Gene expression profile of immune-check point in response to Trastuzumab therapy in patients with HER-2 positive breast cancer.

OBJECTIVE: Aim: To clarify the association between response to Trastuzumab and molecular expression of TIM-3 and FOXP-3 immune checkpoints. PATIENTS AND METHODS: Materials and Methods: FOXP-3 and TIM-3 expression in peripheral blood was analyzed using qPCR, and the serum level of Trastuzumab was estimated using an immune sorbent enzyme assay. RESULTS: Results: During treatment with Trastuzumab, the FOXP-3 gene expression showed a significant decline throughout one year of treatment, going from 0.85 at cycle 9 to 0.75 at cycle 17. While the TIM-3 gene expression showed a significant up regulation at cycle 9 to 2.8 fold, followed by a reduction in the fold change from 2.8 to 1.7 in the font of reference gene expression. CONCLUSION: Conclusions:FOXP-3 and TIM-3 have the potential to be suggestive markers that can anticipate the response to Trastuzumab, but they are not capable of predicting the likelihood of recurrence.

Stunting and Its Associated Factors among Children Below 5 Years Old on the East Coast of Peninsular Malaysia: Evidence from the National Health and Morbidity Survey.

Background: Child malnutrition problems still occur in Malaysia, particularly stunting. This study aimed to determine the proportion of stunting among children below 5 years old and investigate the factors associated with stunting on the East Coast of Peninsular Malaysia. Methods: This study utilised data from the 2016 National Health and Morbidity Survey (NHMS). Multiple logistic regression was used to determine the factors associated with malnutrition among non-stunted and stunted children. Results: The proportion of stunting among children below 5 years old in this East Coast region was 26.2%. When divided by state, Kelantan had the highest proportion of stunting, followed by Pahang and Terengganu, at 28.8%, 26.2% and 23.4%, respectively. In this study, the factors associated with stunting were children aged 24 months old-59 months old (adjusted odds ratio [aOR]: 1.52; 95% CI: 1.26, 1.83; P < 0.001), male children (aOR: 1.47; 95% CI: 1.23, 1.76; P < 0.001), Orang Asli children (aOR: 2.84; 95% CI: 1.86, 4.32; P < 0.001), children with low birth weight from 1,500 g to 2,499 g (aOR: 1.86; 95% CI: 1.36, 2.55; P < 0.001) and children from households that practice unsanitary waste disposal (aOR: 1.42; 95% CI: 1.16, 1.74; P = 0.001). Conclusion: Stunting among children under the age of 5 years old on the East Coast of Peninsular Malaysia remains a public health problem. To reduce the prevalence of stunting in this region, intervention programmes should be intensified. Emphasis should be placed on public health programmes that target the associated factors, such as dietary habits, Orang Asli children, low birth weight and unsanitary waste disposal.

Yield of a second right colon examination during colonoscopy after a first examination using a mucosal exposure device.

BACKGROUND AND AIMS: Double right colon examination during colonoscopy has been advocated to reduce the risk of interval cancer in the right colon. Whether 2 examinations are necessary when the first examination is performed with a mucosal exposure device is uncertain. We documented the rates of missed adenomas, sessile serrated lesions, and hyperplastic polyps after an initial right colon examination by a high-level detector using a mucosal exposure device. METHODS: At a single tertiary hospital outpatient practice, we prospectively collected data on the yield of a second examination of the right colon after an initial examination by a single high-detecting colonoscopist using a mucosal exposure device. RESULTS: During the study period, 1331 eligible consecutive patients underwent colonoscopy. Right colon adenoma, sessile serrated lesion, and hyperplastic polyp miss rates were 15.8%, 14.1%, and 16.7%, respectively. Four percent of patients had adenomas detected in the right colon only with a second examination. CONCLUSIONS: A second examination of the right colon is warranted, even when using a distal mucosal exposure device to perform colonoscopy.

Adverse events and residual lesion rate after cold endoscopic mucosal resection of serrated lesions ≥10 mm.

