The treatment with Jusvinza reduces hyperinflammation and hypercoagulation in critical ill patients with COVID-19
Keywords:
COVID-19, hyperinflammation, hypercoagulation, HSP60, CIGB-258, Jusvinza.Abstract
Introduction: Infection with SARS-CoV-2 induces a prothrombotic state in patients, by the combination of hyperinflammatory response and hypoxia. In Cuba, the drug called Jusvinza, based on an immunomodulatory peptide, is used for the treatment of patients with COVID-19, who present signs and symptoms of hyperinflammation.Objectives: To describe the clinical course and behavior of various biomarkers associated with the inflammation and coagulation, in a group of critically ill patients with COVID-19 treated with Jusvinza, compared to a group of patients who did not receive treatment with this peptide.
Methods: 40 critically ill patients with COVID-19 were included. The patients were divided into 2 groups: 20 patients were treated with Jusvinza and 20 were not treated with this peptide (control group). Demographic characteristics, comorbidities, vital signs, respiratory parameters and inflammation and coagulation biomarkers were obtained from the medical records of each patient.
Results: Treatment with Jusvinza induced a clinical improvement in the patients, associated with the decrease of several inflammation and coagulation biomarkers. Patients treated with Jusvinza had a significantly higher survival than patients not treated with this peptide.
Conclusions: Jusvinza is able to control hyperinflammation and hypercoagulation in critical ill patients with COVID-19.
Downloads
Download data is not yet available.
References
1. WHO. Coronavirus disease (COVID-19) pandemic. WHO/ Europe. 2019 [acceso: 23/06/2020]. Disponible en: https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/novel-coronavirus-2019-ncov
2. Johns Hopkins Medicine. Coronavirus (COVID-19) Information and Updates. Coronavirus (COVID-19) Information and Updates. 2020 [acceso: 28/09/2020]. Disponible en: https://www.hopkinsmedicine.org/coronavirus/index.html
3. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020 [acceso: 25/09/2020]; 324(8):782-93. DOI: 10.1001/jama.2020.12839
4. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID‐19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 [acceso: 14/08/2020]; 8:420‐22. Disponible en: https://covid19.conacyt.mx/jspui/bitstream/1000/1079/1/105281.pdf
5. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 [acceso: 20/06/2020]; 18(4): 844-7. Disponible en: https://onlinelibrary.wiley.com/doi/10.1111/jth.14768
6. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 [acceso: 28/01/2021]; 395(10223):497-506. Disponible en: https://doi.org/10.1016/S0140-6736(20)30183-5
7. Capraa R, DeRossia N, Mattiolib F, Romanelli G, Scarpazza C, Sormani MP, et al. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. European Journal of Internal Medicine. 2020 [acceso: 08/06/2020]; 76: 31-35. Disponible en: https://doi.org/10.1016/j.ejim.2020.05.009
8. Peterson D, Damsky W, King B. The use of Janus kinase inhibitors in the time of SARS-CoV-2. J Am Acad Dermatol. 2020 [acceso: 08/07/2020]; 82(6): e223-e226. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144601
9. CECMED. Autorización de Uso de Emergencia" (AUE) del producto Jusvinza, a emplearse en el tratamiento de pacientes hospitalizados positivos a la COVID-19, que se encuentren graves o críticos y en los que exista sospecha o se identifique un estado de hiperinflamación (BIOL: 077-20/23-018-20B). CECMED; 2020 [acceso: dd/mm/aaaa]. Disponible en: https://www.cecmed.cu/covid-19/aprobaciones/jusvinza-cigb-258-1
10. Ministerio de Salud Pública. Parte del cierre del día 31 de marzo a las 12 de la noche. COVID-19. Minsap. 2021[acceso: 01/04/2021]. Disponible en: https://salud.msp.gob.cu/parte-de-cierre-del-dia-31-de-marzo-a-las-12-de-la-noche
