المؤلفون: Grembi, Jessica, Nguyen, Anna, Riviere, Marie, Heitmann, Gabriella, Patil, Arusha, Athni, Tejas, Djajadi, Stephanie, Ercumen, Ayse, Lin, Audrie, Crider, Yoshika, Mertens, Andrew, Karim, Md, Islam, Md, Miah, Rana, Famida, Syeda, Hossen, Md, Mutsuddi, Palash, Ali, Shahjahan, Rahman, Md, Hussain, Zahir, Shoab, Abul, Haque, Rashidul, Rahman, Mahbubur, Unicomb, Leanne, Luby, Stephen, Arnold, Benjamin, Bennett, Adam, Benjamin-Chung, Jade

المصدر: PLoS Neglected Tropical Diseases. 18(5)

مصطلحات موضوعية: Humans, Bangladesh, Diarrhea, Infant, Child, Preschool, Risk Factors, Rural Population, Prevalence, Male, Female, Weather, Enterotoxigenic Escherichia coli, Cryptosporidium, Temperature, Shiga-Toxigenic Escherichia coli, Climate Change, Cryptosporidiosis

الوصف: BACKGROUND: A number of studies have detected relationships between weather and diarrhea. Few have investigated associations with specific enteric pathogens. Understanding pathogen-specific relationships with weather is crucial to inform public health in low-resource settings that are especially vulnerable to climate change. OBJECTIVES: Our objectives were to identify weather and environmental risk factors associated with diarrhea and enteropathogen prevalence in young children in rural Bangladesh, a population with high diarrheal disease burden and vulnerability to weather shifts under climate change. METHODS: We matched temperature, precipitation, surface water, and humidity data to observational longitudinal data from a cluster-randomized trial that measured diarrhea and enteropathogen prevalence in children 6 months-5.5 years from 2012-2016. We fit generalized additive mixed models with cubic regression splines and restricted maximum likelihood estimation for smoothing parameters. RESULTS: Comparing weeks with 30°C versus 15°C average temperature, prevalence was 3.5% higher for diarrhea, 7.3% higher for Shiga toxin-producing Escherichia coli (STEC), 17.3% higher for enterotoxigenic E. coli (ETEC), and 8.0% higher for Cryptosporidium. Above-median weekly precipitation (median: 13mm; range: 0-396mm) was associated with 29% higher diarrhea (adjusted prevalence ratio 1.29, 95% CI 1.07, 1.55); higher Cryptosporidium, ETEC, STEC, Shigella, Campylobacter, Aeromonas, and adenovirus 40/41; and lower Giardia, sapovirus, and norovirus prevalence. Other associations were weak or null. DISCUSSION: Higher temperatures and precipitation were associated with higher prevalence of diarrhea and multiple enteropathogens; higher precipitation was associated with lower prevalence of some enteric viruses. Our findings emphasize the heterogeneity of the relationships between hydrometeorological variables and specific enteropathogens, which can be masked when looking at composite measures like all-cause diarrhea. Our results suggest that preventive interventions targeted to reduce enteropathogens just before and during the rainy season may more effectively reduce child diarrhea and enteric pathogen carriage in rural Bangladesh and in settings with similar meteorological characteristics, infrastructure, and enteropathogen transmission.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4vk3b4m7Test
https://escholarship.org/content/qt4vk3b4m7/qt4vk3b4m7.pdfTest

المؤلفون: Gwyn, Sarah, Aragie, Solomon, Wittberg, Dionna M, Melo, Jason S, Dagnew, Adane, Hailu, Dagnachew, Tadesse, Zerihun, Haile, Mahteme, Zeru, Taye, Nash, Scott D, Arnold, Benjamin F, Martin, Diana L, Keenan, Jeremy D

