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  1. Lim HY, Dolzhenko AV
    Eur J Med Chem, 2024 Jul 16;276:116680.
    PMID: 39018924 DOI: 10.1016/j.ejmech.2024.116680
    1,3,5-Triazine scaffold has garnered considerable interest due to its wide-ranging pharmacological properties, particularly in the field of cancer research. Breast cancer is the most commonly diagnosed cancer among women. Approximately one in eight women will receive a diagnosis of invasive breast cancer during their lifetime. The five-year survival rate for invasive breast cancer is less than 30 %, indicating a need to develop a more effective therapeutic agent targeting breast cancer. This review discusses bioactive 1,3,5-triazines targeting breast cancer cells by the inhibition of different enzymes, which include PI3K, mTOR, EGFR, VEGFR, FAK, CDK, DHFR, DNA topoisomerase, ubiquitin-conjugating enzyme, carbonic anhydrase, and matrix metalloproteinase. The anticancer agent search in some drug discovery programs is based on compound screening for antiproliferative activity. Often, multiple targets contribute to the anticancer effect of 1,3,5-triazines and this approach allows identification of active molecules prior to identification of their targets.
  2. Lim SW, Lim HY, Kannaiah T, Zuki Z
    Malays Orthop J, 2017 Nov;11(3):50-52.
    PMID: 29326768 MyJurnal DOI: 10.5704/MOJ.1711.004
    Streptococcus constellatus is an extremely rare cause of pyogenic spondylodiscitis. Literature search yielded only one case report in an elderly 72 years old man with spontaneous T10-T11 S. constellatus spondylodiscitis. It is virtually unheard of in young teenage. We report the case of a 14 years old male teenager who presented with worsening low back pain for one year with no neurological deficit. Imaging studies were consistent with features of L4-L5 spondylodiscitis. CT guided biopsy grew a pure culture of streptococcus constellatus sensitive to penicillin and erythromycin. He showed full recovery with six weeks of intravenous antibiotics. Due to the insidious onset, this case highlight the importance of high clinical suspicion and early diagnosis, with image guided biopsy followed by treatment with appropriate intravenous antibiotics to enable full recovery without further neurological deterioration.
  3. Farghadani R, Lim HY, Abdulla MA, Rajarajeswaran J
    Bioorg Chem, 2024 Nov;152:107730.
    PMID: 39216194 DOI: 10.1016/j.bioorg.2024.107730
    Breast cancer is the most prevalent cancer among women globally, with triple-negative breast cancer (TNBC) associated with poor prognosis and low five-year survival rates. Schiff base compounds, known for their extensive pharmacological activities, have garnered significant attention in cancer drug research. This study aimed to evaluate the anticancer potential of a novel β-diiminato compound and elucidate its mechanism of action. The compound's effect on cell viability was assessed using MTT assays in breast cancer cell lines including MCF-7 and MDA-MB-231. Cytotoxic effects were further analyzed using trypan blue exclusion and lactate dehydrogenase (LDH) release assays. In order to assess the mechanism of inhibitory activity and mode of cell death induced by this compound, flow cytometry of cell cycle distribution and apoptosis analysis were carried out. Apoptosis incidence was initially assessed through cell and nuclear morphological changes (Hoechst 33342/Propidium iodide (PI) staining) and further confirmed by Annexin V/PI staining and flow cytometry analysis. In addition, the effect of this compound on the disruption of mitochondrial membrane potential (MMP) and generation of the reactive oxygen species (ROS) was determined using the JC-1 indicator and DCFDA dye, respectively. The results demonstrated that the 24 h treatment with β-diiminato compound significantly suppressed the viability of MDA-MB-231 and MCF-7 cancer cells in a dose-dependent manner with the IC50 value of 2.41 ± 0.29 and 3.51 ± 0.14, respectively. The cytotoxic effect of the compound was further confirmed with a dose-dependent increase in the number of dead cells and enhanced LDH level in the culture medium. This compound exerted its anti-proliferative effect by G2/M phase cell growth arrest in MDA-MB-231 breast cancer cells and induced apoptosis-mediated cell death, which involved characteristic changes in cell and nuclear morphology, phosphatidylserine externalization, mitochondrial membrane depolarization, and increased ROS level. Neither hepatotoxicity nor nephrotoxicity was detected in the biochemical and histopathological analysis confirming the safety characterization of this compound usage. Therefore, the results significantly confirmed the potential anticancer activity of a novel β-diiminato compound, as evidenced by the induction of cell cycle arrest and apoptosis, which might be driven by the ROS‑mediated mitochondrial death pathway. This compound can be a promising candidate for future anticancer drug design and TNBC treatment, and further preclinical and clinical studies are warranted.
  4. Cheah WL, Law LS, Teh KH, Kam SL, Voon GEH, Lim HY, et al.
    Health Sci Rep, 2021 Sep;4(3):e362.
    PMID: 34466663 DOI: 10.1002/hsr2.362
    Background and Aims: This study aimed to examine the quality of life (QoL) and health satisfaction of undergraduate university students in Sarawak during MCO and its association with socio-demographic profiles.

