NPJ Vaccines最新文献

{"title":"A modified mycobacterial growth inhibition assay for the functional assessment of vaccine-mediated immunity.","authors":"Emil Joseph Vergara, Andy Cano Tran, Matthew J Paul, Thomas Harrison, Andrea Cooper, Rajko Reljic","doi":"10.1038/s41541-024-00906-z","DOIUrl":"10.1038/s41541-024-00906-z","url":null,"abstract":"<p><p>The Mycobacterial growth inhibition assay (MGIA) is an ex-vivo assay used to measure the overall functional immune response elicited by infection or vaccination. In tuberculosis (TB) vaccine development, MGIA is a potentially important tool for preclinical evaluation of early-stage vaccine candidates to complement existing assays, and to potentially reduce the need for lengthy and costly pathogenic Mycobacterium tuberculosis (Mtb) animal challenge experiments. The conventional method of MGIA in mice entails directly infecting mixed cell cultures, most commonly splenocytes, from immunised mice with mycobacteria. However, this direct infection of mixed cell populations may yield unreliable results and lacks sufficient sensitivity to discriminate well between different vaccines due to the low number of mycobacteria-permissive cells. Here, we modified the assay by inclusion of mycobacteria-infected congenic murine macrophage cell lines as the target cells, and by measuring the total number of killed cells rather than the relative reduction between different groups. Thus, using splenocytes from Mycobacterium bovis BCG immunised mice, and J774 and MH-S (BALB/c background) or BL/6-M (C57Bl/6 background) macrophage cell lines, we demonstrated that the modified assay resulted in at least 26-fold greater mycobacterial killing per set quantity of splenocytes as compared to the conventional method. This increased sensitivity of measuring mycobacterial killing was confirmed using both the standard culture forming unit (CFU) assay and luminescence readings of luciferase-tagged virulent and avirulent mycobacteria. We propose that the modified MGIA can be used as a highly calibrated tool for quantitating the killing capacity of immune cells in preclinical evaluation of vaccine candidates for TB.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myocarditis associated with COVID-19 vaccination.","authors":"Alessandra Buoninfante, Arno Andeweg, Georgy Genov, Marco Cavaleri","doi":"10.1038/s41541-024-00893-1","DOIUrl":"https://doi.org/10.1038/s41541-024-00893-1","url":null,"abstract":"<p><p>Following the start of the COVID-19 vaccination campaign, the adverse events of myocarditis and pericarditis were linked mainly to mRNA COVID-19 vaccines by the regulatory authorities worldwide. COVID-19 vaccines have been administered to several million people and the risk of myocarditis post COVID-19 vaccination has been characterised in great detail. At the present time the research data available are scarce and there is still no clear understanding of the biological mechanism/s responsible for this disease. This manuscript provides a concise overview of the epidemiology of myocarditis and the most prominent mechanistic insights in the pathophysiology of the disease. Most importantly it underscores the needed next steps in the research agenda required to characterize the pathophysiology of this disease post-COVID-19 vaccination. Finally, it shares our perspectives and considerations for public health.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Development of an anti-tauopathy mucosal vaccine specifically targeting pathologic conformers.","authors":"Wenzhi Tan, Jayalakshmi Thiruppathi, Seol Hee Hong, Sao Puth, Sophea Pheng, Bo-Ram Mun, Won-Seok Choi, Kyung-Hwa Lee, Hyun-Sun Park, Duc Tien Nguyen, Min-Cheol Lee, Kwangjoon Jeong, Jin Hai Zheng, Young Kim, Shee Eun Lee, Joon Haeng Rhee","doi":"10.1038/s41541-024-00910-3","DOIUrl":"https://doi.org/10.1038/s41541-024-00910-3","url":null,"abstract":"","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The direct effect of SARS-CoV-2 virus vaccination on human ovarian granulosa cells explains menstrual irregularities.","authors":"Hadas Bar-Joseph, Yael Raz, Anat Eldar-Boock, Nadav Michaan, Yoel Angel, Esther Saiag, Luba Nemerovsky, Ido Ben-Ami, Ruth Shalgi, Dan Grisaru","doi":"10.1038/s41541-024-00911-2","DOIUrl":"10.1038/s41541-024-00911-2","url":null,"abstract":"<p><p>Following