المصدر: American Journal of Tropical Medicine and Hygiene. 105(3)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Infectious Diseases, Biodefense, Digestive Diseases, Foodborne Illness, Prevention, Vaccine Related, Emerging Infectious Diseases, Pediatric, Infection, Good Health and Well Being, Campylobacter Infections, Campylobacter jejuni, Child, Child, Preschool, Chlamydia trachomatis, Cholera, Cryptosporidiosis, Cryptosporidium parvum, Dried Blood Spot Testing, Entamoeba histolytica, Entamoebiasis, Enterotoxigenic Escherichia coli, Escherichia coli Infections, Ethiopia, Female, Giardia lamblia, Giardiasis, Humans, Infant, Infant, Newborn, Male, Salmonella Infections, Salmonella enteritidis, Salmonella typhimurium, Sensitivity and Specificity, Seroepidemiologic Studies, Serologic Tests, Trachoma, Vibrio cholerae, Medical and Health Sciences, Tropical Medicine, Biomedical and clinical sciences, Health sciences

الوصف: Multiplex bead assays (MBAs) for serologic testing have become more prevalent in public health surveys, but few studies have assessed their test performance. As part of a trachoma study conducted in a rural part of Ethiopia in 2016, dried blood spots (DBS) were collected from a random sample of 393 children aged 0 to 9 years, with at least two separate 6-mm DBS collected on a filter card. Samples eluted from DBS were processed using an MBA on the Luminex platform for antibodies against 13 antigens of nine infectious organisms: Chlamydia trachomatis, Vibrio cholera, enterotoxigenic Escherichia coli, Cryptosporidium parvum, Entamoeba histolytica, Camplyobacter jejuni, Salmonella typhimurium Group B, Salmonella enteritidis Group D, and Giardia lamblia. Two separate DBS from each child were processed. The first DBS was run a single time, with the MBA set to read 100 beads per well. The second DBS was run twice, first at 100 beads per well and then at 50 beads per well. Results were expressed as the median fluorescence intensity minus background (MFI-BG), and classified as seropositive or seronegative according to external standards. Agreement between the three runs was high, with intraclass correlation coefficients of > 0.85 for the two Salmonella antibody responses and > 0.95 for the other 11 antibody responses. Agreement was also high for the dichotomous seropositivity indicators, with Cohen's kappa statistics exceeding 0.87 for each antibody assay. These results suggest that serologic testing on the Luminex platform had strong test performance characteristics for analyzing antibodies using DBS.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4bq1w799Test

المؤلفون: Silwamba, Suwilanji, Chilyabanyama, Obvious N, Liswaniso, Fraser, Chisenga, Caroline C, Chilengi, Roma, Dougan, Gordon, Kwenda, Geoffrey, Chakraborty, Subhra, Simuyandi, Michelo

المصدر: nlmid: 101291488 ; essn: 1935-2735

مصطلحات موضوعية: Bacterial Toxins, Child, Cross-Sectional Studies, Diarrhea, Enterotoxigenic Escherichia coli, Enterotoxins, Escherichia coli Infections, Escherichia coli Proteins, Female, Humans, Male, Molecular Epidemiology, Zambia

الوصف: BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is one of the top aetiologic agents of diarrhea in children under the age of 5 in low-middle income countries (LMICs). The lack of point of care diagnostic tools for routine ETEC diagnosis results in limited data regarding the actual burden and epidemiology in the endemic areas. We evaluated performance of the novel Rapid LAMP based Diagnostic Test (RLDT) for detection of ETEC in stool as a point of care diagnostic assay in a resource-limited setting. METHODS: We conducted a cross-sectional study of 324 randomly selected stool samples from children under 5 presenting with moderate to severe diarrhea (MSD). The samples were collected between November 2012 to September 2013 at selected health facilities in Zambia. The RLDT was evaluated by targeting three ETEC toxin genes [heat labile toxin (LT) and heat stable toxins (STh and STp)]. Quantitative PCR was used as the "gold standard" to evaluate the diagnostic sensitivity and specificity of RLDT for detection of ETEC. We additionally described the prevalence and seasonality of ETEC. RESULTS: The study included 324 participants, 50.6% of which were female. The overall prevalence of ETEC was 19.8% by qPCR and 19.4% by RLDT. The children between 12 to 59 months had the highest prevalence of 22%. The study determined ETEC toxin distribution was LT 28/321(9%), ST 18/321(6%) and LT/ST 16/321(5%). The sensitivity and specificity of the RLDT compared to qPCR using a Ct 35 as the cut-off, were 90.7% and 97.5% for LT, 85.2% and 99.3% for STh and 100% and 99.7% for STp, respectively. CONCLUSION: The results of this study suggest that RLDT is sufficiently sensitive and specific and easy to implement in the endemic countries. Being rapid and simple, the RLDT also presents as an attractive tool for point-of-care testing at the health facilities and laboratories in the resource-limited settings.