11. Ministerio de Salud Pública. Parte del cierre del día 30 de septiembre a las 12 de la noche. COVID-19. Minsap. 2021 [acceso: 01/07/2020]. Disponible en: https://salud.msp.gob.cu/parte-de-cierre-del-dia-30-de-septiembre-a-las-12-de-la-noche
12. Domínguez MC, Lorenzo N, Barberá A, Darrasse-Jeze G, Hernandez MV, Torres AM, et al. An altered peptide ligand corresponding to a novel epitope from heat-shock protein 60 induces regulatory T cells and suppresses pathogenic response in an animal model of adjuvant induced arthritis. Autoimmunity. 2011 [acceso: 03/03/2011]; 44 (6):471-82. DOI: 10.3109/08916934.2010.550590
13. Barberá A, Lorenzo N, van Kooten P, van Roon J, de Jager W, Prada D, et al. APL1, an altered peptide ligand derived from human heat-shock protein 60, increases the frequency of Tregs and its suppressive capacity against antigen responding effector CD4+T cells from rheumatoid arthritis patients. Cell Stress and Chaperones. 2016 [acceso: 30/05/2016]; 21 (4): 735-44. DOI: 10.1007/s12192-016-0698-0
14. Lorenzo N, Altruda F, Silengo L, Dominguez MC. APL-1, an altered peptide ligand derived from heat-shock protein, alone or combined with methotrexate attenuates murine collagen induced arthritis. Clin Exp Med. 2017 [acceso: 09/05/2016]; 17(2): 209-16. DOI: 10.1007/s10238-016-0412-7
15. Domínguez MC, Cabrales A, Lorenzo N, Padrón G, Gonzalez LJ. Biodistribution and pharmacokinetic profiles of an Altered Peptide Ligand derived from Heat-shock proteins 60 in Lewis rats. Cell Stress and Chaperones. 2020 [acceso: 20/11/2020]; 25(1):133-40. Disponible en: https://pubmed.ncbi.nlm.nih.gov/31802366/
16. Prada D, Gómez J, Lorenzo N, Corrales O, Lopez A, Gonzalez E, et al. Phase I Clinical Trial with a Novel Altered Peptide Ligand Derived from Human Heat-Shock Protein 60 for Treatment of Rheumatoid Arthritis: Safety, Pharmacokinetics and Preliminary Therapeutic Effects. Journal of Clinical Trials. 2018 [acceso: 08/02/2018]; 8(1): 2167-0870. DOI: 10.4172/2167-0870.1000339
17. Cabrales-Rico A, Ramos Y, Besada V, Dominguez M C, Lorenzo N, Garcia O, et al. Development and validation of a bioanalytical method based on LC-MS/MS analysis for the quantitation of CIGB-814 peptide in plasma from Rheumatoid Arthritis patients. J Pharm. Biomed Anal. 2017 [acceso: 05/09/2017]; 143: 130-40. Disponible en: https://doi.org/10.1016/j.jpba.2017.05.030
18. Venegas-Rodriguez R, Peña-Ruiz R, Santana-Sánchez R, Bequet-Romero M, Hernández-Cedeño M, Santiesteban-Licea B, et al. Péptido inmunomodulador CIGB-258 para el tratamiento de pacientes graves y críticos con la COVID-19. Revista Cubana de Medicina Militar. 2020 [acceso: 06/10/2020]; 49(4): e0200926. Disponible en: http://revmedmilitar.sld.cu/index.php/mil/article/view/926/625
19. Venegas-Rodriguez R, Santana-Sánchez R, Peña-Ruiz R, Bequet-Romero M, Hernández-Cedeño M, Santiesteban-Licea B, et al. CIGB-258 Immunomodulatory Peptide: Compassionate Use for Critical and Severe COVID-19 Patients. Austin J Pharmacol Ther. 2020 [acceso: 17/09/2020]; 8(1):1119. Disponible en: https://www.researchgate.net/profile/Mabel-Hernandez-Cedeno-2/publication/344405147_CIGB-258_Immunomodulatory_Peptide_Compassionate_Use_for_Critical_and_Severe_COVID-19_Patients/links/5f71f94792851c14bc9b2261/CIGB-258-Immunomodulatory-Peptide-Compassionate-Use-for-Critical-and-Severe-COVID-19-Patients.pdf
20. Hernández-Cedeño M, Venegas-Rodriguez R, Peña-Ruiz R, Bequet-Romero M, Santana-Sánchez R, Pentón-Ariaset E, et al. CIGB-258, a peptide derived from human heat-shock protein 60, decreases hyperinflammation in COVID-19 patients. Cell Stress and Chaperones. 2020 [acceso: 24/02/2021]; 26(3): 515-25. DOI: 10.1007/s12192-021-01197-2
21. World Medical Association. World medical declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Med Assoc. 2013 [acceso: 24/07/2020]; 310(29): 2191-4. Disponible en: https://pubmed.ncbi.nlm.nih.gov/24141714