administration of the SARS-CoV-2 vaccine, many women worldwide reported short-term menstrual irregularities. Although menstrual bleeding, \"the fifth vital sign\", is experienced by more than 300 million people on any given day worldwide, these changes were only partially studied. Irregular periods are important well beyond fertility and the discomfort they impose; they are associated with the risk of cardiovascular morbidity, chronic diseases, and premature mortality. Pre-clinical examination of the vaccine polymeric envelope indicates its accumulation in the ovaries. The somatic endocrine cells of the ovarian follicle - the granulosa cells (GCs)-participate in the strict hypothalamic-pituitary-ovarian (HPO) feedback loop that governs the menstrual cycle via endocrine and paracrine regulators, as AMH and Inhibins. We aimed to unravel the direct effect of the COVID-19 vaccine on GCs and link their post-vaccine activity to changes in menstrual patterns. Human primary GCs exposed in-vitro to the Pfizer COVID-19 vaccine BNT162b2, demonstrated no change in their viability but altered mRNA transcripts, specifically of the regulatory key factors: InhibinB was upregulated, whereas AMH was downregulated. We further examined pre- and post-vaccination blood samples from individual women and found a 2-3 folds change in the post-vaccination FSH/InhibinB protein level ratio, compared to their pre-vaccination values. This altered expression of InhibinB could significantly impact the HPO axis in vaccinated women and may ultimately influence the endometrium cyclicity, manifested clinically by the commonly reported changes in menstrual bleeding patterns.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A safe and potentiated multi-type HPV L2-E7 nanoparticle vaccine with combined prophylactic and therapeutic activity.","authors":"Xueer Zhao, Yueru Zhang, Oscar Trejo-Cerro, Ecem Kaplan, Zhe Li, Femke Albertsboer, Neyla El Hammiri, Filipe Colaço Mariz, Lawrence Banks, Simone Ottonello, Martin Müller","doi":"10.1038/s41541-024-00914-z","DOIUrl":"10.1038/s41541-024-00914-z","url":null,"abstract":"<p><p>Persistent infection with high-risk human papillomavirus (HPV) is widely recognized as the primary cause of cervical and other malignant cancers. There are six licensed prophylactic vaccines available against HPV, but none of them shows any significant therapeutic effect on pre-existing infections or lesions. Thus, a prophylactic vaccine also endowed with therapeutic activity would afford protection regardless of the vaccine recipients HPV-infection status. Here, we describe the refinement and further potentiation of a dual-purpose HPV nanoparticle vaccine (hereafter referred to as cPANHPVAX) relying on eight different HPV L2 peptide epitopes and on the E7 oncoantigens from HPV16 and 18. cPANHPVAX not only induces anti-HPV16 E7 cytotoxic T-cell responses in C57BL/6 mice, but also anti-HPV18 E7 T-cell responses in transgenic mice with the A2.DR1 haplotype. These cytotoxic responses add up to a potent, broad-coverage humoral (HPV-neutralizing) response. cPANHPVAX safety was further improved by deletion of the pRb-binding domains of E7. Our dual-purpose vaccine holds great potential for clinical translation as an immune-treatment capable of targeting active infections as well as established HPV-related malignancies, thus benefiting both uninfected and infected individuals.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic prime mucosal boost significantly increases protective efficacy of bivalent RSV influenza viral vectored vaccine.","authors":"Cameron Bissett, Sandra Belij-Rammerstorfer, Marta Ulaszewska, Holly Smith, Reshma Kailath, Susan Morris, Claire Powers, Sarah Sebastian, Hannah R Sharpe, Elizabeth R Allen, Ziyin Wang, Robert F Cunliffe, Hadijatou J Sallah, Alexandra J Spencer, Sarah Gilbert, John S Tregoning, Teresa Lambe","doi":"10.1038/s41541-024-00912-1","DOIUrl":"10.1038/s41541-024-00912-1","url":null,"abstract":"<p><p>Although licensed vaccines against influenza virus have been successful in reducing pathogen-mediated disease, they have been less effective at preventing viral infection of the airways and current seasonal updates to influenza vaccines do not always successfully accommodate viral drift. Most licensed influenza and recently licensed RSV vaccines