Displaying publications 1 - 20 of 49 in total

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  1. Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Lee JY, et al.
    N Engl J Med, 2015 Mar 26;372(13):1204-12.
    PMID: 25774645 DOI: 10.1056/NEJMoa1415447
    BACKGROUND: Most trials comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG) have not made use of second-generation drug-eluting stents.
    METHODS: We conducted a randomized noninferiority trial at 27 centers in East Asia. We planned to randomly assign 1776 patients with multivessel coronary artery disease to PCI with everolimus-eluting stents or to CABG. The primary end point was a composite of death, myocardial infarction, or target-vessel revascularization at 2 years after randomization. Event rates during longer-term follow-up were also compared between groups.
    RESULTS: After the enrollment of 880 patients (438 patients randomly assigned to the PCI group and 442 randomly assigned to the CABG group), the study was terminated early owing to slow enrollment. At 2 years, the primary end point had occurred in 11.0% of the patients in the PCI group and in 7.9% of those in the CABG group (absolute risk difference, 3.1 percentage points; 95% confidence interval [CI], -0.8 to 6.9; P=0.32 for noninferiority). At longer-term follow-up (median, 4.6 years), the primary end point had occurred in 15.3% of the patients in the PCI group and in 10.6% of those in the CABG group (hazard ratio, 1.47; 95% CI, 1.01 to 2.13; P=0.04). No significant differences were seen between the two groups in the occurrence of a composite safety end point of death, myocardial infarction, or stroke. However, the rates of any repeat revascularization and spontaneous myocardial infarction were significantly higher after PCI than after CABG.
    CONCLUSIONS: Among patients with multivessel coronary artery disease, the rate of major adverse cardiovascular events was higher among those who had undergone PCI with the use of everolimus-eluting stents than among those who had undergone CABG. (Funded by CardioVascular Research Foundation and others; BEST ClinicalTrials.gov number, NCT00997828.).
  2. Tan JW, Chew DP, Abdul Kader MAS, Ako J, Bahl VK, Chan M, et al.
    Eur Cardiol, 2021 Feb;16:e02.
    PMID: 33708263 DOI: 10.15420/ecr.2020.40
    The unique characteristics of patients with acute coronary syndrome in the Asia-Pacific region mean that international guidelines on the use of dual antiplatelet therapy (DAPT) cannot be routinely applied to these populations. Newer generation P2Y12 inhibitors (i.e. ticagrelor and prasugrel) have demonstrated improved clinical outcomes compared with clopidogrel. However, low numbers of Asian patients participated in pivotal studies and few regional studies comparing DAPTs have been conducted. This article aims to summarise current evidence on the use of newer generation P2Y12 inhibitors in Asian patients with acute coronary syndrome and provide recommendations to assist clinicians, especially cardiologists, in selecting a DAPT regimen. Guidance is provided on the management of ischaemic and bleeding risks, including duration of therapy, switching strategies and the management of patients with ST-elevation and non-ST-elevation MI or those requiring surgery. In particular, the need for an individualised DAPT regimen and considerations relating to switching, de-escalating, stopping or continuing DAPT beyond 12 months are discussed.
  3. Lee CY, Huang CH, Rastegari E, Rengganaten V, Liu PC, Tsai PH, et al.
    Int J Mol Sci, 2021 Sep 13;22(18).
    PMID: 34576032 DOI: 10.3390/ijms22189869
    The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.
  4. Hu J, Pradit S, Loh PS, Chen Z, Guo C, Le TPQ, et al.
    Mar Pollut Bull, 2024 Jan 29;200:116064.
    PMID: 38290368 DOI: 10.1016/j.marpolbul.2024.116064
    Mangrove forests can help to mitigate climate change by storing a significant amount of carbon (C) in soils. Planted mangrove forests have been established to combat anthropogenic threats posed by climate change. However, the efficiency of planted forests in terms of soil organic carbon (SOC) storage and dynamics relative to that of natural forests is unclear. We assessed SOC and nutrient storage, SOC sources and drivers in a natural and a planted forest in southern Thailand. Although the planted forest stored more C and nutrients than the natural forest, the early-stage planted forest was not a strong sink relative to mudflat. Both forests were predominated by allochthonous organic C and nitrogen limited, with total nitrogen being a major driver of SOC in both cases. SOC showed a significant decline along land-to-sea and depth gradients as a result of soil texture, nutrient availability, and pH in the natural forest.
  5. Hung SK, Kou HW, Hsu KH, Wu CT, Lee CW, Leonard Goh ZN, et al.
    J Formos Med Assoc, 2021 Mar;120(3):997-1004.
    PMID: 32917483 DOI: 10.1016/j.jfma.2020.08.039
    BACKGROUND/PURPOSE: Splenic abscess is a life-threatening surgical emergency which requires early diagnosis and intervention to maximize patient outcomes. This can be achieved through accurate risk stratification in the emergency department (ED). Sarcopenia refers to an age-related loss of skeletal muscle mass and strength that is accompanied by major physiologic and clinical ramifications, and often signifies decreased physiologic reserves. It is associated with poor clinical outcomes in sepsis, acute respiratory failure, oncological surgery, and liver transplantation. This study evaluates the utility of sarcopenia as a radiological stratification tool to predict in-hospital mortality of splenic abscess patients in the ED. This will assist emergency physicians, internists and surgeons in rapid risk stratification, assessing treatment options, and communicating with family members.

