{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T03:30:19Z","timestamp":1783135819752,"version":"3.54.6"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T00:00:00Z","timestamp":1587513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT201918\/Z\/16\/Z"],"award-info":[{"award-number":["WT201918\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The Nigerian Government is scaling up the distribution of insecticide-treated bed nets for malaria control, but the lack of surveillance data, especially in the Sudan\/Sahel region of the country, may hinder targeting priority populations. Here, the vectorial role and insecticide resistance profile of a population of a major malaria vector Anopheles funestus sensu stricto from Sahel of Nigeria was characterised. An. funestus s.s. was the only vector found, with a high human blood index (100%) and a biting rate of 5.3\/person\/night. High Plasmodium falciparum infection was discovered (sporozoite rate = 54.55%). The population is resistant to permethrin (mortality = 48.30%, LT50 = 65.76 min), deltamethrin, DDT (dichlorodiphenyltrichloroethane) and bendiocarb, with mortalities of 29.44%, 56.34% and 54.05%, respectively. Cone-bioassays established loss of efficacy of the pyrethroid-only long-lasting insecticidal nets (LLINs); but 100% recovery of susceptibility was obtained for piperonylbutoxide (PBO)-containing PermaNet\u00ae3.0. Synergist bioassays with PBO and diethyl maleate recovered susceptibility, implicating CYP450s (permethrin mortality = 78.73%, \u03c72 = 22.33, P &lt; 0.0001) and GSTs (DDT mortality = 81.44%, \u03c72 = 19.12, P &lt; 0.0001). A high frequency of 119F GSTe2 mutation (0.84) was observed (OR = 16, \u03c72 = 3.40, P = 0.05), suggesting the preeminent role of metabolic resistance. These findings highlight challenges associated with deployment of LLINs and indoor residual spraying (IRS) in Nigeria.<\/jats:p>","DOI":"10.3390\/genes11040454","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T02:10:52Z","timestamp":1587607852000},"page":"454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Exploring the Mechanisms of Multiple Insecticide Resistance in a Highly Plasmodium-Infected Malaria Vector Anopheles funestus Sensu Stricto from Sahel of Northern Nigeria"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0744-802X","authenticated-orcid":false,"given":"Sulaiman S.","family":"Ibrahim","sequence":"first","affiliation":[{"name":"Vector Biology Department, Liverpool School of Tropical Medicine (LSTM), Liverpool L3 5QA, UK"},{"name":"Department of Biochemistry, Bayero University, PMB 3011 Kano, Nigeria"},{"name":"LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), P.O. Box 13591 Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0754-3740","authenticated-orcid":false,"given":"Muhammad M.","family":"Mukhtar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Bayero University, PMB 3011 Kano, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Irving","sequence":"additional","affiliation":[{"name":"Vector Biology Department, Liverpool School of Tropical Medicine (LSTM), Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Riveron","sequence":"additional","affiliation":[{"name":"LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), P.O. Box 13591 Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amen N.","family":"Fadel","sequence":"additional","affiliation":[{"name":"LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), P.O. Box 13591 Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9823-8364","authenticated-orcid":false,"given":"Williams","family":"Tchapga","sequence":"additional","affiliation":[{"name":"LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), P.O. Box 13591 Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3358-4949","authenticated-orcid":false,"given":"Jack","family":"Hearn","sequence":"additional","affiliation":[{"name":"Vector Biology Department, Liverpool School of Tropical Medicine (LSTM), Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullahi","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Vector Biology Department, Liverpool School of Tropical Medicine (LSTM), Liverpool L3 5QA, UK"},{"name":"Centre for Biotechnology Research, Bayero University, PMB 3011 Kano, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faruk","family":"Sarkinfada","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Bayero University, PMB 3011 Kano, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-3673","authenticated-orcid":false,"given":"Charles S.","family":"Wondji","sequence":"additional","affiliation":[{"name":"Vector Biology Department, Liverpool School of Tropical Medicine (LSTM), Liverpool L3 5QA, UK"},{"name":"LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), P.O. Box 13591 Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,22]]},"reference":[{"key":"ref_1","unstructured":"WHO (2011). World Malaria Report, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1016\/S0140-6736(17)33080-5","article-title":"The global fight against malaria is at crossroads","volume":"390","author":"Alonso","year":"2017","journal-title":"Lancet"},{"key":"ref_3","unstructured":"WHO (2017). World Malaria Report, World Health Organisation."