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  1. AU="Xavier-Carvalho, Caroline"
  2. AU="Lamb, Keith"
  3. AU="Şenbabaoğlu, Yasin"
  4. AU="Papaparaskeva, Kleo" AU="Papaparaskeva, Kleo"
  5. AU="Hanmer, Stuart B"
  6. AU="de Graaf, Gimon"
  7. AU=Bryan Nathan S
  8. AU="Bhatia, Chitra"
  9. AU="Neufeld, Niko"
  10. AU="Martínez-Cruz, Nayeli"
  11. AU="Joffe, Marshall M"
  12. AU="Wilunda, Calistus"
  13. AU="Das, Partha Pratim"
  14. AU="Staiano, Leopoldo"
  15. AU="Tibbatts, Clare"
  16. AU="Bandeira, Igor D"
  17. AU="Papathanassiou, Dimitri"
  18. AU="Mazurek, Camille"
  19. AU="Jenkinson, Crispin"
  20. AU="Hernández-Huérfano, Emilio Ernesto"
  21. AU="Conowall, Peter"
  22. AU="Nesan, Daniel"
  23. AU="Ueda, Takashi"
  24. AU="Yuan, Jiacheng"
  25. AU="Kahama, C B"
  26. AU="D’Alessio, Roberto"
  27. AU="Reuhl, Kenneth"
  28. AU="Seeleman, Conny"
  29. AU="Delaquis, Pascal"
  30. AU="Bommineni, Gopal R"
  31. AU="Kuhn, Cynthia M."
  32. AU="Olson, Jason C"
  33. AU="Buchholz, V."
  34. AU="Urquhart, Bradley L"
  35. AU="Ezaki, Kazune"
  36. AU="Choi, Jong Hyun"
  37. AU="Xie, Qiaowei"
  38. AU=Rojas-Marte G AU=Rojas-Marte G
  39. AU="Belli, A"
  40. AU="Moolman, M Charl"
  41. AU="Mazzoni, Stefania"
  42. AU=Stryjewski Martin E
  43. AU=Vallon Volker AU=Vallon Volker
  44. AU="Knowland, K E"
  45. AU="Beker, M. G."

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  1. Artikel: Host genetics and dengue fever

    Xavier-Carvalho, Caroline / Antonio Guilherme Pacheco / Cynthia Chester Cardoso / Fernanda de Souza Kehdy / Milton Ozório Moraes

    Infection, genetics, and evolution. 2017 Dec., v. 56

    2017  

    Abstract: Dengue is a major worldwide problem in tropical and subtropical areas; it is caused by four different viral serotypes, and it can manifest as asymptomatic, mild, or severe. Many factors interact to determine the severity of the disease, including the ... ...

    Abstract Dengue is a major worldwide problem in tropical and subtropical areas; it is caused by four different viral serotypes, and it can manifest as asymptomatic, mild, or severe. Many factors interact to determine the severity of the disease, including the genetic profile of the infected patient. However, the mechanisms that lead to severe disease and eventually death have not been determined, and a great challenge is the early identification of patients who are more likely to progress to a worse health condition. Studies performed in regions with cyclic outbreaks such as Cuba, Brazil, and Colombia have demonstrated that African ancestry confers protection against severe dengue. Highlighting the host genetics as an important factor in infectious diseases, a large number of association studies between genetic polymorphisms and dengue outcomes have been published in the last two decades. The most widely used approach involves case-control studies with candidate genes, such as the HLA locus and genes for receptors, cytokines, and other immune mediators. Additionally, a Genome-Wide Association Study (GWAS) identified SNPs associated with African ethnicity that had not previously been identified in case-control studies. Despite the increasing number of publications in America, Africa, and Asia, the results are quite controversial, and a meta-analysis is needed to assess the consensus among the studies. SNPs in the MICB, TNF, CD209, FcγRIIA, TPSAB1, CLEC5A, IL10 and PLCE1 genes are associated with the risk or protection of severe dengue, and the findings have been replicated in different populations. A thorough understanding of the viral, human genetic, and immunological mechanisms of dengue and how they interact is essential for effectively preventing dengue, but also managing and treating patients.
    Schlagwörter ancestry ; case-control studies ; death ; dengue ; disease severity ; genes ; genome-wide association study ; humans ; interleukin-10 ; loci ; meta-analysis ; nationalities and ethnic groups ; patients ; receptors ; risk ; serotypes ; single nucleotide polymorphism ; tumor necrosis factors ; Africa ; Asia ; Brazil ; Colombia ; Cuba
    Sprache Englisch
    Erscheinungsverlauf 2017-12
    Umfang p. 99-110.
    Erscheinungsort Elsevier B.V.
    Dokumenttyp Artikel
    ZDB-ID 2037068-4
    ISSN 1567-1348
    ISSN 1567-1348
    DOI 10.1016/j.meegid.2017.11.009
    Datenquelle NAL Katalog (AGRICOLA)