    METHODS: 99 adult patients at four training and research hospitals who had undergone an abdominal contrast computed tomography scan in the ED with the final diagnosis of splenic abscess from January 2004 to November 2017 were recruited. Evaluation for sarcopenia was performed via calculating the psoas cross-sectional area at the level of the third lumbar vertebra and normalising for height, before checking it against pre-defined values. Univariate analyses were used to evaluate the differences between survivors and non-survivors. Sensitivity, specificity, and predictive values of the presence of sarcopenia in predicting in-hospital mortality were calculated. Kaplan-Meier methods, log-rank test, and Cox proportional hazards model were also performed to examine survival between groups with sarcopenia versus non-sarcopenia.

    RESULTS: Splenic abscess patients with sarcopenia were 7.56 times more at risk of in-hospital mortality than those without sarcopenia (multivariate-adjusted HR: 7.56; 95% CI: 1.55-36.93). Presence of sarcopenia was found to have 84.62% sensitivity and 96.49% negative predictive value in predicting mortality.

    CONCLUSION: Sarcopenia is associated with poor prognoses of in-hospital mortality in patients with splenic abscess presenting to the ED. We recommend its use in the ED to rapidly risk stratify and predict outcome to guide treatment strategies.

  6. Vaezzadeh V, Thomes MW, Kunisue T, Tue NM, Zhang G, Zakaria MP, et al.
    Chemosphere, 2021 Jan;263:128272.
    PMID: 33297216 DOI: 10.1016/j.chemosphere.2020.128272
    Barnacles are ubiquitous in coastal ecosystems of different geographical regions worldwide. This is the first study attempting to assess the suitability of barnacles as bioindicators of persistent organic pollutants (POPs) in coastal environments. Barnacles were collected from the coasts around Peninsular Malaysia and analyzed for POPs including polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs). Among POPs, PCBs showed the highest concentrations with elevated contributions of CB28 and CB153. As for PBDEs, BDE47 was the most frequently detected congener, while BDE209 was detected in barnacles from two stations in Port Klang and the levels reached up to >70% of total PBDE concentrations. Concentrations of OCPs detected in barnacles were in the order of CHLs > DDTs > HCHs > HCB and 4,4'-DDE and cis- and trans-chlordane were the predominant OCP compounds. A comparison with previous studies in Malaysia showed consistent levels of POPs. Green mussels collected from selected barnacles' habitats, for the sake of a comparison, showed almost similar profiles but lower concentrations of POPs. The spatial distribution of POPs observed in barnacles and comparison of POP levels and profiles with mussels indicated that barnacles can be useful bioindicators for monitoring POPs contamination in the coastal ecosystems.
  7. Serebruany V, Tanguay JF, Benavides MA, Cabrera-Fuentes H, Eisert W, Kim MH, et al.
    Am J Ther, 2020 10 29;27(6):e563-e572.
    PMID: 33109913 DOI: 10.1097/MJT.0000000000001286
    BACKGROUND: Excess vascular deaths in the PLATO trial comparing ticagrelor to clopidogrel have been repeatedly challenged by the Food and Drug Administration (FDA) reviewers and academia. Based on the Freedom of Information Act, BuzzFeed won a court order and shared with us the complete list of reported deaths for the ticagrelor FDA New Drug Application (NDA) 22-433. This dataset was matched against local patient-level records from PLATO sites monitored by the sponsor.

    STUDY QUESTION: Whether FDA death data in the PLATO trial matched the local site records.

    STUDY DESIGN: The NDA spreadsheet contains 938 precisely detailed PLATO deaths. We obtained and validated local evidence for 52 deaths among 861 PLATO patients from 14 enrolling sites in 8 countries and matched those with the official NDA dataset submitted to the FDA.

