Standardized Brazilian green propolis extract (EPP-AF®) in COVID-19 outcomes: a randomized double-blind placebo-controlled trial

{ 'indexed': { 'date-parts': [[2023, 10, 28]], 'date-time': '2023-10-28T17:11:03Z', 'timestamp': 1698513063218}, 'reference-count': 31, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2023, 10, 27]], 'date-time': '2023-10-27T00:00:00Z', 'timestamp': 1698364800000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2023, 10, 27]], 'date-time': '2023-10-27T00:00:00Z', 'timestamp': 1698364800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:p>SARS-CoV-2 and its different variants caused a “wave ' 'and wave” pandemic pattern. During the first wave we demonstrated that standardized Brazilian ' 'green propolis extract (EPP-AF®) reduces length of hospital stay in adult patients with ' 'COVID-19. Afterwards, we decided to evaluate the impact of EPP-AF in hospitalized patients ' 'during the third wave of the pandemic. BeeCovid2 was a randomized, double-blind, ' 'placebo-controlled clinical trial in hospitalized COVID-19 adult patients. Patients were ' 'allocated to receive an oral dose of 900\xa0mg/day of EPP-AF® or placebo for 10\xa0days. The ' 'primary outcome was length of hospital stay. Secondary outcomes included safety, secondary ' 'infection rate, duration of oxygen therapy dependency, acute kidney injury and need for ' 'intensive care. Patients were followed up for 28\xa0days after admission. We enrolled 188 ' 'patients; 98 were assigned to the propolis group and 90 to the placebo group. The ' 'post-intervention length of hospital stay was of 6.5\u2009±\u20096.0\xa0days in the propolis ' 'group versus 7.7\u2009±\u20097.1\xa0days in the control group (95% CI − 0.74 [− 1.94 to ' '0.42]; <jats:italic>p</jats:italic>\u2009=\u20090.22). Propolis did not have significant ' 'impact on the need for oxygen supplementation or frequency of AKI. There was a significant ' 'difference in the incidence of secondary infection between groups, with 6.1% in the propolis ' 'group versus 18.9% in the control group (95% CI − 0.28 [0.1–0.76], ' '<jats:italic>p</jats:italic>\u2009=\u20090.01). The use of EPP-AF was considered safe and ' 'associated with a decrease in secondary infections. The drug was not associated with a ' 'significant reduction in length of hospital stay. ClinicalTrials.gov (NCT04800224).</jats:p>', 'DOI': '10.1038/s41598-023-43764-w', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 10, 27]], 'date-time': '2023-10-27T10:02:58Z', 'timestamp': 1698400978000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Standardized Brazilian green propolis extract (EPP-AF®) in COVID-19 outcomes: a randomized ' 'double-blind placebo-controlled trial', 'prefix': '10.1038', 'volume': '13', 'author': [ { 'given': 'Marcelo Augusto Duarte', 'family': 'Silveira', 'sequence': 'first', 'affiliation': []}, { 'given': 'Matheus de Alencar', 'family': 'Menezes', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sergio Pinto', 'family': 'de Souza', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Erica Batista dos Santos', 'family': 'Galvão', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Andresa Aparecida', 'family': 'Berretta', 'sequence': 'additional', 'affiliation': []}, {'given': 'Juliana', 'family': 'Caldas', 'sequence': 'additional', 'affiliation': []}, {'given': 'Maurício Brito', 'family': 'Teixeira', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Marcel Miranda Dantas', 