22. Ministerio de Salud Pública. Protocolo de actuación nacional para la covid-19: versión 1.6. La Habana: MINSAP; 2020. [acceso: 24/08/2020]. Disponible en: https://files.sld.cu/editorhome/files/2020/05/MINSAP_Protocolo-de-Actuación-Nacional-para-la-COVID-19_versión-1.6_mayo-2020.pdf
23. The ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 [acceso: 13/06/2020]; 307:2526-33. Disponible en: http://intensivo.sochipe.cl/subidos/catalogo3/ARDSdefinition.JAMA.2012.pdf
24. Ministerio de Salud Pública. Regulación No. 45-2007: Requerimientos para la notificación y el reporte de eventos adversos graves e inesperados en los ensayos clínicos. La Habana: CECMED; 2007. [acceso: 24/08/2020]. Disponible en: https://www.cecmed.cu/sites/default/files/adjuntos/Reglamentacion/reg_4507_r-equerimientos_para_la_notificacion_y_el_reporte_de_eventos_adversos_graves_e-_inesperados_en_los_ensayos_clinicos.pdf
25. McGonagle D, O'Donnell JS, Sharif K, Emery P, Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. The Lancet Rheumatology. 2020 [acceso: 07/05/2020]; 2(7): e437-e445. DOI: 10.1016/S2665-9913(20)30121-1
26. Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J and Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med. 2020 [acceso: 01/07/2020]; 8(7): 681-6. Disponible en: https://doi.org/10.1016/S2213-2600(20)30243-5
27. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 [acceso: 06/07/2020]; 395(10234): 1417-18. Disponible en: https://doi.org/10.1016/S0140-6736(20)30937-5
28. Liu Y, Du X, Chen J, Jin Y, Peng L, Wang HHX, et al. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J Infect. 2020 [acceso: 14/04/2020]; 81(1):6-12. Disponible en: https://doi.org/10.1016/j.jinf.2020.04.002
29. Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med. 2020 [acceso: 01/12/2020]; 217(6): e20200652. DOI: 10.1084/jem.20200652
30. Klok FA, Kruip M, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 [acceso: 09/11/2020]; 191:145-7. Disponible en: https://doi.org/j.thromres.2020.04.013
2. Johns Hopkins Medicine. Coronavirus (COVID-19) Information and Updates. Coronavirus (COVID-19) Information and Updates. 2020 [acceso: 28/09/2020]. Disponible en: https://www.hopkinsmedicine.org/coronavirus/index.html
3. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020 [acceso: 25/09/2020]; 324(8):782-93. DOI: 10.1001/jama.2020.12839
4. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID‐19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 [acceso: 14/08/2020]; 8:420‐22. Disponible en: https://covid19.conacyt.mx/jspui/bitstream/1000/1079/1/105281.pdf
5. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 [acceso: 20/06/2020]; 18(4): 844-7. Disponible en: https://onlinelibrary.wiley.com/doi/10.1111/jth.14768
6. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 [acceso: 28/01/2021]; 395(10223):497-506. Disponible en: https://doi.org/10.1016/S0140-6736(20)30183-5
7. Capraa R, DeRossia N, Mattiolib F, Romanelli G, Scarpazza C, Sormani MP, et al. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. European Journal of Internal Medicine. 2020 [acceso: 08/06/2020]; 76: 31-35. Disponible en: https://doi.org/10.1016/j.ejim.2020.05.009
8. Peterson D, Damsky W, King B. The use of Janus kinase inhibitors in the time of SARS-CoV-2. J Am Acad Dermatol. 2020 [acceso: 08/07/2020]; 82(6): e223-e226. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144601
9. CECMED. Autorización de Uso de Emergencia" (AUE) del producto Jusvinza, a emplearse en el tratamiento de pacientes hospitalizados positivos a la COVID-19, que se encuentren graves o críticos y en los que exista sospecha o se identifique un estado de hiperinflamación (BIOL: 077-20/23-018-20B). CECMED; 2020 [acceso: dd/mm/aaaa]. Disponible en: https://www.cecmed.cu/covid-19/aprobaciones/jusvinza-cigb-258-1
10. Ministerio de Salud Pública. Parte del cierre del día 31 de marzo a las 12 de la noche. COVID-19. Minsap. 2021[acceso: 01/04/2021]. Disponible en: https://salud.msp.gob.cu/parte-de-cierre-del-dia-31-de-marzo-a-las-12-de-la-noche