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1080\/23288604.2016.1234864","article-title":"An Assessment of Data Availability, Quality, and Use in Malaria Program Decision Making in Nigeria","volume":"2","author":"Ohiri","year":"2016","journal-title":"Health Syst. Reform"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7395","DOI":"10.1038\/s41598-019-43634-4","article-title":"Temporal escalation of Pyrethroid Resistance in the major malaria vector Anopheles coluzzii from Sahelo-Sudanian Region of northern Nigeria","volume":"9","author":"Ibrahim","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ibrahim, S.S., Manu, Y.A., Tukur, Z., Irving, H., and Wondji, C.S. (2014). High frequency of kdr L1014F is associated with pyrethroid resistance in Anopheles coluzzii in Sudan savannah of northern Nigeria. BMC Infect. Dis., 14.","DOI":"10.1186\/1471-2334-14-441"},{"key":"ref_7","first-page":"50","article-title":"Widespread Report of Multiple Insecticide Resistance in Anopheles gambiae s.l. Mosquitoes in Eight Communities in Southern Gombe, North-Eastern Nigeria","volume":"13","author":"Oduola","year":"2019","journal-title":"J. Arthropod-Borne Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1080\/04345545709414952","article-title":"Annual Report of the Malarial Control Pilot Project in Western Sokoto (Northern Nigeria) 1955\u201356","volume":"3","author":"Haworth","year":"1957","journal-title":"Int. J. Pest Manag. A"},{"key":"ref_9","unstructured":"WHO (1959). A Detailed Examination of An. funestus from Southern and Northern Nigeria, World Health Organization."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0035-9203(65)90010-6","article-title":"Some basic entomological factors concerned with the transmission and control of malaria in Northern Nigeria","volume":"59","author":"Service","year":"1965","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/0035-9203(64)90072-0","article-title":"The behaviour of malaria vectors in huts sprayed with DDT and with a mixture of DDT and malathion in Northern Nigeria","volume":"58","author":"Service","year":"1964","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_12","unstructured":"Molineaux, L., and Gramiccia, G. (1980). The Garki Project: Research on the Epidemiology and Control of Malaria in the Sudan Savanna of West Africa, World Health Organisation."},{"key":"ref_13","first-page":"301","article-title":"Malaria in Nigeria","volume":"4","year":"1951","journal-title":"Bull. World Health Organ."},{"key":"ref_14","first-page":"1","article-title":"The Anophelinae of Africa south of the Sahara (Ethiopian zoogeographical region)","volume":"54l","author":"Gillies","year":"1968","journal-title":"S. Afr. Inst. Med. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.ibmb.2004.03.012","article-title":"Advances in the study of Anopheles funestus, a major vector of malaria in Africa","volume":"34","author":"Coetzee","year":"2004","journal-title":"Insect Biochem. Mol. Boil."},{"key":"ref_16","unstructured":"WHO (2015). Global Technical Strategy for Malaria 2016\u20132030, World Health Organisation."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.trstmh.2004.12.003","article-title":"Identification of three members of the Anopheles funestus (Diptera: Culicidae) group and their role in malaria transmission in two ecological zones in Nigeria","volume":"99","author":"Awolola","year":"2005","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1186\/s12936-016-1615-9","article-title":"Evidence of a multiple insecticide resistance in the malaria vector Anopheles funestus in South West Nigeria","volume":"15","author":"Djouaka","year":"2016","journal-title":"Malar. J."},{"key":"ref_19","unstructured":"(2018, October 25). President\u2019s Malaria Initiative. Seventh Annual Report to Congress, Available online: http:\/\/pmi.gov\/countries\/mops\/fy13\/nigeria_mop-fy13.pdf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"R27","DOI":"10.1186\/gb-2014-15-2-r27","article-title":"A single mutation in the GSTe2 gene allows tracking of metabolically based insecticide resistance in a major malaria vector","volume":"15","author":"Riveron","year":"2014","journal-title":"Genome Boil."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1046\/j.1365-2583.1998.72062.x","article-title":"Molecular characterization of pyrethroid knockdown resistance (kdr) in the major malaria vector Anopheles gambiae s.s","volume":"7","author":"Chandre","year":"1998","journal-title":"Insect Mol. Boil."