Caracterização do perfil de microvesículas cirdulantes em pacientes com policitemia vera

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Sousa, Milane Araújo de
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade do Estado do Amazonas
Brasil
UEA
PPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIA
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: https://ri.uea.edu.br/handle/riuea/2265
Resumo: Polycythemia Vera (PV) is part of the group of myeloproliferative neoplasms (PMNs), in which it is characterized by an increase in erythrocyte mass. It is believed that VMs play an important role in the development of neoplasms and may be essential for understanding these pathologies. It has already been described that microvesicles (MVs) contribute to the development of PV with their greater procoagulant activity, increasing the risk of thrombotic complications. Objectives: To characterize the profile of circulating microvesicles in patients diagnosed with Polycythemia Vera treated at the Hospital Foundation for Hematology and Hemotherapy of Amazonas. Material and methods: Sixty-six individuals of both sexes were included and categorized into two groups: 33 patients with a conclusive diagnosis of Polycythemia Vera undergoing treatment and 33 healthy individuals for the control group. Clinical data were obtained from the patients' charts. Laboratory data were obtained from blood samples. Immunophenotypic characterization was performed on a CytoFlex S flow cytometer (Beckman Coulter) using the VM immunophenotyping protocol of the Integrated Group for Biomarker Research (GIPB) of the René Rachou Institute (IRR)-Fiocruz Minas. Results: There was a higher level of MVs CD34, CD13, CD33 (progenitor/myeloid), CD11c (dendritic cells), CD16, CD66b (neutrophils), CD3 (T Lymphocytes), CD19 (B Lymphocytes), CD56 (NK cells) , CD235a (erythrocytes) and CD51/61 (endothelial cells) in patients with PV. There were no significant levels of MVs in the groups of patients with and without thrombotic events. Higher levels of CD3 (lymphocytes) and CD51/61 (endothelial cells) MVs were identified in JAK2V617F+ patients with thrombotic events. Conclusion: In the analysis of the profile of MVs, higher levels of MVs were observed in patients with PV than in healthy individuals. It was also observed that JAK2V617F+ patients who have a history of thrombosis had higher levels of CD3 MVs (T lymphocytes) and CD51/61 (endothelial cells). in the pathogenesis of thrombosis. Future studies are essential to analyze VMs in the context of treatment, in addition to seeking to understand their role in the prognosis, as well as in the prothrombotic state of patients with PV.
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spelling Caracterização do perfil de microvesículas cirdulantes em pacientes com policitemia veraCharacterization of the profile of circulating microvesicles in patients with polycythemia veraNeoplasia mieloproliferativaMicrovesículaPolicitemia veraMyeloproliferative neoplasmPolycythemia Vera (PV) is part of the group of myeloproliferative neoplasms (PMNs), in which it is characterized by an increase in erythrocyte mass. It is believed that VMs play an important role in the development of neoplasms and may be essential for understanding these pathologies. It has already been described that microvesicles (MVs) contribute to the development of PV with their greater procoagulant activity, increasing the risk of thrombotic complications. Objectives: To characterize the profile of circulating microvesicles in patients diagnosed with Polycythemia Vera treated at the Hospital Foundation for Hematology and Hemotherapy of Amazonas. Material and methods: Sixty-six individuals of both sexes were included and categorized into two