Publications by authors named "Venugopal Balakrishnan"

15 Publications

  • Page 1 of 1

Prognostic prospect of soluble programmed cell death ligand-1 in cancer management.

Acta Biochim Biophys Sin (Shanghai) 2021 Jul;53(8):961-978

Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia.

Aggressive tissue biopsy is commonly unavoidable in the management of most suspected tumor cases to conclusively verify the presence of cancerous cells through histological assessment. The extracted tissue is also immunostained for detection of antigens (tissue tumor markers) of potential prognostic or therapeutic importance to assist in treatment decision. Although liquid biopsies can be a powerful tool for monitoring treatment response, they are still excluded from standard cancer diagnostics, and their utility is still being debated in the scientific community. With a myriad of soluble tissue tumor markers now being discovered, liquid biopsies could completely change the current paradigms of cancer management. Recently, soluble programmed cell death ligand-1 (sPD-L1), which is found in the peripheral blood, i.e. serum and plasma, has shown potential as a pre-therapeutic predictive marker as well as a prognostic biomarker to monitor treatment efficacy. Thus, this review focuses on the emergence of sPD-L1 and promising technologies for its detection in order to support liquid biopsies for future cancer management.
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http://dx.doi.org/10.1093/abbs/gmab077DOI Listing
July 2021

The potential applications of T cell receptor (TCR)-like antibody in cervical cancer immunotherapy.

Hum Vaccin Immunother 2021 Sep 14;17(9):2981-2994. Epub 2021 May 14.

Institute for Research in Molecular Medicine, Universiti Sains Malaysia, George Town, Malaysia.

Cervical cancer is ranked as the fourth most common cancer in women worldwide. Monoclonal antibody has created a new dimension in the immunotherapy of many diseases, including cervical cancer. The antibody's ability to target various aspects of cervical cancer (oncoviruses, oncoproteins, and signaling pathways) delivers a promising future for efficient immunotherapy. Besides, technologies such as hybridoma and phage display provide a fundamental platform for monoclonal antibody generation and create the opportunity to generate novel antibody classes including, T cell receptor (TCR)-like antibody. In this review, the current immunotherapy strategies for cervical cancer are presented. We have also proposed a novel concept of T cell receptor (TCR)-like antibody and its potential applications for enhancing cervical cancer therapeutics. Finally, the possible challenges in TCR-like antibody application for cervical cancer therapeutics have been addressed, and strategies to overcome the challenges have been highlighted to maximize the therapeutic benefits.
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http://dx.doi.org/10.1080/21645515.2021.1913960DOI Listing
September 2021

Recycling Waste Cotton Cloths for the Isolation of Cellulose Nanocrystals: A Sustainable Approach.

Polymers (Basel) 2021 Feb 19;13(4). Epub 2021 Feb 19.

Universiti Kuala Lumpur-Malaysian Institute of Chemical & Bioengineering Technology (UniKL-MICET), Melaka 78000, Malaysia.

There is an interest in the sustainable utilization of waste cotton cloths because of their enormous volume of generation and high cellulose content. Waste cotton cloths generated are disposed of in a landfill, which causes environmental pollution and leads to the waste of useful resources. In the present study, cellulose nanocrystals (CNCs) were isolated from waste cotton cloths collected from a landfill. The waste cotton cloths collected from the landfill were sterilized and cleaned using supercritical CO (scCO) technology. The cellulose was extracted from scCO-treated waste cotton cloths using alkaline pulping and bleaching processes. Subsequently, the CNCs were isolated using the HSO hydrolysis of cellulose. The isolated CNCs were analyzed to determine the morphological, chemical, thermal, and physical properties with various analytical methods, including attenuated total reflection-Fourier transform-infrared spectroscopy (ATR-FTIR), field-emission scanning electron microscopy (FE-SEM), energy-filtered transmission electron microscopy (EF-TEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The results showed that the isolated CNCs had a needle-like structure with a length and diameter of 10-30 and 2-6 nm, respectively, and an aspect ratio of 5-15, respectively. Additionally, the isolated CNCs had a high crystallinity index with a good thermal stability. The findings of the present study revealed the potential of recycling waste cotton cloths to produce a value-added product.
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http://dx.doi.org/10.3390/polym13040626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922772PMC
February 2021

Triple Negative Breast Cancer: A Review of Present and Future Diagnostic Modalities.

