Displaying publications 1 - 20 of 33 in total

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  1. Grand challenges in bioinformatics education and training
    Işık EB, Brazas MD, Schwartz R, Gaeta B, Palagi PM, van Gelder CWG, et al.
    Nat Biotechnol, 2023 Aug;41(8):1171-1174.
    PMID: 37568018 DOI: 10.1038/s41587-023-01891-9
  2. Fulltext Divergent HLA variations and heterogeneous expression but recurrent HLA loss-of- heterozygosity and common HLA-B and TAP transcriptional silencing across advanced pediatric solid cancers
    Lim WC, Marques Da Costa ME, Godefroy K, Jacquet E, Gragert L, Rondof W, et al.
    Front Immunol, 2023;14:1265469.
    PMID: 38318504 DOI: 10.3389/fimmu.2023.1265469
    The human leukocyte antigen (HLA) system is a major factor controlling cancer immunosurveillance and response to immunotherapy, yet its status in pediatric cancers remains fragmentary. We determined high-confidence HLA genotypes in 576 children, adolescents and young adults with recurrent/refractory solid tumors from the MOSCATO-01 and MAPPYACTS trials, using normal and tumor whole exome and RNA sequencing data and benchmarked algorithms. There was no evidence for narrowed HLA allelic diversity but discordant homozygosity and allele frequencies across tumor types and subtypes, such as in embryonal and alveolar rhabdomyosarcoma, neuroblastoma MYCN and 11q subtypes, and high-grade glioma, and several alleles may represent protective or susceptibility factors to specific pediatric solid cancers. There was a paucity of somatic mutations in HLA and antigen processing and presentation (APP) genes in most tumors, except in cases with mismatch repair deficiency or genetic instability. The prevalence of loss-of-heterozygosity (LOH) ranged from 5.9 to 7.7% in HLA class I and 8.0 to 16.7% in HLA class II genes, but was widely increased in osteosarcoma and glioblastoma (~15-25%), and for DRB1-DQA1-DQB1 in Ewing sarcoma (~23-28%) and low-grade glioma (~33-50%). HLA class I and HLA-DR antigen expression was assessed in 194 tumors and 44 patient-derived xenografts (PDXs) by immunochemistry, and class I and APP transcript levels quantified in PDXs by RT-qPCR. We confirmed that HLA class I antigen expression is heterogeneous in advanced pediatric solid tumors, with class I loss commonly associated with the transcriptional downregulation of HLA-B and transporter associated with antigen processing (TAP) genes, whereas class II antigen expression is scarce on tumor cells and occurs on immune infiltrating cells. Patients with tumors expressing sufficient HLA class I and TAP levels such as some glioma, osteosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft-tissue sarcoma cases may more likely benefit from T cell-based approaches, whereas strategies to upregulate HLA expression, to expand the immunopeptidome, and to target TAP-independent epitopes or possibly LOH might provide novel therapeutic opportunities in others. The consequences of HLA class II expression by immune cells remain to be established. Immunogenetic profiling should be implemented in routine to inform immunotherapy trials for precision medicine of pediatric cancers.
  3. Fourth-Generation Antibiotic Gatifloxacin Encapsulated by Microemulsions: Structural and Probing Dynamics
    Nazar MF, Yasir Siddique M, Saleem MA, Zafar M, Nawaz F, Ashfaq M, et al.
    Langmuir, 2018 Sep 11;34(36):10603-10612.