groups: 33 patients with a conclusive diagnosis of Polycythemia Vera undergoing treatment and 33 healthy individuals for the control group. Clinical data were obtained from the patients' charts. Laboratory data were obtained from blood samples. Immunophenotypic characterization was performed on a CytoFlex S flow cytometer (Beckman Coulter) using the VM immunophenotyping protocol of the Integrated Group for Biomarker Research (GIPB) of the René Rachou Institute (IRR)-Fiocruz Minas. Results: There was a higher level of MVs CD34, CD13, CD33 (progenitor/myeloid), CD11c (dendritic cells), CD16, CD66b (neutrophils), CD3 (T Lymphocytes), CD19 (B Lymphocytes), CD56 (NK cells) , CD235a (erythrocytes) and CD51/61 (endothelial cells) in patients with PV. There were no significant levels of MVs in the groups of patients with and without thrombotic events. Higher levels of CD3 (lymphocytes) and CD51/61 (endothelial cells) MVs were identified in JAK2V617F+ patients with thrombotic events. Conclusion: In the analysis of the profile of MVs, higher levels of MVs were observed in patients with PV than in healthy individuals. It was also observed that JAK2V617F+ patients who have a history of thrombosis had higher levels of CD3 MVs (T lymphocytes) and CD51/61 (endothelial cells). in the pathogenesis of thrombosis. Future studies are essential to analyze VMs in the context of treatment, in addition to seeking to understand their role in the prognosis, as well as in the prothrombotic state of patients with PV.A Policitemia Vera (PV) faz parte do grupo de neoplasias mieloproliferativas (NMPs), na qual é caracterizada pelo aumento da massa eritrócitária. Acredita-se que as MVs possuem um importante papel no desenvolvimento das neoplasias e podem ser essenciais para entendimento dessas patologias. Já foi descrito que as microvesículas (MVs) contribuem no desenvolvimento da PV com sua maior atividade pró-coagulante, aumentando o risco das complicações trombóticas. Objetivos: Caracterizar o perfil das Microvesículas circulantes em pacientes com diagnóstico de Policitemia Vera atendidos na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas. Material e métodos: Sessenta e seis indivíduos, de ambos os sexos, foram incluídos e categorizados em dois grupos: 33 pacientes com diagnóstico conclusivo para Policitemia Vera em tratamento e 33 indivíduos saudáveis para o grupo controle. Dados clínicos foram obtidos dos prontuários dos pacientes. Dados laboratoriais foram obtidos de amostras de sangue. A caracterização imunofenotípica foi realizada no citômetro de fluxo CytoFlex S (Beckman Coulter) através do protocolo de imunofenotipagem de MVs do Grupo Integrado em Pesquisas de Biomarcadores (GIPB) do Instituto René Rachou (IRR)-Fiocruz Minas. Resultados: Observou-se maior nível de MVs CD34, CD13, CD33 (progenitoras/mieloides), CD11c (células dendríticas), CD16, CD66b (neutrófilos), CD3 (Linfócitos T), CD19 (Linfócitos B), CD56 (células NK), CD235a (eritrócitos) e CD51/61 (células endoteliais)em pacientes com PV. Não foi apresentando níves significativos de MVs nos grupos de pacientes com e sem eventos trombóticos. Foi identificado níves maiores de MVs CD3 (linfócitos) e CD51/61 (células endoteliais) em pacientes JAK2V617F+ com eventos trombóticos. Conclusão: Na análise do perfil de MVs foi observado níveis maiores de MVs em pacientes com PV do que os indíviduos saudáveis. Foi observado também que os pacientes JAK2V617F+ que apresentam histórico de trombose apresentaram níves maiores de MVs CD3 (linfócitos T) e CD51/61 (células endoteliais), esses resultados mostram que a variante genética JAK2V617F possui um papel importante no desencadeamento das MVs e que favoreçem na patogênese da trombose. Estudos futuros são essenciais para analisar as