11. Ministerio de Salud Pública. Parte del cierre del día 30 de septiembre a las 12 de la noche. COVID-19. Minsap. 2021 [acceso: 01/07/2020]. Disponible en: https://salud.msp.gob.cu/parte-de-cierre-del-dia-30-de-septiembre-a-las-12-de-la-noche
12. Domínguez MC, Lorenzo N, Barberá A, Darrasse-Jeze G, Hernandez MV, Torres AM, et al. An altered peptide ligand corresponding to a novel epitope from heat-shock protein 60 induces regulatory T cells and suppresses pathogenic response in an animal model of adjuvant induced arthritis. Autoimmunity. 2011 [acceso: 03/03/2011]; 44 (6):471-82. DOI: 10.3109/08916934.2010.550590
13. Barberá A, Lorenzo N, van Kooten P, van Roon J, de Jager W, Prada D, et al. APL1, an altered peptide ligand derived from human heat-shock protein 60, increases the frequency of Tregs and its suppressive capacity against antigen responding effector CD4+T cells from rheumatoid arthritis patients. Cell Stress and Chaperones. 2016 [acceso: 30/05/2016]; 21 (4): 735-44. DOI: 10.1007/s12192-016-0698-0
14. Lorenzo N, Altruda F, Silengo L, Dominguez MC. APL-1, an altered peptide ligand derived from heat-shock protein, alone or combined with methotrexate attenuates murine collagen induced arthritis. Clin Exp Med. 2017 [acceso: 09/05/2016]; 17(2): 209-16. DOI: 10.1007/s10238-016-0412-7
15. Domínguez MC, Cabrales A, Lorenzo N, Padrón G, Gonzalez LJ. Biodistribution and pharmacokinetic profiles of an Altered Peptide Ligand derived from Heat-shock proteins 60 in Lewis rats. Cell Stress and Chaperones. 2020 [acceso: 20/11/2020]; 25(1):133-40. Disponible en: https://pubmed.ncbi.nlm.nih.gov/31802366/
16. Prada D, Gómez J, Lorenzo N, Corrales O, Lopez A, Gonzalez E, et al. Phase I Clinical Trial with a Novel Altered Peptide Ligand Derived from Human Heat-Shock Protein 60 for Treatment of Rheumatoid Arthritis: Safety, Pharmacokinetics and Preliminary Therapeutic Effects. Journal of Clinical Trials. 2018 [acceso: 08/02/2018]; 8(1): 2167-0870. DOI: 10.4172/2167-0870.1000339
17. Cabrales-Rico A, Ramos Y, Besada V, Dominguez M C, Lorenzo N, Garcia O, et al. Development and validation of a bioanalytical method based on LC-MS/MS analysis for the quantitation of CIGB-814 peptide in plasma from Rheumatoid Arthritis patients. J Pharm. Biomed Anal. 2017 [acceso: 05/09/2017]; 143: 130-40. Disponible en: https://doi.org/10.1016/j.jpba.2017.05.030
18. Venegas-Rodriguez R, Peña-Ruiz R, Santana-Sánchez R, Bequet-Romero M, Hernández-Cedeño M, Santiesteban-Licea B, et al. Péptido inmunomodulador CIGB-258 para el tratamiento de pacientes graves y críticos con la COVID-19. Revista Cubana de Medicina Militar. 2020 [acceso: 06/10/2020]; 49(4): e0200926. Disponible en: http://revmedmilitar.sld.cu/index.php/mil/article/view/926/625
19. Venegas-Rodriguez R, Santana-Sánchez R, Peña-Ruiz R, Bequet-Romero M, Hernández-Cedeño M, Santiesteban-Licea B, et al. CIGB-258 Immunomodulatory Peptide: Compassionate Use for Critical and Severe COVID-19 Patients. Austin J Pharmacol Ther. 2020 [acceso: 17/09/2020]; 8(1):1119. Disponible en: https://www.researchgate.net/profile/Mabel-Hernandez-Cedeno-2/publication/344405147_CIGB-258_Immunomodulatory_Peptide_Compassionate_Use_for_Critical_and_Severe_COVID-19_Patients/links/5f71f94792851c14bc9b2261/CIGB-258-Immunomodulatory-Peptide-Compassionate-Use-for-Critical-and-Severe-COVID-19-Patients.pdf
20. Hernández-Cedeño M, Venegas-Rodriguez R, Peña-Ruiz R, Bequet-Romero M, Santana-Sánchez R, Pentón-Ariaset E, et al. CIGB-258, a peptide derived from human heat-shock protein 60, decreases hyperinflammation in COVID-19 patients. Cell Stress and Chaperones. 2020 [acceso: 24/02/2021]; 26(3): 515-25. DOI: 10.1007/s12192-021-01197-2
21. World Medical Association. World medical declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Med Assoc. 2013 [acceso: 24/07/2020]; 310(29): 2191-4. Disponible en: https://pubmed.ncbi.nlm.nih.gov/24141714