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1046\/j.1365-2583.2000.00209.x","article-title":"Identification of a point mutation in the voltage-gated sodium channel gene of Kenyan Anopheles gambiae associated with resistance to DDT and pyrethroids","volume":"9","author":"Ranson","year":"2000","journal-title":"Insect Mol. Boil."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2583.2004.00452.x","article-title":"The unique mutation in ace-1 giving high insecticide resistance is easily detectable in mosquito vectors","volume":"13","author":"Weill","year":"2004","journal-title":"Insect Mol. Boil."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1111\/mec.13673","article-title":"The P450 CYP6Z1 confers carbamate\/pyrethroid cross-resistance in a major African malaria vector beside a novel carbamate-insensitive N485I acetylcholinesterase-1 mutation","volume":"25","author":"Ibrahim","year":"2016","journal-title":"Mol. Ecol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s12936-019-2816-9","article-title":"A subnational profiling analysis reveals regional differences as the main predictor of ITN ownership and use in Nigeria","volume":"18","author":"Andrada","year":"2019","journal-title":"Malar. J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Morgan, J.C., Irving, H., Okedi, L.M., Steven, A., and Wondji, C.S. (2010). Pyrethroid Resistance in an Anopheles funestus Population from Uganda. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011872"},{"key":"ref_27","first-page":"1","article-title":"A supplement to anophelinae of Africa south of Sahara (Afro-tropical region)","volume":"55","author":"Gillies","year":"1987","journal-title":"S. Afr. Inst. Med. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"804","DOI":"10.4269\/ajtmh.2002.66.804","article-title":"A cocktail polymerase chain reaction assay to identify members of the Anopheles funestus (Diptera: Culicidae) group","volume":"66","author":"Koekemoer","year":"2002","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/genetics\/107.4.611","article-title":"Organization and mapping of a sequence on the Drosophila melanogaster X and Y chromosomes that is transcribed during spermatogenesis","volume":"107","author":"Livak","year":"1984","journal-title":"Genetics"},{"key":"ref_30","unstructured":"WHO (2013). Malaria Entomology and Vector Control. Guide for Participants, World Health Organization."},{"key":"ref_31","unstructured":"WHO (2016). A Toolkit for Integrated Vector Management in Sub-Saharan Africa, World Health Organization."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"267","DOI":"10.4269\/ajtmh.2007.76.267","article-title":"Seasonality, Blood Feeding Behavior, and Transmission of Plasmodium falciparum by Anopheles Arabiensis after an Extended Drought in Southern Zambia","volume":"76","author":"Kent","year":"2007","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/1475-2875-7-177","article-title":"PCR-based detection of Plasmodium in Anopheles mosquitoes: A comparison of a new high-throughput assay with existing methods","volume":"7","author":"Bass","year":"2008","journal-title":"Malar. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/0166-6851(93)90077-B","article-title":"High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction","volume":"61","author":"Snounou","year":"1993","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_35","unstructured":"WHO (2016). Test Procedures for Insecticide Resistance Monitoring in Malaria Vector Mosquitoes, World Health Organization."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1365-2915.2005.00574.x","article-title":"Laboratory selection for and characteristics of pyrethroid resistance in the malaria vector Anopheles funestus","volume":"19","author":"Hunt","year":"2005","journal-title":"Med. Vet. Entomol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1186\/s12936-015-0877-y","article-title":"Rise of multiple insecticide resistance in Anopheles funestus in Malawi: A major concern for malaria vector control","volume":"14","author":"Riveron","year":"2015","journal-title":"Malar. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1002\/ps.3895","article-title":"Insect P450 inhibitors and insecticides: Challenges and opportunities","volume":"71","author":"Feyereisen","year":"2014","journal-title":"Pest Manag. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5772","DOI":"10.1038\/s41598-019-42015-1","article-title":"A marker of glutathione S-transferase-mediated resistance to insecticides is associated with higher Plasmodium infection in the African malaria vector Anopheles funestus","volume":"9","author":"Tchouakui","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_40","first-page":"95","article-title":"BioEdit: A user-friendly biological sequence alignment editor and analysis program for Windows 95\/98\/NT","volume":"18","author":"Hall","year":"1999","journal-title":"Nucleic Acids Symp. Ser."