    PMID: 30109940 DOI: 10.1021/acs.langmuir.8b01775
    To overcome the increased disease rate, utilization of the versatile broad spectrum antibiotic drugs in controlled drug-delivery systems has been a challenging and complex consignment. However, with the development of microemulsion (μE)-based formulations, drugs can be effectively encapsulated and transferred to the target source. Herein, two biocompatible oil-in-water (o/w) μE formulations comprising clove oil/Tween 20/ethylene glycol/water (formulation A) and clove oil/Tween 20/1-butanol/water (formulation B) were developed for encapsulating the gatifloxacin (GTF), a fourth-generation antibiotic. The pseudoternary phase diagrams were mapped at a constant surfactant/co-surfactant (1:1) ratio to bound the existence of a monophasic isotropic region for as-formulated μEs. Multiple complementary characterization techniques, namely, conductivity (σ), viscosity (η), and optical microscopy analyses, were used to study the gradual changes that occurred in the microstructure of the as-formulated μEs, indicating the presence of a percolation transformation to a bicontinuous permeate flow. GTF showed good solubility, 3.2 wt % at pH 6.2 and 4.0 wt % at pH 6.8, in optimum μE of formulation A and formulation B, respectively. Each loaded μE formulation showed long-term stability over 8 months of storage. Moreover, no observable aggregation of GTF was found, as revealed by scanning transmission electron microscopy and peak-to-peak correlation of IR analysis, indicating the stability of GTF inside the formulation. The average particle size of each μE, measured by dynamic light scattering, increased upon loading GTF, intending the accretion of drug in the interfacial layers of microdomains. Likewise, fluorescence probing sense an interfacial hydrophobic environment to GTF molecules in any of the examined formulations, which may be of significant interest for understanding the kinetics of drug release.
  4. Genomic analysis and biological characterization of a novel Schitoviridae phage infecting Vibrio alginolyticus
    Tajuddin S, Khan AM, Chong LC, Wong CL, Tan JS, Ina-Salwany MY, et al.
    Appl Microbiol Biotechnol, 2023 Feb;107(2-3):749-768.
    PMID: 36520169 DOI: 10.1007/s00253-022-12312-3
    Vibrio alginolyticus is a Gram-negative bacterium commonly associated with mackerel poisoning. A bacteriophage that specifically targets and lyses this bacterium could be employed as a biocontrol agent for treating the bacterial infection or improving the shelf-life of mackerel products. However, only a few well-characterized V. alginolyticus phages have been reported in the literature. In this study, a novel lytic phage, named ΦImVa-1, specifically infecting V. alginolyticus strain ATCC 17749, was isolated from Indian mackerel. The phage has a short latent period of 15 min and a burst size of approximately 66 particles per infected bacterium. ΦImVa-1 remained stable for 2 h at a wide temperature (27-75 °C) and within a pH range of 5 to 10. Transmission electron microscopy revealed that ΦImVa-1 has an icosahedral head of approximately 60 nm in diameter with a short tail, resembling those in the Schitoviridae family. High throughput sequencing and bioinformatics analysis elucidated that ΦImVa-1 has a linear dsDNA genome of 77,479 base pairs (bp), with a G + C content of ~ 38.72% and 110 predicted gene coding regions (106 open reading frames and four tRNAs). The genome contains an extremely large virion-associated RNA polymerase gene and two smaller non-virion-associated RNA polymerase genes, which are hallmarks of schitoviruses. No antibiotic genes were found in the ΦImVa-1 genome. This is the first paper describing the biological properties, morphology, and the complete genome of a V. alginolyticus-infecting schitovirus. When raw mackerel fish flesh slices were treated with ΦImVa-1, the pathogen loads reduced significantly, demonstrating the potential of the phage as a biocontrol agent for V. alginolyticus strain ATCC 17749 in the food. KEY POINTS: • A novel schitovirus infecting Vibrio alginolyticus ATCC 17749 was isolated from Indian mackerel. • The complete genome of the phage was determined, analyzed, and compared with other phages. • The phage is heat stable making it a potential biocontrol agent in extreme environments.
  5. Acute pancreatitis associated with the antibiotic levofloxacin: A rare case report
    Inban P, Gulla V, Devani A, Akuma CM, Gowthavaram CA, Hussain A, et al.
    Clin Case Rep, 2023 Dec;11(12):e8186.
