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  1. Article ; Online: Utilizing coordination chemistry through formation of a Cu

    Chatterjee, Sayantani / Jain, Chetan Kumar / Saha, Tanmoy / Roychoudhury, Susanta / Majumder, Hemanta Kumar / Das, Saurabh

    Journal of inorganic biochemistry

    2023  Volume 249, Page(s) 112369

    Abstract: Quinalizarin, an analogue of anthracycline anticancer agents, is an anticancer agent itself. A ... ...

    Abstract Quinalizarin, an analogue of anthracycline anticancer agents, is an anticancer agent itself. A Cu
    MeSH term(s) Humans ; DNA Topoisomerases, Type I/metabolism ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/chemistry ; Antibiotics, Antineoplastic ; Topoisomerase II Inhibitors/pharmacology ; Superoxides/metabolism ; Anthracyclines ; Free Radicals/metabolism ; Copper/chemistry ; Coordination Complexes/chemistry
    Chemical Substances 1,2,5,8-tetrahydroxy anthraquinone (6D43C3LYSG) ; DNA Topoisomerases, Type I (EC 5.99.1.2) ; Antineoplastic Agents ; Antibiotics, Antineoplastic ; Topoisomerase II Inhibitors ; Superoxides (11062-77-4) ; Anthracyclines ; Free Radicals ; Copper (789U1901C5) ; Coordination Complexes
    Language English
    Publishing date 2023-09-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 162843-4
    ISSN 1873-3344 ; 0162-0134
    ISSN (online) 1873-3344
    ISSN 0162-0134
    DOI 10.1016/j.jinorgbio.2023.112369
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Natural Compounds as Anticancer Agents Targeting DNA Topoisomerases.

    Jain, Chetan Kumar / Majumder, Hemanta Kumar / Roychoudhury, Susanta

    Current genomics

    2017  Volume 18, Issue 1, Page(s) 75–92

    Abstract: DNA topoisomerases are important cellular enzymes found in almost all types of living cells (eukaryotic and prokaryotic). These enzymes are essential for various DNA metabolic processes e.g. replication, transcription, recombination, chromosomal ... ...

    Abstract DNA topoisomerases are important cellular enzymes found in almost all types of living cells (eukaryotic and prokaryotic). These enzymes are essential for various DNA metabolic processes e.g. replication, transcription, recombination, chromosomal decatenation etc. These enzymes are important molecular drug targets and inhibitors of these enzymes are widely used as effective anticancer and antibacterial drugs. However, topoisomerase inhibitors have some therapeutic limitations and they exert serious side effects during cancer chemotherapy. Thus, development of novel anticancer topoisomerase inhibitors is necessary for improving cancer chemotherapy. Nature serves as a repertoire of structurally and chemically diverse molecules and in the recent years many DNA topoisomerase inhibitors have been identified from natural sources. The present review discusses anticancer properties and therapeutic importance of eighteen recently identified natural topoisomerase inhibitors (from the year 2009 to 2015). Structural characteristics of these novel inhibitors provide backbones for designing and developing new anticancer drugs.
    Language English
    Publishing date 2017-04-28
    Publishing country United Arab Emirates
    Document type Journal Article ; Review
    ZDB-ID 2033677-9
    ISSN 1875-5488 ; 1389-2029
    ISSN (online) 1875-5488
    ISSN 1389-2029
    DOI 10.2174/1389202917666160808125213
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Residues at the interface between zinc binding and winged helix domains of human RECQ1 play a significant role in DNA strand annealing activity.

    Mukhopadhyay, Swagata / Das, Tulika / Bose, Madhuparna / Jain, Chetan Kumar / Chakraborty, Mayukh / Mukherjee, Sunandan / Shikha, Kumari / Das, Amit K / Ganguly, Agneyo

    Nucleic acids research

    2021  Volume 49, Issue 20, Page(s) 11834–11854

    Abstract: RECQ1 is the shortest among the five human RecQ helicases comprising of two RecA like domains, a zinc-binding domain and a RecQ C-terminal domain containing the winged-helix (WH). Mutations or deletions on the tip of a β-hairpin located in the WH domain ... ...

