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  1. Article ; Online: A close shave: How SARS-CoV-2 induces the loss of cilia.

    Fonseca, Barbara F / Chakrabarti, Lisa A

    The Journal of cell biology

    2022  Volume 221, Issue 7

    Abstract: Wang et al. report in this issue (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202108015) that the SARS-CoV-2 protein ORF10 increases the activity of the E3 ligase CUL2ZYG11B, leading to the degradation of multiple ciliary proteins. The resulting loss ... ...

    Abstract Wang et al. report in this issue (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202108015) that the SARS-CoV-2 protein ORF10 increases the activity of the E3 ligase CUL2ZYG11B, leading to the degradation of multiple ciliary proteins. The resulting loss of cilia may facilitate the spread of SARS-CoV-2 in the respiratory tree.
    MeSH term(s) COVID-19/pathology ; Cell Cycle Proteins ; Cilia/pathology ; Cullin Proteins ; Genes, Viral ; Humans ; Proteins/metabolism ; SARS-CoV-2 ; Ubiquitin-Protein Ligases/metabolism
    Chemical Substances CUL2 protein, human ; Cell Cycle Proteins ; Cullin Proteins ; Proteins ; ZYG11A protein, human ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
    Language English
    Publishing date 2022-06-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.202206023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Respective contribution of the cephalic neural crest and mesoderm to SIX1-expressing head territories in the avian embryo.

    Fonseca, Barbara F / Couly, Gérard / Dupin, Elisabeth

    BMC developmental biology

    2017  Volume 17, Issue 1, Page(s) 13

    Abstract: Background: Vertebrate head development depends on a series of interactions between many cell populations of distinct embryological origins. Cranial mesenchymal tissues have a dual embryonic source: - the neural crest (NC), which generates most of ... ...

    Abstract Background: Vertebrate head development depends on a series of interactions between many cell populations of distinct embryological origins. Cranial mesenchymal tissues have a dual embryonic source: - the neural crest (NC), which generates most of craniofacial skeleton, dermis, pericytes, fat cells, and tenocytes; and - the mesoderm, which yields muscles, blood vessel endothelia and some posterior cranial bones. The molecular players that orchestrate co-development of cephalic NC and mesodermal cells to properly construct the head of vertebrates remain poorly understood. In this regard, Six1 gene, a vertebrate homolog of Drosophila Sine Oculis, is known to be required for development of ear, nose, tongue and cranial skeleton. However, the embryonic origin and fate of Six1-expressing cells have remained unclear. In this work, we addressed these issues in the avian embryo model by using quail-chick chimeras, cephalic NC cultures and immunostaining for SIX1.
    Results: Our data show that, at early NC migration stages, SIX1 is expressed by mesodermal cells but excluded from the NC cells (NCC). Then, SIX1 becomes widely expressed in NCC that colonize the pre-otic mesenchyme. In contrast, in the branchial arches (BAs), SIX1 is present only in mesodermal cells that give rise to jaw muscles. At later developmental stages, the distribution of SIX1-expressing cells in mesoderm-derived tissues is consistent with a possible role of this factor in the myogenic program of all types of head muscles, including pharyngeal, extraocular and tongue muscles. In NC derivatives, SIX1 is notably expressed in perichondrium and chondrocytes of the nasal septum and in the sclera, although other facial cartilages such as Meckel's were negative at the stages considered. Moreover, in cephalic NC cultures, chondrocytes and myofibroblasts, not the neural and melanocytic cells express SIX1.
    Conclusion: The present results point to a dynamic tissue-specific expression of SIX1 in a variety of cephalic NC- and mesoderm-derived cell types and tissues, opening the way for further analysis of Six1 function in the coordinated development of these two cellular populations during vertebrate head formation.
    MeSH term(s) Animals ; Embryo, Nonmammalian/embryology ; Mesoderm/embryology ; Neural Crest/embryology ; Quail/embryology
    Language English
    Publishing date 2017-10-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1471-213X
    ISSN (online) 1471-213X
    DOI 10.1186/s12861-017-0155-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Recapitulating memory B cell responses in a Lymphoid Organ-Chip to evaluate mRNA vaccine boosting strategies

    Jeger-Madiot, Raphaël / Planas, Delphine / Staropoli, Isabelle / Kervevan, Jérôme / Mary, Héloïse / Collina, Camilla / Fonseca, Barbara F. / Debarnot, Hippolyte / Robinot, Rémy / Gellenoncourt, Stacy / Schwartz, Olivier / Ewart, Lorna / Bscheider, Michael / Gobaa, Samy / Chakrabarti, Lisa A.

    bioRxiv

    Abstract: Predicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed a Lymphoid Organ-Chip (LO chip) model based on a microfluidic chip seeded with human PBMC at high density within a 3D collagen matrix. ... ...