'family': 'Gomes', 'sequence': 'additional', 'affiliation': []}, {'given': 'Lucas Petri', 'family': 'Damiani', 'sequence': 'additional', 'affiliation': []}, {'given': 'Bruno Andrade', 'family': 'Bahiense', 'sequence': 'additional', 'affiliation': []}, {'given': 'Julia Barros', 'family': 'Cabral', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Cicero Wandson Luiz Macedo', 'family': 'De Oliveira', 'sequence': 'additional', 'affiliation': []}, {'given': 'Talita Rocha', 'family': 'Mascarenhas', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Priscila Carvalho Guedes', 'family': 'Pinheiro', 'sequence': 'additional', 'affiliation': []}, {'given': 'Milena Souza', 'family': 'Alves', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Rodrigo Morel Vieira', 'family': 'de Melo', 'sequence': 'additional', 'affiliation': []}, {'given': 'Flávia Mendes', 'family': 'Leite', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Carolina Kymie Vasques', 'family': 'Nonaka', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Bruno Solano de Freitas', 'family': 'Souza', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nathália Ursoli', 'family': 'Baptista', 'sequence': 'additional', 'affiliation': []}, {'given': 'Flávio', 'family': 'Teles', 'sequence': 'additional', 'affiliation': []}, {'given': 'Suzete Farias', 'family': 'da Guarda', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Ana Verena Almeida', 'family': 'Mendes', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rogério da Hora', 'family': 'Passos', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2023, 10, 27]]}, 'reference': [ { 'issue': '2', 'key': '43764_CR1', 'doi-asserted-by': 'publisher', 'first-page': '206', 'DOI': '10.3390/cells10020206', 'volume': '10', 'author': 'R Chilamakuri', 'year': '2021', 'unstructured': 'Chilamakuri, R. & Agarwal, S. COVID-19: Characteristics and ' 'therapeutics. Cells. 10(2), 206. https://doi.org/10.3390/cells10020206 ' '(2021).', 'journal-title': 'Cells.'}, { 'issue': '4', 'key': '43764_CR2', 'doi-asserted-by': 'publisher', 'first-page': 'e12998', 'DOI': '10.1111/sji.12998', 'volume': '93', 'author': 'AU Anka', 'year': '2021', 'unstructured': 'Anka, A. U. et al. Coronavirus disease 2019 (COVID-19): An overview of ' 'the immunopathology, serological diagnosis and management. Scand. J. ' 'Immunol. 93(4), e12998. https://doi.org/10.1111/sji.12998 (2021).', 'journal-title': 'Scand. J. Immunol.'}, { 'issue': '4', 'key': '43764_CR3', 'doi-asserted-by': 'publisher', 'first-page': '591', 'DOI': '10.1007/s15010-021-01602-z', 'volume': '49', 'author': 'WH Chong', 'year': '2021', 'unstructured': 'Chong, W. H. et al. State-of-the-art review of secondary pulmonary ' 'infections in patients with COVID-19 pneumonia. Infection. 49(4), ' '591–605. https://doi.org/10.1007/s15010-021-01602-z (2021).', 'journal-title': 'Infection.'}, { 'issue': '23', 'key': '43764_CR4', 'doi-asserted-by': 'publisher', 'first-page': '2255', 'DOI': '10.1056/NEJMra2026131', 'volume': '383', 'author': 'DC Fajgenbaum', 'year': '2020', 'unstructured': 'Fajgenbaum, D. C. & June, C. H. Cytokine storm. N. Engl. J. Med. ' '383(23), 2255–2273. https://doi.org/10.1056/NEJMra2026131 (2020).', 'journal-title': 'N. Engl. J. Med.'}, { 'key': '43764_CR5', 'doi-asserted-by': 'publisher', 'first-page': '157652', 'DOI': '10.1155/2012/157652', 'volume': '2012', 'author': 'JL Machado', 'year': '2012', 'unstructured': 'Machado, J. L. et al. Brazilian green propolis: Anti-inflammatory ' 'property by an immunomodulatory activity. Evid. Based Complement. ' 'Alternat. Med. 2012, 157652. https://doi.org/10.1155/2012/157652 (2012).', 'journal-title': 'Evid. Based Complement. Alternat. Med.'