Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1193
N. Bartlett, T. Williams, S. Loo, J. Girkin
Rationale We have previously reported blocking the IL-25 receptor (IL-17RB) prevented viral increased allergic airways inflammation and this was associated with reduced lung viral load. To investigate IL-25 regulation of airway anti-viral immunity we hypothesised that IL-25 directly inhibits airway epithelial cell (AEC) type I/III interferon expression and antibody blockade of IL-25 in vivo boosts lung interferon expression and reduces lung viral load in parallel with reduced type 2 airway inflammation. Methods In vitro Immunofluorescence was used to visualise epithelial IL-25 and IL- 17RB proteins in endobronchial biopsies from patients with asthma and healthy subjects and in AEC differentiated at ALI. AEC from n = 14 donors with asthma were differentiated at the air-liquid interface (ALI) and infected with RV-A1, MOI=0.1. A subset of AECs was treated with anti-IL-25 mAb (LNR125) before infecting with RV-A1 or human coronavirus 229E. Differentiated AEC from healthy donors were treated with recombinant IL-25 protein and infected with RV-A1. Nanostring immune transcriptomic data expressed as digital mRNA counts for exact copy number or was expressed as log2 fold change ratio against -log10 Bejamini-Yekutieli-corrected p-values. In vivo 6- 8-week-old, BALB/c mice sensitised and intranasally challenged daily for 3 days with ovalbumin to induced allergic airways disease. A single subcutaneous injection of 250 μg LNR125 was administered during ovalbumin challenge. Mice were then infected i.n. with RV-A1, 6 hours after final allergen challenge. On day 1 and day 7 post-infection, BAL were collected, lung lobe tissue was collected for viral RNA and cytokine expression. Results IL-25 and IL-17RB were constitutively expressed at the apical surface of airway epithelium in biopsies and AEC cultures. RV infection increased IL-25 expression by AEC from asthmatic donors. LNR125 treatment reduced IL-25 mRNA and significantly increased RV induced IFN-β a and IFN-λ protein expression and this was confirmed by Nanostring transcriptomic analyses which also identified down-regulated type-2 immune genes CCL26 (eotaxin 3) and IL1RL1(IL-33 receptor). LN125 treatment also increased IFN-λ expression by 229E-infected differentiated AECs. IL-25 treatment increased viral load associated with 50% reduced expression of IFN-β and CXCL10 and 75% reduced IFN-λ. Allergen challenged, RV-infected mice treated with LNR125 had significantly increased BAL IFN-β protein and 60% reduction in lung viral load associated with reduced IL-25, IL-4, IL-5 and IL-13 BAL proteins compared to controls. Conclusion IL-25-induced inflammation combined with suppression of AEC anti-viral immunity identify IL-25 as a central mediator of viral asthma exacerbations and therefore a target for mAb-based treatment.