    Volltext online

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  2. Artikel ; Online: Activation of an Effective Immune Response after Yellow Fever Vaccination Is Associated with the Genetic Background and Early Response of IFN-γ and CLEC5A.

    Azamor, Tamiris / da Silva, Andréa Marques Vieira / Melgaço, Juliana Gil / Dos Santos, Ana Paula / Xavier-Carvalho, Caroline / Alvarado-Arnez, Lucia Elena / Batista-Silva, Leonardo Ribeiro / de Souza Matos, Denise Cristina / Bayma, Camilla / Missailidis, Sotiris / Ano Bom, Ana Paula Dinis / Moraes, Milton Ozorio / da Costa Neves, Patrícia Cristina

    Viruses

    2021  Band 13, Heft 1

    Abstract: The yellow fever vaccine (YF17DD) is highly effective with a single injection conferring protection for at least 10 years. The YF17DD induces polyvalent responses, with a TH1/TH2 ... ...

    Abstract The yellow fever vaccine (YF17DD) is highly effective with a single injection conferring protection for at least 10 years. The YF17DD induces polyvalent responses, with a TH1/TH2 CD4
    Mesh-Begriff(e) Adult ; Animals ; Female ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immunity ; Immunogenicity, Vaccine ; Interferon-gamma/metabolism ; Lectins, C-Type/genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Cell Surface/genetics ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Vaccination ; Yellow Fever/etiology ; Yellow Fever/prevention & control ; Yellow Fever Vaccine/immunology ; Young Adult
    Chemische Substanzen CLEC5A protein, human ; Lectins, C-Type ; Receptors, Cell Surface ; Yellow Fever Vaccine ; Interferon-gamma (82115-62-6)
    Sprache Englisch
    Erscheinungsdatum 2021-01-12
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13010096
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Host genetics and dengue fever.

    Xavier-Carvalho, Caroline / Cardoso, Cynthia Chester / de Souza Kehdy, Fernanda / Pacheco, Antonio Guilherme / Moraes, Milton Ozório

    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases

    2017  Band 56, Seite(n) 99–110

    Abstract: Dengue is a major worldwide problem in tropical and subtropical areas; it is caused by four different viral serotypes, and it can manifest as asymptomatic, mild, or severe. Many factors interact to determine the severity of the disease, including the ... ...