    PMID: 38033693 DOI: 10.1002/ccr3.8186
    Drug-induced acute pancreatitis is a potentially ignored diagnosis that must be precisely valued. Drug-induced acute pancreatitis can be considered the third common cause of acute pancreatitis after ruling out alcohol and gallstones. Levofloxacin belongs to a class of fluoroquinolone antibiotics used for treating various infections. Besides photosensitivity and liver toxicity, levofloxacin can induce acute pancreatitis, although rarely described. We highlight a case of acute pancreatitis in a female induced by levofloxacin. She presented with typical signs and symptoms of acute pancreatitis and had been taking levofloxacin for urinary tract infections for the last 3 days. After ruling out all other possible causes, her clinical picture, laboratory results, and imaging findings confirmed acute pancreatitis induced by levofloxacin.
  6. Fulltext African Trypanosome-Induced Blood-Brain Barrier Dysfunction under Shear Stress May Not Require ERK Activation
    Sumpio BJ, Chitragari G, Moriguchi T, Shalaby S, Pappas-Brown V, Khan AM, et al.
    Int. J. Angiol., 2015 Mar;24(1):41-6.
    PMID: 27053915 DOI: 10.1055/s-0034-1370890
    African trypanosomes are tsetse fly transmitted protozoan parasites responsible for human African trypanosomiasis, a disease characterized by a plethora of neurological symptoms and death. How the parasites under microvascular shear stress (SS) flow conditions in the brain cross the blood-brain barrier (BBB) is not known. In vitro studies using static models comprised of human brain microvascular endothelial cells (BMEC) show that BBB activation and crossing by trypanosomes requires the orchestration of parasite cysteine proteases and host calcium-mediated cell signaling. Here, we examine BMEC barrier function and the activation of extracellular signal-regulated kinase (ERK)1/2 and ERK5, mitogen-activated protein kinase family regulators of microvascular permeability, under static and laminar SS flow and in the context of trypanosome infection. Confluent human BMEC were cultured in electric cell-substrate impedance sensing (ECIS) and parallel-plate glass slide chambers. The human BMEC were exposed to 2 or 14 dyn/cm(2) SS in the presence or absence of trypanosomes. Real-time changes in transendothelial electrical resistance (TEER) were monitored and phosphorylation of ERK1/2 and ERK5 analyzed by immunoblot assay. After reaching confluence under static conditions human BMEC TEER was found to rapidly increase when exposed to 2 dyn/cm(2) SS, a condition that mimics SS in brain postcapillary venules. Addition of African trypanosomes caused a rapid drop in human BMEC TEER. Increasing SS to 14 dyn/cm(2), a condition mimicking SS in brain capillaries, led to a transient increase in TEER in both control and infected human BMEC. However, no differences in ERK1/2 and ERK5 activation were found under any condition tested. African trypanosomiasis alters BBB permeability under low shear conditions through an ERK1/2 and ERK5 independent pathway.
  7. Fulltext Analysis of viral diversity for vaccine target discovery
    Khan AM, Hu Y, Miotto O, Thevasagayam NM, Sukumaran R, Abd Raman HS, et al.
    BMC Med Genomics, 2017 12 21;10(Suppl 4):78.
    PMID: 29322922 DOI: 10.1186/s12920-017-0301-2
    BACKGROUND: Viral vaccine target discovery requires understanding the diversity of both the virus and the human immune system. The readily available and rapidly growing pool of viral sequence data in the public domain enable the identification and characterization of immune targets relevant to adaptive immunity. A systematic bioinformatics approach is necessary to facilitate the analysis of such large datasets for selection of potential candidate vaccine targets.

    RESULTS: This work describes a computational methodology to achieve this analysis, with data of dengue, West Nile, hepatitis A, HIV-1, and influenza A viruses as examples. Our methodology has been implemented as an analytical pipeline that brings significant advancement to the field of reverse vaccinology, enabling systematic screening of known sequence data in nature for identification of vaccine targets. This includes key steps (i) comprehensive and extensive collection of sequence data of viral proteomes (the virome), (ii) data cleaning, (iii) large-scale sequence alignments, (iv) peptide entropy analysis, (v) intra- and inter-species variation analysis of conserved sequences, including human homology analysis, and (vi) functional and immunological relevance analysis.