Medicina (Kaunas) 2021 Jan 12;57(1). Epub 2021 Jan 12.

Institute for Research in Molecular Medicine, Universiti Sains Malaysia, USM, Penang 11800, Malaysia.

Triple-negative breast cancer (TNBC) is an aggressive breast type of cancer with no expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). It is a highly metastasized, heterogeneous disease that accounts for 10-15% of total breast cancer cases with a poor prognosis and high relapse rate within five years after treatment compared to non-TNBC cases. The diagnostic and subtyping of TNBC tumors are essential to determine the treatment alternatives and establish personalized, targeted medications for every TNBC individual. Currently, TNBC is diagnosed via a two-step procedure of imaging and immunohistochemistry (IHC), which are operator-dependent and potentially time-consuming. Therefore, there is a crucial need for the development of rapid and advanced technologies to enhance the diagnostic efficiency of TNBC. This review discusses the overview of breast cancer with emphasis on TNBC subtypes and the current diagnostic approaches of TNBC along with its challenges. Most importantly, we have presented several promising strategies that can be utilized as future TNBC diagnostic modalities and simultaneously enhance the efficacy of TNBC diagnostic.
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http://dx.doi.org/10.3390/medicina57010062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826673PMC
January 2021

Isolation and Characterization of Magnetic Oil Palm Empty Fruits Bunch Cellulose Nanofiber Composite as a Bio-Sorbent for Cu(II) and Cr(VI) Removal.

Polymers (Basel) 2020 Dec 30;13(1). Epub 2020 Dec 30.

University of Kuala Lumpur-Malaysian Institute Chemical & Bioengineering Technology (UniKL-MICET), Lot 1988, Taboh Naning, Alor Gajah, Melaka 78000, Malaysia.

In the present study, magnetic oil palm empty fruits bunch cellulose nanofiber (M-OPEFB-CNF) composite was isolated by sol-gel method using cellulose nanofiber (CNF) obtained from oil palm empty fruits bunch (OPEFB) and FeO as magnetite. Several analytical methods were utilized to characterize the mechanical, chemical, thermal, and morphological properties of the isolated CNF and M-OPEFB-CNF. Subsequently, the isolated M-OPEFB-CNF composite was utilized for the adsorption of Cr(VI) and Cu(II) from aqueous solution with varying parameters, such as pH, adsorbent doses, treatment time, and temperature. Results showed that the M-OPEFB-CNF as an effective bio-sorbent for the removal of Cu(II) and Cr(VI) from aqueous solution. The adsorption isotherm modeling revealed that the Freundlich equation better describes the adsorption of Cu(II) and Cr(VI) on M-OPEFB-CNF composite. The kinetics studies revealed the pseudo-second-order kinetics model was a better-described kinetics model for the removal of Cu(II) and Cr(VI) using M-OPEFB-CNF composite as bio-sorbent. The findings of the present study showed that the M-OPEFB-CNF composite has the potential to be utilized as a bio-sorbent for heavy metals removal.
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http://dx.doi.org/10.3390/polym13010112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795890PMC
December 2020

A Review on Plant Cellulose Nanofibre-Based Aerogels for Biomedical Applications.

Polymers (Basel) 2020 Aug 6;12(8). Epub 2020 Aug 6.

Chemistry Institute, Federal University of Uberlandia-UFU, Campus Santa Monica-Bloco1D-CP 593, Uberlandia 38400-902, Brazil.

Cellulose nanomaterials from plant fibre provide various potential applications (i.e., biomedical, automotive, packaging, etc.). The biomedical application of nanocellulose isolated from plant fibre, which is a carbohydrate-based source, is very viable in the 21st century. The essential characteristics of plant fibre-based nanocellulose, which include its molecular, tensile and mechanical properties, as well as its biodegradability potential, have been widely explored for functional materials in the preparation of aerogel. Plant cellulose nano fibre (CNF)-based aerogels are novel functional materials that have attracted remarkable interest. In recent years, CNF aerogel has been extensively used in the biomedical field due to its biocompatibility, renewability and biodegradability. The effective surface area of CNFs influences broad applications in biological and medical studies such as sustainable antibiotic delivery for wound healing, the preparation of scaffolds for tissue cultures, the development of drug delivery systems, biosensing and an antimicrobial film for wound healing. Many researchers have a growing interest in using CNF-based aerogels in the mentioned applications. The application of cellulose-based materials is widely reported in the literature. However, only a few studies discuss the potential of cellulose nanofibre aerogel in detail. The potential applications of CNF aerogel include composites, organic-inorganic hybrids, gels, foams, aerogels/xerogels, coatings and nano-paper, bioactive and wound dressing materials and bioconversion. The potential applications of CNF have rarely been a subject of extensive review. Thus, extensive studies to develop materials with cheaper and better properties, high prospects and effectiveness for many applications are the focus of the present work. The present review focuses on the evolution of aerogels via characterisation studies on the isolation of CNF-based aerogels. The study concludes with a description of the potential and challenges of developing sustainable materials for biomedical applications.
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http://dx.doi.org/10.3390/polym12081759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465206PMC
August 2020