MVs no contexto do tratamento, além de buscar entender o seu papel no prognóstico, assim como, no estado pró-trombótico de pacientes com PVUniversidade do Estado do AmazonasBrasilUEAPPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIATarragô, Andréa MonteiroMourão, Lucivana Prata de SouzaTarragô, Andréa MonteiroSilva Neto, Pedro Vieira daOliveira, Sâmela Silva deSousa, Milane Araújo de2023-11-21T13:00:55Z2024-09-05T18:56:39Z2023-11-082023-11-21T13:00:55Z2023-07-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttps://ri.uea.edu.br/handle/riuea/2265por1. Ratajczak, J. et al. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: Evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20, 847–856 (2006). 2. Shifrin, D. A., Beckler, M. D., Coffey, R. J. & Tyska, M. J. Extracellular vesicles: Communication, coercion, and conditioning. Molecular Biology of the Cell vol. 24 1253–1259 Preprint at https://doi.org/10.1091/mbc.E12-08-0572 (2013). 3. Gonda, D. D. et al. Neuro-oncologic applications of exosomes, microvesicles, and other nano-sized extracellular particles. Neurosurgery 72, 501–510 (2013). 4. Lv, Y. M., Tan, J., Miao, Y. & Zhang, Q. The role of microvesicles and its active molecules in regulating cellular biology. Journal of Cellular and Molecular Medicine vol. 23 7894–7904 Preprint at https://doi.org/10.1111/jcmm.14667 (2019). 5. Ahadon M, Abdul Aziz S, Wong CL, Leong CF. Plasma-derived microparticles in polycythaemia vera. Malays J Pathol. 2018;40(1):41-48. 6. Tan, X. et al. Role of erythrocytes and platelets in the hypercoagulable status in polycythemia vera through phosphatidylserine exposure and microparticle generation. Thromb Haemost 109, 1025–1032 (2013). 7. Swerdlow, S. H. et al. Review Series the updated who classification of hematological malignancies the 2016 revision of the World Health Organization classification of lymphoid neoplasms. doi:10.1182/blood-2016. 8. Lev PR & Heller PG. Estudio molecular en Neoplasias Mieloproliferativas Crónicas: mutación JAK2V617F laboratorio en hematologia. hematología vol. 17 (2013). 9. Besses, C. et al. Modulation of JAK2 V617F allele burden dynamics by hydroxycarbamide in polycythaemia vera and essential thrombocythaemia patients. Br J Haematol 152, 413–419 (2011). 10. Girodon, F. et al. Frequent reduction or absence of detection of the JAK2-mutated clone in JAK2V617F-positive patients within the first years of hydroxyurea therapy. Haematologica 93, 1723–1727 (2008). 11. Landolfi, R., Di Gennaro, L. & Falanga, A. Thrombosis in myeloproliferative disorders: Pathogenetic facts and speculation. Leukemia vol. 22 2020–2028 Preprint at https://doi.org/10.1038/leu.2008.253 (2008). 12. Tefferi, A. & Barbui, T. Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management. Am J Hematol 94, 133–143 (2019). 13. Zhang, W. et al. Clinical significance of circulating microparticles in Ph- myeloproliferative neoplasms. Oncol Lett 14, 2531–2536 (2017). 14. Aswad, M. H., Kissová, J., Rihova, L., Zavrelova, J., Ovesná, P., & Penka, M. (2019). High Level of Circulating Microparticles in Patients with BCR/ABL Negative Myeloproliferative 53 Neoplasm - a Pilot Study. Vysoká hladina cirkulujících mikropartikulí u pacientů s BCR/ABL negativními myeloproliferativními chorobami - pilotní studie. Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti, 32(2), 109–116. https://doi.org/10.14735/amko2019109 15. McKenzie, C. V., Colonne, C. K., Yeo, J. H. & Fraser, S. T. Splenomegaly: Pathophysiological bases and therapeutic options. International Journal of Biochemistry and Cell Biology vol. 94 40–43 Preprint at https://doi.org/10.1016/j.biocel.2017.11.011 (2018). 16. Martin, K. Risk Factors for and Management of MPN-Associated Bleeding and Thrombosis. Current Hematologic Malignancy Reports vol. 12 389–396 Preprint at https://doi.org/10.1007/s11899-017-0400-3 (2017). 