    Abstract RECQ1 is the shortest among the five human RecQ helicases comprising of two RecA like domains, a zinc-binding domain and a RecQ C-terminal domain containing the winged-helix (WH). Mutations or deletions on the tip of a β-hairpin located in the WH domain are known to abolish the unwinding activity. Interestingly, the same mutations on the β-hairpin of annealing incompetent RECQ1 mutant (RECQ1T1) have been reported to restore its annealing activity. In an attempt to unravel the strand annealing mechanism, we have crystallized a fragment of RECQ1 encompassing D2-Zn-WH domains harbouring mutations on the β-hairpin. From our crystal structure data and interface analysis, we have demonstrated that an α-helix located in zinc-binding domain potentially interacts with residues of WH domain, which plays a significant role in strand annealing activity. We have shown that deletion of the α-helix or mutation of specific residues on it restores strand annealing activity of annealing deficient constructs of RECQ1. Our results also demonstrate that mutations on the α-helix induce conformational changes and affects DNA stimulated ATP hydrolysis and unwinding activity of RECQ1. Our study, for the first time, provides insight into the conformational requirements of the WH domain for efficient strand annealing by human RECQ1.
    MeSH term(s) Binding Sites ; DNA, Single-Stranded/chemistry ; DNA, Single-Stranded/metabolism ; Humans ; Molecular Dynamics Simulation ; Mutation ; Protein Binding ; Protein Conformation, alpha-Helical ; RecQ Helicases/chemistry ; RecQ Helicases/genetics ; RecQ Helicases/metabolism ; Zinc/metabolism
    Chemical Substances DNA, Single-Stranded ; RECQL protein, human (EC 3.6.1.-) ; RecQ Helicases (EC 3.6.4.12) ; Zinc (J41CSQ7QDS)
    Language English
    Publishing date 2021-11-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkab968
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Selective killing of G2 decatenation checkpoint defective colon cancer cells by catalytic topoisomerase II inhibitor.

    Jain, Chetan Kumar / Roychoudhury, Susanta / Majumder, Hemanta Kumar

    Biochimica et biophysica acta

    2015  Volume 1853, Issue 5, Page(s) 1195–1204

    Abstract: Cancer cells with defective DNA decatenation checkpoint can be selectively targeted by the catalytic inhibitors of DNA topoisomerase IIα (topo IIα) enzyme. Upon treatment with catalytic topo IIα inhibitors, cells with defective decatenation checkpoint ... ...

    Abstract Cancer cells with defective DNA decatenation checkpoint can be selectively targeted by the catalytic inhibitors of DNA topoisomerase IIα (topo IIα) enzyme. Upon treatment with catalytic topo IIα inhibitors, cells with defective decatenation checkpoint fail to arrest their cell cycle in G2 phase and enter into M phase with catenated and under-condensed chromosomes resulting into impaired mitosis and eventually cell death. In the present work we analyzed decatenation checkpoint in five different colon cancer cell lines (HCT116, HT-29, Caco2, COLO 205 and SW480) and in one non-cancerous cell line (HEK293T). Four out of the five colon cancer cell lines i.e. HCT116, HT-29, Caco2, and COLO 205 were found to be compromised for the decatenation checkpoint function at different extents, whereas SW480 and HEK293T cell lines were found to be proficient for the checkpoint function. Upon treatment with ICRF193, decatenation checkpoint defective cell lines failed to arrest the cell cycle in G2 phase and entered into M phase without proper chromosomal decatenation, resulting into the formation of tangled mass of catenated and under-condensed chromosomes. Such cells underwent mitotic catastrophe and rapid apoptosis like cell death and showed higher sensitivity for ICRF193. Our study suggests that catalytic inhibitors of topoisomerase IIα are promising therapeutic agents for the treatment of colon cancers with defective DNA decatenation checkpoint.
    MeSH term(s) Biocatalysis/drug effects ; Cell Cycle Checkpoints/drug effects ; Cell Death/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Chromosomes, Human/metabolism ; Colonic Neoplasms/pathology ; Etoposide/pharmacology ; G2 Phase/drug effects ; HEK293 Cells ; Humans ; Mitosis/drug effects ; Mitotic Index ; Piperazines/pharmacology ; Topoisomerase II Inhibitors/pharmacology ; Tumor Stem Cell Assay
    Chemical Substances Piperazines ; Topoisomerase II Inhibitors ; 4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione (21416-68-2) ; Etoposide (6PLQ3CP4P3)
    Language English
    Publishing date 2015-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbamcr.2015.02.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Assessment of Knowledge and Attitude among School Teachers Regarding HIV/AIDS Education in Field Practice Area of a Medical College in Southern Rajasthan

    Goyal Bharat Kumar / Jain Chetan Kumar / Garg Kapil / Choudhary Mahesh / Kothari Nitin / Bhatnagar Rekh

    Journal of Research in Medical and Dental Science, Vol 3, Iss 2, Pp 113-

    2015  Volume 118

    Abstract: Background: Teachers can play a very significant role in reducing the occurrence and spread of HIV infection among their students by educating regarding causation and prevention of HIV/AIDS. This depends on their own knowledge regarding HIV/AIDS and ... ...