Comparative transcriptomic profiling in HPV-associated cervical carcinogenesis: Implication of MHC class II and immunoglobulin heavy chain genes.

Life Sci 2020 Sep 29;256:118026. Epub 2020 Jun 29.

Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia. Electronic address:

Aim: We aimed to determine the biological processes and pathways involved in cervical carcinogenesis associated with high-risk human papillomavirus (HPV) infection.

Materials And Methods: Total RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Transcriptomic profiling by microarrays was conducted followed by downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.

Results: We examined the difference in GOs enriched for each transition stage from normal cervix to LSIL, HSIL, and SCC, and found 307 genes to be differentially expressed. In the transition from normal cervix to LSIL, the extracellular matrix (ECM) genes were significantly downregulated. The MHC class II genes were significantly upregulated in the LSIL to HSIL transition. In the final transition from HSIL to SCC, the immunoglobulin heavy locus genes were significantly upregulated and the ECM pathway was implicated.

Conclusion: Deregulation of the immune-related genes including MHC II and immunoglobulin heavy chain genes were involved in the transitions from LSIL to HSIL and SCC, suggesting immune escape from host anti-tumour response. The extracellular matrix plays an important role during the early and late stages of cervical carcinogenesis.
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http://dx.doi.org/10.1016/j.lfs.2020.118026DOI Listing
September 2020

Minichromosome Maintenance Complex (MCM) Genes Profiling and MCM2 Protein Expression in Cervical Cancer Development.

Asian Pac J Cancer Prev 2019 Oct 1;20(10):3043-3049. Epub 2019 Oct 1.

Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.

Objective: Minichromosome maintenance complex (MCM) proteins are essential for the process of DNA replication and cell division. This study aimed to evaluate MCM genes expression profiles and MCM2 protein in HPV-associated cervical carcinogenesis.

Methodology: MCM2, 4, 5 and 7 genes expression profiles were evaluated in three cervical tissue samples each of normal cervix, human papillomavirus (HPV)-infected low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC), using Human Transcriptome Array 2.0 and validated by nCounter® PanCancer Pathway NanoString Array. Immunohistochemical expression of MCM2 protein was semi-quantitatively assessed by histoscore in tissue microarrays containing 9 cases of normal cervix, 10 LSIL, 10 HSIL and 42 cases of SCC.

Results: MCM2, 4, 5 and 7 genes expressions were upregulated with increasing fold change during the progression from LSIL to HSIL and the highest in SCC. MCM2 gene had the highest fold change in SCC compared to normal cervix. Immunohistochemically, MCM2 protein was localised in the nuclei of basal cells of normal cervical epithelium and dysplastic-neoplastic cells of CIN and SCC. There was a significant difference in MCM2 protein expression between the histological groups (P = 0.039), and histoscore was the highest in HSIL compared to normal cervix (P = 0.010).

Conclusion: The upregulation of MCM genes expressions in cervical carcinogenesis reaffirms MCM as a proliferative marker in DNA replication pathway, whereby proliferation of dysplastic and cancer cells become increasingly dysregulated and uncontrolled. A strong expression of MCM2 protein in HSIL may aid as a concatenated screening tool in detecting pre-cancerous cervical lesions.
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http://dx.doi.org/10.31557/APJCP.2019.20.10.3043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982666PMC
October 2019

Key Molecular Events in Cervical Cancer Development.

Medicina (Kaunas) 2019 Jul 17;55(7). Epub 2019 Jul 17.

Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.