17. Aswad, M. H., Kissova, J., Ovesna, P., Rihova, L. & Penka, M. The clinical significance of circulating microparticles concerning thrombosis in BCR/ABL1-negative myeloproliferative neoplasms. In Vivo (Brooklyn) 35, 3345–3353 (2021). 18. Barbui, T. & Falanga, A. Molecular biomarkers of thrombosis in myeloproliferative neoplasms. Thromb Res 140, S71–S75 (2016). 19. Shahneh, F. et al. Specialized regulatory T cells control venous blood clot resolution through SPARC Specialized regulatory T cells control venous blood clot resolution through SPARC Short Title: Specialized Treg regulate thrombus resolution. doi:10.1182/blood.2020005407/1758409/blood.2020005407.pdf. 20. Hilal Hekimoğlu1, 2, Selin Fulya Toprak1,2, Selçuk Sözer1. JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive Microparticles. Turkish Journal of Hematology 39, 22–28 (2022). 21. Taniguchi, Y. et al. Elevated plasma levels of procoagulant microparticles are a novel risk factor for thrombosis in patients with myeloproliferative neoplasms. Int J Hematol 106, 691–703 (2017). 22. Saban, N. & Bujak, M. Hydroxyurea and hydroxamic acid derivatives as antitumor drugs. Cancer Chemotherapy and Pharmacology vol. 64 213–221 Preprint at https://doi.org/10.1007/s00280-009-0991-z (2009)info:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade do Estado do Amazonas (UEA)instname:Universidade do Estado do Amazonas (UEA)instacron:UEA2024-09-25T21:09:45Zoai:ri.uea.edu.br:riuea/2265Repositório InstitucionalPUBhttps://ri.uea.edu.br/server/oai/requestbibliotecacentral@uea.edu.bropendoar:2024-09-25T21:09:45Repositório Institucional da Universidade do Estado do Amazonas (UEA) - Universidade do Estado do Amazonas (UEA)false
dc.title.none.fl_str_mv Caracterização do perfil de microvesículas cirdulantes em pacientes com policitemia vera
Characterization of the profile of circulating microvesicles in patients with polycythemia vera
title Caracterização do perfil de microvesículas cirdulantes em pacientes com policitemia vera
spellingShingle Caracterização do perfil de microvesículas cirdulantes em pacientes com policitemia vera
Sousa, Milane Araújo de
Neoplasia mieloproliferativa
Microvesícula
Policitemia vera
Myeloproliferative neoplasm
title_short Caracterização do perfil de microvesículas cirdulantes em pacientes com policitemia vera
title_full Caracterização do perfil de microvesículas cirdulantes em pacientes com policitemia vera
title_fullStr Caracterização do perfil de microvesículas cirdulantes em pacientes com policitemia vera
title_full_unstemmed Caracterização do perfil de microvesículas cirdulantes em pacientes com policitemia vera
title_sort Caracterização do perfil de microvesículas cirdulantes em pacientes com policitemia vera
author Sousa, Milane Araújo de
author_facet Sousa, Milane Araújo de
author_role author
dc.contributor.none.fl_str_mv Tarragô, Andréa Monteiro
Mourão, Lucivana Prata de Souza
Tarragô, Andréa Monteiro
Silva Neto, Pedro Vieira da
Oliveira, Sâmela Silva de
dc.contributor.author.fl_str_mv Sousa, Milane Araújo de
dc.subject.por.fl_str_mv Neoplasia mieloproliferativa
Microvesícula
Policitemia vera
Myeloproliferative neoplasm
topic Neoplasia mieloproliferativa
Microvesícula
Policitemia vera
Myeloproliferative neoplasm