وصف الملف: application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/340752Test

الإتاحة: https://doi.org/10.17863/CAM.88190Test
https://www.repository.cam.ac.uk/handle/1810/340752Test

المؤلفون: Higginson, Ellen E, Sayeed, M Abu, Pereira Dias, Joana, Shetty, Vignesh, Ballal, Mamatha, Srivastava, Sunil Kumar, Willis, Ian, Qadri, Firdausi, Dougan, Gordon, Mutreja, Ankur

مصطلحات موضوعية: ETEC, metagenomics, microbiome, Adult, Bacteria, Child, Diarrhea, Enterotoxigenic Escherichia coli, Escherichia coli Infections, Gastrointestinal Microbiome, Humans, Microbiota

الوصف: Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea in children in low- and middle-income countries (LMICs). However, large-scale pathogen burden studies in children have identified ETEC in the guts of both symptomatic patients and controls. The factors that influence this balance are poorly understood, but it is postulated that the gut microbiome may play a role in either resistance or progression to disease. In this study, we profiled the microbiomes of children and adults from Bangladesh who were asymptomatically or symptomatically infected with ETEC. Symptomatic patients had significantly higher numbers of sequenced reads mapping to both E. coli and two ETEC toxins, suggesting higher bacterial burden. They were also significantly more likely to be coinfected with enteroaggregative E. coli (EAEC) and had higher proportions of other Gammaproteobacteria, including Klebsiella, Salmonella, and Haemophilus. Colonization with ETEC was also associated with increased prevalence of antimicrobial resistance (AMR) genes, most notably those of the β-lactamase class. Taxonomic profiles were distinctly different between all groups in both species richness and composition, although the direction of these changes was different in adults and children. As seen previously, children with high E. coli burdens also had higher proportions of Streptococcus spp., while healthy children were more heavily colonized by Bifidobacterium spp. Our study provides insight into the microbiome changes that occur upon infection with ETEC in an endemic setting and provides rationale for future studies investigating how the microbiome may protect or predispose individuals to symptomatic infections with gastrointestinal pathogens. IMPORTANCE Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea in children in low- and middle-income countries. However, these bacteria are often identified in both patients and healthy controls. We do not yet understand why only some people get sick, but it has been suggested ...

وصف الملف: Print-Electronic; application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/339298Test

الإتاحة: https://doi.org/10.17863/CAM.86706Test
https://www.repository.cam.ac.uk/handle/1810/339298Test

المؤلفون: David, Lawrence A, Weil, Ana, Ryan, Edward T, Calderwood, Stephen B, Harris, Jason B, Chowdhury, Fahima, Begum, Yasmin, Qadri, Firdausi, LaRocque, Regina C, Turnbaugh, Peter J

المصدر: mBio. 6(3)

مصطلحات موضوعية: Genetics, Emerging Infectious Diseases, Human Genome, Biodefense, Infectious Diseases, Foodborne Illness, Vaccine Related, Prevention, Digestive Diseases, Biotechnology, Infection, Good Health and Well Being, Cholera, Diarrhea, Enterotoxigenic Escherichia coli, Escherichia coli Infections, Gastrointestinal Microbiome, Gastrointestinal Tract, Humans, Metagenomics, Vibrio cholerae, Microbiology