    Abstract Predicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed a Lymphoid Organ-Chip (LO chip) model based on a microfluidic chip seeded with human PBMC at high density within a 3D collagen matrix. Perfusion of the SARS-CoV-2 Spike protein mimicked a vaccine boost by inducing a massive amplification of Spike-specific memory B cells, plasmablast differentiation, and Spike-specific antibody secretion. Features of lymphoid tissue, including the formation of activated CD4+ T cell/B cell clusters and the emigration of matured plasmablasts, were recapitulated in the LO chip. Importantly, myeloid cells were competent at capturing and expressing mRNA vectored by lipid nanoparticles, enabling the assessment of responses to mRNA vaccines. Comparison of on-chip responses to Wuhan monovalent and Wuhan/Omicron bivalent mRNA vaccine boosts showed equivalent induction of Omicron neutralizing antibodies, pointing at immune imprinting as reported in vivo. The LO chip thus represents a versatile platform suited to the preclinical evaluation of vaccine boosting strategies.
    Keywords covid19
    Language English
    Publishing date 2024-02-02
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2024.02.02.578553
    Database COVID19

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  4. Article ; Online: Global loss of cellular m

    Vaid, Roshan / Mendez, Akram / Thombare, Ketan / Burgos-Panadero, Rebeca / Robinot, Rémy / Fonseca, Barbara F / Gandasi, Nikhil R / Ringlander, Johan / Hassan Baig, Mohammad / Dong, Jae-June / Cho, Jae Yong / Reinius, Björn / Chakrabarti, Lisa A / Nystrom, Kristina / Mondal, Tanmoy

    Genome research

    2023  Volume 33, Issue 3, Page(s) 299–313

    Abstract: Insights into host-virus interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics. ...

    Abstract Insights into host-virus interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics.
    MeSH term(s) Humans ; SARS-CoV-2/genetics ; COVID-19/genetics ; Methylation ; RNA ; RNA, Viral/genetics ; Methyltransferases/genetics
    Chemical Substances RNA (63231-63-0) ; RNA, Viral ; METTL3 protein, human (EC 2.1.1.62) ; Methyltransferases (EC 2.1.1.-)
    Language English
    Publishing date 2023-03-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1284872-4
    ISSN 1549-5469 ; 1088-9051 ; 1054-9803
    ISSN (online) 1549-5469
    ISSN 1088-9051 ; 1054-9803
    DOI 10.1101/gr.276407.121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Global loss of cellular m6A RNA methylation following infection with different SARS-CoV-2 variants

    Vaid, Roshan / Mendez, Akram / Thombare, Ketan / Burgos-Panadero, Rebeca / Robinot, Rémy / Fonseca, Barbara F / Gandasi, Nikhil R / Ringlander, Johan / Baig, Mohammad Hassan / Dong, Jae-June / Cho, Jae Yong / Reinius, Björn / Chakrabarti, Lisa A / Nystrom, Kristina / Mondal, Tanmoy

    bioRxiv

    Abstract: Host-viral interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics. N6-methyladenosine modification (m6A), one of the most abundant cellular RNA ... ...

