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  1. Lee L, Teh L, Zainuddin Z, Salleh M
    Stand Genomic Sci, 2014 Jun 15;9(3):933-9.
    PMID: 25197474 DOI: 10.4056/sigs.3887716
    We report the genome sequence of a healthcare-associated MRSA type ST239 clone isolated from a patient with septicemia in Malaysia. This clone typifies the characteristics of ST239 lineage, including resistance to multiple antibiotics and antiseptics.
  2. Goh RY, Lee LS, Seow HV, Gopal K
    Entropy (Basel), 2020 Sep 04;22(9).
    PMID: 33286758 DOI: 10.3390/e22090989
    Credit scoring is an important tool used by financial institutions to correctly identify defaulters and non-defaulters. Support Vector Machines (SVM) and Random Forest (RF) are the Artificial Intelligence techniques that have been attracting interest due to their flexibility to account for various data patterns. Both are black-box models which are sensitive to hyperparameter settings. Feature selection can be performed on SVM to enable explanation with the reduced features, whereas feature importance computed by RF can be used for model explanation. The benefits of accuracy and interpretation allow for significant improvement in the area of credit risk and credit scoring. This paper proposes the use of Harmony Search (HS), to form a hybrid HS-SVM to perform feature selection and hyperparameter tuning simultaneously, and a hybrid HS-RF to tune the hyperparameters. A Modified HS (MHS) is also proposed with the main objective to achieve comparable results as the standard HS with a shorter computational time. MHS consists of four main modifications in the standard HS: (i) Elitism selection during memory consideration instead of random selection, (ii) dynamic exploration and exploitation operators in place of the original static operators, (iii) a self-adjusted bandwidth operator, and (iv) inclusion of additional termination criteria to reach faster convergence. Along with parallel computing, MHS effectively reduces the computational time of the proposed hybrid models. The proposed hybrid models are compared with standard statistical models across three different datasets commonly used in credit scoring studies. The computational results show that MHS-RF is most robust in terms of model performance, model explainability and computational time.
  3. Hamid A, Lee LS, Karim SR, Jufri NF
    Malays J Med Sci, 2018 Mar;25(2):64-71.
    PMID: 30918456 MyJurnal DOI: 10.21315/mjms2018.25.2.7
    Background: Zerumbone (ZER) is a major bioactive compound of Zingiber zerumbet, a wild ginger plant that has been documented to have anti-proliferative, anti-inflammatory and anti-oxidant properties. To investigate its hepatoprotective potential, this study was designed to determine the treatment effects of ZER on acute hepatotoxicity induced by paracetamol (PCM) in rats.

    Methods: The control group was administered with phosphate buffer solution (PBS) while the other two groups received PCM alone (1000 mg/kg) and PCM + 25 mg/kg ZER, respectively, at 0 h and 4 h after PCM injection. After 24 h, the blood and liver were collected for differential white blood cell count, liver histological observation and biochemical analysis including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total protein concentration in serum and liver.

    Results: Treatment with ZER was found to significantly reduce ALT (P = 0.041), AST (P = 0.044) and total hepatic protein (P = 0.045) in comparison to PCM-induced rats. Rats treated with ZER exhibited the normal structure of hepatocytes with no vacuolisation or necrosis and showed significantly reduced neutrophil count (P = 0.037). This finding suggests its ability to suppress the inflammatory processes caused by PCM overdosage and decrease the hepatocytes tendency to go through necrotic processes.

    Conclusion: ZER possessed protective activity against PCM-induced acute hepatotoxicity in a rat model.