    Methods: In this cross-sectional study, QoL and satisfaction of health of 503 undergraduate university students (63.4% females) from a public university was assessed online using the World Health Organization QoL (WHOQOL)-BREF instrument.

    Results: The overall QoL and satisfaction with health were 3.7 ± 0.87 and 3.9 ± 0.82, respectively. Male students showed significantly lower mean scores for the environmental domains than female students (63.37 ± 16.21 vs 68.10 ± 14.00, P 

  5. Mohamed W, Ishak KN, Baharum N, Zainudin N, Lim HY, Noh M, et al.
    Adipocyte, 2024 Dec;13(1):2314032.
    PMID: 38373876 DOI: 10.1080/21623945.2024.2314032
    Excessive deposit of epicardial adipose tissue (EAT) were recently shown to be positively correlated with cardiovascular disease (CVD). This study aims to investigate the thickness of EAT and its association with the components of metabolic syndrome among multi-ethnic Malaysians with and without acute coronary syndrome (ACS). A total of 213 patients were recruited, with the thickness of EAT were quantified non-invasively using standard two-dimensional echocardiography. EAT thickness among the Malaysian population was prompted by several demographic factors and medical comorbidities, particularly T2DM and dyslipidaemia. ACS patients have significantly thicker EAT compared to those without ACS (4.1 mm vs 3.7 mm, p = 0.035). Interestingly, among all the races, Chinese had the thickest EAT distribution (4.6 mm vs 3.8 mm), with age (p = 0.04 vs p 
  6. Mahendran S, Ng BH, Lim HY, Zailanalhuddin NE, Chandran Y, Wong WF, et al.
    Med J Malaysia, 2024 Jul;79(4):408-413.
    PMID: 39086337
    INTRODUCTION: Febrile seizures in children can be associated with various underlying conditions, including COVID-19. Differentiating COVID-19 and non-COVID-19 related febrile seizures is crucial for tailored patient management and for implementing appropriate infection control measures to prevent nosocomial transmission. This study aimed to describe the clinical features of children hospitalised for COVID-19 and non-COVID-19 febrile seizures and to identify factors that differentiate between the two groups.

    MATERIALS AND METHODS: This retrospective cross-sectional study involved children aged 6 months to 6 years who were hospitalised for febrile seizures in Hospital Tuanku Ja'afar Seremban (HTJS) from January 2021 to June 2022. Descriptive statistics were used to summarise the differences in demographics and clinical presentations. Logistic regression analyses were performed to identify factors associated with COVID-19 and non-COVID-19 febrile seizures.

    RESULTS: Of the 345 patients (median age 22 months, IQR 15- 32; 59.7% were males) included in the study, 130 (37.7%) tested positive for COVID-19, while 215 (62.3%) tested negative. There were no significant differences between both groups based on age, comorbidities, history of febrile seizures, seizure types, temperature on arrival, cough and rhinorrhoea. Multivariate analysis revealed that a family history of febrile seizures and leucocytosis were associated with increased odds of non-COVID-19 febrile seizures. In contrast, lymphopenia was associated with decreased odds.

    CONCLUSION: The clinical presentation of COVID-19 and non- COVID-19 febrile seizures are remarkably similar, highlighting the importance of including COVID-19 screening in febrile seizures workup. Full blood count readings may be potentially useful for differentiating between these conditions.

  7. Soon SS, Lim HY, Lopes G, Ahn J, Hu M, Ibrahim HM, et al.
    Asian Pac J Cancer Prev, 2013;14(4):2159-65.
    PMID: 23725106
    Cancer registries help to establish and maintain cancer incidence reporting systems, serve as a resource for investigation of cancer and its causes, and provide information for planning and evaluation of preventive and control programs. However, their wider role in directly enhancing oncology drug access has not been fully explored. We examined the value of cancer registries in oncology drug access in the Asia-Pacific region on three levels: (1) specific registry variable types; (2) macroscopic strategies on the national level; and (3) a regional cancer registry network. Using literature search and proceedings from an expert forum, this paper covers recent cancer registry developments in eight economies in the Asia-Pacific region - Australia, China, Hong Kong, Malaysia, Singapore, South Korea, Taiwan, and Thailand - and the ways they can contribute to oncology drug access. Specific registry variables relating to demographics, tumor characteristics, initial treatment plans, prognostic markers, risk factors, and mortality help to anticipate drug needs, identify high-priority research area and design access programs. On a national level, linking registry data with clinical, drug safety, financial, or drug utilization databases allows analyses of associations between utilization and outcomes. Concurrent efforts should also be channeled into developing and implementing data integrity and stewardship policies, and providing clear avenues to make data available. Less mature registry systems can employ modeling techniques and ad-hoc surveys while increasing coverage. Beyond local settings, a cancer registry network for the Asia-Pacific region would offer cross-learning and research opportunities that can exert leverage through the experiences and capabilities of a highly diverse region.
  8. Ng DC, Liew CH, Tan KK, Chin L, Ting GSS, Fadzilah NF, et al.
    BMC Infect Dis, 2023 Jun 12;23(1):398.
    PMID: 37308825 DOI: 10.1186/s12879-023-08357-y
    BACKGROUND: Children account for a significant proportion of COVID-19 hospitalizations, but data on the predictors of disease severity in children are limited. We aimed to identify risk factors associated with moderate/severe COVID-19 and develop a nomogram for predicting children with moderate/severe COVID-19.