    Abstract Background: Teachers can play a very significant role in reducing the occurrence and spread of HIV infection among their students by educating regarding causation and prevention of HIV/AIDS. This depends on their own knowledge regarding HIV/AIDS and their attitude towards HIV/AIDS education. Objective: Purpose of this study was to assess the knowledge and attitude towards HIV/AIDS education among school teachers in Udaipur. Material and methods: Cross-sectional, pre-structured questionnaire based study. Study was conducted among 138 school teachers in both urban and rural field practice area of Rabindra Nath Tagore Medical College, Udaipur. Data were analyzed statistically by simple proportions and test of significance (one way ANOVA) and Mann Whitney U test using SPSS ver.16. Results: The participants were 138 school teachers comprised 42 (30.4%) males and 96 (69.6%) females. The mean age was 38.5±10.7 years. All the teachers had heard about HIV/AIDS. Commonest sources of information were News papers/ magazines/ posters (88.4%). Overall mean score of knowledge was found to be 18.2±1.92 There were significant differences in knowledge by the type of school and teaching subject (p value <0.05). The mean attitude score was found to be 20.4±5.75. There was significant differences in attitude by the type of school, teacher’s age and teaching subject (p value <0.05). No statistically significant association seen between adequate knowledge and favourable positive attitude (p >0.05). Conclusion: Knowledge about HIV/AIDS is adequate but there is a gap between knowledge and attitude. Teachers training programme to impact on behaviour change needed.
    Keywords HIV/AIDS ; knowledge ; attitude ; school teachers ; Dentistry ; RK1-715 ; Medicine (General) ; R5-920
    Subject code 370
    Language English
    Publishing date 2015-06-01T00:00:00Z
    Publisher Amber Publication
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Activity of Co

    Mukherjee Chatterjee, Sayantani / Jain, Chetan Kumar / Singha, Soumen / Das, Piyal / Roychoudhury, Susanta / Majumder, Hemanta Kumar / Das, Saurabh

    ACS omega

    2018  Volume 3, Issue 8, Page(s) 10255–10266

    Abstract: Quinalizarin (THAQ), a hydroxy-9,10-anthraquinone analogue of the family of anthracycline anticancer drugs and an inhibitor of protein kinase, was observed for its anticancer activity. Because apart from showing anticancer activity, anthracyclines and ... ...

    Abstract Quinalizarin (THAQ), a hydroxy-9,10-anthraquinone analogue of the family of anthracycline anticancer drugs and an inhibitor of protein kinase, was observed for its anticancer activity. Because apart from showing anticancer activity, anthracyclines and their analogues also show cardiotoxic side effects, believed to be addressed through metal complex formation; an effort was made to realize this by preparing a Co
    Language English
    Publishing date 2018-08-30
    Publishing country United States
    Document type Journal Article
    ISSN 2470-1343
    ISSN (online) 2470-1343
    DOI 10.1021/acsomega.8b00706
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: The biological in vitro effect and selectivity shown by a Coᴵᴵ complex of 2-(2-hydroxyphenylazo)-indole-3′-acetic acid on three distinctly different cancer cells [Erratum: Jan. 2017, v.7(6), p.3428]

    Ganguly, Durba / Jain, Chetan Kumar / Chandra Santra, Ramesh / Roychoudhury, Susanta / Majumder, Hemanta Kumar / Das, Saurabh

    RSC advances. 2016 Dec. 12, v. 6, no. 115

    2016  

    Abstract: A major intention of this study was to use the modified toxicity of the azo moiety in [2-(2-hydroxyphenylazo)-1H-indol-3-yl]-acetic acid (HPIA), achieved through complex formation with Coᴵᴵ on some cancer cell lines. This is important because the azo ... ...

