inhibitory and anti-proliferative effects on the human submaxillary salivary gland epidermoid carcinoma cells (HTB-41), while it acted in a tumour-selective manner by not inducing any significant changes on human gingival fibroblast cell (HGF-1).
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    Classification of glioma brain tumors in mr images using imagej-based radiomic analysis
    (2024-07)
    Zafrin, Nurizzatul Hadawiyah Mohamed
    The aim of this study is to classify glioma brain tumor grades using ImageJ-based radiomic analysis. This study utilizes magnetic resonance imaging (MRI) with ImageJ (Fiji) software to perform radiomic analysis, providing a quantitative method to evaluate Glioma tumor without the use of Gadolinium based contrast agents (GBCAs). Gliomas can range from low grade gliomas (LGGs) (Grades I and II) to high grade gliomas (HGGs) (Grades III and IV) tumors. Accurate grading of tumor is vital in determination of the appropriate treatment. This is a retrospective study on 12 T2-weighted (T2W) images (n=12) of patients with pathologically diagnosed glioma of different grades retrieved at the Radiology Department, Hospital Universiti Sains Malaysia from Picture Archiving and Communications System (PACS). A single slice of T2W image is chosen for analysis and all of the images were analysed for its image quality. Then, a workflow and protocol for image processing were explored using ImageJ. The lesion and normal appearing white matter (NAWM) region of interest (ROI) were selected for histogram analysis, along with lesion to normal tissue ratio (LNR) calculations and standard deviation of lesion (SDL) analysis for the assessment of tumor heterogeneity and intensity. Additionally, color thresholding, lookup table (LUT) images with 3D plot surface images, and midline shift angle measurements were used to assess tumor characteristics such as the margin, edema, and mass effect. The result of this study shows no specific trend for the tumor intensity based on LNR findings; however the SDL of the tumor shows an increasing trend across the glioma grades, which proves the increasing heterogeneity as the glioma grades increase. The margin of the tumor can be depicted by entropy thresholding, the edema is depicted by LUT images. Finally, the mass effect is depicted by the measurement of midline shift angle where higher-grade tumor depicts further deviation from 180.0° and in 3D surface plot images. In conclusion, ImageJ-based radiomic analysis provides an accessible and simple method for classifying glioma brain tumors. This approach may potentially facilitate tumor grading without the use of GBCAs.
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    Exploring mental toughness and perceived stress of nursing students of Universiti Sains Malaysia
    (2023-06)
    Celina, Tan
    Possessing mental toughness (MT) enables one to bounce back from adversities, feel confident in completing tasks and be assertive in social situations while remaining committed in the face of stress. Stress can serve as a driving force, but too much stress can cause poor performance and stress-related disorders. Nursing students are vulnerable groups with higher risk of burning out, with anxiety and self-efficacy being among the strongest intrinsic predictors of stress. MT has not been explicitly studied in the context of nursing students hence this research was carried out to contribute to the gap in research. This study aimed to explore the suitability of MT in the nursing context and identify stressors pertaining to the current study’s population of interest and pin-pointing visual themes useful for developing exploratory stress-coping neuroimaging paradigm suited for healthcare education context. The current research was broken down and carried out in three phases with nursing students from Universiti Sains Malaysia (USM) exploring: 1) the suitability of the 4/6Cs MT model via reliability testing of MTQ-48 and its correlation with the Nursing Anxiety and Self-Confidence with Clinical Decision Making (NASC-CDM) scale; 2) the visual themes nursing students perceive as stressful by validating images showing scenarios from daily life, academic and clinical situations; lastly, 3) the relationship between Perceived Stress and MT with images/ visual cues perceived as stressful using Perceived Stress Scale (PSS-10) and MTQ-10. Findings from this research show MT have fair to moderate significant correlations with Anxiety (r=-0.293, p<0.001) and Self-Confidence (r=0.429, p<0.001). The initial 48-item MTQ-48 has good reliability with Cronbach’s coefficient alpha of 0.851 but reported unsatisfactory fit across indices after running confirmatory factor analysis (CFA). After refining the items, a modified 10-item Mental Toughness Questionnaire (MTQ-10) presented decent reliability (α=0.789) achieving all recommended minimum values for CFA fit indices. Image validation via Self-Assessment Manikin (SAM) yielded 36 images with low valence and low arousal reflecting stressful emotions when viewing the images. Finally, concurrent stress rating of images with assessment of MT and Perceived Stress reported 31 images have significant correlation with both MT and Perceived Stress, with strong significant negative correlation between total MT scores and Perceived Stress scores (r=-0.768, p<0.001). The goal of this research to explore the suitability of MT in nursing student context and produce relevant visual themes for perceived stress-coping as surrogate of MT for future neuroimaging research is achieved.
