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  1. Article ; Online: SARS-CoV-2 Causes a Different Cytokine Response Compared to Other Cytokine Storm-Causing Respiratory Viruses in Severely Ill Patients.

    Olbei, Marton / Hautefort, Isabelle / Modos, Dezso / Treveil, Agatha / Poletti, Martina / Gul, Lejla / Shannon-Lowe, Claire D / Korcsmaros, Tamas

    Frontiers in immunology

    2021  Volume 12, Page(s) 629193

    Abstract: Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS), is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive ... ...

    Abstract Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS), is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells activate and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with coronavirus 2019 (COVID-19) for a subgroup of patients. CRS is not unique to the SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, and H7N9). With a comprehensive literature search, we collected changing the cytokine levels from patients upon infection with the viral pathogens mentioned above. We analyzed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. Our curation indicates that the cytokine response induced by SARS-CoV-2 is different compared to other CRS-causing respiratory viruses, as SARS-CoV-2 does not always induce specific cytokines like other coronaviruses or influenza do, such as IL-2, IL-10, IL-4, or IL-5. Comparing the collated cytokine responses caused by the analyzed viruses highlights a SARS-CoV-2-specific dysregulation of the type-I interferon (IFN) response and its downstream cytokine signatures. The map of responses gathered in this study could help specialists identify interventions that alleviate CRS in different diseases and evaluate whether they could be used in the COVID-19 cases.
    MeSH term(s) COVID-19/blood ; COVID-19/immunology ; COVID-19/pathology ; COVID-19/virology ; Cytokine Release Syndrome/blood ; Cytokine Release Syndrome/immunology ; Cytokine Release Syndrome/virology ; Cytokines/blood ; Humans ; Inflammation/immunology ; Influenza A virus/immunology ; Influenza, Human/blood ; Influenza, Human/immunology ; Influenza, Human/virology ; Middle East Respiratory Syndrome Coronavirus/immunology ; Severe acute respiratory syndrome-related coronavirus/immunology ; SARS-CoV-2/immunology ; Severe Acute Respiratory Syndrome/blood ; Severe Acute Respiratory Syndrome/immunology ; Severe Acute Respiratory Syndrome/virology ; Severity of Illness Index
    Chemical Substances Cytokines
    Language English
    Publishing date 2021-03-01
    Publishing country Switzerland
    Document type Research Support, Non-U.S. Gov't ; Systematic Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.629193
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cytokine responsive networks in human colonic epithelial organoids unveil a molecular classification of inflammatory bowel disease.

    Pavlidis, Polychronis / Tsakmaki, Anastasia / Treveil, Agatha / Li, Katherine / Cozzetto, Domenico / Yang, Feifei / Niazi, Umar / Hayee, Bu Hussain / Saqi, Mansoor / Friedman, Joshua / Korcsmaros, Tamas / Bewick, Gavin / Powell, Nick

    Cell reports

    2022  Volume 40, Issue 13, Page(s) 111439

    Abstract: Interactions between the epithelium and the immune system are critical in the pathogenesis of inflammatory bowel disease (IBD). In this study, we mapped the transcriptional landscape of human colonic epithelial organoids in response to different ... ...

    Abstract Interactions between the epithelium and the immune system are critical in the pathogenesis of inflammatory bowel disease (IBD). In this study, we mapped the transcriptional landscape of human colonic epithelial organoids in response to different cytokines responsible for mediating canonical mucosal immune responses. By profiling the transcriptome of human colonic organoids treated with the canonical cytokines interferon gamma, interleukin-13, -17A, and tumor necrosis factor alpha with next-generation sequencing, we unveil shared and distinct regulation patterns of epithelial function by different cytokines. An integrative analysis of cytokine responses in diseased tissue from patients with IBD (n = 1,009) reveals a molecular classification of mucosal inflammation defined by gradients of cytokine-responsive transcriptional signatures. Our systems biology approach detected signaling bottlenecks in cytokine-responsive networks and highlighted their translational potential as theragnostic targets in intestinal inflammation.
    MeSH term(s) Colon/pathology ; Cytokines ; Humans ; Inflammation/pathology ; Inflammatory Bowel Diseases/pathology ; Interferon-gamma/pharmacology ; Interleukin-13 ; Intestinal Mucosa/pathology ; Organoids/pathology ; Tumor Necrosis Factor-alpha
    Chemical Substances Cytokines ; Interleukin-13 ; Tumor Necrosis Factor-alpha ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2022-09-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2022.111439
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Bifidobacterium breve UCC2003 Induces a Distinct Global Transcriptomic Program in Neonatal Murine Intestinal Epithelial Cells.