description Polycythemia Vera (PV) is part of the group of myeloproliferative neoplasms (PMNs), in which it is characterized by an increase in erythrocyte mass. It is believed that VMs play an important role in the development of neoplasms and may be essential for understanding these pathologies. It has already been described that microvesicles (MVs) contribute to the development of PV with their greater procoagulant activity, increasing the risk of thrombotic complications. Objectives: To characterize the profile of circulating microvesicles in patients diagnosed with Polycythemia Vera treated at the Hospital Foundation for Hematology and Hemotherapy of Amazonas. Material and methods: Sixty-six individuals of both sexes were included and categorized into two groups: 33 patients with a conclusive diagnosis of Polycythemia Vera undergoing treatment and 33 healthy individuals for the control group. Clinical data were obtained from the patients' charts. Laboratory data were obtained from blood samples. Immunophenotypic characterization was performed on a CytoFlex S flow cytometer (Beckman Coulter) using the VM immunophenotyping protocol of the Integrated Group for Biomarker Research (GIPB) of the René Rachou Institute (IRR)-Fiocruz Minas. Results: There was a higher level of MVs CD34, CD13, CD33 (progenitor/myeloid), CD11c (dendritic cells), CD16, CD66b (neutrophils), CD3 (T Lymphocytes), CD19 (B Lymphocytes), CD56 (NK cells) , CD235a (erythrocytes) and CD51/61 (endothelial cells) in patients with PV. There were no significant levels of MVs in the groups of patients with and without thrombotic events. Higher levels of CD3 (lymphocytes) and CD51/61 (endothelial cells) MVs were identified in JAK2V617F+ patients with thrombotic events. Conclusion: In the analysis of the profile of MVs, higher levels of MVs were observed in patients with PV than in healthy individuals. It was also observed that JAK2V617F+ patients who have a history of thrombosis had higher levels of CD3 MVs (T lymphocytes) and CD51/61 (endothelial cells). in the pathogenesis of thrombosis. Future studies are essential to analyze VMs in the context of treatment, in addition to seeking to understand their role in the prognosis, as well as in the prothrombotic state of patients with PV.
publishDate 2023
dc.date.none.fl_str_mv 2023-11-21T13:00:55Z
2023-11-08
2023-11-21T13:00:55Z
2023-07-28
2024-09-05T18:56:39Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
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dc.identifier.uri.fl_str_mv https://ri.uea.edu.br/handle/riuea/2265
url https://ri.uea.edu.br/handle/riuea/2265
dc.language.iso.fl_str_mv por
language por
dc.relation.none.fl_str_mv 1. Ratajczak, J. et al. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: Evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20, 847–856 (2006). 2. Shifrin, D. A., Beckler, M. D., Coffey, R. J. & Tyska, M. J. Extracellular vesicles: Communication, coercion, and conditioning. Molecular Biology of the Cell vol. 24 1253–1259 Preprint at https://doi.org/10.1091/mbc.E12-08-0572 (2013). 3. Gonda, D. D. et al. Neuro-oncologic applications of exosomes, microvesicles, and other nano-sized extracellular particles. Neurosurgery 72, 501–510 (2013). 4. Lv, Y. M., Tan, J., Miao, Y. & Zhang, Q. The role of microvesicles and its active molecules in regulating cellular biology. Journal of Cellular and Molecular Medicine vol. 23 7894–7904 Preprint at https://doi.org/10.1111/jcmm.14667 (2019). 5. Ahadon M, Abdul Aziz S, Wong CL, Leong CF. Plasma-derived microparticles in polycythaemia vera. Malays J Pathol. 2018;40(1):41-48. 6. Tan, X. et al. Role of erythrocytes and platelets in the hypercoagulable status in polycythemia vera through phosphatidylserine exposure and microparticle generation. Thromb Haemost 109, 1025–1032 (2013). 7. Swerdlow, S. H. et al. Review Series the updated who classification of hematological malignancies the 2016 revision of the World Health Organization classification of lymphoid neoplasms. doi:10.1182/blood-2016. 8. Lev PR & Heller PG. Estudio molecular en Neoplasias Mieloproliferativas Crónicas: mutación JAK2V617F laboratorio en hematologia. hematología vol. 17 (2013). 