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    Investigating the expression of soluble pd-l1 (spd-l1) of breast cancer patients using elisa in Hospital USM, Kelantan
    (2024-04)
    Anwar, Nur Amira Khairil
    There are limited data on soluble PD-L1 (sPD-L1) in breast cancer, particularly those involving Asian (Malaysian) women, despite the fact that increased serum and plasma levels of sPD-L1 have been observed in numerous malignancies. This study was designed to achieve three aims: (1) to recruit breast cancer patients at Hospital University Sains Malaysia (HUSM) and examine the overall survival (OS) with clinicopathological properties and patient baseline, (2) to develop a sensitive and specific enzyme-linked immunosorbent assay (ELISA) using commercialised PD-L1 monoclonal antibody clones (mAb), 22C3 (Dako) and 28-8 (Abcam) for sPD-L1 detection and measurement in human peripheral blood , and finally (3) measure sPD-L1 level using the developed ELISA followed by analyse its correlation and OS with clinical characteristics in breast cancer patients at HUSM. Blood specimens were obtained from three cohorts of breast cancer patient: 92 malignant, 16 benign and 23 healthy controls. Our study demonstrated that triple negative breast cancer (TNBC) molecular subtype have lower OS than the non-TNBC (53 months (SD 5.4 months) vs 272.7 months (SD 7.5 months), p= 0.029, log-rank test). Similarly, patients presenting with advanced tumour staging at diagnosis has poorer prognostic (p<0.001, log-rank test). Using 22C3 as the capture antibody, and clone 28-8 as the detection antibody, a sandwich ELISA was successfully developed with the limit of detection (LoD) of 0.063 ng/mL in human serum and 0.078 ng/mL in human plasma. The median serum sPD-L1 concentration of malignant and benign patient cohorts was significantly elevated compared to the healthy cohorts (12.50 ng/mL vs 13.97 ng/mL vs 8.75 ng/mL, p<0.05). Optimal cut-off value of serum sPD-L1 for this study was 8.84 ng/mL. Significant association existed between elevated serum sPD-L1 levels and menarche age, ethnicity, birth control usage, comorbidity and HER2 status (p<0.05). Menarche age and birth control were identified as independent variables impacting sPD-L1 level by multivariate analysis. However, the OS for patients with high vs low sPD-L1 level was not significant (266.3 months (SD 9.3 months) vs 60.0 months (SD 3.3 months), p=0.647, log-rank test). Additionally, there was no discernible correlation between tissue PD-L1 and serum sPD-L1 levels (p= 0.275, U-test). Elevated blood levels of sPD-L1 were strongly related with a number of clinical traits, and this relationship justifies the need for additional research for diagnostic and prognostic of breast cancer patients.
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    Percentage depth dose (PDD) of 9 MEV electron beam in the medium with the presence of inhomogeneous tissue by using optically stimulated luminescence dosimeter (OSLD), EBT3 film and ionization chamber
    (2024-07)
    Malek, Nur Syazwany
    The human body has variations in tissue density such as high-density bone tissue and low-density lung tissue, which will impact the dose distribution in the medium. The study aims to evaluate the dosimetric accuracy of optically stimulated luminescence dosimeters (OSLD) and their ability to detect and measure dose perturbation by measuring the percentage depth dose (PDD) in the medium consisting of solid water, bone equivalent, and cork(lung) equivalent phantom. Three phantom setups of solid water phantom, solid water-bone phantom, and solid water-cork (lung) phantom were irradiated with a 9 MeV electron beam, and the PDD was measured using OSLD, EBT3 film, and ionization chamber. The PDD curve and electron range parameter obtained by OSLD was compared to other dosimeters and statistical test was conducted to determine the agreement between the PDD using the p-value. The results showed that PDD measured by OSLD was in good agreement with the ionization chamber and EBT3 film dosimetry in a homogenous solid water phantom setup. PDD in the inhomogeneous solid water-bone and solid water cork (lung) phantom setups measured by OSLD was also consistent with the EBT3 film and previous studies. No significant differences were observed between PDD measured by OSLD and the reference dosimetry, evidenced by p-value > 0.05 obtained from statistical tests. The overall results indicated the suitability of OSLD as a passive dosimeter in electron beam dosimetry in the medium with the presence of inhomogeneous tissue.