{"title":"IL-25 Inhibits Airway Anti-Viral Immunity and Promotes Virus Exacerbation of Allergic Airways Disease","authors":"N. Bartlett, T. Williams, S. Loo, J. Girkin","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1193","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1193","url":null,"abstract":"Rationale We have previously reported blocking the IL-25 receptor (IL-17RB) prevented viral increased allergic airways inflammation and this was associated with reduced lung viral load. To investigate IL-25 regulation of airway anti-viral immunity we hypothesised that IL-25 directly inhibits airway epithelial cell (AEC) type I/III interferon expression and antibody blockade of IL-25 in vivo boosts lung interferon expression and reduces lung viral load in parallel with reduced type 2 airway inflammation. Methods In vitro Immunofluorescence was used to visualise epithelial IL-25 and IL- 17RB proteins in endobronchial biopsies from patients with asthma and healthy subjects and in AEC differentiated at ALI. AEC from n = 14 donors with asthma were differentiated at the air-liquid interface (ALI) and infected with RV-A1, MOI=0.1. A subset of AECs was treated with anti-IL-25 mAb (LNR125) before infecting with RV-A1 or human coronavirus 229E. Differentiated AEC from healthy donors were treated with recombinant IL-25 protein and infected with RV-A1. Nanostring immune transcriptomic data expressed as digital mRNA counts for exact copy number or was expressed as log2 fold change ratio against -log10 Bejamini-Yekutieli-corrected p-values. In vivo 6- 8-week-old, BALB/c mice sensitised and intranasally challenged daily for 3 days with ovalbumin to induced allergic airways disease. A single subcutaneous injection of 250 μg LNR125 was administered during ovalbumin challenge. Mice were then infected i.n. with RV-A1, 6 hours after final allergen challenge. On day 1 and day 7 post-infection, BAL were collected, lung lobe tissue was collected for viral RNA and cytokine expression. Results IL-25 and IL-17RB were constitutively expressed at the apical surface of airway epithelium in biopsies and AEC cultures. RV infection increased IL-25 expression by AEC from asthmatic donors. LNR125 treatment reduced IL-25 mRNA and significantly increased RV induced IFN-β a and IFN-λ protein expression and this was confirmed by Nanostring transcriptomic analyses which also identified down-regulated type-2 immune genes CCL26 (eotaxin 3) and IL1RL1(IL-33 receptor). LN125 treatment also increased IFN-λ expression by 229E-infected differentiated AECs. IL-25 treatment increased viral load associated with 50% reduced expression of IFN-β and CXCL10 and 75% reduced IFN-λ. Allergen challenged, RV-infected mice treated with LNR125 had significantly increased BAL IFN-β protein and 60% reduction in lung viral load associated with reduced IL-25, IL-4, IL-5 and IL-13 BAL proteins compared to controls. Conclusion IL-25-induced inflammation combined with suppression of AEC anti-viral immunity identify IL-25 as a central mediator of viral asthma exacerbations and therefore a target for mAb-based treatment.","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125770540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1215
M. A. Torres Acosta, S. Weinberg, K. Helmin, L. Morales-Nebreda, C. P. Reyes Flores, A. M. Joudi, B. D. Singer
{"title":"AMP-Activated Protein Kinase Is Required for Treg Cell Function During Microenvironmental Stress","authors":"M. A. Torres Acosta, S. Weinberg, K. Helmin, L. Morales-Nebreda, C. P. Reyes Flores, A. M. Joudi, B. D. Singer","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1215","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1215","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131422009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1201
V. Kulkarni, Y. Wang, J. Pantaleón García, S. Evans
{"title":"Pam2-ODN Induces Protection Against Acute Bacterial Pneumonia by Redox Based Activation of Lung Epithelial STAT3","authors":"V. Kulkarni, Y. Wang, J. Pantaleón García, S. Evans","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1201","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1201","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131855134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1209
J. Girkin, N.E. Bryant, S. Loo, C. Demaison, F. Mercuri, N. Bartlett
{"title":"TLR2/6 Agonist Treatment Enhances Antiviral Innate Immune Responses in a Novel Mouse Coronavirus Respiratory Infection Model","authors":"J. Girkin, N.E. Bryant, S. Loo, C. Demaison, F. Mercuri, N. Bartlett","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1209","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1209","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"28 2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133593592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1194