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1093\/bioinformatics\/btp187","article-title":"DnaSP v5: A software for comprehensive analysis of DNA polymorphism data","volume":"25","author":"Librado","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1093\/molbev\/mst197","article-title":"MEGA6: Molecular Evolutionary Genetics Analysis version 6.0","volume":"30","author":"Tamura","year":"2013","journal-title":"Mol. Boil. Evol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Djouaka, R., Irving, H., Tukur, Z., and Wondji, C.S. (2011). Exploring Mechanisms of Multiple Insecticide Resistance in a Population of the Malaria Vector Anopheles funestus in Benin. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027760"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Venables, W.N., and Ripley, B.D. (2002). Modern Applied Statistics with S, Springer Science and Business Media LLC.","DOI":"10.1007\/978-0-387-21706-2"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1186\/s12936-018-2632-7","article-title":"Using the human blood index to investigate host biting plasticity: A systematic review and meta-regression of the three major African malaria vectors","volume":"17","author":"Orsborne","year":"2018","journal-title":"Malar. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1093\/infdis\/jiz139","article-title":"Escalation of Pyrethroid Resistance in the Malaria Vector Anopheles funestus Induces a Loss of Efficacy of Piperonyl Butoxide\u2013Based Insecticide-Treated Nets in Mozambique","volume":"220","author":"Riveron","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1186\/s13071-016-1787-8","article-title":"Multiple insecticide resistance in the major malaria vector Anopheles funestus in southern Ghana: Implications for malaria control","volume":"9","author":"Riveron","year":"2016","journal-title":"Parasites Vectors"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1186\/s13071-016-1735-7","article-title":"Investigating molecular basis of lambda-cyhalothrin resistance in an Anopheles funestus population from Senegal","volume":"9","author":"Samb","year":"2016","journal-title":"Parasites Vectors"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Menze, B.D., Riveron, J.M., Ibrahim, S.S., Irving, H., Antonio-Nkondjio, C., Awono-Ambene, P.H., and Wondji, C.S. (2016). Multiple Insecticide Resistance in the Malaria Vector Anopheles funestus from Northern Cameroon Is Mediated by Metabolic Resistance Alongside Potential Target Site Insensitivity Mutations. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163261"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Menze, B., Kouamo, M., Wondji, M.J., Tchapga, W., Tchoupo, M., Kusimo, M.O., Mouhamadou, C.S., Riveron, J., and Wondji, C.S. (2020). An Experimental Hut Evaluation of PBO-Based and Pyrethroid-Only Nets against the Malaria Vector Anopheles funestus Reveals a Loss of Bed Nets Efficacy Associated with GSTe2 Metabolic Resistance. Genes, 11.","DOI":"10.3390\/genes11020143"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/infdis\/jix570","article-title":"High Plasmodium Infection Rate and Reduced Bed Net Efficacy in Multiple Insecticide-Resistant Malaria Vectors in Kinshasa, Democratic Republic of Congo","volume":"217","author":"Riveron","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1186\/s12936-018-2467-2","article-title":"Bionomics and insecticides resistance profiling of malaria vectors at a selected site for experimental hut trials in central Cameroon","volume":"17","author":"Menze","year":"2018","journal-title":"Malar. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s13071-019-3523-7","article-title":"A combination of metabolic resistance and high frequency of the 1014F kdr mutation is driving pyrethroid resistance in Anopheles coluzzii population from Guinea savanna of Cameroon","volume":"12","author":"Fadel","year":"2019","journal-title":"Parasites Vectors"},{"key":"ref_54","first-page":"13","article-title":"Investigation of the influence of a glutathione S-transferase metabolic resistance to pyrethroids\/DDT on mating competitiveness in males of the African malaria vector, Anopheles funestus","volume":"4","author":"Tchouakui","year":"2019","journal-title":"Wellcome Open Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Irving, H., and Wondji, C.S. (2017). Investigating knockdown resistance (kdr) mechanism against pyrethroids\/DDT in the malaria vector Anopheles funestus across Africa. BMC Genet., 18.","DOI":"10.1186\/s12863-017-0539-x"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/4\/454\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:45:13Z","timestamp":1760363113000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/4\/454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,22]]},"references-count":55,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["genes11040454"],"URL":"https:\/\/doi.org\/10.3390\/genes11040454","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,22]]}}}