  4. Mirsalehy A, Abu Bakar MR, Lee LS, Jaafar AB, Heydar M
    ScientificWorldJournal, 2014;2014:138923.
    PMID: 24883350 DOI: 10.1155/2014/138923
    A novel technique has been introduced in this research which lends its basis to the Directional Slack-Based Measure for the inverse Data Envelopment Analysis. In practice, the current research endeavors to elucidate the inverse directional slack-based measure model within a new production possibility set. On one occasion, there is a modification imposed on the output (input) quantities of an efficient decision making unit. In detail, the efficient decision making unit in this method was omitted from the present production possibility set but substituted by the considered efficient decision making unit while its input and output quantities were subsequently modified. The efficiency score of the entire DMUs will be retained in this approach. Also, there would be an improvement in the efficiency score. The proposed approach was investigated in this study with reference to a resource allocation problem. It is possible to simultaneously consider any upsurges (declines) of certain outputs associated with the efficient decision making unit. The significance of the represented model is accentuated by presenting numerical examples.
  5. Zulkifli MH, Teh LK, Lee LS, Zakaria ZA, Salleh MZ
    Genome Announc, 2013;1(4).
    PMID: 23950113 DOI: 10.1128/genomeA.00418-13
    Klebsiella pneumoniae PR04 was isolated from a patient hospitalized in Malaysia. The draft genome sequence of K. pneumoniae PR04 shows differences compared to the reference sequences of K. pneumoniae strains MGH 78578 and NTUH-K2044 in terms of their genomic structures.
  6. Khalid MI, Teh LK, Lee LS, Zakaria ZA, Salleh MZ
    Genome Announc, 2013;1(3).
    PMID: 23792750 DOI: 10.1128/genomeA.00327-13
    Proteus mirabilis is one of the pathogenic agents that commonly causes urinary tract infections among elderly individuals and long-term catheterized patients. Here, we report a draft genome sequence of Proteus mirabilis strain PR03 (3,932,623 bp, with a G+C content of 38.6%) isolated from a local hospital in Malaysia.
  7. Lee LS, Goh KM, Chan CS, Annie Tan GY, Yin WF, Chong CS, et al.
    Microbiologyopen, 2018 12;7(6):e00615.
    PMID: 29602271 DOI: 10.1002/mbo3.615
    The ability of thermophilic microorganisms and their enzymes to decompose biomass have attracted attention due to their quick reaction time, thermostability, and decreased risk of contamination. Exploitation of efficient thermostable glycoside hydrolases (GHs) could accelerate the industrialization of biofuels and biochemicals. However, the full spectrum of thermophiles and their enzymes that are important for biomass degradation at high temperatures have not yet been thoroughly studied. We examined a Malaysian Y-shaped Sungai Klah hot spring located within a wooded area. The fallen foliage that formed a thick layer of biomass bed under the heated water of the Y-shaped Sungai Klah hot spring was an ideal environment for the discovery and analysis of microbial biomass decay communities. We sequenced the hypervariable regions of bacterial and archaeal 16S rRNA genes using total community DNA extracted from the hot spring. Data suggested that 25 phyla, 58 classes, 110 orders, 171 families, and 328 genera inhabited this hot spring. Among the detected genera, members of Acidimicrobium, Aeropyrum, Caldilinea, Caldisphaera, Chloracidobacterium, Chloroflexus, Desulfurobacterium, Fervidobacterium, Geobacillus, Meiothermus, Melioribacter, Methanothermococcus, Methanotorris, Roseiflexus, Thermoanaerobacter, Thermoanaerobacterium, Thermoanaerobaculum, and Thermosipho were the main thermophiles containing various GHs that play an important role in cellulose and hemicellulose breakdown. Collectively, the results suggest that the microbial community in this hot spring represents a good source for isolating efficient biomass degrading thermophiles and thermozymes.
  8. Farah Naquiah MZ, James RJ, Suratman S, Lee LS, Mohd Hafidz MI, Salleh MZ, et al.
    Behav Brain Funct, 2016 Aug 31;12(1):23.
    PMID: 27582026 DOI: 10.1186/s12993-016-0107-y
    Heroin addiction is a growing concern, affecting the socioeconomic development of many countries. Little is known about transgenerational effects on phenotype changes due to heroin addiction. This study aims to investigate changes in level of anxiety and aggression up to four different generations of adult male rats due to paternal exposure to heroin.
  9. Chan KG, See-Too WS, Chua KO, Peix Á, Goh KM, Hong KW, et al.
    Microbiologyopen, 2019 Jul;8(7):e00793.
    PMID: 30656855 DOI: 10.1002/mbo3.793
    A bacterial strain designated as P08T was isolated from laboratory tap water during a water quality assessment in University of Malaya, Malaysia. The strain was a Gram-negative, rod-shaped, nonmotile, and aerobic bacterium. Complete genome of P08T comprised of a 2,820,660 bp chromosome with a G + C content of 36.43%. Both 16S rRNA phylogeny and phylogenetic tree inferred from the core gene matrix demonstrated that P08T formed a hitherto unknown subline within the family Neisseriaceae. Ortho average nucleotide identity (OrthoANI) values and the percentage of conserved proteins (POCP) calculated from complete genome sequence indicated low relatedness between P08T and its phylogenetic neighbors. Respiratory quinone analysis revealed Q-8 as the only detectable quinone. The predominant cellular fatty acids were identified as C14:0 , iso-C15:0 , and summed feature 3 (C16:1 ω7c/C16:1 ω6c). The polar lipids consisted of uncharacterized aminolipid, phosphatidylglycerol, and phosphatidylethanolamine. All aspects of phenotypic and phylogenetic data suggested that strain P08T represents a novel genus within family Neisseriaceae, for which the name Aquella gen. nov. is proposed. The type species of the genus is Aquella oligotrophica sp. nov., and the type strain is P08T (=LMG 29629T =DSM 100970T ).
  10. Kwek SK, Chew WM, Ong KC, Ng AW, Lee LS, Kaw G, et al.
    J Psychosom Res, 2006 May;60(5):513-9.
    PMID: 16650592
    BACKGROUND: Little is known about the long-term consequence of severe acute respiratory syndrome (SARS). We carried out an assessment on SARS patients after their recovery from their acute illness.