Cervical cancer is the fourth most common cancer among women. Infection by high-risk human papillomavirus (HPV) is the main aetiology for the development of cervical cancer. Infection by high-risk human papillomavirus (HPV) and the integration of the HPV genome into the host chromosome of cervical epithelial cells are key early events in the neoplastic progression of cervical lesions. The viral oncoproteins, mainly E6 and E7, are responsible for the initial changes in epithelial cells. The viral proteins inactivate two main tumour suppressor proteins, p53, and retinoblastoma (pRb). Inactivation of these host proteins disrupts both the DNA repair mechanisms and apoptosis, leading to rapid cell proliferation. Multiple genes involved in DNA repair, cell proliferation, growth factor activity, angiogenesis, as well as mitogenesis genes become highly expressed in cervical intraepithelial neoplasia (CIN) and cancer. This genomic instability encourages HPV-infected cells to progress towards invasive carcinoma. The key molecular events involved in cervical carcinogenesis will be discussed in this review.
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http://dx.doi.org/10.3390/medicina55070384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681523PMC
July 2019

Establishment and Analysis of the 3-dimensional (3D) Spheroids Generated from the Nasopharyngeal Carcinoma Cell Line HK1.

Trop Life Sci Res 2016 Nov;27(supp1):125-130

School of Biological Sciences, Universiti Sains Malaysia, 11800 USM, Pulau Pinang, Malaysia.

Spheroids have been shown to recapitulate the tumour in vivo with properties such as the tumour microenvironment, concentration gradients, and tumour phenotype. As such, it can serve as a platform for determining the growth and invasion behaviour pattern of the cancer cells as well as be utilised for drug sensitivity assays; capable of exhibiting results that are closer to what is observed in vivo compared to two-dimensional (2D) cell culture assays. This study focused on establishing a three-dimensional (3D) cell culture model using the Nasopharyngeal Carcinoma (NPC) cell line, HK1 and analysing its growth and invasion phenotypes. The spheroids will also serve as a model to elucidate their sensitivity to the chemotherapeutic drug, Flavopiridol. The liquid overlay method was employed to generate the spheroids which was embedded in bovine collagen I matrix for growth and invasion phenotypes observation. The HK1 cells formed compact spheroids within 72 hours. Our observation from the 3 days experiments revealed that the spheroids gradually grew and invaded into the collagen matrix, showing that the HK1 spheroids are capable of growth and invasion. Progressing from these experiments, the HK1 spheroids were employed to perform a drug sensitivity assay using the chemotherapeutic drug, Flavopiridol. The drug had a dose-dependent inhibition on spheroid growth and invasion.
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http://dx.doi.org/10.21315/tlsr2016.27.3.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131665PMC
November 2016

Optimizing supercritical carbon dioxide in the inactivation of bacteria in clinical solid waste by using response surface methodology.

Waste Manag 2015 Apr 27;38:462-73. Epub 2015 Jan 27.

Department of Environmental Technology, School of Industrial Technology, Universiti Sains Malaysia, 11800 Penang, Malaysia. Electronic address:

Clinical solid waste (CSW) poses a challenge to health care facilities because of the presence of pathogenic microorganisms, leading to concerns in the effective sterilization of the CSW for safe handling and elimination of infectious disease transmission. In the present study, supercritical carbon dioxide (SC-CO2) was applied to inactivate gram-positive Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, and gram-negative Escherichia coli in CSW. The effects of SC-CO2 sterilization parameters such as pressure, temperature, and time were investigated and optimized by response surface methodology (RSM). Results showed that the data were adequately fitted into the second-order polynomial model. The linear quadratic terms and interaction between pressure and temperature had significant effects on the inactivation of S. aureus, E. coli, E. faecalis, and B. subtilis in CSW. Optimum conditions for the complete inactivation of bacteria within the experimental range of the studied variables were 20 MPa, 60 °C, and 60 min. The SC-CO2-treated bacterial cells, observed under a scanning electron microscope, showed morphological changes, including cell breakage and dislodged cell walls, which could have caused the inactivation. This espouses the inference that SC-CO2 exerts strong inactivating effects on the bacteria present in CSW, and has the potential to be used in CSW management for the safe handling and recycling-reuse of CSW materials.
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http://dx.doi.org/10.1016/j.wasman.2015.01.003DOI Listing
April 2015

Isolation and genotyping of Toxoplasma gondii from free-range ducks in Malaysia.