    CONCLUSION: These steps are combined into the pipeline ensuring that a more refined process, as compared to a simple evolutionary conservation analysis, will facilitate a better selection of vaccine targets and their prioritization for subsequent experimental validation.

  8. Fulltext Human ACE2 orthologous peptide sequences show better binding affinity to SARS-CoV-2 RBD domain: Implications for drug design
    Mahmoudi Azar L, Öncel MM, Karaman E, Soysal LF, Fatima A, Choi SB, et al.
    Comput Struct Biotechnol J, 2023;21:4096-4109.
    PMID: 37671240 DOI: 10.1016/j.csbj.2023.07.022
    Computational methods coupled with experimental validation play a critical role in the identification of novel inhibitory peptides that interact with viral antigenic determinants. The interaction between the receptor binding domain (RBD) of SARS-CoV-2 spike protein and the helical peptide of human angiotensin-converting enzyme-2 (ACE2) is a necessity for the initiation of viral infection. Herein, natural orthologs of human ACE2 helical peptide were evaluated for competitive inhibitory binding to the viral RBD by use of a computational approach, which was experimentally validated. A total of 624 natural ACE2 orthologous 32-amino acid long peptides were identified through a similarity search. Molecular docking was used to virtually screen and rank the peptides based on binding affinity metrics, benchmarked against human ACE2 peptide docked to the RBD. Molecular dynamics (MD) simulations were done for the human reference and the Nipponia nippon peptide as it exhibited the highest binding affinity (Gibbs free energy; -14 kcal/mol) predicted from the docking results. The MD simulation confirmed the stability of the assessed peptide in the complex (-12.3 kcal/mol). The top three docked-peptides (from Chitinophaga sancti, Nipponia nippon, and Mus musculus) and the human reference were experimentally validated by use of surface plasmon resonance technology. The human reference exhibited the weakest binding affinity (Kd of 318-441 pM) among the peptides tested, in agreement with the docking prediction, while the peptide from Nipponia nippon was the best, with 267-538-fold higher affinity than the reference. The validated peptides merit further investigation. This work showcases that the approach herein can aid in the identification of inhibitory biosimilar peptides for other viruses.
  9. Fulltext Cytokine expression profile of dengue patients at different phases of illness
    Rathakrishnan A, Wang SM, Hu Y, Khan AM, Ponnampalavanar S, Lum LC, et al.
    PLoS One, 2012;7(12):e52215.
    PMID: 23284941 DOI: 10.1371/journal.pone.0052215
    BACKGROUND: Dengue is an important medical problem, with symptoms ranging from mild dengue fever to severe forms of the disease, where vascular leakage leads to hypovolemic shock. Cytokines have been implicated to play a role in the progression of severe dengue disease; however, their profile in dengue patients and the synergy that leads to continued plasma leakage is not clearly understood. Herein, we investigated the cytokine kinetics and profiles of dengue patients at different phases of illness to further understand the role of cytokines in dengue disease.

    METHODS AND FINDINGS: Circulating levels of 29 different types of cytokines were assessed by bead-based ELISA method in dengue patients at the 3 different phases of illness. The association between significant changes in the levels of cytokines and clinical parameters were analyzed. At the febrile phase, IP-10 was significant in dengue patients with and without warning signs. However, MIP-1β was found to be significant in only patients with warning signs at this phase. IP-10 was also significant in both with and without warning signs patients during defervescence. At this phase, MIP-1β and G-CSF were significant in patients without warning signs, whereas MCP-1 was noted to be elevated significantly in patients with warning signs. Significant correlations between the levels of VEGF, RANTES, IL-7, IL-12, PDGF and IL-5 with platelets; VEGF with lymphocytes and neutrophils; G-CSF and IP-10 with atypical lymphocytes and various other cytokines with the liver enzymes were observed in this study.

    CONCLUSIONS: The cytokine profile patterns discovered between the different phases of illness indicate an essential role in dengue pathogenesis and with further studies may serve as predictive markers for progression to dengue with warning signs.