    Abstract Host-viral interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics. N6-methyladenosine modification (m6A), one of the most abundant cellular RNA modifications, regulates key processes in RNA metabolism during a stress response. Gene expression profiles observed post-infection with different SARS-CoV-2 variants show changes in the expression of genes related to RNA catabolism, including m6A readers and erasers. We found that infection with SARS-CoV-2 variants caused a loss of m6A in cellular RNAs, whereas m6A was detected abundantly in viral RNA. METTL3, the m6A methyltransferase, showed an unusual cytoplasmic localization post-infection. The B.1.351 variant had a less pronounced effect on METTL3 localization and loss of m6A than the B.1 and B.1.1.7 variants. We also observed a loss of m6A upon SARS-CoV-2 infection in air/liquid interface cultures of human airway epithelia, confirming that m6A loss is characteristic of SARS-CoV-2 infected cells. Further, transcripts with m6A modification were preferentially down-regulated post-infection. Inhibition of the export protein XPO1 resulted in the restoration of METTL3 localization, recovery of m6A on cellular RNA, and increased mRNA expression. Stress granule formation, which was compromised by SARS-CoV-2 infection, was restored by XPO1 inhibition and accompanied by a reduced viral infection in vitro. Together, our study elucidates how SARS-CoV-2 inhibits the stress response and perturbs cellular gene expression in an m6A-dependent manner.
    Keywords covid19
    Language English
    Publishing date 2022-12-09
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.12.08.519593
    Database COVID19

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  6. Article ; Online: Flavonoids: potential Wnt/beta-catenin signaling modulators in cancer.

    Amado, Nathália G / Fonseca, Bárbara F / Cerqueira, Débora M / Neto, Vivaldo Moura / Abreu, José G

    Life sciences

    2011  Volume 89, Issue 15-16, Page(s) 545–554

    Abstract: Flavonoids are polyphenolic compounds found throughout the plant kingdom. They occur in every organ but are usually concentrated in leaves and flowers. During the last two decades, in vitro and in vivo studies demonstrated that flavonoids have inhibitory ...

    Abstract Flavonoids are polyphenolic compounds found throughout the plant kingdom. They occur in every organ but are usually concentrated in leaves and flowers. During the last two decades, in vitro and in vivo studies demonstrated that flavonoids have inhibitory effects on human diseases through targeting of multiple cellular signaling components. Wnt/β-catenin signaling regulates proliferation, differentiation and fate specification in developmental stages and controls tissue homeostasis in adult life. For these reasons, this pathway has received great attention in the last years as potential pathway involved in distinct Human pathologies. In this review we discuss the emerging potential mechanisms for flavonoids on Wnt/β-catenin signaling in cancer and possible investigation strategies to understand flavonoids mode of action on this signaling pathway.
    MeSH term(s) Animals ; Flavonoids/pharmacology ; Humans ; Neoplasms/physiopathology ; Plants/chemistry ; Signal Transduction/drug effects ; Wnt Proteins/drug effects ; beta Catenin/physiology
    Chemical Substances Flavonoids ; Wnt Proteins ; beta Catenin
    Language English
    Publishing date 2011-10-10
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2011.05.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Flavonoids: Potential Wnt/beta-catenin signaling modulators in cancer

    Amado, Nathália G / Fonseca, Bárbara F / Cerqueira, Débora M / Neto, Vivaldo Moura / Abreu, José G

    Life sciences. 2011 Oct. 10, v. 89, no. 15-16

    2011  

    Abstract: Flavonoids are polyphenolic compounds found throughout the plant kingdom. They occur in every organ but are usually concentrated in leaves and flowers. During the last two decades, in vitro and in vivo studies demonstrated that flavonoids have inhibitory ...

    Abstract Flavonoids are polyphenolic compounds found throughout the plant kingdom. They occur in every organ but are usually concentrated in leaves and flowers. During the last two decades, in vitro and in vivo studies demonstrated that flavonoids have inhibitory effects on human diseases through targeting of multiple cellular signaling components. Wnt/β-catenin signaling regulates proliferation, differentiation and fate specification in developmental stages and controls tissue homeostasis in adult life. For these reasons, this pathway has received great attention in the last years as potential pathway involved in distinct Human pathologies. In this review we discuss the emerging potential mechanisms for flavonoids on Wnt/β-catenin signaling in cancer and possible investigation strategies to understand flavonoids mode of action on this signaling pathway.
    Keywords adults ; anticarcinogenic activity ; flavonoids ; flowers ; homeostasis ; human diseases ; humans ; in vivo studies ; leaves ; mechanism of action ; neoplasms ; polyphenols ; signal transduction
    Language English
    Dates of publication 2011-1010
    Size p. 545-554.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2011.05.003
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Derricin and derricidin inhibit Wnt/β-catenin signaling and suppress colon cancer cell growth in vitro.