    MEASURES AND OUTCOMES: Existence, precise time, and primary cause of deaths in PLATO.

    RESULTS: Discrepant to the NDA document, sites confirmed 2 extra unreported deaths (Poland and Korea) and failed to confirm 4 deaths (Malaysia). Of the remaining 46 deaths, dates were reported correctly for 42 patients, earlier (2 clopidogrel), or later (2 ticagrelor) than the actual occurrence of death. In 12 clopidogrel patients, cause of death was changed to "vascular," whereas 6 NDA ticagrelor "nonvascular" or "unknown" deaths were site-reported as of "vascular" origin. Sudden death was incorrectly reported in 4 clopidogrel patients, but omitted in 4 ticagrelor patients directly affecting the primary efficacy PLATO endpoint.

    CONCLUSIONS: Many deaths were inaccurately reported in PLATO favoring ticagrelor. The full extent of mortality misreporting is currently unclear, while especially worrisome is a mismatch in identifying primary death cause. Because all PLATO events are kept in the cloud electronic Medidata Rave capture system, securing the database content, examining the dataset changes or/and repeated entries, identifying potential interference origin, and assessing full magnitude of the problem are warranted.

  8. Du P, Liu X, Zhong G, Zhou Z, Thomes MW, Lee CW, et al.
    PMID: 32023897 DOI: 10.3390/ijerph17030889
    Southeast Asian countries including Malaysia play a major role in global drug trade and abuse. Use of amphetamine-type stimulants has increased in the past decade in Malaysia. This study aimed to apply wastewater-based epidemiology for the first time in Kuala Lumpur, Malaysia, to estimate the consumption of common illicit drugs in urban population. Influent wastewater samples were collected from two wastewater treatment plants in Kuala Lumpur in the summer of 2017. Concentrations of twenty-four drug biomarkers were analyzed for estimating drug consumption. Fourteen drug residues were detected with concentrations of up to 1640 ng/L. Among the monitored illicit drugs, 3,4-methylenedioxy-methamphetamine (MDMA) or ecstasy had the highest estimated per capita consumptions. Consumption and dose of amphetamine-type stimulants (methamphetamine and MDMA) were both an order of magnitude higher than those of opioids (heroin and codeine, methadone and tramadol). Amphetamine-type stimulants were the most prevalent drugs, replacing opioids in the drug market. The prevalence trend measured by wastewater-based epidemiology data reflected the shift to amphetamine-type stimulants as reported by the Association of Southeast Asian Nations Narcotics Cooperation Center. Most of the undetected drug residues were new psychoactive substances (NPSs), suggesting a low prevalence of NPSs in the drug market.
  9. Chau SC, Chong PS, Jin H, Tsui KC, Khairuddin S, Tse ACK, et al.
    Int J Mol Sci, 2023 Mar 23;24(7).
    PMID: 37047062 DOI: 10.3390/ijms24076089
    Cerebellar ataxia is a neurodegenerative disorder with no definitive treatment. Although previous study demonstrated the neuroprotective effects of Hericium erinaceus (H.E.), the mechanisms of H.E. treatment on the neuroinflammatory response, neurotransmission, and related metabolites remain largely unknown. We demonstrated that 3-AP rats treated with 25 mg/kg H.E. extracts had improved motor coordination and balance in the accelerated rotarod and rod tests. We showed that the H.E. treatment upregulated the expression of Tgfb1, Tgfb2, and Smad3 genes to levels comparable to those in the non-3-AP control group. Interestingly, we also observed a significant correlation between Tgfb2 gene expression and rod test performance in the 3-AP saline group, but not in the non-3-AP control or H.E.+3-AP groups, indicating a relationship between Tgfb2 gene expression and motor balance in the 3-AP rat model. Additionally, we also found that the H.E. treatment increased mitochondrial COX-IV protein expression and normalized dopamine-serotonin neurotransmission and metabolite levels in the cerebellum of the H.E.+3-AP group compared to the 3-AP saline group. In conclusion, our findings suggest that the H.E. treatment improved motor function in the 3-AP rat model, which was potentially mediated through neuroprotective mechanisms involving TGFB2-Smad3 signaling via normalization of neurotransmission and metabolic pathways.
  10. Herr DR, Reolo MJ, Peh YX, Wang W, Lee CW, Rivera R, et al.
    Sci Rep, 2016 Apr 15;6:24541.
    PMID: 27080739 DOI: 10.1038/srep24541