    METHODS: We identified children ≤ 12 years old hospitalized for COVID-19 across five hospitals in Negeri Sembilan, Malaysia, from 1 January 2021 to 31 December 2021 from the state's pediatric COVID-19 case registration system. The primary outcome was the development of moderate/severe COVID-19 during hospitalization. Multivariate logistic regression was performed to identify independent risk factors for moderate/severe COVID-19. A nomogram was constructed to predict moderate/severe disease. The model performance was evaluated using the area under the curve (AUC), sensitivity, specificity, and accuracy.

    RESULTS: A total of 1,717 patients were included. After excluding the asymptomatic cases, 1,234 patients (1,023 mild cases and 211 moderate/severe cases) were used to develop the prediction model. Nine independent risk factors were identified, including the presence of at least one comorbidity, shortness of breath, vomiting, diarrhea, rash, seizures, temperature on arrival, chest recessions, and abnormal breath sounds. The nomogram's sensitivity, specificity, accuracy, and AUC for predicting moderate/severe COVID-19 were 58·1%, 80·5%, 76·8%, and 0·86 (95% CI, 0·79 - 0·92) respectively.

    CONCLUSION: Our nomogram, which incorporated readily available clinical parameters, would be useful to facilitate individualized clinical decisions.

  9. Chun-Ern Ng D, Liew CH, Tan KK, Lim HY, Zailanalhuddin NEB, Tan SF, et al.
    Pediatr Int, 2023;65(1):e15690.
    PMID: 38037505 DOI: 10.1111/ped.15690
    BACKGROUND: We describe the epidemiology, clinical characteristics, and outcomes of multisystem inflammatory syndrome in children (MIS-C) among children from Negeri Sembilan, Malaysia.

    METHODS: A retrospective, multicentre, observational study was performed among children ≤15 years old who were hospitalized for MIS-C between January 18, 2021 and June 30, 2023. The incidence of MIS-C was estimated using reported SARS-CoV-2 cases and census population data. Descriptive analyses were used to summarize the clinical presentation and outcomes.

    RESULTS: The study included 53 patients with a median age of 5.7 years (IQR 1.8-8.7 years); 75.5% were males. The overall incidence of MIS-C was approximately 5.9 cases per 1,000,000 person-months. Pediatric intensive care unit (PICU) admission was required for 22 (41.5%) patients. No mortalities were recorded. Children aged 6-12 years were more likely to present with cardiac dysfunction/shock (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.67-17.66), whereas children below 6 years were more likely to present with a Kawasaki disease phenotype (OR 5.50, 95% CI 1.33-22.75). Twenty patients (37.7%) presented with involvement of at least four organ systems, but four patients (7.5%) demonstrated single-organ system involvement.

    CONCLUSION: An age-based variation in the clinical presentation of MIS-C was demonstrated. Our findings suggest MIS-C could manifest in a spectrum, including single-organ involvement. Despite the high requirement for PICU admission, the prognosis of MIS-C was favorable, with no recorded mortalities.

  10. Chen LT, Martinelli E, Cheng AL, Pentheroudakis G, Qin S, Bhattacharyya GS, et al.
    Ann Oncol, 2020 03;31(3):334-351.
    PMID: 32067677 DOI: 10.1016/j.annonc.2019.12.001
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.
  11. Szulkin R, Karlsson R, Whitington T, Aly M, Gronberg H, Eeles RA, et al.
    Cancer Epidemiol Biomarkers Prev, 2015 Nov;24(11):1796-800.
    PMID: 26307654 DOI: 10.1158/1055-9965.EPI-15-0543
    BACKGROUND: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical.

    METHODS: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR).

    RESULTS: We observed no significant association between genetic variants and prostate cancer survival.

    CONCLUSIONS: Common genetic variants with large impact on prostate cancer survival were not observed in this study.

    IMPACT: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes.

  12. Kar SP, Beesley J, Amin Al Olama A, Michailidou K, Tyrer J, Kote-Jarai Z, et al.
    Cancer Discov, 2016 Sep;6(9):1052-67.
    PMID: 27432226 DOI: 10.1158/2159-8290.CD-15-1227
    Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis.

    SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

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