    Kiu, Raymond / Treveil, Agatha / Harnisch, Lukas C / Caim, Shabhonam / Leclaire, Charlotte / van Sinderen, Douwe / Korcsmaros, Tamas / Hall, Lindsay J

    iScience

    2020  Volume 23, Issue 7, Page(s) 101336

    Abstract: The underlying health-driving mechanisms of Bifidobacterium during early life are not well understood, particularly how this microbiota member may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). We investigated the ... ...

    Abstract The underlying health-driving mechanisms of Bifidobacterium during early life are not well understood, particularly how this microbiota member may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). We investigated the impact of Bifidobacterium breve UCC2003 on the transcriptome of neonatal murine IECs. Small IECs from two-week-old neonatal mice administered B. breve UCC2003 or PBS (control) were subjected to global RNA sequencing, and differentially expressed genes, pathways, and affected cell types were determined. We observed extensive regulation of the IEC transcriptome with ∼4,000 genes significantly up-regulated, including key genes linked with epithelial barrier function. Enrichment of cell differentiation pathways was observed, along with an overrepresentation of stem cell marker genes, indicating an increase in the regenerative potential of the epithelial layer. In conclusion, B. breve UCC2003 plays a central role in driving intestinal epithelium homeostatic development during early life and suggests future avenues for next-stage clinical studies.
    Language English
    Publishing date 2020-07-02
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2020.101336
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Mapping the epithelial-immune cell interactome upon infection in the gut and the upper airways.

    Poletti, Martina / Treveil, Agatha / Csabai, Luca / Gul, Leila / Modos, Dezso / Madgwick, Matthew / Olbei, Marton / Bohar, Balazs / Valdeolivas, Alberto / Turei, Denes / Verstockt, Bram / Triana, Sergio / Alexandrov, Theodore / Saez-Rodriguez, Julio / Stanifer, Megan L / Boulant, Steeve / Korcsmaros, Tamas

    NPJ systems biology and applications

    2022  Volume 8, Issue 1, Page(s) 15

    Abstract: Increasing evidence points towards the key role of the epithelium in the systemic and over-activated immune response to viral infection, including SARS-CoV-2 infection. Yet, how viral infection alters epithelial-immune cell interactions regulating ... ...

    Abstract Increasing evidence points towards the key role of the epithelium in the systemic and over-activated immune response to viral infection, including SARS-CoV-2 infection. Yet, how viral infection alters epithelial-immune cell interactions regulating inflammatory responses, is not well known. Available experimental approaches are insufficient to properly analyse this complex system, and computational predictions and targeted data integration are needed as an alternative approach. In this work, we propose an integrated computational biology framework that models how infection alters intracellular signalling of epithelial cells and how this change impacts the systemic immune response through modified interactions between epithelial cells and local immune cell populations. As a proof-of-concept, we focused on the role of intestinal and upper-airway epithelial infection. To characterise the modified epithelial-immune interactome, we integrated intra- and intercellular networks with single-cell RNA-seq data from SARS-CoV-2 infected human ileal and colonic organoids as well as from infected airway ciliated epithelial cells. This integrated methodology has proven useful to point out specific epithelial-immune interactions driving inflammation during disease response, and propose relevant molecular targets to guide focused experimental analysis.
    MeSH term(s) COVID-19 ; Epithelial Cells ; Humans ; SARS-CoV-2 ; Signal Transduction ; Virus Diseases
    Language English
    Publishing date 2022-05-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2056-7189
    ISSN (online) 2056-7189
    DOI 10.1038/s41540-022-00224-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: ViralLink: An integrated workflow to investigate the effect of SARS-CoV-2 on intracellular signalling and regulatory pathways.