BACKGROUND AND AIMS: Cold EMR is being increasingly used for large serrated lesions. We sought to measure residual lesion rates and adverse events after cold EMR of large serrated lesions. METHODS: In a single academic center, we retrospectively examined a database of serrated class lesions ≥10 mm removed with cold EMR for safety and efficacy. RESULTS: Five hundred sixty-six serrated lesions ≥10 mm in size were removed from 312 patients. We successfully contacted 223 patients (71.5%) with no reported serious adverse events that required hospitalization, repeat endoscopy, or transfusion. The residual lesion rate per lesion at first follow-up colonoscopy was 18 of 225 (8%; 95% confidence interval, 5-12.1). Lesions with residual were larger at polypectomy compared with lesions without recurrence (median, 23 mm versus 16 mm, P = .017). CONCLUSION: Cold EMR appears to be safe and effective for the removal of large serrated lesions.

Modelling excess mortality among breast cancer patients in the North East Region of Peninsular Malaysia, 2007-2011: a population-based study.

BACKGROUND: Measurement of breast cancer burden and identification of its influencing factors help in the development of public health policy and strategy against the disease. This study aimed to examine the variability of the excess mortality of female breast cancer patients in the North East Region of Peninsular Malaysia. METHODS: This retrospective cohort study was conducted using breast cancer data from the Kelantan Cancer Registry between 2007 and 2011, and Kelantan general population mortality data. The breast cancer cases were followed up for 5 years until 2016. Out of 598 cases, 549 cases met the study criteria and were included in the analysis. Modelling of excess mortality was conducted using Poisson regression. RESULTS: Excess mortality of breast cancer varied according to age group (50 years old and below vs above 50 years old, Adj. EHR: 1.47; 95% CI: 1.31, 4.09; P = 0.004), ethnicity (Malay vs non-Malay, Adj. EHR: 2.31; 95% CI: 1.11, 1.96; P = 0.008), and stage (stage III and IV vs. stage I and II, Adj. EHR: 5.75; 95% CI: 4.24, 7.81; P < 0.001). CONCLUSIONS: Public health policy and strategy aim to improve cancer survival should focus more on patients presented at age below 50 years old, Malay ethnicity, and at a later stage.

Immunity in young adult survivors of childhood leukemia is similar to the elderly rather than age-matched controls: Role of cytomegalovirus.

Many treatment complications that occur late in childhood cancer survivors resemble age-related comorbidities observed in the elderly. An immune phenotype characterized by increased immune activation, systemic inflammation, and accumulation of late-differentiated memory CD57(+) CD28(-) T cells has been associated with comorbidities in the elderly. Here, we explored if this phenotype was present in young adult leukemia survivors following an average of 19 years from chemotherapy and/or radiotherapy completion, and compared this with that in age-matched controls. We found that markers of systemic inflammation-IL-6 and human C-reactive protein and immune activation-CD38 and HLA-DR on T cells, soluble CD (sCD)163 from monocytes and macrophages-were increased in survivors compared to controls. T-cell responses specific to cytomegalovirus (CMV) were also increased in survivors compared to controls while CMV IgG levels in survivors were comparable to levels measured in the elderly (>50years) and correlated with IL-6, human C-reactive protein, sCD163, and CD57(+) CD28(-) memory T cells. Immune activation and inflammation markers correlated poorly with prior chemotherapy and radiotherapy exposure. These data suggest that CMV infection/reactivation is strongly correlated with the immunological phenotype seen in young childhood leukemia survivors and these changes may be associated with the early onset of age-related comorbidities in this group.

Mutations of pvdhfr and pvdhps genes in vivax endemic-malaria areas in Kota Marudu and Kalabakan, Sabah.