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    Quantitative study of iterative reconstruction algorithms of spect/ct in bone scan: a clinical and phantom study
    (2024-07)
    Hao, Lau Lik
    The integration of single photon emission computed tomography (SPECT) with computed tomography (CT), along with advancements in iterative image reconstruction algorithms, significantly enhances the feasibility of SPECT quantification in bone scan. Quantitative bone SPECT enables the precise measurement of radiotracer accumulation in bone lesions. This capability allows for the accurate assessments of the presence and extent of bone abnormalities, thereby improving diagnostic accuracy of bone scan. This study evaluates the impact of iterative reconstruction algorithms with various attenuation correction methods on SPECT quantification accuracy and image quality in bone scan across different iteration numbers in both phantom and clinical settings. In the phantom study, spheres in the NEMA 2012/ IEC 2008 phantom were filled with 300 kBq/ml of mixture of K2HPO4 solution and a 99mTc source, while the background region contained only 30 kBq/ml of 99mTc source, establishing a tumor-to-background ratio (TBR) of 10:1. The phantom underwent bone imaging using the standard protocol applied at Hospital Universiti Sains Malysia (HUSM). In the clinical study, a pelvic bone scan image with multiple lesions was retrieved from the XelerisTM workstation. Both phantom and clinical images were reconstructed using MLEM-CHANG, OSEM-CHANG, and OSEM-CT, with varying iteration products (4, 8, 12, 16, and 20 iterations for MLEM; 40, 80, 120, 160, and 200 iterations for OSEM). Quantitative analysis of activity concentration, recovery coefficient (RC), standardized uptake value (SUV), signal-to-noise ratio (SNR), and noise were performed using Dosimetry Toolkit and Q.Metrix software. OSEM-CT (-73.3% to 6.7%) demonstrated the smallest percentage difference between measured and actual activity concentration (300 kBq/ml) across all sphere volumes and iteration numbers compared to MLEM-CHANG (-86.7% to -43.3%) and OSEM-CHANG (-83.3% to -33.3%). For all algorithms, increasing the iteration numbers elevated RC, SUV, and noise, while SNR dropped. In the phantom study, there were no significant difference in RC and SNR among the algorithm pairs (MLEM-CHANG vs OSEM-CHANG, MLEM-CHANG vs OSEM-CT, and OSEM-CHANG vs OSEM-CT) across different iteration numbers (p>0.05), as tested using the Kruskal-Wallis test with post-hoc Bonferroni’s correction. In the clinical study, significant differences in SUV were displayed between MLEM-CHANG vs OSEM-CT and OSEM-CHANG vs OSEM-CT at all iteration numbers (p< 0.05). Additionally, the SNR of the lesions in clinical study showed significant differences between MLEM-CHANG and OSEM-CT at iterations of 8, 12 and 16 (p< 0.05). In summary, OSEM-CT illustrated higher activity concentration accuracy, RC, SUV, and SNR, along with lower noise level compared to OSEM-CHANG and MLEM-CHANG. Thus, OSEM-CT is recommended for accurate SPECT quantification and optimal image quality in bone scan.