    Treveil, Agatha / Bohar, Balazs / Sudhakar, Padhmanand / Gul, Lejla / Csabai, Luca / Olbei, Marton / Poletti, Martina / Madgwick, Matthew / Andrighetti, Tahila / Hautefort, Isabelle / Modos, Dezso / Korcsmaros, Tamas

    PLoS computational biology

    2021  Volume 17, Issue 2, Page(s) e1008685

    Abstract: The SARS-CoV-2 pandemic of 2020 has mobilised scientists around the globe to research all aspects of the coronavirus virus and its infection. For fruitful and rapid investigation of viral pathomechanisms, a collaborative and interdisciplinary approach is ...

    Abstract The SARS-CoV-2 pandemic of 2020 has mobilised scientists around the globe to research all aspects of the coronavirus virus and its infection. For fruitful and rapid investigation of viral pathomechanisms, a collaborative and interdisciplinary approach is required. Therefore, we have developed ViralLink: a systems biology workflow which reconstructs and analyses networks representing the effect of viruses on intracellular signalling. These networks trace the flow of signal from intracellular viral proteins through their human binding proteins and downstream signalling pathways, ending with transcription factors regulating genes differentially expressed upon viral exposure. In this way, the workflow provides a mechanistic insight from previously identified knowledge of virally infected cells. By default, the workflow is set up to analyse the intracellular effects of SARS-CoV-2, requiring only transcriptomics counts data as input from the user: thus, encouraging and enabling rapid multidisciplinary research. However, the wide-ranging applicability and modularity of the workflow facilitates customisation of viral context, a priori interactions and analysis methods. Through a case study of SARS-CoV-2 infected bronchial/tracheal epithelial cells, we evidence the functionality of the workflow and its ability to identify key pathways and proteins in the cellular response to infection. The application of ViralLink to different viral infections in a context specific manner using different available transcriptomics datasets will uncover key mechanisms in viral pathogenesis.
    MeSH term(s) Algorithms ; Bronchi/virology ; COVID-19/metabolism ; Cluster Analysis ; Computational Biology/methods ; Gene Expression Profiling ; Gene Expression Regulation, Viral ; Host-Pathogen Interactions ; Humans ; Interdisciplinary Research ; Lung/virology ; Models, Statistical ; SARS-CoV-2/pathogenicity ; Signal Transduction ; Systems Biology ; Transcriptome ; Workflow
    Language English
    Publishing date 2021-02-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1008685
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: CytokineLink: A Cytokine Communication Map to Analyse Immune Responses-Case Studies in Inflammatory Bowel Disease and COVID-19.

    Olbei, Marton / Thomas, John P / Hautefort, Isabelle / Treveil, Agatha / Bohar, Balazs / Madgwick, Matthew / Gul, Lejla / Csabai, Luca / Modos, Dezso / Korcsmaros, Tamas

    Cells

    2021  Volume 10, Issue 9

    Abstract: Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence ... ...