  10. Fulltext Patient Characteristics, Disease Burden, Treatment Patterns and Outcomes in Patients with Acromegaly: Real-World Evidence from the Malaysian Acromegaly Registry
    Long Bidin MB, Khan AM, Tan FHS, Aziz NA, Ali NM, Kamaruddin NA, et al.
    J ASEAN Fed Endocr Soc, 2023;38(1):75-80.
    PMID: 37252416 DOI: 10.15605/jafes.038.01.06
    OBJECTIVE: This study aims to report the demographic features of patients with acromegaly, the disease burden, and the corresponding treatment patterns and outcomes in Malaysia.

    METHODOLOGY: This is a retrospective study that included patients from the Malaysian Acromegaly registry who were diagnosed with acromegaly from 1970 onwards. Data collected included patient demographics, clinical manifestations of acromegaly, biochemical results and imaging findings. Information regarding treatment modalities and their outcomes was also obtained.

    RESULTS: Registry data was collected from 2013 to 2016 and included 140 patients with acromegaly from 12 participating hospitals. Median disease duration was 5.5 years (range 1.0 - 41.0 years). Most patients had macroadenoma (67%), while 15% were diagnosed with microadenoma. Hypertension (49.3%), diabetes (37.1%) and hypopituitarism (27.9%) were the most common co-morbidities for patients with acromegaly. Majority of patients had surgical intervention as primary treatment (65.9%) while 20.7% were treated medically, mainly with dopamine agonists (18.5%). Most patients had inadequate disease control after first-line treatment regardless of treatment modality (79.4%).

    CONCLUSION: This registry study provides epidemiological data on patients with acromegaly in Malaysia and serves as an initial step for further population-based studies.

  11. Release, deposition and elimination of radiocesium ((137)Cs) in the terrestrial environment
    Ashraf MA, Khan AM, Ahmad M, Akib S, Balkhair KS, Bakar NK
    Environ Geochem Health, 2014 12;36(6):1165-90.
    PMID: 24804829 DOI: 10.1007/s10653-014-9620-9
    Radionuclide contamination in terrestrial ecosystems has reached a dangerous level. The major artificial radionuclide present in the environment is (137)Cs, which is released as a result of weapon production related to atomic projects, accidental explosions of nuclear power plants and other sources, such as reactors, evaporation ponds, liquid storage tanks, and burial grounds. The release of potentially hazardous radionuclides (radiocesium) in recent years has provided the opportunity to conduct multidisciplinary studies on their fate and transport. Radiocesium's high fission yield and ease of detection made it a prime candidate for early radio-ecological investigations. The facility setting provides a diverse background for the improved understanding of various factors that contribute toward the fate and transfer of radionuclides in the terrestrial ecosystem. In this review, we summarize the significant environmental radiocesium transfer factors to determine the damaging effects of radiocesium on terrestrial ecosystem. It has been found that (137)Cs can trace the transport of other radionuclides that have a high affinity for binding to soil particles (silts and clays). Possible remedial methods are also discussed for contaminated terrestrial systems. This review will serve as a guideline for future studies of the fate and transport of (137)Cs in terrestrial environments in the wake of the Fukushima Nuclear Power Plant disaster in 2011.
  12. Fulltext Dissecting the dynamics of HIV-1 protein sequence diversity
    Hu Y, Tan PT, Tan TW, August JT, Khan AM
    PLoS One, 2013;8(4):e59994.