BACKGROUND: Malaria cases persist in some remote areas in Sabah and Sarawak despite the ongoing and largely successful malaria control programme conducted by the Vector Borne Disease Control Programme, Ministry Of Health, Malaysia. Point mutations in the genes that encode the two enzymes involved in the folate biosynthesis pathway, dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) enzymes confer resistance to pyrimethamine and sulfadoxine respectively, in both Plasmodium falciparum and P. vivax. The aim of the current study was to determine the mutation on both pvdhfr at codon 13, 33, 57, 58, 61, 117, and 173 and pvdhps genes at codon 383 and 553, which are potentially associated with resistance to pyrimethamine and sulfadoxine in P. vivax samples in Sabah. METHODS: Every individual was screened for presence of malaria infection using a commercial rapid dipstick assay, ParaMax-3™ (Zephyr Biomedical, India). Individuals tested positive for P. vivax had blood collected and parasite DNA extracted. The pvdhfr and pvdhps genes were amplified by nested-PCR. Restriction fragment length polymorphism (RFLP) was carried out for detection of specific mutations in pvdhfr at codons 13Leu, 33Leu, 57Ile/Leu, 58Arg, 61Met, 117Asn/Thr, and 173Leu and pvdhps at codons 383Gly and 553Gly. The PCR-RFLP products were analysed using the Agilent 2100 Bioanalyzer (Agilent Technology, AS). RESULTS: A total of 619 and 2119 individuals from Kalabakan and Kota Marudu, respectively participated in the study. In Kalabakan and Kota Marudu, 9.37 and 2.45 % were tested positive for malaria and the positivity for P. vivax infection was 4.2 and 0.52 %, respectively. No mutation was observed at codon 13, 33 and 173 on pvdhfr and at codon 553 on pvdhps gene on samples from Kalabakan and Kota Marudu. One-hundred per cent mutations on pvdhfr were at 57Leu and 117Thr. Mutation at 58Arg and 61Met was observed to be higher in Kota Marudu 72.73 %. Mutation at 383Gly on pvdhps was highest in Kalabakan with 80.77 %. There are four distinct haplotypes of pvdhfr/pvdhps combination. CONCLUSIONS: The presence of triple and quintuple mutation combination suggest that the P. vivax isolates exhibit a high degree of resistant to sulfadoxine, pyrimethamine and sulfadoxine-pyrimethamine combination therapy.

Potential Health Impacts of Bauxite Mining in Kuantan.

Bauxite mining is not known to most Malaysian except recently due to environmental pollution issues in Kuantan, Pahang. Potential impacts are expected to go beyond physical environment and physical illness if the situation is not controlled. Loss of economic potentials, and the presence of unpleasant red dust causing mental distress, anger and community outrage. More studies are needed to associate it with chronic physical illness. While evidences are vital for action, merely waiting for a disease to occur is a sign of failure in prevention. All responsible agencies should focus on a wider aspect of health determinants rather than merely on the occurrence of diseases to act and the need to emphasize on sustainable mining to ensure health of people is not compromised.

The CD14 C-260T single nucleotide polymorphism (SNP) modulates monocyte/macrophage activation in treated HIV-infected individuals.

BACKGROUND: HIV-infected individuals have an increased risk of cardiovascular disease (CVD). T-allele carriers of the CD14 C-260T single-nucleotide polymorphism (SNP) have reported increased expression of the LPS-binding receptor, CD14 and inflammation in the general population. Our aim was to explore the relationship of this SNP with monocyte/macrophage activation and inflammation and its association with sub-clinical atherosclerosis in HIV-infected individuals. METHODS: Patients with no pre-existing CVD risk factors on suppressive antiretroviral therapy were recruited from University Malaya Medical Centre, Malaysia (n = 84). The CD14 C-260T and TLR4 SNPs, Asp299Gly and Thr399Ile were genotyped and soluble(s) CD14 and sCD163 and high-sensitivity C-reactive protein, hsCRP were measured in plasma. Subclinical atherosclerosis was assessed by measuring carotid intima media thickness (cIMT). The association between CD14 C-260T SNP carriage and cIMT was assessed in a multivariable quantile regression model where a p-value of <0.05 was considered significant. RESULTS: We found the CD14 C-260T T-allele in 56% of the cohort and evidence of subclinical atherosclerosis in 27%. TT genotype was associated with higher sCD163 (p = 0.009) but only marginally higher sCD14 (p = 0.209) and no difference in hsCRP (p = 0.296) compared to CC/CT. In multivariable analysis, only Framingham risk score was independently associated with higher cIMT while lower sCD163 was trending towards significance. No association was found in TT-genotype carriers and cIMT measurements. CONCLUSION: The CD14 C-260T SNP was associated with increased monocyte activation but not systemic inflammation or cIMT in this HIV-infected cohort with low CVD risk profile.

Effect of selected local medicinal plants on the asexual blood stage of chloroquine resistant Plasmodium falciparum.