}, { 'key': '43764_CR6', 'doi-asserted-by': 'publisher', 'first-page': '110622', 'DOI': '10.1016/j.biopha.2020.110622', 'volume': '131', 'author': 'AA Berretta', 'year': '2020', 'unstructured': 'Berretta, A. A., Silveira, M. A. D., Cóndor Capcha, J. M. & De Jong, D. ' 'Propolis and its potential against SARS-CoV-2 infection mechanisms and ' 'COVID-19 disease: Running title: Propolis against SARS-CoV-2 infection ' 'and COVID-19. Biomed. Pharmacother. 131, 110622. ' 'https://doi.org/10.1016/j.biopha.2020.110622 (2020).', 'journal-title': 'Biomed. Pharmacother.'}, { 'issue': '2', 'key': '43764_CR7', 'doi-asserted-by': 'publisher', 'first-page': '271', 'DOI': '10.1016/j.cell.2020.02.052', 'volume': '181', 'author': 'M Hoffmann', 'year': '2020', 'unstructured': 'Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 ' 'and is blocked by a clinically proven protease inhibitor. Cell. 181(2), ' '271-280.e8. https://doi.org/10.1016/j.cell.2020.02.052 (2020).', 'journal-title': 'Cell.'}, { 'issue': '6', 'key': '43764_CR8', 'doi-asserted-by': 'publisher', 'first-page': '3557', 'DOI': '10.1007/s00203-021-02351-1', 'volume': '203', 'author': 'HI Guler', 'year': '2021', 'unstructured': 'Guler, H. I., Tatar, G., Yildiz, O., Belduz, A. O. & Kolayli, S. ' 'Investigation of potential inhibitor properties of ethanolic propolis ' 'extracts against ACE-II receptors for COVID-19 treatment by molecular ' 'docking study. Arch. Microbiol. 203(6), 3557–3564. ' 'https://doi.org/10.1007/s00203-021-02351-1 (2021).', 'journal-title': 'Arch. Microbiol.'}, { 'key': '43764_CR9', 'doi-asserted-by': 'publisher', 'first-page': '100039', 'DOI': '10.1016/j.medidd.2020.100039', 'volume': '6', 'author': 'H Maruta', 'year': '2020', 'unstructured': 'Maruta, H. & He, H. PAK1-blockers: Potential therapeutics against ' 'COVID-19. Med. Drug. Discov. 6, 100039. ' 'https://doi.org/10.1016/j.medidd.2020.100039 (2020).', 'journal-title': 'Med. Drug. Discov.'}, { 'key': '43764_CR10', 'doi-asserted-by': 'publisher', 'first-page': '1907698', 'DOI': '10.1155/2019/1907698', 'volume': '2019', 'author': 'J Da', 'year': '2019', 'unstructured': 'Da, J. et al. Kaempferol promotes apoptosis while inhibiting cell ' 'proliferation via androgen-dependent pathway and suppressing ' 'vasculogenic mimicry and invasion in prostate cancer. Anal Cell Pathol ' '(Amst). 2019, 1907698. https://doi.org/10.1155/2019/1907698 (2019).', 'journal-title': 'Anal Cell Pathol (Amst).'}, { 'key': '43764_CR11', 'doi-asserted-by': 'publisher', 'first-page': '111526', 'DOI': '10.1016/j.biopha.2021.111526', 'volume': '138', 'author': 'MAD Silveira', 'year': '2021', 'unstructured': 'Silveira, M. A. D. et al. Efficacy of Brazilian green propolis (EPP-AF®) ' 'as an adjunct treatment for hospitalized COVID-19 patients: A ' 'randomized, controlled clinical trial. Biomed. Pharmacother. 138, ' '111526. https://doi.org/10.1016/j.biopha.2021.111526 (2021).', 'journal-title': 'Biomed. Pharmacother.'}, { 'issue': '1', 'key': '43764_CR12', 'doi-asserted-by': 'publisher', 'first-page': '255', 'DOI': '10.1186/s13063-022-06176-1', 'volume': '23', 'author': 'MAD Silveira', 'year': '2022', 'unstructured': 'Silveira, M. A. D. et al. The use of standardized Brazilian green ' 'propolis extract (EPP-AF) as an adjunct treatment for hospitalized ' 'COVID-19 patients (BeeCovid2): A structured summary of a study protocol ' 'for a randomized controlled trial. Trials. 