J. Pantaléon-García, L.M. Pacheco Hernandez, V. Kulkarni, M. Longmire, Y. Wang, S. Evans
Rationale: The SARS-CoV-2 pandemic has underscored the need for novel anti-infectious strategies, including host-directed therapeutics, against existing and emerging respiratory pathogens. We have reported that an aerosolized therapeutic comprised of a Toll-like receptor (TLR)-2/6 agonist, Pam2CSK4, and a TLR-9 agonist, ODN M362, stimulate pathogen-agnostic innate immune responses in lung epithelial cells. This therapeutic (“Pam2-ODN”) promotes synergistic microbicidal activity and host survival benefit against pneumonia caused by a wide range of pathogens. Here, we study the immunomodulatory signaling mechanisms required to effect this inducible epithelial resistance. Methods: Bioinformatic analysis of transcriptional responses from human and mouse lung epithelium al cells to influenza A H1N1 or SARS-CoV-2 (GSE147507) or Pam2-ODN (GSE289984, GSE26864) were analyzed using R and IPA software to identify essential transcription factors (TFs). Lung cell population dynamics were studied for TFs related to Pam2-ODN immunomodulatory signaling using high-throughput imaging flow cytometry (IFC). Human or mouse lung epithelial cells were stimulated with PBS or Pam2-ODN and single or dual inhibitors of TFs before challeng with influenza A H3N2 (IAV) or coronavirus OC43 (CoV) to compare the epithelium-specific transcriptional control of relevant TFs using in-cell western blotting, IFC and hemagglutination for viral burdens. Results: Functional enrichment analysis revealed RelA and cJUN to be major immunomodulatory TFs of Pam2-ODN and activators of leukocyte- and epithelial-derived antiviral immune mechanisms targeting replication of influenza A and SARS-CoV-2. Cell population dynamics studied from mouse lungs confirmed activation of RelA and cJUN in CD45+, EpCAM- leukocytes and in CD45-, EpCAM+ epithelial cells, with predominant activation of the lung epithelium and none or minimal activation of structural cell populations such as fibroblasts or endothelial cells. Studies of epithelium-specific signaling in vitro revealed co-activation of RelA-(pS536) and cJun- (pS73) TFs with Pam2-ODN, and earlier onset of cJUN phosphorylation and nuclear translocation with Pam2-ODN after IAV or CoV infection. Individual or dual inhibition of RelA and/or cJUN activity in vitro disrupted the antiviral activity of Pam2-ODN of IAV infected cells. Conclusion: Pam2-ODN induces unique, pathogen-agnostic protective signaling in lung epithelial cells that involves cooperative activation of RelA and cJUN. This combined TF signaling mechanism is not observed in other structural lung cell populations after Pam2-ODN exposure. Further, the phospho-regulation dynamics of RelA and cJUN are not replicated by IAV or CoV infection alone, suggesting a novel therapeutic process that can be leveraged to protect individuals against pneumonia. (Figure Presented).
{"title":"Inducible Resistance Against Viral Pneumonia Requires a Lung Epithelium-Specific Transcriptional Interaction Between RelA and cJUN","authors":"J. Pantaléon-García, L.M. Pacheco Hernandez, V. Kulkarni, M. Longmire, Y. Wang, S. Evans","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1194","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1194","url":null,"abstract":"Rationale: The SARS-CoV-2 pandemic has underscored the need for novel anti-infectious strategies, including host-directed therapeutics, against existing and emerging respiratory pathogens. We have reported that an aerosolized therapeutic comprised of a Toll-like receptor (TLR)-2/6 agonist, Pam2CSK4, and a TLR-9 agonist, ODN M362, stimulate pathogen-agnostic innate immune responses in lung epithelial cells. This therapeutic (“Pam2-ODN”) promotes synergistic microbicidal activity and host survival benefit against pneumonia caused by a wide range of pathogens. Here, we study the immunomodulatory signaling mechanisms required to effect this inducible epithelial resistance. Methods: Bioinformatic analysis of transcriptional responses from human and mouse lung epithelium al cells to influenza A H1N1 or SARS-CoV-2 (GSE147507) or Pam2-ODN (GSE289984, GSE26864) were analyzed using R and IPA software to identify essential transcription factors (TFs). Lung cell population dynamics were studied for TFs related to Pam2-ODN immunomodulatory signaling using high-throughput imaging flow cytometry (IFC). Human or mouse lung epithelial cells were stimulated with