BACKGROUND: The development of resistant to current antimalarial drugs is a major challenge in achieving malaria elimination status in many countries. Therefore there is a need for new antimalarial drugs. Medicinal plants have always been the major source for the search of new antimalarial drugs. The aim of this study was to screen selected Malaysian medicinal plants for their antiplasmodial properties. METHODS: Each part of the plants were processed, defatted by hexane and sequentially extracted with dichloromethane, methanol and water. The antiplasmodial activities of 54 plant extracts from 14 species were determined by Plasmodium falciparum Histidine Rich Protein II ELISA technique. In order to determine the selectivity index (SI), all plant extracts demonstrating a good antiplasmodial activity were tested for their cytotoxicity activity against normal Madin-Darby Bovine Kidney (MDBK) cell lines by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Twenty three extracts derived from Curcuma zedoaria (rhizome), Curcuma aeruginosa (rhizome), Alpinia galanga (rhizome), Morinda elliptica (leaf), Curcuma mangga (rhizome), Elephantopus scaber (leaf), Vitex negundo (leaf), Brucea javanica (leaf, root and seed), Annona muricata (leaf), Cinnamomun iners (leaf) and Vernonia amygdalina (leaf) showed promising antiplasmodial activities against the blood stage chloroquine resistant P. falciparum (EC50 < 10 µg/ml) with negligible toxicity effect to MDBK cells in vitro (SI ≥10). CONCLUSION: The extracts belonging to eleven plant species were able to perturb the growth of chloroquine resistant P. falciparum effectively. The findings justified the bioassay guided fractionation on these plants for the search of potent antimalarial compounds or formulation of standardized extracts which may enhance the antimalarial effect in vitro and in vivo.

Effect of choline kinase inhibitor hexadecyltrimethylammonium bromide on Plasmodium falciparum gene expression.

Investigations on the fundamental of malaria parasite biology, such as invasion, growth cycle, metabolism and cell signalling have uncovered a number of potential antimalarial drug targets, including choline kinase, a key enzyme involved in the synthesis of phosphatidylcholine, an important component in parasite membrane compartment. The effect on gene expression of Plasmodium falciparum K1 strain following 72 hours exposure to 2 microM (IC50 concentration) of the choline kinase inhibitor, hexadecyltrimethylammonium bromide (HDTAB) was evaluated by DNA microarray analysis. Genes important in P. falciparum intraerythrocytic life cycle, such as invasion, cytoadherance and growth were among those affected by at least 2-fold changes in their expression levels compared with non HDTAB-treated control.

Responding to the Potential of Ebola Virus Disease (EVD) Importation into Malaysia.

The current Ebola outbreak, which is the first to affect West African countries, has been declared to have met the conditions for a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO). Thus, the Ministry of Health (MOH) of Malaysia has taken steps to strengthen and enhanced the five core components of preparedness and response to mitigate the outbreak. The National Crisis Preparedness and Response Centre (CPRC) commands, controls and coordinates the preparedness and response plans for disasters, outbreaks, crises and emergencies (DOCE) related to health in a centralised way. Through standardised case definition and mandatory notification of Ebola by public and private practitioners, surveillance of Ebola is made possible. Government hospitals and laboratories have been identified to manage and diagnose Ebola virus infections, and medical staff members have been trained to handle an Ebola outbreak, with emphasis on strict infection prevention and control practices. Monitoring of the points of entry, focusing on travellers and students visiting or coming from West African countries is made possible by interagency collaborations. To alleviate the public's anxiety, effective risk communications are being delivered through various channels. With experience in past outbreak control, the MOH's preparedness and response plans are in place to abate an Ebola outbreak.

High prevalence of mutation in the Plasmodium falciparum dhfr and dhps genes in field isolates from Sabah, Northern Borneo.