    Abstract Dengue is a major worldwide problem in tropical and subtropical areas; it is caused by four different viral serotypes, and it can manifest as asymptomatic, mild, or severe. Many factors interact to determine the severity of the disease, including the genetic profile of the infected patient. However, the mechanisms that lead to severe disease and eventually death have not been determined, and a great challenge is the early identification of patients who are more likely to progress to a worse health condition. Studies performed in regions with cyclic outbreaks such as Cuba, Brazil, and Colombia have demonstrated that African ancestry confers protection against severe dengue. Highlighting the host genetics as an important factor in infectious diseases, a large number of association studies between genetic polymorphisms and dengue outcomes have been published in the last two decades. The most widely used approach involves case-control studies with candidate genes, such as the HLA locus and genes for receptors, cytokines, and other immune mediators. Additionally, a Genome-Wide Association Study (GWAS) identified SNPs associated with African ethnicity that had not previously been identified in case-control studies. Despite the increasing number of publications in America, Africa, and Asia, the results are quite controversial, and a meta-analysis is needed to assess the consensus among the studies. SNPs in the MICB, TNF, CD209, FcγRIIA, TPSAB1, CLEC5A, IL10 and PLCE1 genes are associated with the risk or protection of severe dengue, and the findings have been replicated in different populations. A thorough understanding of the viral, human genetic, and immunological mechanisms of dengue and how they interact is essential for effectively preventing dengue, but also managing and treating patients.
    Mesh-Begriff(e) Alleles ; Dengue/genetics ; Dengue/immunology ; Dengue/virology ; Dengue Virus/physiology ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; HLA Antigens/genetics ; Host-Pathogen Interactions ; Humans ; Immunity, Innate ; Immunomodulation/genetics ; Patient Outcome Assessment ; Polymorphism, Genetic ; Prognosis ; Research Design
    Chemische Substanzen HLA Antigens
    Sprache Englisch
    Erscheinungsdatum 2017
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2037068-4
    ISSN 1567-7257 ; 1567-1348
    ISSN (online) 1567-7257
    ISSN 1567-1348
    DOI 10.1016/j.meegid.2017.11.009
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: Single nucleotide polymorphisms in candidate genes and dengue severity in children: A case–control, functional and meta-analysis study

    Xavier-Carvalho, Caroline / Gibson, Gerusa / Brasil, Patrícia / Ferreira, Ralph X / de Souza Santos, Reinaldo / Gonçalves Cruz, Oswaldo / de Oliveira, Solange Artimos / de Sá Carvalho, Marília / Pacheco, Antonio G / Kubelka, Claire F / Moraes, Milton O

    Infection, genetics, and evolution. 2013 Dec., v. 20

    2013  

    Abstract: Dengue is an arthropod-borne emerging viral disease with high morbidity and mortality risk in tropical countries like Brazil. Clinical manifestations are vast, ranging from asymptomatic to most severe forms of dengue such as shock. Previous data have ... ...

    Abstract Dengue is an arthropod-borne emerging viral disease with high morbidity and mortality risk in tropical countries like Brazil. Clinical manifestations are vast, ranging from asymptomatic to most severe forms of dengue such as shock. Previous data have shown that host genetics play a role in disease susceptibility and severity. Herein, we have tested the association of single nucleotide polymorphisms (SNPs) at TNF, IL10, MIF, DCSIGN, CLEC5A, NOD2, CCR5 and MRC1 as candidate genes using a matched case–control study design including 88 severe children cases of dengue patients and 335 healthy unrelated subjects that was also separated in IgG⁺ and IgG⁻ controls. We demonstrated that the TT genotype of CLEC5A SNP (rs1285933 C>T) is associated with dengue severity (OR=2.25; p=0.03) and that GG genotype of −336G>A DCSIGN (CD209) SNP is associated with protection to severe dengue (OR=0.12; p=0.04). Both comparisons were borderline significant when cases were compared with IgG⁺ controls subgroup. Nevertheless, genotype–phenotype correlation was also assessed using serum levels of TNF from infected patients at the onset of dengue fever, and CT/TT carriers in CLEC5A secreted higher levels of TNF than CC individuals in 5–7days of infection. No significant difference was observed in TNF levels between genotypes GG versus AG/AA at DCSIGN promoter. Next, we performed a meta-analysis retrieving results from the literature for −336G>A DCSIGN and −308G>A TNF SNPs demonstrating that the consensus estimates of these SNPs indicated no association with dengue severity (when compared to Dengue fever) in the overall analysis. But, a subgroup analysis in the −336G>A DCSIGN, the G allele was associated with severe dengue susceptibility in Asians (ORₐₗₗₑₗₑ=2.77; p=0.0001; ORcₐᵣᵣᵢₑᵣₛ=2.99; p=0.0001) and protection in Brazilians (ORₐₗₗₑₗₑ=0.66; p=0.013). In summary, our results suggest that genetic variations at CLEC5A increase the risk and regulate TNF secretion in dengue severity among Brazilians. Also, combined data of the literature suggest population-specific effect of the −336 DCSIGN SNP more prominent in Asians and in a different direction than Brazilians.
    Schlagwörter Asians ; alleles ; blood serum ; case-control studies ; children ; dengue ; disease resistance ; disease severity ; experimental design ; genetic variation ; genotype ; interleukin-10 ; intracellular signaling peptides and proteins ; meta-analysis ; morbidity ; mortality ; patients ; risk ; secretion ; single nucleotide polymorphism ; tumor necrosis factors ; Brazil
    Sprache Englisch
    Erscheinungsverlauf 2013-12
    Umfang p. 197-205.
    Erscheinungsort Elsevier B.V.
    Dokumenttyp Artikel
    ZDB-ID 2037068-4
    ISSN 1567-1348
    ISSN 1567-1348
    DOI 10.1016/j.meegid.2013.08.017
    Datenquelle NAL Katalog (AGRICOLA)