    PMID: 23593157 DOI: 10.1371/journal.pone.0059994
    The rapid mutation of human immunodeficiency virus-type 1 (HIV-1) and the limited characterization of the composition and incidence of the variant population are major obstacles to the development of an effective HIV-1 vaccine. This issue was addressed by a comprehensive analysis of over 58,000 clade B HIV-1 protein sequences reported over at least 26 years. The sequences were aligned and the 2,874 overlapping nonamer amino acid positions of the viral proteome, each a possible core binding domain for human leukocyte antigen molecules and T-cell receptors, were quantitatively analyzed for four patterns of sequence motifs: (1) "index", the most prevalent sequence; (2) "major" variant, the most common variant sequence; (3) "minor" variants, multiple different sequences, each with an incidence less than that of the major variant; and (4) "unique" variants, each observed only once in the alignment. The collective incidence of the major, minor, and unique variants at each nonamer position represented the total variant population for the position. Positions with more than 50% total variants contained correspondingly reduced incidences of index and major variant sequences and increased minor and unique variants. Highly diverse positions, with 80 to 98% variant nonamer sequences, were present in each protein, including 5% of Gag, and 27% of Env and Nef, each. The multitude of different variant nonamer sequences (i.e. nonatypes; up to 68%) at the highly diverse positions, represented by the major, multiple minor, and multiple unique variants likely supported variants function both in immune escape and as altered peptide ligands with deleterious T-cell responses. The patterns of mutational change were consistent with the sequences of individual HXB2 and C1P viruses and can be considered applicable to all HIV-1 viruses. This characterization of HIV-1 protein mutation provides a foundation for the design of peptide-based vaccines and therapeutics.
  13. Retraction Note to: Release, deposition and elimination of radiocesium (137Cs) in the terrestrial environment
    Ashraf MA, Khan AM, Ahmad M, Akib S, Balkhair KS, Bakar NKA
    Environ Geochem Health, 2017 06;39(3):703.
    PMID: 26932556 DOI: 10.1007/s10653-016-9811-7
  14. Selective adsorption and ultrafast fluorescent detection of Cr(VI) in wastewater using neodymium doped polyaniline supported layered double hydroxide nanocomposite
    Wani AA, Khan AM, Manea YK, Salem MAS, Shahadat M
    J Hazard Mater, 2021 08 15;416:125754.
    PMID: 33813294 DOI: 10.1016/j.jhazmat.2021.125754
    Neodymium-doped polyaniline supported Zn-Al layered double hydroxide (PANI@Nd-LDH) nanocomposite has been prepared via an ex-situ oxidative polymerization process. The as-prepared nanocomposite shows selective fluorescence detection and adsorption of hexavalent chromium Cr(VI) within a short period. The fluorescence intensity of PANI@Nd-LDH decreases linearly with Cr(VI) concentrations ranging from 200 ppb to 1000 ppb with a limit of detection (LOD) of 1.5 nM and a limit of quantification (LOQ) of 96 nM. The sensing mechanism can be ascribed by the inner filter effect of Cr(VI), the intercalation of Cr(VI) within the intergallery region of LDH, and the synergistic affinity of metal ions along with the polymer chain for Cr(VI). The adsorption performance of PANI@Nd-LDH nanocomposite is evaluated for Cr(VI) from wastewaters, which displayed high removal capacity towards Cr(VI) (219 mg/g) as compared on bare Nd-LDH (123 mg/g) and LDH (88 mg/g) respectively. The adsorption of Cr(VI) on PANI@Nd-LDH depends on the pH of the aqueous solution. The adsorption isotherm and kinetics are supported by the Langmuir model and pseudo-second-order model, respectively. Owing to the highly sensitive detection and adsorption of Cr(VI) from aqueous water samples demonstrated the potential application of PANI@Nd-LDH as an excellent environmental probe can be exploited.
  15. Fulltext The Relationship of Orofacial Pain and Dental Health Status and Oral Health Behaviours in Facial Burn Patients
    Chaudhary FA, Ahmad B, Javed MQ, Yakub SS, Arjumand B, Khan AM, et al.
    Pain Res Manag, 2021;2021:5512755.