23(1), 255. ' 'https://doi.org/10.1186/s13063-022-06176-1 (2022).', 'journal-title': 'Trials.'}, { 'issue': '4', 'key': '43764_CR13', 'doi-asserted-by': 'publisher', 'first-page': '512', 'DOI': '10.7150/ijbs.3641', 'volume': '8', 'author': 'AA Berretta', 'year': '2012', 'unstructured': 'Berretta, A. A., Nascimento, A. P., Bueno, P. C., Vaz, M. M. & ' 'Marchetti, J. M. Propolis standardized extract (EPP-AF®), an innovative ' 'chemically and biologically reproducible pharmaceutical compound for ' 'treating wounds. Int. J. Biol. Sci. 8(4), 512–521. ' 'https://doi.org/10.7150/ijbs.3641 (2012).', 'journal-title': 'Int. J. Biol. Sci.'}, { 'issue': '1', 'key': '43764_CR14', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.7243/2050-120X-4-1', 'volume': '4', 'author': 'FS Marquiafável', 'year': '2015', 'unstructured': 'Marquiafável, F. S. et al. Development and characterization of a novel ' 'standardized propolis dry extract obtained by factorial design with high ' 'artepillin C content. J. Pharm. Technol. Drug Res. 4(1), 1–13. ' 'https://doi.org/10.7243/2050-120X-4-1 (2015).', 'journal-title': 'J. Pharm. Technol. Drug Res.'}, { 'issue': '2', 'key': '43764_CR15', 'doi-asserted-by': 'publisher', 'first-page': '99', 'DOI': '10.1080/00218839.1998.11100961', 'volume': '37', 'author': 'RG Woisky', 'year': '1998', 'unstructured': 'Woisky, R. G. & Salatino, A. Analysis of propolis: Some parameters and ' 'procedures for chemical quality control. J. Apic. Res. 37(2), 99–105. ' 'https://doi.org/10.1080/00218839.1998.11100961 (1998).', 'journal-title': 'J. Apic. Res.'}, { 'key': '43764_CR16', 'doi-asserted-by': 'publisher', 'first-page': '670451', 'DOI': '10.1155/2013/670451', 'volume': '2013', 'author': 'BA Rocha', 'year': '2013', 'unstructured': 'Rocha, B. A. et al. Evaluation of a propolis water extract using a ' 'reliable RP-HPLC methodology and in vitro and in vivo efficacy and ' 'safety characterisation. Evid. Based Complement. Alternat. Med. 2013, ' '670451. https://doi.org/10.1155/2013/670451 (2013).', 'journal-title': 'Evid. Based Complement. Alternat. Med.'}, { 'issue': '1', 'key': '43764_CR17', 'doi-asserted-by': 'publisher', 'first-page': '140', 'DOI': '10.1186/s12882-019-1337-7', 'volume': '20', 'author': 'MAD Silveira', 'year': '2019', 'unstructured': 'Silveira, M. A. D. et al. Effects of Brazilian green propolis on ' 'proteinuria and renal function in patients with chronic kidney disease: ' 'A randomized, double-blind, placebo-controlled trial. BMC Nephrol. ' '20(1), 140. https://doi.org/10.1186/s12882-019-1337-7 (2019).', 'journal-title': 'BMC Nephrol.'}, { 'key': '43764_CR18', 'doi-asserted-by': 'publisher', 'first-page': '112174', 'DOI': '10.1016/j.jep.2019.112174', 'volume': '245', 'author': 'DAC Cusinato', 'year': '2019', 'unstructured': 'Cusinato, D. A. C. et al. Evaluation of potential herbal-drug ' 'interactions of a standardized propolis extract (EPP-AF®) using an in ' 'vivo cocktail approach. J. Ethnopharmacol. 245, 112174. ' 'https://doi.org/10.1016/j.jep.2019.112174 (2019).', 'journal-title': 'J. Ethnopharmacol.'