9. Besses, C. et al. Modulation of JAK2 V617F allele burden dynamics by hydroxycarbamide in polycythaemia vera and essential thrombocythaemia patients. Br J Haematol 152, 413–419 (2011). 10. Girodon, F. et al. Frequent reduction or absence of detection of the JAK2-mutated clone in JAK2V617F-positive patients within the first years of hydroxyurea therapy. Haematologica 93, 1723–1727 (2008). 11. Landolfi, R., Di Gennaro, L. & Falanga, A. Thrombosis in myeloproliferative disorders: Pathogenetic facts and speculation. Leukemia vol. 22 2020–2028 Preprint at https://doi.org/10.1038/leu.2008.253 (2008). 12. Tefferi, A. & Barbui, T. Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management. Am J Hematol 94, 133–143 (2019). 13. Zhang, W. et al. Clinical significance of circulating microparticles in Ph- myeloproliferative neoplasms. Oncol Lett 14, 2531–2536 (2017). 14. Aswad, M. H., Kissová, J., Rihova, L., Zavrelova, J., Ovesná, P., & Penka, M. (2019). High Level of Circulating Microparticles in Patients with BCR/ABL Negative Myeloproliferative 53 Neoplasm - a Pilot Study. Vysoká hladina cirkulujících mikropartikulí u pacientů s BCR/ABL negativními myeloproliferativními chorobami - pilotní studie. Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti, 32(2), 109–116. https://doi.org/10.14735/amko2019109 15. McKenzie, C. V., Colonne, C. K., Yeo, J. H. & Fraser, S. T. Splenomegaly: Pathophysiological bases and therapeutic options. International Journal of Biochemistry and Cell Biology vol. 94 40–43 Preprint at https://doi.org/10.1016/j.biocel.2017.11.011 (2018). 16. Martin, K. Risk Factors for and Management of MPN-Associated Bleeding and Thrombosis. Current Hematologic Malignancy Reports vol. 12 389–396 Preprint at https://doi.org/10.1007/s11899-017-0400-3 (2017). 17. Aswad, M. H., Kissova, J., Ovesna, P., Rihova, L. & Penka, M. The clinical significance of circulating microparticles concerning thrombosis in BCR/ABL1-negative myeloproliferative neoplasms. In Vivo (Brooklyn) 35, 3345–3353 (2021). 18. Barbui, T. & Falanga, A. Molecular biomarkers of thrombosis in myeloproliferative neoplasms. Thromb Res 140, S71–S75 (2016). 19. Shahneh, F. et al. Specialized regulatory T cells control venous blood clot resolution through SPARC Specialized regulatory T cells control venous blood clot resolution through SPARC Short Title: Specialized Treg regulate thrombus resolution. doi:10.1182/blood.2020005407/1758409/blood.2020005407.pdf. 20. Hilal Hekimoğlu1, 2, Selin Fulya Toprak1,2, Selçuk Sözer1. JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive Microparticles. Turkish Journal of Hematology 39, 22–28 (2022). 21. Taniguchi, Y. et al. Elevated plasma levels of procoagulant microparticles are a novel risk factor for thrombosis in patients with myeloproliferative neoplasms. Int J Hematol 106, 691–703 (2017). 22. Saban, N. & Bujak, M. Hydroxyurea and hydroxamic acid derivatives as antitumor drugs. Cancer Chemotherapy and Pharmacology vol. 64 213–221 Preprint at https://doi.org/10.1007/s00280-009-0991-z (2009)
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dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade do Estado do Amazonas
Brasil
UEA
PPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIA
publisher.none.fl_str_mv Universidade do Estado do Amazonas
Brasil
UEA
PPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIA
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade do Estado do Amazonas (UEA)
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collection Repositório Institucional da Universidade do Estado do Amazonas (UEA)
repository.name.fl_str_mv Repositório Institucional da Universidade do Estado do Amazonas (UEA) - Universidade do Estado do Amazonas (UEA)
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