    Fonseca, Barbara F / Predes, Danilo / Cerqueira, Debora M / Reis, Alice H / Amado, Nathalia G / Cayres, Marina C L / Kuster, Ricardo M / Oliveira, Felipe L / Mendes, Fabio A / Abreu, Jose G

    PloS one

    2015  Volume 10, Issue 3, Page(s) e0120919

    Abstract: Overactivation of the Wnt/β-catenin pathway in adult tissues has been implicated in many diseases, such as colorectal cancer. Finding chemical substances that can prevent this phenomenon is an emerging problem. Recently, several natural compounds have ... ...

    Abstract Overactivation of the Wnt/β-catenin pathway in adult tissues has been implicated in many diseases, such as colorectal cancer. Finding chemical substances that can prevent this phenomenon is an emerging problem. Recently, several natural compounds have been described as Wnt/β-catenin inhibitors and might be promising agents for the control of carcinogenesis. Here, we describe two natural substances, derricin and derricidin, belonging to the chalcone subclass, that show potent transcriptional inhibition of the Wnt/β-catenin pathway. Both chalcones are able to affect the cell distribution of β-catenin, and inhibit Wnt-specific reporter activity in HCT116 cells and in Xenopus embryos. Derricin and derricidin also strongly inhibited canonical Wnt activity in vitro, and rescued the Wnt-induced double axis phenotype in Xenopus embryos. As a consequence of Wnt/β-catenin inhibition, derricin and derricidin treatments reduce cell viability and lead to cell cycle arrest in colorectal cancer cell lines. Taken together, our results strongly support these chalcones as novel negative modulators of the Wnt/β-catenin pathway and colon cancer cell growth in vitro.
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Cell Proliferation/drug effects ; Chalcones/chemistry ; Chalcones/pharmacology ; Colonic Neoplasms/metabolism ; Flavonoids/pharmacology ; HCT116 Cells ; Hemiterpenes/chemistry ; Hemiterpenes/pharmacology ; Humans ; Wnt Signaling Pathway ; Xenopus ; beta Catenin/genetics ; beta Catenin/metabolism
    Chemical Substances Antineoplastic Agents ; Chalcones ; Flavonoids ; Hemiterpenes ; beta Catenin ; derricidin ; derricin
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0120919
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Isoquercitrin suppresses colon cancer cell growth in vitro by targeting the Wnt/β-catenin signaling pathway.

    Amado, Nathália G / Predes, Danilo / Fonseca, Barbara F / Cerqueira, Débora M / Reis, Alice H / Dudenhoeffer, Ana C / Borges, Helena L / Mendes, Fábio A / Abreu, Jose G

    The Journal of biological chemistry

    2014  Volume 289, Issue 51, Page(s) 35456–35467

    Abstract: Flavonoids are plant-derived polyphenolic molecules that have potential biological effects including anti-oxidative, anti-inflammatory, anti-viral, and anti-tumoral effects. These effects are related to the ability of flavonoids to modulate signaling ... ...