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  5. Artikel ; Online: Single nucleotide polymorphisms in candidate genes and dengue severity in children: a case-control, functional and meta-analysis study.

    Xavier-Carvalho, Caroline / Gibson, Gerusa / Brasil, Patrícia / Ferreira, Ralph X / de Souza Santos, Reinaldo / Gonçalves Cruz, Oswaldo / de Oliveira, Solange Artimos / de Sá Carvalho, Marília / Pacheco, Antonio G / Kubelka, Claire F / Moraes, Milton O

    Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases

    2013  Band 20, Seite(n) 197–205

    Abstract: Dengue is an arthropod-borne emerging viral disease with high morbidity and mortality risk in tropical countries like Brazil. Clinical manifestations are vast, ranging from asymptomatic to most severe forms of dengue such as shock. Previous data have ... ...

    Abstract Dengue is an arthropod-borne emerging viral disease with high morbidity and mortality risk in tropical countries like Brazil. Clinical manifestations are vast, ranging from asymptomatic to most severe forms of dengue such as shock. Previous data have shown that host genetics play a role in disease susceptibility and severity. Herein, we have tested the association of single nucleotide polymorphisms (SNPs) at TNF, IL10, MIF, DCSIGN, CLEC5A, NOD2, CCR5 and MRC1 as candidate genes using a matched case-control study design including 88 severe children cases of dengue patients and 335 healthy unrelated subjects that was also separated in IgG(+) and IgG(-) controls. We demonstrated that the TT genotype of CLEC5A SNP (rs1285933 C>T) is associated with dengue severity (OR=2.25; p=0.03) and that GG genotype of -336G>A DCSIGN (CD209) SNP is associated with protection to severe dengue (OR=0.12; p=0.04). Both comparisons were borderline significant when cases were compared with IgG(+) controls subgroup. Nevertheless, genotype-phenotype correlation was also assessed using serum levels of TNF from infected patients at the onset of dengue fever, and CT/TT carriers in CLEC5A secreted higher levels of TNF than CC individuals in 5-7 days of infection. No significant difference was observed in TNF levels between genotypes GG versus AG/AA at DCSIGN promoter. Next, we performed a meta-analysis retrieving results from the literature for -336G>A DCSIGN and -308G>A TNF SNPs demonstrating that the consensus estimates of these SNPs indicated no association with dengue severity (when compared to Dengue fever) in the overall analysis. But, a subgroup analysis in the -336G>A DCSIGN, the G allele was associated with severe dengue susceptibility in Asians (ORallele=2.77; p=0.0001; ORcarriers=2.99; p=0.0001) and protection in Brazilians (ORallele=0.66; p=0.013). In summary, our results suggest that genetic variations at CLEC5A increase the risk and regulate TNF secretion in dengue severity among Brazilians. Also, combined data of the literature suggest population-specific effect of the -336 DCSIGN SNP more prominent in Asians and in a different direction than Brazilians.
    Mesh-Begriff(e) Case-Control Studies ; Cell Adhesion Molecules/genetics ; Child ; Dengue/genetics ; Dengue/immunology ; Dengue Virus/immunology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Humans ; Inflammation/genetics ; Inflammation/immunology ; Lectins, C-Type/genetics ; Male ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Receptors, Cell Surface/genetics ; Risk ; Tumor Necrosis Factor-alpha/blood
    Chemische Substanzen CLEC5A protein, human ; Cell Adhesion Molecules ; DC-specific ICAM-3 grabbing nonintegrin ; Lectins, C-Type ; Receptors, Cell Surface ; Tumor Necrosis Factor-alpha
    Sprache Englisch
    Erscheinungsdatum 2013-12
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
    ZDB-ID 2037068-4
    ISSN 1567-7257 ; 1567-1348
    ISSN (online) 1567-7257
    ISSN 1567-1348
    DOI 10.1016/j.meegid.2013.08.017
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects.