    Ototoxic drugs, such as platinum-based chemotherapeutics, often lead to permanent hearing loss through apoptosis of neuroepithelial hair cells and afferent neurons of the cochlea. There is no approved therapy for preventing or reversing this process. Our previous studies identified a G protein-coupled receptor (GPCR), S1P2, as a potential mediator of otoprotection. We therefore sought to identify a pharmacological approach to prevent cochlear degeneration via activation of S1P2. The cochleae of S1pr2(-/-) knockout mice were evaluated for accumulation of reactive oxygen species (ROS) with a nitro blue tetrazolium (NBT) assay. This showed that loss of S1P2 results in accumulation of ROS that precedes progressive cochlear degeneration as previously reported. These findings were supported by in vitro cell-based assays to evaluate cell viability, induction of apoptosis, and accumulation of ROS following activation of S1P2 in the presence of cisplatin. We show for the first time, that activation of S1P2 with a selective receptor agonist increases cell viability and reduces cisplatin-mediated cell death by reducing ROS. Cumulatively, these results suggest that S1P2 may serve as a therapeutic target for attenuating cisplatin-mediated ototoxicity.
  11. Liew PS, Chen Q, Ng AWR, Chew YC, Ravin NV, Sim EUH, et al.
    Anal Biochem, 2019 10 15;583:113361.
    PMID: 31306622 DOI: 10.1016/j.ab.2019.113361
    Phage N15 protelomerase (TelN) cleaves double-stranded circular DNA containing a telomerase-occupancy-site (tos) and rejoins the resulting linear-ends to form closed-hairpin-telomeres in Escherichia coli (E. coli). Continued TelN expression is essential to support resolution of the linear structure. In mammalian cells, no enzyme with TelN-like activities has been found. In this work, we show that phage TelN, expressed transiently and stably in human and mouse cells, recapitulates its native activities in these exogenous environments. We found TelN to accurately resolve tos-DNA in vitro and in vivo within human and mouse cells into linear DNA-containing terminal telomeres that are resistant to RecBCD degradation, a hallmark of protelomerase processing. In stable cells, TelN activity was detectable for at least 60 days, which suggests the possibility of limited silencing of its expression. Correspondingly, linear plasmid containing a 100 kb human β-globin gene expressed for at least 120 h in non-β-globin-expressing mouse cells with TelN presence. Our results demonstrate TelN is able to cut and heal DNA as hairpin-telomeres within mammalian cells, providing a tool for creating novel structures by DNA resolution in these hosts. The TelN protelomerase may be useful for exploring novel technologies for genome interrogation and chromosome engineering.
  12. Santos HM, Tsai CY, Maquiling KRA, Tayo LL, Mariatulqabtiah AR, Lee CW, et al.
    Aquac Int, 2020;28(1):169-185.
    PMID: 32834683 DOI: 10.1007/s10499-019-00451-w
    Acute hepatopancreatic necrosis disease (AHPND) or formerly known as early mortality syndrome (EMS) is an emerging disease that has caused significant economic losses to the aquaculture industry. The primary causative agent of AHPND is Vibrio parahaemolyticus, a Gram-negative rod-shaped bacterium that has gained plasmids encoding the fatal binary toxins Pir A/Pir B that cause rapid death of the infected shrimp. In this review, the current research studies and information about AHPND in shrimps have been presented. Molecular diagnostic tools and potential treatments regarding AHPND were also included. This review also includes relevant findings which may serve as guidelines that can help for further investigation and studies on AHPND or other shrimp diseases.
  13. Wong YY, Lee CW, Chai SCY, Lim JH, Bong CW, Sim EUH, et al.
    Mar Pollut Bull, 2022 Dec;185(Pt A):114297.
    PMID: 36327936 DOI: 10.1016/j.marpolbul.2022.114297
    We investigated the appropriateness of faecal indicator bacteria in tropical waters. We compared total coliform (undetectable to 7.2 × 105 cfu 100 mL-1), faecal coliform (undetectable to 6.1 × 105 cfu 100 mL-1) and enterococci (undetectable to 3.1 × 104 cfu 100 mL-1) distribution in Peninsular Malaysia. Faecal indicator bacteria was highest in freshwater, and lowest in seawater (q > 4.18, p 
  14. Vaezzadeh V, Yi X, Rais FR, Bong CW, Thomes MW, Lee CW, et al.
    Mar Pollut Bull, 2021 Nov;172:112871.
    PMID: 34428623 DOI: 10.1016/j.marpolbul.2021.112871