    PMID: 34055118 DOI: 10.1155/2021/5512755
    This study aims to examine the association of orofacial pain and oral health status and oral health behaviours in facial burn patients. The participants in this cross-sectional study were randomly recruited from the Burn Care Center, Institute of Medical Sciences, Islamabad, Pakistan. An intraoral evaluation was carried out to record the DMFT and OHI-S. A self-administered questionnaire was used to collect information on sociodemographic status, brushing frequency, and dental visits. Orofacial pain during mandibular movement was assessed using the Visual Analogue Scale (VAS). Psychological status was assessed using the Generalized Anxiety Disorder Scale and Impact of Events Scale. ANOVA and simple and multiple linear regression tests were used to analyse the data. From the 90 facial burn patients included, the majority were below 34 years of age, female, single or divorced, and unemployed. The mean DMFT was 10.7, and 71% had poor oral hygiene. 56% of the participants had moderate-to-severe anxiety, and 68% had posttraumatic stress disorder. 53% of the participants had moderate-to-severe pain during mouth opening or moving the mandible with a mean score of 41.5. Analyses showed that orofacial pain was associated with less frequent brushing, irregular dental visits, greater DMFT score, and more plaque accumulation (OHI-S). It was also associated with employment status, the severity of a burn, anxiety, and stress. The treatment and management of dental and oral conditions in burn patients need judicious balance in controlling and accurate assessment of the pain and improving psychological problems in burn patients.
  16. Geochemical characteristics of rare earth elements in different types of soil: A chemometric approach
    Khan AM, Behkami S, Yusoff I, Md Zain SB, Bakar NKA, Bakar AFA, et al.
    Chemosphere, 2017 Oct;184:673-678.
    PMID: 28628904 DOI: 10.1016/j.chemosphere.2017.06.032
    Rare earth elements (REEs) are becoming significant due to their huge applications in many industries, large-scale mining and refining activities. Increasing usage of such metals pose negative environmental impacts. In this research ICP-MS has been used to analyze soil samples collected from former ex-mining areas in the depths of 0-20 cm, 21-40 cm, and 41-60 cm of residential, mining, natural, and industrial areas of Perak. Principal component analysis (PCA) revealed that soil samples taken from different mining, industrial, residential, and natural areas are separated into four clusters. It was observed that REEs were abundant in most of the samples from mining areas. Concentration of the rare elements decrease in general as we move from surface soil to deeper soils.
  17. Fulltext Advancing Personalized Medicine Through the Application of Whole Exome Sequencing and Big Data Analytics
    Suwinski P, Ong C, Ling MHT, Poh YM, Khan AM, Ong HS
    Front Genet, 2019;10:49.
    PMID: 30809243 DOI: 10.3389/fgene.2019.00049
    There is a growing attention toward personalized medicine. This is led by a fundamental shift from the 'one size fits all' paradigm for treatment of patients with conditions or predisposition to diseases, to one that embraces novel approaches, such as tailored target therapies, to achieve the best possible outcomes. Driven by these, several national and international genome projects have been initiated to reap the benefits of personalized medicine. Exome and targeted sequencing provide a balance between cost and benefit, in contrast to whole genome sequencing (WGS). Whole exome sequencing (WES) targets approximately 3% of the whole genome, which is the basis for protein-coding genes. Nonetheless, it has the characteristics of big data in large deployment. Herein, the application of WES and its relevance in advancing personalized medicine is reviewed. WES is mapped to Big Data "10 Vs" and the resulting challenges discussed. Application of existing biological databases and bioinformatics tools to address the bottleneck in data processing and analysis are presented, including the need for new generation big data analytics for the multi-omics challenges of personalized medicine. This includes the incorporation of artificial intelligence (AI) in the clinical utility landscape of genomic information, and future consideration to create a new frontier toward advancing the field of personalized medicine.
  18. High dengue virus load differentially modulates human microvascular endothelial barrier function during early infection
    Soe HJ, Khan AM, Manikam R, Samudi Raju C, Vanhoutte P, Sekaran SD
    J Gen Virol, 2017 Dec;98(12):2993-3007.