الوصف: UnlabelledDisability after childhood diarrhea is an important burden on global productivity. Recent studies suggest that gut bacterial communities influence how humans recover from infectious diarrhea, but we still lack extensive data and mechanistic hypotheses for how these bacterial communities respond to diarrheal disease and its treatment. Here, we report that after Vibrio cholerae infection, the human gut microbiota undergoes an orderly and reproducible succession that features transient reversals in relative levels of enteric Bacteroides and Prevotella. Elements of this succession may be a common feature in microbiota recovery from acute secretory diarrhea, as we observed similar successional dynamics after enterotoxigenic Escherichia coli (ETEC) infection. Our metagenomic analyses suggest that multiple mechanisms drive microbial succession after cholera, including bacterial dispersal properties, changing enteric oxygen and carbohydrate levels, and phage dynamics. Thus, gut microbiota recovery after cholera may be predictable at the level of community structure but is driven by a complex set of temporally varying ecological processes. Our findings suggest opportunities for diagnostics and therapies targeting the gut microbiota in humans recovering from infectious diarrhea.ImportanceDisability after diarrhea is a major burden on public health in the developing world. Gut bacteria may affect this recovery, but it remains incompletely understood how resident microbes in the digestive tract respond to diarrheal illness. Here, we observed an orderly and reproducible succession of gut bacterial groups after cholera in humans. Genomic analyses associated the succession with bacterial dispersal in food, an altered microbial environment, and changing phage levels. Our findings suggest that it may one day be feasible to manage resident bacterial populations in the gut after infectious diarrhea.

الوصول الحر: https://escholarship.org/uc/item/1zk1m68mTest

المؤلفون: von Mentzer, Astrid, Blackwell, Grace A, Pickard, Derek, Boinett, Christine J, Joffré, Enrique, Page, Andrew J, Svennerholm, Ann-Mari, Dougan, Gordon, Sjöling, Åsa

مصطلحات موضوعية: Antineoplastic Agents, Diarrhea, Drug Resistance, Bacterial, Enterotoxigenic Escherichia coli, Escherichia coli Infections, Escherichia coli Proteins, Genome, Genomics, Humans, Phylogeny, Reference Standards, Virulence, Virulence Factors

الوصف: Enterotoxigenic Escherichia coli (ETEC) is an enteric pathogen responsible for the majority of diarrheal cases worldwide. ETEC infections are estimated to cause 80,000 deaths annually, with the highest rates of burden, ca 75 million cases per year, amongst children under 5 years of age in resource-poor countries. It is also the leading cause of diarrhoea in travellers. Previous large-scale sequencing studies have found seven major ETEC lineages currently in circulation worldwide. We used PacBio long-read sequencing combined with Illumina sequencing to create high-quality complete reference genomes for each of the major lineages with manually curated chromosomes and plasmids. We confirm that the major ETEC lineages all harbour conserved plasmids that have been associated with their respective background genomes for decades, suggesting that the plasmids and chromosomes of ETEC are both crucial for ETEC virulence and success as pathogens. The in-depth analysis of gene content, synteny and correct annotations of plasmids will elucidate other plasmids with and without virulence factors in related bacterial species. These reference genomes allow for fast and accurate comparison between different ETEC strains, and these data will form the foundation of ETEC genomics research for years to come.

وصف الملف: Electronic; application/pdf

العلاقة: https://www.repository.cam.ac.uk/handle/1810/324506Test

الإتاحة: https://doi.org/10.17863/CAM.71959Test
https://www.repository.cam.ac.uk/handle/1810/324506Test

المؤلفون: Xi Lu, Dingyan Wu, Xin Zhao, Mingxin Zhang, Ke Ren, Ningning Zhou, Yanni Zhao, Weisheng Qian

المصدر: Applied Microbiology and Biotechnology. 106:8195-8210

مصطلحات موضوعية: Swine, Metabolome, Humans, Animals, Enterotoxigenic Escherichia coli, Metabolomics, Ethanolamine, General Medicine, Caco-2 Cells, Applied Microbiology and Biotechnology, Biotechnology

الوصف: Bacterial pathogenicity is greatly affected by nutrient recognition and utilization in the host microenvironment. The characterization of enteral nutrients that promote intestinal pathogen virulence is helpful for developing new adjuvant therapies and inhibiting host damage. Ethanolamine (EA), as a major component of intestinal epithelial cells and bacterial membranes, is abundant in the intestine. Here, we provide the first demonstration that the critical human and porcine pathogen enterotoxigenic Escherichia coli (ETEC) can utilize EA as a nitrogen source, which affects its virulence phenotype. We found that compared with that in M9 medium (containing NH