    Concentrations, sources and interactions between black carbon (BC) and polycyclic aromatic hydrocarbons (PAHs) were investigated in 42 sediment samples collected from riverine, coastal and shelf areas in Peninsular Malaysia. The concentrations of BC measured by benzene polycarboxylic acid (BPCA) method and PAHs showed broad spatial variations between the relatively pristine environment of the East coast and developed environment of the West and South coast ranging from 0.02 to 0.36% dw and 57.7 ng g-1 dw to 19,300 ng g-1 dw, respectively. Among diagnostic ratios of PAHs, the ratios of Ant/(Ant+Phe) and LMW/HMW drew the clearest distinctions between the East coast versus the West and South coast sediments indicating the predominance of petrogenic sources in the former versus pyrogenic sources in the latter. PAHs significantly correlated with BC and total organic carbon (TOC) in the sediments (p 
  15. Tay ZH, Ng FL, Thong CH, Lee CW, Gnana Kumar G, Al-Sehemi AG, et al.
    Appl Microbiol Biotechnol, 2024 Dec;108(1):1-14.
    PMID: 38194143 DOI: 10.1007/s00253-023-12951-0
    In this study, the bioelectrical power generation potential of four tropical marine microalgal strains native to Malaysia was investigated using BPV platforms. Chlorella UMACC 258 produced the highest power density (0.108 mW m-2), followed by Halamphora subtropica UMACC 370 (0.090 mW m-2), Synechococcus UMACC 371 (0.065 mW m-2) and Parachlorella UMACC 245 (0.017 mW m-2). The chlorophyll-a (chl-a) content was examined to have a linear positive relationship with the power density (p 
  16. Tee JY, Ng FL, Keng FS, Lee CW, Zhang B, Lin S, et al.
    iScience, 2024 Apr 19;27(4):109564.
    PMID: 38617563 DOI: 10.1016/j.isci.2024.109564
    The successful commercialization of algal biophotovoltaics (BPV) technology hinges upon a multifaceted approach, encompassing factors such as the development of a cost-efficient and highly conductive anode material. To address this issue, we developed an environmentally benign method of producing reduced graphene oxide (rGO), using concentrated Chlorella sp. UMACC 313 suspensions as the reducing agent. The produced rGO was subsequently coated on the carbon paper (rGO-CP) and used as the BPV device's anode. As a result, maximum power density was increased by 950% for Chlorella sp. UMACC 258 (0.210 mW m-2) and 781% for Synechococcus sp. UMACC 371 (0.555 mW m-2) compared to bare CP. The improved microalgae adhesion to the anode and improved electrical conductivity of rGO brought on by the effective removal of oxygen functional groups may be the causes of this. This study has demonstrated how microalgal-reduced GO may improve the efficiency of algal BPV for producing bioelectricity.
  17. Osahor AN, Tan CY, Sim EU, Lee CW, Narayanan K
    Anal Biochem, 2014 Oct 1;462:26-8.
    PMID: 24929088 DOI: 10.1016/j.ab.2014.05.030
    When recombineering bacterial artificial chromosomes (BACs), it is common practice to design the ends of the donor molecule with 50 bp of homology specifying its insertion site. We demonstrate that desired recombinants can be produced using intermolecular homologies as short as 15 bp. Although the use of shorter donor end regions decreases total recombinants by several fold, the frequency of recombinants with correctly inserted donor molecules was high enough for easy detection by simple polymerase chain reaction (PCR) screening. This observation may have important implications for the design of oligonucleotides for recombineering, including significant cost savings, especially for high-throughput projects that use large quantities of primers.
  18. Sim EU, Ang CH, Ng CC, Lee CW, Narayanan K
    J Hum Genet, 2010 Feb;55(2):118-20.
    PMID: 19927161 DOI: 10.1038/jhg.2009.124
    Extraribosomal functions of human ribosomal proteins (RPs) include the regulation of cellular growth and differentiation, and are inferred from studies that linked congenital disorders and cancer to the deregulated expression of RP genes. We have previously shown the upregulation and downregulation of RP genes in tumors of colorectal and nasopharyngeal carcinomas (NPCs), respectively. Herein, we show that a subset of RP genes for the large ribosomal subunit is differentially expressed among cell lines derived from the human nasopharyngeal epithelium. Three such genes (RPL27, RPL37a and RPL41) were found to be significantly downregulated in all cell lines derived from NPC tissues compared with a nonmalignant nasopharyngeal epithelial cell line. The expression of RPL37a and RPL41 genes in human nasopharyngeal tissues has not been reported previously. Our findings support earlier suspicions on the existence of NPC-associated RP genes, and indicate their importance in human nasopharyngeal organogenesis.
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