    PMID: 29182510 DOI: 10.1099/jgv.0.000981
    Plasma leakage is the main pathophysiological feature in severe dengue, resulting from altered vascular barrier function associated with an inappropriate immune response triggered upon infection. The present study investigated functional changes using an electric cell-substrate impedance sensing system in four (brain, dermal, pulmonary and retinal) human microvascular endothelial cell (MEC) lines infected with purified dengue virus, followed by assessment of cytokine profiles and the expression of inter-endothelial junctional proteins. Modelling of changes in electrical impedance suggests that vascular leakage in dengue-infected MECs is mostly due to the modulation of cell-to-cell interactions, while this loss of vascular barrier function observed in the infected MECs varied between cell lines and DENV serotypes. High levels of inflammatory cytokines (IL-6 and TNF-α), chemokines (CXCL1, CXCL5, CXCL11, CX3CL1, CCL2 and CCL20) and adhesion molecules (VCAM-1) were differentially produced in the four infected MECs. Further, the tight junctional protein, ZO-1, was down-regulated in both the DENV-1-infected brain and pulmonary MECs, while claudin-1, PECAM-1 and VE-cadherin were differentially expressed in these two MECs after infection. Non-purified virus stock was also studied to investigate the impact of virus stock purity on dengue-specific immune responses, and the results suggest that virus stock propagated through cell culture may include factors that mask or alter the DENV-specific immune responses of the MECs. The findings of the present study show that high DENV load differentially modulates human microvascular endothelial barrier function and disrupts the function of inter-endothelial junctional proteins during early infection with organ-specific cytokine production.
  19. Assessing anthropogenic levels, speciation, and potential mobility of rare earth elements (REEs) in ex-tin mining area
    Khan AM, Yusoff I, Bakar NKA, Bakar AFA, Alias Y
    Environ Sci Pollut Res Int, 2016 Dec;23(24):25039-25055.
    PMID: 27677993 DOI: 10.1007/s11356-016-7641-x
    A study was carried out to determine the level of rare earth elements (REEs) in water and sediment samples from ex-mining lakes and River in Kinta Valley, Perak, Malaysia. Surface water and sediments from an ex-mining lake and Kinta River water samples were analyzed for REEs by inductively coupled plasma mass spectrometry. The total concentration of REEs in the ex-mining lake water samples and sediments were found to be 3685 mg/l and 14159 mg/kg, respectively, while the total concentration of REEs in Kinta River water sample was found to be 1224 mg/l. REEs in mining lake water were found to be within 2.42 mg/l (Tb) to 46.50 mg/l (Ce), while for the Kinta River, it was 1.33 mg/l (Ho) to 29.95 mg/l (Ce). Sediment samples were also found with REEs from 9.81 mg/kg (Ho) to 765.84 mg/kg (Ce). Ce showed the highest average concentrations for mining lake (3.88 to 49.08 mg/l) and Kinta River (4.44 to 33.15 mg/l) water samples, while the concentration of La was the highest (11.59 to 771.61 mg/kg) in the mining lake sediment. Lu was shown to have the highest enrichment of REEs in ex-mining lake sediments (107.3). Multivariate statistical analyses such as factor analysis and principal component analysis indicated that REEs were associated and controlled by mixed origin, with similar contributions from anthropogenic and geogenic sources. The speciation study of REEs in ex-tin mining sediments using a modified five-stage sequential extraction procedure indicated that yttrium (Y), gadolinium (Gd), and lanthanum (La) were obtained at higher percentages from the adsorbed/exchanged/carbonate fraction. The average potential mobility of the REEs was arranged in a descending order: Yb > Gd > Y = Dy > Pr > Er > Tm > Eu > Nd > Tb > Sc > Lu > Ce > La, implying that under favorable conditions, these REEs could be released and subsequently pollute the environment.
  20. Erratum to: Assessing anthropogenic levels, speciation, and potential mobility of rare earth elements (REEs) in ex-tin mining area
    Khan AM, Yusoff I, Bakar NKA, Bakar AFA, Alias Y
    Environ Sci Pollut Res Int, 2017 06;24(17):15207.
    PMID: 28470494 DOI: 10.1007/s11356-017-9087-1
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