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd628f2e3d487ec00ed428e092775eaeTest
https://doi.org/10.1007/s00253-022-12261-xTest

المؤلفون: Ntui, Clifford Manyo, Fleckenstein, James M, Schubert, Wolf-Dieter

المصدر: 2020-Current year OA Pubs

مصطلحات موضوعية: Child, Humans, Preschool, Enterotoxigenic Escherichia coli, Escherichia coli Proteins, Adhesins, Bacterial, Membrane Transport Proteins, Diarrhea, Membrane Glycoproteins, ICTS (Institute of Clinical and Translational Sciences), Medicine and Health Sciences

الوصف: Enterotoxigenic Escherichia coli (ETEC) is a diarrhoeal pathogen associated with high morbidity and mortality especially among young children in developing countries. At present, there is no vaccine for ETEC. One candidate vaccine antigen, EtpA, is a conserved secreted adhesin that binds to the tips of flagellae to bridge ETEC to host intestinal glycans. EtpA is exported through a Gram-negative, two-partner secretion system (TPSS, type Vb) comprised of the secreted EtpA passenger (TpsA) protein and EtpB (TpsB) transporter that is integrated into the outer bacterial membrane. TpsA proteins share a conserved, N-terminal TPS domain followed by an extensive C-terminal domain with divergent sequence repeats. Two soluble, N-terminal constructs of EtpA were prepared and analysed respectively including residues 67 to 447 (EtpA67-447) and 1 to 606 (EtpA1-606). The crystal structure of EtpA67-447 solved at 1.76 Å resolution revealed a right-handed parallel β-helix with two extra-helical hairpins and an N-terminal β-strand cap. Analyses by circular dichroism spectroscopy confirmed the β-helical fold and indicated high resistance to chemical and thermal denaturation as well as rapid refolding. A theoretical AlphaFold model of full-length EtpA largely concurs with the crystal structure adding an extended β-helical C-terminal domain after an interdomain kink. We propose that robust folding of the TPS domain upon secretion provides a template to extend the N-terminal β-helix into the C-terminal domains of TpsA proteins.

وصف الملف: application/pdf

العلاقة: https://digitalcommons.wustl.edu/oa_4/2185Test; https://digitalcommons.wustl.edu/context/oa_4/article/3180/viewcontent/Structural_and_biophysical_PLoS_One.pdfTest

الإتاحة: https://doi.org/10.1371/journal.pone.0287100Test
https://digitalcommons.wustl.edu/oa_4/2185Test
https://digitalcommons.wustl.edu/context/oa_4/article/3180/viewcontent/Structural_and_biophysical_PLoS_One.pdfTest

المؤلفون: George Armah, A. Louis Bourgeois, Ann-Mari Svennerholm, Margaret Kosek, Richard Guerrant, Shahida Baqar, Mateusz Hasso-Agopsowicz, Roma Chilengi, Thomas F. Wierzba, Firdausi Qadri, Claudio F. Lanata, Farzana Muhib, Ibrahim A Khalil, Chad K. Porter, Alejandro Cravioto, Richard I. Walker, Gagandeep Kang, Birgitte Giersing

المصدر: Vaccine

مصطلحات موضوعية: Diarrhea, medicine.medical_specialty, Sanitation, 030231 tropical medicine, Psychological intervention, Review, Disease, World Health Organization, medicine.disease_cause, Diarrhoeal diseases, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Enterotoxigenic Escherichia coli, Humans, Medicine, 030212 general & internal medicine, Child, Escherichia coli Infections, Disease burden, Licensure, General Veterinary, General Immunology and Microbiology, Escherichia coli Vaccines, business.industry, Public health, Vaccine research, Public Health, Environmental and Occupational Health, Enterotoxigenic Escherichia coli (ETEC), Vaccination, Infectious Diseases, Molecular Medicine, business, Childhood growth and development