BACKGROUND: Sulphadoxine-pyrimethamine (SP) has been in use for the treatment of uncomplicated falciparum malaria in Malaysia since the 1970s and is still widely employed in spite of widespread clinical resistance. Resistance to SP is known to be mediated by mutations in the pfdhfr and pfdhps genes. The aim of the present study was to investigate the distribution of pfdhfr and pfdhps gene polymorphism in Plasmodium falciparum field isolates from Kalabakan, Sabah, in northern Borneo. METHODS: A total number of 619 individuals were screened from 23 study sites of which 31 were positive for P. falciparum. Analysis of restriction fragment length polymorphisms (RFLP) was used to identify polymorphism in the pfdhfr and pfdhps genes at positions 16, 51, 59, 108, 164 and 437, 540, 581, respectively. RESULTS: All samples had at least one mutation in each of the genes associated with drug resistance. The prevalence of pfdhfr 59arg, 164leu and 108asn were 100%, 80.65% and 58.06%, respectively. Pfdhps mutants 437gly and 581gly accounted for 100% and 74.19% respectively. In pfdhfr, the most common mutant genotypes were combination 59arg + 164leu (22.58%) and 59arg + 108asn + 164leu (51.61%). In pfdhps the most common genotype was 437gly + 581gly (74.19%). One individual (3.22%) harboured parasites with four pfdhfr (16 val + 59arg + 108asn + 164leu) and two pfdhps (437gly + 581gly) mutations. The highest quintuple pfdhfr/pfdhps (41.94%) was three pfdhfr (59arg + 108asn + 164gly) and two pfdhps (437gly + 581gly). CONCLUSION: The data suggest a high prevalence of genetic variations conferring resistance to SP which can predict treatment failure before becoming clinically evident. In areas like this, the use of SP may no longer be indicated.

Willingness to receive a COVID-19 booster vaccine and its associated factors among adults with chronic disease: A cross-sectional study in Putrajaya, Malaysia.

Introduction: Booster vaccination has been shown to reduce transmission and serious infection with COVID-19. This study examined the willingness to receive a COVID-19 booster vaccine and its associated factors among high-risk patients at Klinik Kesihatan Putrajaya Presint 9. Method: A cross-sectional study was conducted among patients aged >18 years attending Klinik Kesihatan Putrajaya Presint 9 with a high risk of contracting COVID-19 recruited via systematic random sampling. Data were collected using a self-administered questionnaire. A multiple logistic regression analysis was performed to identify the associated factors. Results: The response rate for this study was 97.4% (N=489). The median patient age was 55 years. Approximately 51.7% were men, and 90.4% were Malays. Approximately 81.2% were willing to receive a COVID-19 booster vaccine. The patients who perceived COVID-19 as a serious illness (Adjusted Odd Ratio, AOR=2.414), those who perceived COVID-19 booster vaccines as beneficial (AOR=7.796), those who disagreed that COVID-19 booster vaccines have many side effects (AOR=3.266), those who had no doubt about the content of COVID-19 vaccines (AOR=2.649) and those who were employed (AOR=2.559) and retired (AOR=2.937) were more likely to be willing to receive a booster vaccine than those who were unemployed and those who did not have close friends or family members who contracted severe COVID-19 (AOR=2.006). Conclusion: The majority of the participants were willing to receive a COVID-19 booster vaccine. Healthcare authorities should take initiatives to design targeted public intervention programmes to increase the willingness for COVID-19 booster vaccination.

Molecular and serological biomarkers to predict trastuzumab responsiveness in HER-2 positive breast cancer.

HER-2-positive breast cancer is characterized by its aggressive nature, poor prognosis, and reduced overall survival. The emergence of trastuzumab resistance is currently considered a global problem. The immune system plays a pivotal role in tumor progression and development. Cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and other immune checkpoint proteins may be potential prognostic factors and therapeutic targets for breast cancer. This study aimed to determine the correlation between CTLA-4 expression in peripheral blood and insulin-like growth factor-1 (IGF-1) serum levels and their impact on trastuzumab responsiveness in HER-2-positive patients with breast cancer. CTLA-4 expression was analyzed in peripheral blood cells using quantitative PCR, while IGF-1 serum levels were assessed through electrochemiluminescence assays. There was a significant increase in CTLA-4 expression at cycle 9, which continued to increase until it reached 4.6 at cycle 17. High IGF-1 levels were observed in newly diagnosed HER-2 positive patients before trastuzumab therapy, significantly decreasing post-therapy (p=0.001). Co-targeting HER-2 and IGF-1 receptors may reduce the risk of recurrence and improve outcomes. In addition, targeted CTLA-4 molecules may improve patient survival and prevent recurrence.

Evaluating Cataract Surgical Rate through Smart Partnership between Ministry of Health, Malaysia and Federal Territory Islamic Religious Council.