    Abstract Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence numerous intracellular processes in the target cells, including the secretion of other cytokines downstream. However, there are no readily available bioinformatic resources that can model cytokine-cytokine interactions. In this effort, we built a communication map between major tissues and blood cells that reveals how cytokine-mediated intercellular networks form during homeostatic conditions. We collated the most prevalent cytokines from the literature and assigned the proteins and their corresponding receptors to source tissue and blood cell types based on enriched consensus RNA-Seq data from the Human Protein Atlas database. To assign more confidence to the interactions, we integrated the literature information on cell-cytokine interactions from two systems of immunology databases, immuneXpresso and ImmunoGlobe. From the collated information, we defined two metanetworks: a cell-cell communication network connected by cytokines; and a cytokine-cytokine interaction network depicting the potential ways in which cytokines can affect the activity of each other. Using expression data from disease states, we then applied this resource to reveal perturbations in cytokine-mediated intercellular signalling in inflammatory and infectious diseases (ulcerative colitis and COVID-19, respectively). For ulcerative colitis, with CytokineLink, we demonstrated a significant rewiring of cytokine-mediated intercellular communication between non-inflamed and inflamed colonic tissues. For COVID-19, we were able to identify cell types and cytokine interactions following SARS-CoV-2 infection, highlighting important cytokine interactions that might contribute to severe illness in a subgroup of patients. Such findings have the potential to inform the development of novel, cytokine-targeted therapeutic strategies. CytokineLink is freely available for the scientific community through the NDEx platform and the project github repository.
    MeSH term(s) COVID-19/immunology ; Cell Communication ; Colitis, Ulcerative/immunology ; Colitis, Ulcerative/pathology ; Cytokines/metabolism ; Databases, Genetic ; Humans ; Immunity ; Inflammatory Bowel Diseases/immunology ; Inflammatory Bowel Diseases/pathology ; Signal Transduction
    Chemical Substances Cytokines
    Language English
    Publishing date 2021-08-29
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10092242
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Bifidobacterium breve UCC2003 Induces a Distinct Global Transcriptomic Program in Neonatal Murine Intestinal Epithelial Cells

    Raymond Kiu / Agatha Treveil / Lukas C. Harnisch / Shabhonam Caim / Charlotte Leclaire / Douwe van Sinderen / Tamas Korcsmaros / Lindsay J. Hall

    iScience, Vol 23, Iss 7, Pp 101336- (2020)

    2020  

    Abstract: Summary: The underlying health-driving mechanisms of Bifidobacterium during early life are not well understood, particularly how this microbiota member may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). We ... ...

    Abstract Summary: The underlying health-driving mechanisms of Bifidobacterium during early life are not well understood, particularly how this microbiota member may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). We investigated the impact of Bifidobacterium breve UCC2003 on the transcriptome of neonatal murine IECs. Small IECs from two-week-old neonatal mice administered B. breve UCC2003 or PBS (control) were subjected to global RNA sequencing, and differentially expressed genes, pathways, and affected cell types were determined. We observed extensive regulation of the IEC transcriptome with ∼4,000 genes significantly up-regulated, including key genes linked with epithelial barrier function. Enrichment of cell differentiation pathways was observed, along with an overrepresentation of stem cell marker genes, indicating an increase in the regenerative potential of the epithelial layer. In conclusion, B. breve UCC2003 plays a central role in driving intestinal epithelium homeostatic development during early life and suggests future avenues for next-stage clinical studies.
    Keywords Microbiology ; Microbiome ; Transcriptomics ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Bifidobacterium breve

    Püngel, Deborah / Treveil, Agatha / Dalby, Matthew J / Caim, Shabhonam / Colquhoun, Ian J / Booth, Catherine / Ketskemety, Jennifer / Korcsmaros, Tamas / van Sinderen, Douwe / Lawson, Melissa Ae / Hall, Lindsay J

    Nutrients

    2020  Volume 12, Issue 4

    Abstract: Background: Bifidobacterium: Methods: Differential gene expression and growth characteristics were determined for each strain; : Results: Transcriptomics of EPS mutant vs. : Conclusions: These data indicate ... ...

    Abstract Background: Bifidobacterium
    Methods: Differential gene expression and growth characteristics were determined for each strain;
    Results: Transcriptomics of EPS mutant vs.
    Conclusions: These data indicate that
    MeSH term(s) Bifidobacterium breve/genetics ; Bifidobacterium breve/growth & development ; Bifidobacterium breve/physiology ; Colon/metabolism ; Colon/microbiology ; Dietary Supplements ; Gastrointestinal Microbiome/physiology ; Gene Expression ; Host Microbial Interactions/physiology ; Humans ; Infant ; Infant Health ; Mutation ; Polysaccharides, Bacterial/genetics ; Polysaccharides, Bacterial/metabolism ; RNA, Ribosomal, 16S/genetics
    Chemical Substances Polysaccharides, Bacterial ; RNA, Ribosomal, 16S ; exopolysaccharide, Bacillus
    Language English
    Publishing date 2020-03-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu12040948
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Mapping the epithelial–immune cell interactome upon infection in the gut and the upper airways