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    The role of probiotics with lactic acid-producing bacteria in modulating the behaviour of rodent model following contusive spinal cord injury: preliminary study
    (2023-06)
    Manickam, Danniya Lakshmi
    The disruption of gut dysbiosis after spinal cord injury (SCI) is a crucial but poorly understood phenomenon that might affect SCI healing. This study addresses the need to examine locomotor recovery after SCI and presents an animal model that may help restore a healthy gut flora and improve SCI therapies. The primary objective is to create a reliable animal model of SCI with gut dysbiosis to test probiotic treatments. With a 10% dropout rate (1 additional rat), this study included 13 rats. Adult female Wistar rats were carefully weighed and randomly allocated to one of four groups: Group 1 (control, n = 3), Group 2 (control with antibiotic intake, n = 4), Group 3 (SCI with antibiotic intake, n = 3), and Group 4 (SCI with antibiotic intake and probiotic therapy, n = 3). A rod was dropped from 25 mm to cause a moderate contusion injury in the T9/T10 thoracic area after a laminectomy. Successful surgery was established by the rats' hindlimb paralysis. Five days before SCI, rats received antibiotic mixtures to produce intestinal dysbiosis. Their drinking water included 2 g/L streptomycin, 0.17 g/L gentamicin, 0.125 mg/L ciprofloxacin, and 1 g/L bacitracin. After surgery, the rats returned to their usual drinking water. Multi-strain probiotic therapy began on the thirteenth day post-SCI and lasted until the eighteenth. Oral forced feeding of 3g of 30 x 109 CFU/kg probiotics in sterile water was performed. Post-injury faeces were tested for gut dysbiosis on days 4, 11, 18, and 25. In addition to faecal sample analysis, the Basso Beattie Bresnahan Locomotor Rating Scale was used to evaluate the rats' behavioural and locomotor recovery on the 4th, 11th, 18th, and 25th dpi for 4 minutes per rat. After six days of probiotic therapy, faecal sample morphology and BBB locomotor assessments showed a mild effect. Overall, this study sheds light on the significant connection between SCI, intestinal dysbiosis, and probiotics. The study found that probiotics may help SCI patients recover locomotion and gut eubiosis. More study is needed to determine the full range of probiotic benefits. This research reveals new ways to improve SCI patients' results and quality of life.
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    The study of early orthodontic screening and referral practices by dental therapists in Malaysia
    (2024-03)
    Nie, Lim Yen
    In Malaysia, the orthodontic treatment needs of schoolchildren are high. Effective orthodontic treatment delivery depends on timely referrals of cases that have undergone an appropriate screening process. Dental therapists are among the first to identify any malocclusion in Malaysian primary schoolchildren. This study aimed to determine the prevalence of early orthodontic screening and referral practices by dental therapists among primary schoolchildren. The association between dental therapists’ referral practice and the training of dental therapists were determined. A cross-sectional study was conducted among 360 dental therapists in Malaysia. The questionnaire tool was adapted from the study of Lim et al. and translated into Malay. The adapted and translated questionnaire was pre-tested. The following variables were gathered using an online self-administered questionnaire: (1) the socio-demographic profile, (2) orthodontic screening and referral practices, (3) training of dental therapists, and (4) views on orthodontic treatment. A stratified random sampling was done. Descriptive analysis and bivariate analysis (Fisher’s Exact Test and Spearman correlation) were conducted on collected data using IBM SPSS (version 26). In addition, SPSS Modeler (version 18.0.0) was used to visually explore the co-occurrence frequency of the variables via the web graphs. This survey obtained a response rate of 97.8% (n=352). The study revealed that less than one-quarter of the dental therapists (22.7%) performed orthodontic screening on all primary schoolchildren, and almost one-third (32.7%) did not routinely do orthodontic screening. The common orthodontic assessment done during the orthodontic screening was overjet (92.8%), the presence of spacing or crowding (92.4%), overbite (86.9%) and the presence of crossbite (78.9%). Almost half of the dental therapists (47.7%) preferred dentists’ advice during screening instead of using guidelines (32.9%). More than half of them (65.6%) referred less than five patients per month, while almost one-quarter (24.1%) did not refer patients. Dental therapists used a variety of referral documents. The average orthodontic referral number is associated with exposure to orthodontic theory, practice and experience with orthodontic diagnosis during their career. In conclusion, this study obtained a high response rate. The orthodontic screening rate of dental therapists in all primary schoolchildren is poor. Variation in referral documents is identified. A standardized referral form from the school to the primary dental clinic is recommended to ensure timely monitoring and treatment of diagnosed cases. Oral health personnel working with schoolchildren are strongly encouraged to use a proforma in orthodontic screening and participate in continuing professional development (CPD).