الوصف: Diarrhoeal disease attributable to enterotoxigenic Escherichia coli (ETEC) causes substantial morbidity and mortality predominantly in paediatric populations in low- and middle-income countries. In addition to acute illness, there is an increasing appreciation of the long-term consequences of enteric infections, including ETEC, on childhood growth and development. Provision of potable water and sanitation and appropriate clinical care for acute illness are critical to reduce the ETEC burden. However, these interventions are not always practical and may not achieve equitable and sustainable coverage. Vaccination may be the most cost-effective and equitable means of primary prevention; however, additional data are needed to accelerate the investment and guide the decision-making process for ETEC vaccines. First, to understand and quantify the ETEC disease burden, additional data are needed on the association between ETEC infection and physical and cognitive stunting as well as delayed educational attainment. Furthermore, the role of inappropriate or inadequate antibiotic treatment of ETEC-attributable diarrhoea may contribute to the development of antimicrobial resistance (AMR) and needs further elucidation. An ETEC vaccine that mitigates acute diarrhoeal illness and minimizes the longer-term disease manifestations could have significant public health impact and be a cost-effective countermeasure. Herein we review the ETEC vaccine pipeline, led by candidates compatible with the general parameters of the Preferred Product Characteristics (PPC) recently developed by the World Health Organization. Additionally, we have developed an ETEC Vaccine Development Strategy to provide a framework to underpin priority activities for researchers, funders and vaccine manufacturers, with the goal of addressing globally unmet data needs in the areas of research, product development, and policy, as well as commercialization and delivery. The strategy also aims to guide prioritization and co-ordination of the priority activities needed to minimize the timeline to licensure and use of ETEC vaccines, especially in in low- and middle-income countries, where they are most urgently needed.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e121c5b17a594b1e8e2b9806e6b82070Test
https://doi.org/10.1016/j.vaccine.2021.04.018Test

المؤلفون: Ali Akgul, Massimo Maddaloni, David W. Pascual, Carol Hoffman, Andrew S. Nelson, Ella Bhagyaraj

المصدر: Immunol Lett

مصطلحات موضوعية: Blood Glucose, CD4-Positive T-Lymphocytes, Primary Cell Culture, Immunology, Fimbria, Administration, Oral, Mice, Transgenic, Spleen, Biology, medicine.disease_cause, Article, Mice, Antigen, Transforming Growth Factor beta, Enterotoxigenic Escherichia coli, Bystander effect, medicine, Animals, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, Immunology and Allergy, Indoleamine 2,3-dioxygenase, Cells, Cultured, NOD mice, Antigens, Bacterial, Probiotics, Dendritic Cells, Coculture Techniques, Lactococcus lactis, Bacterial adhesin, Disease Models, Animal, Diabetes Mellitus, Type 1, medicine.anatomical_structure, Female, Fimbriae Proteins, Lymph Nodes

الوصف: Colonization factor antigen I (CFA/I) fimbria, an adhesin from enterotoxigenic Escherichia coli, confers protection in murine autoimmune models for type 1 diabetes (T1D), multiple sclerosis, and rheumatoid arthritis. Although CFA/I fimbriae's initial mode of action is in a bystander or in an antigen (Ag)-independent fashion, protection is ultimately dependent upon the induction and/or activation of auto-Ag-specific regulatory T cells (Tregs). However, little is known about how protection transitions from bystander suppression to Ag-specific Tregs. Since dendritic cells (DCs) play an integral role in fate decisions for T cells becoming inflammatory or tolerogenic, the described study tests the hypothesis that Lactococcus lactis expressing CFA/I (LL-CFA/I) stimulates DCs to establish a regulatory microenvironment. To this end, bone marrow-derived dendritic cells (BMDCs) were infected in vitro with LL-CFA/I. Results revealed increased production of IL-10, TGF-β, and indoleamine 2,3-deoxygenase (IDO). Although co-culture of LL-CFA/I infected BMDCs with naive T cells did not promote Foxp3 expression, TNF-α and IFN-γ production was suppressed. NOD mice orally dosed with LL-CFA/I showed an increase in regulatory plasmacytoid DCs (pDCs) expressing IDO and TGF-β in pancreatic lymph nodes (PaLNs) and spleen three days post-treatment. However, Tregs did not appear in the mucosal inductive sites until much later. These findings show that LL-CFA/I influences specific DC populations to establish tolerance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0299421e3af10d90364d5c97d708dfb6Test
https://doi.org/10.1016/j.imlet.2021.07.009Test