    Xavier-Carvalho, Caroline / Cezar, Renata Duarte da Silva / Freire, Naishe Matos / Vasconcelos, Carla Maria Mola de / Solorzano, Victor Edgar Fiestas / de Toledo-Pinto, Thiago Gomes / Fialho, Luciana Gomes / do Carmo, Rodrigo Feliciano / Vasconcelos, Luydson Richardson Silva / Cordeiro, Marli Tenório / Baptista, Paulo / de Azeredo, Elzinandes Leal / da Cunha, Rivaldo Venâncio / de Souza, Luiz José / Pacheco, Antonio Guilherme / Kubelka, Claire Fernandes / Moura, Patrícia Muniz Mendes Freire de / Moraes, Milton Ozorio

    Human immunology

    2017  Band 78, Heft 10, Seite(n) 649–656

    Abstract: Outbreaks of the Zika, dengue, and chikungunya viruses, especially in the Americas, pose a global threat due to their rapid spread and difficulty controlling the vector. Extreme phenotypes are often observed, from asymptomatic to severe clinical ... ...

    Abstract Outbreaks of the Zika, dengue, and chikungunya viruses, especially in the Americas, pose a global threat due to their rapid spread and difficulty controlling the vector. Extreme phenotypes are often observed, from asymptomatic to severe clinical manifestations, which are well-studied in dengue. Host variations are also important contributors to disease outcomes, and many case-control studies have associated single nucleotide polymorphisms (SNPs) with severe dengue. Here, we found that the TC genotype and T-carriers for SNP rs1285933 in the C-type lectin superfamily member 5 (CLEC5A) gene was associated with severe dengue in a Northern Brazilian population (OR=2.75 and p-value=0.01, OR=2.11 and p-value=0.04, respectively). We also tested the functional effect of the CLEC5A protein and found that it is upregulated on the surface of human monocytes after in vitro dengue infection. CLEC5A was correlated with viral load inside the monocytes (Spearman r=0.55, p=0.008) and TNF production in culture supernatants (Spearman r=0.72, p=0.03). Analysis of mRNA in blood samples from DENV4-infected patients exhibiting mild symptoms showed that CLEC5A mRNA expression is correlated with TNF (r=0.67, p=0.0001) and other immune mediators. Monocytes from rs1285933 TT/TC individuals showed lower CLEC5A expression compared to CC genotypes. However, in these cells, CLEC5A was not correlated with TNF production. In summary, we confirmed that CLEC5A is genetically associated with dengue severity outcome, playing a central role during the immune response triggered by a dengue viral infection, and rs1285933 is a relevant SNP that is able to regulate signaling pathways after interactions between the dengue virus and CLEC5A receptors.
    Sprache Englisch
    Erscheinungsdatum 2017-10
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 801524-7
    ISSN 1879-1166 ; 0198-8859
    ISSN (online) 1879-1166
    ISSN 0198-8859
    DOI 10.1016/j.humimm.2017.07.013
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel: Single nucleotide polymorphisms in candidate genes and dengue severity in children: A case–control, functional and meta-analysis study