Avian Dis 2013 Mar;57(1):128-32

Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, USM, Penang, Malaysia.

Toxoplasma gondii is a parasitic protozoan that infects nearly one-third of humans. The present study was performed to isolate and genotype T. gondii from free-range ducks in Malaysia. Sera, heads, and hearts from 205 ducks were obtained from four states in Peninsular Malaysia, and 30 (14.63%) sera were found to be seropositive when assayed with the modified agglutination test (MAT > or = 1:6). All the positive samples were inoculated into mice, and T. gondii was successfully isolated from four individual duck samples (1.95%), which were initially found to be strongly seropositive (MAT > or = 1:24). The isolates were subjected to PCR-RFLP analysis, and two T. gondii strains were identified: type I and type II. This is the first reported study on the genetic characterization of T. gondii isolates from free-range farm animals in Southeast Asia.
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http://dx.doi.org/10.1637/10304-071212-ResNote.1DOI Listing
March 2013

Genotyping of Toxoplasma gondii isolates from wild boars in Peninsular Malaysia.

PLoS One 2013 17;8(4):e61730. Epub 2013 Apr 17.

Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia.

Toxoplasma gondii is a parasitic protozoan that infects nearly one-third of the world population. The present study was done to isolate and genotype T. gondii from wild boar from forests of Pahang, Malaysia. A total of 30 wild boars' blood, heads and hearts were obtained for this study and 30 (100.0%) were found to be seropositive when assayed with modified agglutination test (MAT ≥ 6). The positive samples were inoculated into mice and T. gondii was only isolated from samples that had strong seropositivity (MAT ≥ 1:24).The isolates were subjected to PCR-RFLP analysis and all the Peninsular Malaysia isolates of T. gondii are of clonal type I.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0061730PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629149PMC
November 2013

Infectious risk assessment of unsafe handling practices and management of clinical solid waste.

Int J Environ Res Public Health 2013 Jan 31;10(2):556-67. Epub 2013 Jan 31.

Department of Environmental Technology, School of Industrial Technology, Universiti Sains Malaysia, Penang 11800, Malaysia.

The present study was undertaken to determine the bacterial agents present in various clinical solid wastes, general waste and clinical sharp waste. The waste was collected from different wards/units in a healthcare facility in Penang Island, Malaysia. The presence of bacterial agents in clinical and general waste was determined using the conventional bacteria identification methods. Several pathogenic bacteria including opportunistic bacterial agent such as Pseudomonas aeruginosa, Salmonella spp., Klebsiella pneumoniae, Serratia marcescens, Acinetobacter baumannii, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes were detected in clinical solid wastes. The presence of specific pathogenic bacterial strains in clinical sharp waste was determined using 16s rDNA analysis. In this study, several nosocomial pathogenic bacteria strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Lysinibacillus sphaericus, Serratia marcescens, and Staphylococcus aureus were detected in clinical sharp waste. The present study suggests that waste generated from healthcare facilities should be sterilized at the point of generation in order to eliminate nosocomial infections from the general waste or either of the clinical wastes.
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http://dx.doi.org/10.3390/ijerph10020556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635162PMC
January 2013

Treatment of clinical solid waste using a steam autoclave as a possible alternative technology to incineration.

Int J Environ Res Public Health 2012 03 9;9(3):855-67. Epub 2012 Mar 9.

Department of Environmental Technology, School of Industrial Technology, Universiti Sains Malaysia, 11800 Penang, Malaysia.

A steam autoclave was used to sterilize bacteria in clinical solid waste in order to determine an alternative to incineration technology in clinical solid waste management. The influence of contact time (0, 5, 15, 30 and 60 min) and temperature (111 °C, 121 °C and 131 °C) at automated saturated steam pressure was investigated. Results showed that with increasing contact time and temperature, the number of surviving bacteria decreased. The optimum experimental conditions as measured by degree of inactivation of bacteria were 121 °C for 15 minutes (min) for Gram negative bacteria, 121 °C and 131 °C for 60 and 30 min for Gram positive bacteria, respectively. The re-growth of bacteria in sterilized waste was also evaluated in the present study. It was found that bacterial re-growth started two days after the inactivation. The present study recommends that the steam autoclave cannot be considered as an alternative technology to incineration in clinical solid waste management.
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http://dx.doi.org/10.3390/ijerph9030855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367282PMC
March 2012
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