22. Ministerio de Salud Pública. Protocolo de actuación nacional para la covid-19: versión 1.6. La Habana: MINSAP; 2020. [acceso: 24/08/2020]. Disponible en: https://files.sld.cu/editorhome/files/2020/05/MINSAP_Protocolo-de-Actuación-Nacional-para-la-COVID-19_versión-1.6_mayo-2020.pdf
23. The ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 [acceso: 13/06/2020]; 307:2526-33. Disponible en: http://intensivo.sochipe.cl/subidos/catalogo3/ARDSdefinition.JAMA.2012.pdf
24. Ministerio de Salud Pública. Regulación No. 45-2007: Requerimientos para la notificación y el reporte de eventos adversos graves e inesperados en los ensayos clínicos. La Habana: CECMED; 2007. [acceso: 24/08/2020]. Disponible en: https://www.cecmed.cu/sites/default/files/adjuntos/Reglamentacion/reg_4507_r-equerimientos_para_la_notificacion_y_el_reporte_de_eventos_adversos_graves_e-_inesperados_en_los_ensayos_clinicos.pdf
25. McGonagle D, O'Donnell JS, Sharif K, Emery P, Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. The Lancet Rheumatology. 2020 [acceso: 07/05/2020]; 2(7): e437-e445. DOI: 10.1016/S2665-9913(20)30121-1
26. Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J and Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med. 2020 [acceso: 01/07/2020]; 8(7): 681-6. Disponible en: https://doi.org/10.1016/S2213-2600(20)30243-5
27. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 [acceso: 06/07/2020]; 395(10234): 1417-18. Disponible en: https://doi.org/10.1016/S0140-6736(20)30937-5
28. Liu Y, Du X, Chen J, Jin Y, Peng L, Wang HHX, et al. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J Infect. 2020 [acceso: 14/04/2020]; 81(1):6-12. Disponible en: https://doi.org/10.1016/j.jinf.2020.04.002
29. Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med. 2020 [acceso: 01/12/2020]; 217(6): e20200652. DOI: 10.1084/jem.20200652
30. Klok FA, Kruip M, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 [acceso: 09/11/2020]; 191:145-7. Disponible en: https://doi.org/j.thromres.2020.04.013
Published
2021-11-23
How to Cite
1.
Venegas Rodríguez R, Serrano Díaz A, Peña Ruiz R, Santana Sánchez R, Rittoles Navarro A, Grecesqui Cruz I, et al. The treatment with Jusvinza reduces hyperinflammation and hypercoagulation in critical ill patients with COVID-19. Rev Cubana Med Milit [Internet]. 2021 Nov. 23 [cited 2025 Apr. 3];50(4):e02101675. Available from: https://revmedmilitar.sld.cu/index.php/mil/article/view/1675
Issue
Section
Research Article
License
Authors who have publications with this Journal accept the following terms:
- The authors will retain their copyright and guarantee the Journal the right of first publication of their work, which will simultaneously be subject to the Creative Commons Attribution License. The content presented here can be shared, copied and redistributed in any medium or format; Can be adapted, remixed, transformed or created from the material, using the following terms: Attribution (giving appropriate credit to the work, providing a link to the license, and indicating if changes have been made); non-commercial (you cannot use the material for commercial purposes) and share-alike (if you remix, transform or create new material from this work, you can distribute your contribution as long as you use the same license as the original work).
- The authors may adopt other non-exclusive license agreements for the distribution of the published version of the work (for example: depositing it in an institutional electronic archive or publishing it in a monographic volume) as long as the initial publication in this Journal is indicated.
- Authors are allowed and recommended to disseminate their work through the Internet (e.g., in institutional electronic archives or on their website) before and during the submission process, which can produce interesting exchanges and increase citations. of the published work.