    Abstract A major intention of this study was to use the modified toxicity of the azo moiety in [2-(2-hydroxyphenylazo)-1H-indol-3-yl]-acetic acid (HPIA), achieved through complex formation with Coᴵᴵ on some cancer cell lines. This is important because the azo functional group has not been tried in cancer chemotherapy. Keeping in mind aspects of drug resistance of some of the common anticancer drugs, a serious problem and a major clinical challenge in cancer chemotherapy, it is essential that new molecules are identified with anticancer activity. Although cytotoxicity of azo compounds is established there are not many reports that utilize them in cancer treatment. Another important aspect is to prepare compounds having preferential activity on cancer cells over normal cells so that toxic side effects are a minimum. Enzyme assay on the reductive cleavage of the azo bond showed complex formation with Coᴵᴵ almost completely checked the generation of cytotoxic amines implying that the complex could be less cytotoxic which was actually observed in case of normal healthy cells. Even though the complex formed less cytotoxic amines and possessed an almost similar binding ability with DNA like that of HPIA surprisingly its activity on three cancer cell lines namely human colon carcinoma HCT116 cells, acute lymphoblastic leukemia MOLT-4 cells and MCF-7 breast cancer cells was much greater than HPIA. The difference in activity between HPIA and its Coᴵᴵ complex on cancer cells showed no correlation with DNA binding or amine formation like that observed for normal cells. The complex probably possesses multiple modes of action whereby it is able to inhibit one or more cellular processes or functioning of different enzymes involved in the cell cycle of cancer cells for which it was found more effective.
    Keywords DNA ; antineoplastic activity ; breast neoplasms ; cancer therapy ; cell cycle ; colorectal neoplasms ; cytotoxicity ; drug resistance ; drug therapy ; enzymes ; humans ; lymphocytic leukemia ; moieties ; neoplasm cells
    Language English
    Dates of publication 2016-1212
    Size p. 114906-114915.
    Publishing place The Royal Society of Chemistry
    Document type Article
    ISSN 2046-2069
    DOI 10.1039/c6ra23163b
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: Synthesis, crystal structure, DNA interaction and in vitro anticancer activity of a Cu(ii) complex of purpurin: dual poison for human DNA topoisomerase I and II

    Das, Piyal / Chowdhury, Abhishek Dutta / Das, Saurabh / Dey, Sanjoy K / Jain, Chetan Kumar / Kumar, Sanjay / Majumder, Hemanta Kumar / Roychoudhury, Susanta / Saha, Rajat

    RSC advances. 2014 Nov. 07, v. 4, no. 103

    2014  

    Abstract: Although generation of reactive oxygen species (ROS) by anthracycline anticancer drugs is essential for anti-tumor activity, they make these drugs cardiotoxic. Metal–anthracyclines that generate relatively fewer ROS are however, effective antitumor ... ...

    Abstract Although generation of reactive oxygen species (ROS) by anthracycline anticancer drugs is essential for anti-tumor activity, they make these drugs cardiotoxic. Metal–anthracyclines that generate relatively fewer ROS are however, effective antitumor agents. Purpurin (LH3), a hydroxy-9,10-anthraquinone, closely resembles doxorubicin, an established anthracycline drug. This molecule was chosen to study the extent to which simpler analogues are effective. A Cu(ii) complex of LH3 [Cu(II)–(LH2)2] was synthesized to mimic the metal–anthracycline complexes. The crystal structure of [Cu(II)–(LH2)2] was determined by Rietveld refinement of PXRD data using an appropriate structural model developed on the basis of spectroscopic data. This is the first report on the crystal structure of any hydroxy-9,10-anthraquinone with a 3d-transition metal ion. The bond lengths and bond angles obtained by structural refinement corroborate those calculated by the DFT method. DNA binding of the complex was slightly better than purpurin. However, more importantly, unlike purpurin, binding constant values did not decrease with increasing pH of the medium. DNA relaxation assays show Cu(II)–(LH2)2 as a novel potent dual inhibitor of human DNA topoisomerase I and topoisomerase II enzymes. Cu(II)–(LH2)2 stabilizes covalent topoisomerase–DNA adducts both in vitro and within cancer cells. The cleavage assay keeps the complex well ahead of LH3 with regard to efficacy. These results paralleled those of cell growth inhibition and showed that the complex was more effective in killing ALL MOLT-4 cells than LH3, suggesting it targets topoisomerase enzymes within cells. The NADH dehydrogenase assay revealed further that the generation of superoxide was less in the case of the complex as compared to LH3.
    Keywords antineoplastic activity ; cell growth ; copper ; crystal structure ; DNA ; DNA topoisomerase ; DNA topoisomerase (ATP-hydrolysing) ; doxorubicin ; growth retardation ; humans ; models ; NAD (coenzyme) ; NADH dehydrogenase ; neoplasm cells ; neoplasms ; pH ; quinones ; reactive oxygen species ; spectral analysis
    Language English
    Dates of publication 2014-1107
    Size p. 59344-59357.
    Publishing place The Royal Society of Chemistry
    Document type Article
    ISSN 2046-2069
    DOI 10.1039/c4ra07127a
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Non-ST elevation myocardial infarction in organophorous compound (DEMETHOATE) poisoning.