}, { 'issue': '4', 'key': '43764_CR19', 'doi-asserted-by': 'publisher', 'first-page': '101609', 'DOI': '10.1016/j.bjid.2021.101609', 'volume': '25', 'author': 'A Miethke-Morais', 'year': '2021', 'unstructured': 'Miethke-Morais, A. et al. COVID-19-related hospital cost-outcome ' 'analysis: The impact of clinical and demographic factors. Braz. J. ' 'Infect. Dis. 25(4), 101609. https://doi.org/10.1016/j.bjid.2021.101609 ' '(2021).', 'journal-title': 'Braz. J. Infect. Dis.'}, { 'issue': '8', 'key': '43764_CR20', 'doi-asserted-by': 'publisher', 'first-page': '665', 'DOI': '10.1016/S1473-3099(13)70081-1', 'volume': '13', 'author': 'WG Melsen', 'year': '2013', 'unstructured': 'Melsen, W. G. Attributable mortality of ventilator-associated pneumonia: ' 'A meta-analysis of individual patient data from randomised prevention ' 'studies. Lancet Infect. Dis. 13(8), 665–671. ' 'https://doi.org/10.1016/S1473-3099(13)70081-1 (2013).', 'journal-title': 'Lancet Infect. Dis.'}, { 'issue': '6', 'key': '43764_CR21', 'doi-asserted-by': 'publisher', 'first-page': '992', 'DOI': '10.1016/j.chom.2020.04.009', 'volume': '27', 'author': 'EJ Giamarellos-Bourboulis', 'year': '2020', 'unstructured': 'Giamarellos-Bourboulis, E. J. et al. Complex immune dysregulation in ' 'COVID-19 patients with severe respiratory failure. Cell Host. Microbe. ' '27(6), 992-1000.e3. https://doi.org/10.1016/j.chom.2020.04.009 (2020).', 'journal-title': 'Cell Host. Microbe.'}, { 'issue': '1', 'key': '43764_CR22', 'doi-asserted-by': 'publisher', 'first-page': '207', 'DOI': '10.1186/s12879-022-07192-x', 'volume': '22', 'author': 'A De Bruyn', 'year': '2022', 'unstructured': 'De Bruyn, A. et al. Secondary infection in COVID-19 critically ill ' 'patients: A retrospective single-center evaluation. BMC Infect Dis. ' '22(1), 207. https://doi.org/10.1186/s12879-022-07192-x (2022).', 'journal-title': 'BMC Infect Dis.'}, { 'key': '43764_CR23', 'doi-asserted-by': 'publisher', 'first-page': '29', 'DOI': '10.1016/j.jhin.2022.04.007', 'volume': '126', 'author': 'B Minihan', 'year': '2022', 'unstructured': 'Minihan, B. et al. Association between tocilizumab treatment of ' 'hyperinflammatory patients with COVID-19 in a critical care setting and ' 'elevated incidence of hospital-acquired bacterial and invasive fungal ' 'infections. J Hosp Infect. 126, 29–36. ' 'https://doi.org/10.1016/j.jhin.2022.04.007 (2022).', 'journal-title': 'J Hosp Infect.'}, { 'issue': '1', 'key': '43764_CR24', 'doi-asserted-by': 'publisher', 'first-page': '317', 'DOI': '10.1186/s13054-021-03672-9', 'volume': '25', 'author': 'G Grasselli', 'year': '2021', 'unstructured': 'Grasselli, G., Cattaneo, E. & Florio, G. Secondary infections in ' 'critically ill patients with COVID-19. Crit. Care. 25(1), 317. ' 'https://doi.org/10.1186/s13054-021-03672-9 (2021).', 'journal-title': 'Crit. Care.'}, { 'issue': '2', 'key': '43764_CR25', 'doi-asserted-by': 'publisher', 'first-page': 'e22363', 'DOI': '10.7759/cureus.22363', 'volume': '14', 'author': 'I Bahceci', 'year': '2022', 'unstructured': 'Bahceci, I. et al. Secondary bacterial infection rates among patients ' 'With COVID-19. Cureus 14(2), e22363. ' 'https://doi.org/10.7759/cureus.22363 (2022).', 'journal-title': 'Cureus'}, { 'key': '43764_CR26', 'doi-asserted-by': 'publisher', 'first-page': '1035475', 'DOI': '10.1155/2022/1035475', 'volume': '2022', 'author': 'MA Duarte Silveira', 'year': '2022', 'unstructured': 'Duarte Silveira, M. A. et al. Effects of standardized Brazilian green ' 'propolis extract (EPP-AF®) on inflammation in haemodialysis patients: A ' 'clinical trial. Int. J. Nephrol. 2022, 1035475. ' 'https://doi.org/10.1155/2022/1035475 (2022).', 'journal-title': 'Int. J. Nephrol.'