    METHOD: Postal survey comprising Health-Related Quality of Life (HRQoL) questionnaires and anxiety and depression measures was sent to them at 3 months' postdischarge.

    RESULTS: There was a significant impairment in both the HRQoL and mental functioning. Forty-one percent had scores indicative of a posttraumatic stress disorder (PTSD); about 30% had likely anxiety and depression.

    CONCLUSION: SARS has significant impact on HRQoL and psychological status at 3 months.

  11. Ohtani M, Kondo T, Tani N, Ueno S, Lee LS, Ng KK, et al.
    Mol Ecol, 2013 Apr;22(8):2264-79.
    PMID: 23432376 DOI: 10.1111/mec.12243
    Tropical rainforests in South-East Asia have been affected by climatic fluctuations during past glacial eras. To examine how the accompanying changes in land areas and temperature have affected the genetic properties of rainforest trees in the region, we investigated the phylogeographic patterns of a widespread dipterocarp species, Shorea leprosula. Two types of DNA markers were used: expressed sequence tag-based simple sequence repeats and chloroplast DNA (cpDNA) sequence variations. Both sets of markers revealed clear genetic differentiation between populations in Borneo and those in the Malay Peninsula and Sumatra (Malay/Sumatra). However, in the south-western part of Borneo, genetic admixture of the lineages was observed in the two marker types. Coalescent simulation based on cpDNA sequence variation suggested that the two lineages arose 0.28-0.09 million years before present and that following their divergence migration from Malay/Sumatra to Borneo strongly exceeded migration in the opposite direction. We conclude that the genetic structure of S. leprosula was largely formed during the middle Pleistocene and was subsequently modified by eastward migration across the subaerially exposed Sunda Shelf.
  12. Halim MZ, Jaafar MM, Teh LK, Ismail MI, Lee LS, Ngeow YF, et al.
    Genom Data, 2016 Mar;7:245-6.
    PMID: 26981419 DOI: 10.1016/j.gdata.2016.01.002
    Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10) isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968.
  13. Koo SH, Deng J, Ang DSW, Hsiang JC, Lee LS, Aazmi S, et al.
    Singapore Med J, 2019 Oct;60(10):512-521.
    PMID: 30488079 DOI: 10.11622/smedj.2018152
    INTRODUCTION: The objectives of this study were to examine the effects of ethnicity, gender and a proton pump inhibitor (PPI), omeprazole, on the human gut microbiome. PPIs are commonly used for the treatment of acid-related disorders. We hypothesised that PPI therapy might perturb microbial communities and alter the gut microbiome.

    METHODS: Healthy subjects of Chinese (n = 12), Malay (n = 12) and Indian (n = 10) ancestry, aged 21-37 years, were enrolled. They provided a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for seven days. Stool samples were collected again on Day 7 and 14 (one week after stopping omeprazole). Microbial DNA was extracted from the stool samples, followed by polymerase chain reaction, library construction, 16S rRNA sequencing using Illumina MiSeq, and statistical and bioinformatics analyses.