    Meena, Jagan Lal / Jain, Chetan Kumar / Jain, Dilip Kumar / Jain, Pradeep Kumar / Gupta, Rudraksh / Gupta, A K

    The Journal of the Association of Physicians of India

    2012  Volume 60, Page(s) 67–68

    MeSH term(s) Electrocardiography ; Humans ; Insecticides/adverse effects ; Male ; Myocardial Infarction/chemically induced ; Organophosphates/adverse effects ; Young Adult
    Chemical Substances Insecticides ; Organophosphates
    Language English
    Publishing date 2012-10
    Publishing country India
    Document type Case Reports ; Letter
    ZDB-ID 800766-4
    ISSN 0004-5772
    ISSN 0004-5772
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Sulfonoquinovosyl diacylglyceride selectively targets acute lymphoblastic leukemia cells and exerts potent anti-leukemic effects in vivo.

    Jain, Chetan Kumar / Pradhan, Bhola Shankar / Banerjee, Sukdeb / Mondal, Nirup Bikash / Majumder, Subeer S / Bhattacharyya, Madhumita / Chakrabarti, Saikat / Roychoudhury, Susanta / Majumder, Hemanta Kumar

    Scientific reports

    2015  Volume 5, Page(s) 12082

    Abstract: DNA topoisomerase II inhibitors e.g. doxorubicin and etoposide are currently used in the chemotherapy for acute lymphoblastic leukemia (ALL). These inhibitors have serious side effects during the chemotherapy e.g. cardiotoxicity and secondary ... ...

    Abstract DNA topoisomerase II inhibitors e.g. doxorubicin and etoposide are currently used in the chemotherapy for acute lymphoblastic leukemia (ALL). These inhibitors have serious side effects during the chemotherapy e.g. cardiotoxicity and secondary malignancies. In this study we show that sulfonoquinovosyl diacylglyceride (SQDG) isolated from Azadirachta indica exerts potent anti-ALL activity both in vitro and in vivo in nude mice and it synergizes with doxorubicin and etoposide. SQDG selectively targets ALL MOLT-4 cells by inhibiting catalytic activity of topoisomerase I enzyme and inducing p53 dependent apoptotic pathway. SQDG treatment induces recruitment of ATR at chromatin and arrests the cells in S-phase. Down-regulation of topoisomerase I or p53 renders the cells less sensitive for SQDG, while ectopic expression of wild type p53 protein in p53 deficient K562 cells results in chemosensitization of the cells for SQDG. We also show that constant ratio combinations of SQDG and etoposide or SDQG and doxorubicin exert synergistic effects on MOLT-4 cell killing. This study suggests that doses of etoposide/doxorubicin can be substantially reduced by combining SQDG with these agents during ALL chemotherapy and side effects caused can be minimized. Thus dual targeting of topoisomerase I and II enzymes is a promising strategy for improving ALL chemotherapy.
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; DNA Replication/drug effects ; Dose-Response Relationship, Drug ; Doxorubicin/pharmacology ; Drug Synergism ; Etoposide/pharmacology ; Glycolipids/pharmacology ; Mice ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Signal Transduction/drug effects ; Topoisomerase I Inhibitors/pharmacology ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances Antineoplastic Agents ; Glycolipids ; Topoisomerase I Inhibitors ; Tumor Suppressor Protein p53 ; sulfoquinovosyl diglyceride ; Etoposide (6PLQ3CP4P3) ; Doxorubicin (80168379AG)
    Language English
    Publishing date 2015-07-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep12082
    Database MEDical Literature Analysis and Retrieval System OnLINE

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