INTRODUCTION: Cataract is the leading cause of blindness. About 90% of cataract blindness occurs in low- and middle-income countries. The prevalence of blindness and low vision in any country depends on the socioeconomic status, the availability of medical and healthcare facilities, and the literacy of the population. AIM: This paper aims to estimate the cataract surgery rate (CSR) at Pusat Pembedahan Katarak, MAIWP-Hospital Selayang (Cataract Operation Centre), and provide descriptive assessments of the patients who received eye treatments in the center. METHODS: The data were retrieved from the clinical database from 2013 to 2016. Information on the patient's sociodemographic and clinical and treatment history was collected. RESULTS: The cataract surgery rate for 2013 was about 27 and increased to 37.3 in 2014. However, it declined to 25 in 2015 before it resumed to 36 in 2016. For female patients who received eye treatments at Pusat Pembedahan Katarak, MAIWP-Hospital Selayang, the rate was higher (53.7%) compared to male patients (46.3%). The mean duration of cataract surgery from 2013 to 2016 was 21.25 ± 11.071 min. CONCLUSION: The increased cataract surgery rate for MAIWP-HS through smart partnerships for day care cataract surgery proved that better accessibility makes the short- and long-term strategies for the reduction and prevention of blindness in Malaysia possible to achieve.

Carbon dots labeled Lactiplantibacillus plantarum: a fluorescent multifunctional biocarrier for anticancer drug delivery.

A carbon dots (CDs)-biolabeled heat-inactivated Lactiplantibacillus plantarum (HILP) hybrid was investigated as a multifunctional probiotic drug carrier with bioimaging properties using prodigiosin (PG) as anticancer agent. HILP, CDs and PG were prepared and characterized using standard methods. CDs-labeled HILP (CDs/HILP) and PG loaded CDs/HILP were characterized by transmission electron microscopy (TEM), laser scanning confocal microscopy (LSCM) and for entrapment efficiency (EE%) of CDs and PG, respectively. PG-CDs/HILP was examined for stability and PG release. the anticancer activity of PG-CDs/HILP was assessed using different methods. CDs imparted green fluorescence to HILP cells and induced their aggregation. HILP internalized CDs via membrane proteins, forming a biostructure with retained fluorescence in PBS for 3 months at 4°C. Loading PG into CDs/HILP generated a stable green/red bicolor fluorescent combination permitting tracking of both drug carrier and cargo. Cytotoxicity assay using Caco-2 and A549 cells revealed enhanced PG activity by CDs/HILP. LCSM imaging of PG-CDs/HILP-treated Caco-2 cells demonstrated improved cytoplasmic and nuclear distribution of PG and nuclear delivery of CDs. CDs/HILP promoted PG-induced late apoptosis of Caco-2 cells and reduced their migratory ability as affirmed by flow cytometry and scratch assay, respectively. Molecular docking indicated PG interaction with mitogenic molecules involved in cell proliferation and growth regulation. Thus, CDs/HILP offers great promise as an innovative multifunctional nanobiotechnological biocarrier for anticancer drug delivery. This hybrid delivery vehicle merges the physiological activity, cytocompatibility, biotargetability and sustainability of probiotics and the bioimaging and therapeutic potential of CDs.

Early phase oncology clinical trials in Malaysia: current status and future perspectives.

Historically, the majority of oncology clinical trials are conducted in Western Europe and North America. Globalization of drug development has resulted in sponsors shifting their focus to the Asia-Pacific region. In Malaysia, implementation of various government policies to promote clinical trials has been initiated over a decade ago and includes the establishment of Clinical Research Malaysia, which functions as a facilitator and enabler of industry-sponsored clinical trials on a nationwide basis. Although oncology clinical trials in Malaysia have seen promising growth, there are still only a limited number of early phase oncology studies being conducted. Hence, the Phase 1 Realization Project was initiated to develop Malaysia's early phase clinical trial capabilities. In addition, the adaptation of good practices from other countries contribute to the effective implementation of existing initiatives to drive progress in the development of early phase drug development set up in Malaysia. Furthermore, holistic approaches with emphasis in training and education, infrastructure capacities, strategic alliances, reinforcement of upstream activities in the value chain of drug development, enhanced patient advocacy, coupled with continued commitment from policy makers are imperative in nurturing a resilient clinical research ecosystem in Malaysia.