    RESULTS: The findings showed an increase in species richness (p = 0.018) after omeprazole consumption on Day 7, which reverted to baseline on Day 14. There were significant increases in the relative abundance of Streptococcus vestibularis (p = 0.0001) and Veillonella dispar (p = 0.0001) on Day 7, which diminished on Day 14. Faecalibacterium prausnitzii, Sutterella stercoricanis and Bacteroides denticanum were characteristic of Chinese, Malays and Indians, respectively. Lactobacillaceae and Bacteroides xylanisolvens were the signature taxa of male and female subjects, respectively.

    CONCLUSION: The study demonstrated alterations in the gut microbiome following omeprazole treatment. This may explain the underlying pathology of increased risk of Clostridium difficile infections associated with omeprazole therapy.

  14. Salleh MZ, Teh LK, Lee LS, Ismet RI, Patowary A, Joshi K, et al.
    PLoS One, 2013;8(8):e71554.
    PMID: 24009664 DOI: 10.1371/journal.pone.0071554
    BACKGROUND: With a higher throughput and lower cost in sequencing, second generation sequencing technology has immense potential for translation into clinical practice and in the realization of pharmacogenomics based patient care. The systematic analysis of whole genome sequences to assess patient to patient variability in pharmacokinetics and pharmacodynamics responses towards drugs would be the next step in future medicine in line with the vision of personalizing medicine.

    METHODS: Genomic DNA obtained from a 55 years old, self-declared healthy, anonymous male of Malay descent was sequenced. The subject's mother died of lung cancer and the father had a history of schizophrenia and deceased at the age of 65 years old. A systematic, intuitive computational workflow/pipeline integrating custom algorithm in tandem with large datasets of variant annotations and gene functions for genetic variations with pharmacogenomics impact was developed. A comprehensive pathway map of drug transport, metabolism and action was used as a template to map non-synonymous variations with potential functional consequences.

    PRINCIPAL FINDINGS: Over 3 million known variations and 100,898 novel variations in the Malay genome were identified. Further in-depth pharmacogenetics analysis revealed a total of 607 unique variants in 563 proteins, with the eventual identification of 4 drug transport genes, 2 drug metabolizing enzyme genes and 33 target genes harboring deleterious SNVs involved in pharmacological pathways, which could have a potential role in clinical settings.

    CONCLUSIONS: The current study successfully unravels the potential of personal genome sequencing in understanding the functionally relevant variations with potential influence on drug transport, metabolism and differential therapeutic outcomes. These will be essential for realizing personalized medicine through the use of comprehensive computational pipeline for systematic data mining and analysis.

  15. Teh LK, Subramaniam V, Tuan Abdu Aziz TA, Lee LS, Ismail MI, Yu CY, et al.
    Drug Metab. Pharmacokinet., 2016 Aug;31(4):304-13.
    PMID: 27325019 DOI: 10.1016/j.dmpk.2016.04.004
    We conducted a systematic characterization of CYP2C9 variants in 61 Orang Asli and 96 Singaporean Malays using the whole genome sequences data and compared the variants with the other 11 HapMap populations. The frequency of rs1057910 (CYP2C9*3) is the highest in the Orang Asli compared to other populations. Three alleles with clinical implication were detected in the Orang Asli while 2 were found in the Singaporean Malays. Large numbers of the Orang Asli are predicted to have reduced metabolic capacity and therefore they would require a lower dose of drugs which are metabolized by CYP2C9. They are also at increased risks of adverse effects and therapeutic failures. A large number of CYP2C9 variants in the Orang Asli were not in the Hardy Weinberg Equilibrium which could be due to small sample size or mutations that disrupt the equilibrium of allele frequencies. In conclusion, different polymorphism patterns, allele frequencies, genotype frequencies and LD blocks are observed between the Orang Asli, the Singaporean Malays and the other populations. The study provided new information on the genetic polymorphism of CYP2C9 which is important for the implementation of precision medicine for the Orang Asli.
  16. Rahman AY, Usharraj AO, Misra BB, Thottathil GP, Jayasekaran K, Feng Y, et al.
    BMC Genomics, 2013;14:75.
    PMID: 23375136 DOI: 10.1186/1471-2164-14-75
    Hevea brasiliensis, a member of the Euphorbiaceae family, is the major commercial source of natural rubber (NR). NR is a latex polymer with high elasticity, flexibility, and resilience that has played a critical role in the world economy since 1876.
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