    Martina Poletti / Agatha Treveil / Luca Csabai / Leila Gul / Dezso Modos / Matthew Madgwick / Marton Olbei / Balazs Bohar / Alberto Valdeolivas / Denes Turei / Bram Verstockt / Sergio Triana / Theodore Alexandrov / Julio Saez-Rodriguez / Megan L. Stanifer / Steeve Boulant / Tamas Korcsmaros

    npj Systems Biology and Applications, Vol 8, Iss 1, Pp 1-

    2022  Volume 19

    Abstract: Abstract Increasing evidence points towards the key role of the epithelium in the systemic and over-activated immune response to viral infection, including SARS-CoV-2 infection. Yet, how viral infection alters epithelial–immune cell interactions ... ...

    Abstract Abstract Increasing evidence points towards the key role of the epithelium in the systemic and over-activated immune response to viral infection, including SARS-CoV-2 infection. Yet, how viral infection alters epithelial–immune cell interactions regulating inflammatory responses, is not well known. Available experimental approaches are insufficient to properly analyse this complex system, and computational predictions and targeted data integration are needed as an alternative approach. In this work, we propose an integrated computational biology framework that models how infection alters intracellular signalling of epithelial cells and how this change impacts the systemic immune response through modified interactions between epithelial cells and local immune cell populations. As a proof-of-concept, we focused on the role of intestinal and upper-airway epithelial infection. To characterise the modified epithelial–immune interactome, we integrated intra- and intercellular networks with single-cell RNA-seq data from SARS-CoV-2 infected human ileal and colonic organoids as well as from infected airway ciliated epithelial cells. This integrated methodology has proven useful to point out specific epithelial–immune interactions driving inflammation during disease response, and propose relevant molecular targets to guide focused experimental analysis.
    Keywords Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: CytokineLink

    Marton Olbei / John P. Thomas / Isabelle Hautefort / Agatha Treveil / Balazs Bohar / Matthew Madgwick / Lejla Gul / Luca Csabai / Dezso Modos / Tamas Korcsmaros

    Cells, Vol 10, Iss 2242, p

    A Cytokine Communication Map to Analyse Immune Responses—Case Studies in Inflammatory Bowel Disease and COVID-19

    2021  Volume 2242

    Abstract: Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence ... ...

    Abstract Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence numerous intracellular processes in the target cells, including the secretion of other cytokines downstream. However, there are no readily available bioinformatic resources that can model cytokine–cytokine interactions. In this effort, we built a communication map between major tissues and blood cells that reveals how cytokine-mediated intercellular networks form during homeostatic conditions. We collated the most prevalent cytokines from the literature and assigned the proteins and their corresponding receptors to source tissue and blood cell types based on enriched consensus RNA-Seq data from the Human Protein Atlas database. To assign more confidence to the interactions, we integrated the literature information on cell–cytokine interactions from two systems of immunology databases, immuneXpresso and ImmunoGlobe. From the collated information, we defined two metanetworks: a cell–cell communication network connected by cytokines; and a cytokine–cytokine interaction network depicting the potential ways in which cytokines can affect the activity of each other. Using expression data from disease states, we then applied this resource to reveal perturbations in cytokine-mediated intercellular signalling in inflammatory and infectious diseases (ulcerative colitis and COVID-19, respectively). For ulcerative colitis, with CytokineLink, we demonstrated a significant rewiring of cytokine-mediated intercellular communication between non-inflamed and inflamed colonic tissues. For COVID-19, we were able to identify cell types and cytokine interactions following SARS-CoV-2 infection, highlighting important cytokine interactions that might contribute to severe illness in a subgroup of patients. Such findings have the potential to inform the development of novel, ...
    Keywords cytokine ; network ; resource ; Cytoscape ; NDEx ; COVID-19 ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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