PBS or Pam2-ODN and single or dual inhibitors of TFs before challeng with influenza A H3N2 (IAV) or coronavirus OC43 (CoV) to compare the epithelium-specific transcriptional control of relevant TFs using in-cell western blotting, IFC and hemagglutination for viral burdens. Results: Functional enrichment analysis revealed RelA and cJUN to be major immunomodulatory TFs of Pam2-ODN and activators of leukocyte- and epithelial-derived antiviral immune mechanisms targeting replication of influenza A and SARS-CoV-2. Cell population dynamics studied from mouse lungs confirmed activation of RelA and cJUN in CD45+, EpCAM- leukocytes and in CD45-, EpCAM+ epithelial cells, with predominant activation of the lung epithelium and none or minimal activation of structural cell populations such as fibroblasts or endothelial cells. Studies of epithelium-specific signaling in vitro revealed co-activation of RelA-(pS536) and cJun- (pS73) TFs with Pam2-ODN, and earlier onset of cJUN phosphorylation and nuclear translocation with Pam2-ODN after IAV or CoV infection. Individual or dual inhibition of RelA and/or cJUN activity in vitro disrupted the antiviral activity of Pam2-ODN of IAV infected cells. Conclusion: Pam2-ODN induces unique, pathogen-agnostic protective signaling in lung epithelial cells that involves cooperative activation of RelA and cJUN. This combined TF signaling mechanism is not observed in other structural lung cell populations after Pam2-ODN exposure. Further, the phospho-regulation dynamics of RelA and cJUN are not replicated by IAV or CoV infection alone, suggesting a novel therapeutic process that can be leveraged to protect individuals against pneumonia. (Figure Presented).","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"65 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134087951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1211
M. El Sheikh, I. Angers, S. Qureshi
{"title":"Genetic Regulation of the Host Immune Response to Cryptococcus Neoformans Infection","authors":"M. El Sheikh, I. Angers, S. Qureshi","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1211","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1211","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133891064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1210
K. Park, I. Advani, J.A. Masso Silva, J. Pham, L. C. Crotty Alexander
{"title":"The Effects of E-cigarette Use, Cigarette Smoke and Dual-Use of Both on Murine Susceptibility to Streptococcal Pneumonia","authors":"K. Park, I. Advani, J.A. Masso Silva, J. Pham, L. C. Crotty Alexander","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1210","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1210","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128884272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1195
L. M. Rich, E. Vanderwall, K. Barrow, M. White, D. Jackson, M. Altman, J. Debley
{"title":"Bronchial Epithelial ACE-2 and SARS-CoV-2 Replication in Asthmatic and Healthy Children","authors":"L. M. Rich, E. Vanderwall, K. Barrow, M. White, D. Jackson, M. Altman, J. Debley","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1195","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1195","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115009526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1216
C. Langouet-Astrie, K. Oshima, S. McMurty, Y. Yang, J. Kwiecinski, J. Liu, A. Horswill, E. Schmidt
{"title":"The Influenza-Injured Lung Microenvironment Promotes Methicillin-Resistant Staphylococcus Aureus (MRSA) Virulence, Leading to Secondary Pneumonia","authors":"C. Langouet-Astrie, K. Oshima, S. McMurty, Y. Yang, J. Kwiecinski, J. Liu, A. Horswill, E. Schmidt","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1216","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1216","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132197111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1200
M. Maishan, H. Taenaka, S. Matsumoto, X. Fang, S. Sridhar, R. Lucas, M. Matthay
{"title":"Targeted Activation of the Apical Epithelial Sodium Channel Alpha Subunit Preserves Alveolar Fluid Clearance in Bacterial Pneumonia (S. pneumoniae) in the Ex Vivo Perfused Human Lung","authors":"M. Maishan, H. Taenaka, S. Matsumoto, X. Fang, S. Sridhar, R. Lucas, M. Matthay","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1200","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1200","url":null,"abstract":"","PeriodicalId":307658,"journal":{"name":"A28. THE HOST DELIVERS","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129905388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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