    Xavier-Carvalho, Caroline / Gibson, Gerusa / Brasil, Patrícia / Ferreira, Ralph X. / de Souza Santos, Reinaldo / Gonçalves Cruz, Oswaldo / de Oliveira, Solange Artimos / de Sá Carvalho, Marília / Pacheco, Antonio G. / Kubelka, Claire F. / Moraes, Milton O.

    Infection, genetics, and evolution

    Band v. 20

    Abstract: Dengue is an arthropod-borne emerging viral disease with high morbidity and mortality risk in tropical countries like Brazil. Clinical manifestations are vast, ranging from asymptomatic to most severe forms of dengue such as shock. Previous data have ... ...

    Abstract Dengue is an arthropod-borne emerging viral disease with high morbidity and mortality risk in tropical countries like Brazil. Clinical manifestations are vast, ranging from asymptomatic to most severe forms of dengue such as shock. Previous data have shown that host genetics play a role in disease susceptibility and severity. Herein, we have tested the association of single nucleotide polymorphisms (SNPs) at TNF, IL10, MIF, DCSIGN, CLEC5A, NOD2, CCR5 and MRC1 as candidate genes using a matched case–control study design including 88 severe children cases of dengue patients and 335 healthy unrelated subjects that was also separated in IgG⁺ and IgG⁻ controls. We demonstrated that the TT genotype of CLEC5A SNP (rs1285933 C>T) is associated with dengue severity (OR=2.25; p=0.03) and that GG genotype of −336G>A DCSIGN (CD209) SNP is associated with protection to severe dengue (OR=0.12; p=0.04). Both comparisons were borderline significant when cases were compared with IgG⁺ controls subgroup. Nevertheless, genotype–phenotype correlation was also assessed using serum levels of TNF from infected patients at the onset of dengue fever, and CT/TT carriers in CLEC5A secreted higher levels of TNF than CC individuals in 5–7days of infection. No significant difference was observed in TNF levels between genotypes GG versus AG/AA at DCSIGN promoter. Next, we performed a meta-analysis retrieving results from the literature for −336G>A DCSIGN and −308G>A TNF SNPs demonstrating that the consensus estimates of these SNPs indicated no association with dengue severity (when compared to Dengue fever) in the overall analysis. But, a subgroup analysis in the −336G>A DCSIGN, the G allele was associated with severe dengue susceptibility in Asians (ORₐₗₗₑₗₑ=2.77; p=0.0001; ORcₐᵣᵣᵢₑᵣₛ=2.99; p=0.0001) and protection in Brazilians (ORₐₗₗₑₗₑ=0.66; p=0.013). In summary, our results suggest that genetic variations at CLEC5A increase the risk and regulate TNF secretion in dengue severity among Brazilians. Also, combined data of the literature suggest population-specific effect of the −336 DCSIGN SNP more prominent in Asians and in a different direction than Brazilians.
    Schlagwörter blood serum ; disease resistance ; experimental design ; secretion ; single nucleotide polymorphism ; alleles ; children ; genotype ; case-control studies ; disease severity ; risk ; meta-analysis ; intracellular signaling peptides and proteins ; patients ; genetic variation ; interleukin-10 ; mortality ; tumor necrosis factors ; dengue ; Asians ; morbidity
    Sprache Englisch
    Dokumenttyp Artikel
    ISSN 1567-1348
    Datenquelle AGRIS - International Information System for the Agricultural Sciences and Technology

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