    Abstract Flavonoids are plant-derived polyphenolic molecules that have potential biological effects including anti-oxidative, anti-inflammatory, anti-viral, and anti-tumoral effects. These effects are related to the ability of flavonoids to modulate signaling pathways, such as the canonical Wnt signaling pathway. This pathway controls many aspects of embryonic development and tissue maintenance and has been found to be deregulated in a range of human cancers. We performed several in vivo assays in Xenopus embryos, a functional model of canonical Wnt signaling studies, and also used in vitro models, to investigate whether isoquercitrin affects Wnt/β-catenin signaling. Our data provide strong support for an inhibitory effect of isoquercitrin on Wnt/β-catenin, where the flavonoid acts downstream of β-catenin translocation to the nuclei. Isoquercitrin affects Xenopus axis establishment, reverses double axes and the LiCl hyperdorsalization phenotype, and reduces Xnr3 expression. In addition, this flavonoid shows anti-tumoral effects on colon cancer cells (SW480, DLD-1, and HCT116), whereas exerting no significant effect on non-tumor colon cell (IEC-18), suggesting a specific effect in tumor cells in vitro. Taken together, our data indicate that isoquercitrin is an inhibitor of Wnt/β-catenin and should be further investigated as a potential novel anti-tumoral agent.
    MeSH term(s) Active Transport, Cell Nucleus/drug effects ; Animals ; Antineoplastic Agents/pharmacology ; Blotting, Western ; Body Patterning/drug effects ; Body Patterning/genetics ; Cell Line ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Nucleus/drug effects ; Cell Nucleus/metabolism ; Cell Proliferation/drug effects ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Early Growth Response Protein 2/genetics ; Embryo, Nonmammalian/drug effects ; Embryo, Nonmammalian/embryology ; Embryo, Nonmammalian/metabolism ; Gene Expression Regulation, Developmental ; HCT116 Cells ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Lithium Chloride/pharmacology ; Quercetin/analogs & derivatives ; Quercetin/pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Wnt Signaling Pathway/drug effects ; Wnt Signaling Pathway/genetics ; Xenopus/embryology ; Xenopus/genetics ; Xenopus/metabolism ; Xenopus Proteins/genetics ; beta Catenin/genetics ; beta Catenin/metabolism
    Chemical Substances Antineoplastic Agents ; Early Growth Response Protein 2 ; Xenopus Proteins ; beta Catenin ; isoquercitrin (0YX10VRV6J) ; Quercetin (9IKM0I5T1E) ; Lithium Chloride (G4962QA067)
    Language English
    Publishing date 2014-10-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M114.621599
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Effects of natural compounds on Xenopus embryogenesis: a potential read out for functional drug discovery targeting Wnt/β-catenin signaling.

    Amado, Nathalia G / Fonseca, Barbara F / Cerqueira, Debora Malta / Reis, Alice H / Simas, Alessandro Bolis Costa / Kuster, Ricardo Machado / Mendes, Fabio A / Abreu, Jose G

    Current topics in medicinal chemistry

    2012  Volume 12, Issue 19, Page(s) 2103–2113

    Abstract: Maternal Wnt/β-Catenin signaling is essential to establish dorsal-specific gene expression required for axial patterning in Xenopus. Deregulation of this pathway causes axis phenotypes in frog embryos. In adult life, mutations in the Wnt pathway ... ...

    Abstract Maternal Wnt/β-Catenin signaling is essential to establish dorsal-specific gene expression required for axial patterning in Xenopus. Deregulation of this pathway causes axis phenotypes in frog embryos. In adult life, mutations in the Wnt pathway components are associated with many diseases, such as polyposis coli; osteoporosis-pseudoglioma syndrome (OPPG); skeletal dysplasia; neural tube defects, cancer and many others. Thus, a better understanding of Wnt/β-catenin signaling will have great and significant impact on Biology and Medicine. In this aspect, natural compounds are potential targets as novel molecules that could modulate the Wnt pathway. For instance, flavonoids are a large group of natural compounds found in plants that modulate important cellular and molecular mechanisms related to diseases, but the specific in vivo mechanism of action of most flavonoids remain unknown. In this way, Xenopus embryos may provide an efficient model, since it is frequently used to test and identify the role of molecules that affect Wnt/β-catenin signaling. Here, we describe a combination of approaches to outline and characterize the role of two flavonoids, quercetin and rutin, on Wnt/β-catenin signaling, using Xenopus embryos as an experimental model. Our data support that quercetin is potential in vivo modulator of canonical Wnt signaling and that this effect might depend on the structure of this molecule, as we did not observe any effect with rutin treatment, a flavonol structurally-related to quercetin. This model is useful to analyze effects of quercetin and other flavonoids in vivo and to provide further understanding of how natural compounds can modulate signaling pathways, using Xenopus embryos as a fast and efficient reading of in vivo effects of those compounds.
    MeSH term(s) Animals ; Base Sequence ; Biological Products/pharmacology ; DNA Primers ; Drug Discovery ; Embryonic Development/drug effects ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/drug effects ; Wnt Proteins/metabolism ; Xenopus/embryology ; beta Catenin/metabolism
    Chemical Substances Biological Products ; DNA Primers ; Wnt Proteins ; beta Catenin
    Language English
    Publishing date 2012-11-16
    Publishing country United Arab Emirates
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2064823-6
    ISSN 1873-4294 ; 1568-0266
    ISSN (online) 1873-4294
    ISSN 1568-0266
    DOI 10.2174/156802612804910241
    Database MEDical Literature Analysis and Retrieval System OnLINE

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