}, { 'issue': '5', 'key': '43764_CR27', 'doi-asserted-by': 'publisher', 'first-page': '283', 'DOI': '10.5501/wjv.v11.i5.283', 'volume': '11', 'author': 'GM Nogueira', 'year': '2022', 'unstructured': 'Nogueira, G. M., Silva, N. L. O. R., Moura, A. F., Duarte Silveira, M. ' 'A. & Moura-Neto, J. A. Acute kidney injury and electrolyte disorders in ' 'COVID-19. World J. Virol. 11(5), 283–292. ' 'https://doi.org/10.5501/wjv.v11.i5.283 (2022).', 'journal-title': 'World J. Virol.'}, { 'issue': '3', 'key': '43764_CR28', 'doi-asserted-by': 'publisher', 'first-page': 'e2176', 'DOI': '10.1002/rmv.2176', 'volume': '31', 'author': 'E Ahmadian', 'year': '2021', 'unstructured': 'Ahmadian, E. et al. Covid-19 and kidney injury: Pathophysiology and ' 'molecular mechanisms. Rev. Med. Virol. 31(3), e2176. ' 'https://doi.org/10.1002/rmv.2176 (2021).', 'journal-title': 'Rev. Med. Virol.'}, { 'key': '43764_CR29', 'doi-asserted-by': 'publisher', 'first-page': '692828', 'DOI': '10.3389/fphar.2022.692828', 'volume': '13', 'author': 'B Wu', 'year': '2022', 'unstructured': 'Wu, B. et al. Acute kidney injury associated with remdesivir: A ' 'comprehensive pharmacovigilance analysis of COVID-19 reports in FAERS. ' 'Front. Pharmacol. 13, 692828. https://doi.org/10.3389/fphar.2022.692828 ' '(2022).', 'journal-title': 'Front. Pharmacol.'}, { 'issue': '1', 'key': '43764_CR30', 'doi-asserted-by': 'publisher', 'first-page': '5925', 'DOI': '10.1038/s41598-021-85124-6', 'volume': '11', 'author': 'MAD Silveira', 'year': '2021', 'unstructured': 'Silveira, M. A. D. et al. Green propolis extract attenuates acute kidney ' 'injury and lung injury in a rat model of sepsis. Sci. Rep. 11(1), 5925. ' 'https://doi.org/10.1038/s41598-021-85124-6 (2021).', 'journal-title': 'Sci. Rep.'}, { 'issue': '5', 'key': '43764_CR31', 'doi-asserted-by': 'publisher', 'first-page': '474', 'DOI': '10.1177/00045632211020029', 'volume': '58', 'author': 'L Bojko', 'year': '2021', 'unstructured': 'Bojko, L. et al. Drug dosing using estimated glomerular filtration rate: ' 'Misclassification due to metamizole interference in a creatinine assay. ' 'Ann. Clin. Biochem. 58(5), 474–480. ' 'https://doi.org/10.1177/00045632211020029 (2021).', 'journal-title': 'Ann. Clin. Biochem.'}], 'container-title': 'Scientific Reports', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41598-023-43764-w.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41598-023-43764-w', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41598-023-43764-w.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 10, 27]], 'date-time': '2023-10-27T10:04:21Z', 'timestamp': 1698401061000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41598-023-43764-w'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 10, 27]]}, 'references-count': 31, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2023, 12]]}}, 'alternative-id': ['43764'], 'URL': 'http://dx.doi.org/10.1038/s41598-023-43764-w', 'relation': {}, 'ISSN': ['2045-2322'], 'subject': ['Multidisciplinary'], 'container-title-short': 'Sci Rep', 'published': {'date-parts': [[2023, 10, 27]]}, 'assertion': [ { 'value': '8 March 2023', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '28 September 2023', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '27 October 2023', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'The authors declare no competing interests.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '18405'}