are administered via the intramuscular route. Alternative immunisation strategies, such as intranasal vaccinations, and \"prime-pull\" regimens, may deliver a more sterilising form of protection against respiratory viruses. A bivalent ChAdOx1-based vaccine (ChAdOx1-NP + M1-RSVF) encoding conserved nucleoprotein and matrix 1 proteins from influenza A virus and a modified pre-fusion stabilised RSV A F protein, was designed, developed and tested in preclinical animal models. The aim was to induce broad, cross-protective tissue-resident T cells against heterotypic influenza viruses and neutralising antibodies against RSV in the respiratory mucosa and systemically. When administered via an intramuscular prime-intranasal boost (IM-IN) regimen in mice, superior protection was generated against challenge with either RSV A, Influenza A H3N2 or H1N1. These results support further clinical development of a pan influenza & RSV vaccine administered in a prime-pull regimen.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A gH/gL-encoding replicon vaccine elicits neutralizing antibodies that protect humanized mice against EBV challenge.","authors":"Kristina R Edwards, Harman Malhi, Karina Schmidt, Amelia R Davis, Leah J Homad, Nikole L Warner, Crystal B Chhan, Samuel C Scharffenberger, Karen Gaffney, Troy Hinkley, Nicole B Potchen, Jing Yang Wang, Jason Price, M Juliana McElrath, James Olson, Neil P King, Jennifer M Lund, Zoe Moodie, Jesse H Erasmus, Andrew T McGuire","doi":"10.1038/s41541-024-00907-y","DOIUrl":"10.1038/s41541-024-00907-y","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) is associated with several malignancies, neurodegenerative disorders and is the causative agent of infectious mononucleosis. A vaccine that prevents EBV-driven morbidity and mortality remains an unmet need. EBV is orally transmitted, infecting both B cells and epithelial cells. Several virally encoded proteins are involved in entry. The gH/gL glycoprotein complex is essential for infectivity irrespective of cell type, while gp42 is essential for infection of B cells. gp350 promotes viral attachment by binding to CD21 or CD35 and is the most abundant glycoprotein on the virion. gH/gL, gp42 and gp350, are known targets of neutralizing antibodies and therefore relevant immunogens for vaccine development. Here, we developed and optimized the delivery of several alphavirus-derived replicon RNA (repRNA) vaccine candidates encoding gH/gL, gH/gL/gp42 or gp350 delivered by a cationic nanocarrier termed LION™. The lead candidate, encoding full-length gH/gL, elicited high titers of neutralizing antibodies that persisted for at least 8 months and a vaccine-specific CD8⁺ T cell response. Transfer of vaccine-elicited IgG protected humanized mice from EBV-driven tumor formation and death following high-dose viral challenge. These data demonstrate that LION/repRNA-gH/gL is an ideal candidate vaccine for preventing EBV infection and/or related malignancies in humans.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A replication-deficient gammaherpesvirus vaccine protects mice from lytic disease and reduces latency establishment.","authors":"Wesley A Bland, Dipanwita Mitra, Shana Owens, Kyle McEvoy, Chad H Hogan, Luciarita Boccuzzi, Varvara Kirillov, Thomas J Meyer, Camille Khairallah, Brian S Sheridan, J Craig Forrest, Laurie T Krug","doi":"10.1038/s41541-024-00908-x","DOIUrl":"10.1038/s41541-024-00908-x","url":null,"abstract":"<p><p>Gammaherpesviruses are oncogenic viruses that establish lifelong infections and are significant causes of morbidity and mortality. Vaccine strategies to limit gammaherpesvirus infection and disease are in development, but there are no FDA-approved vaccines for Epstein-Barr or Kaposi sarcoma herpesvirus. As a new approach to gammaherpesvirus vaccination, we developed and tested a replication-deficient virus (RDV) platform, using murine gammaherpesvirus 68 (MHV68), a well-established mouse model for gammaherpesvirus pathogenesis studies and preclinical therapeutic evaluations. We employed codon-shuffling-based complementation to generate revertant-free RDV lacking expression of the essential replication and transactivator protein encoded by ORF50 to arrest viral gene expression early after de novo infection. Inoculation with RDV-50.stop exposes the host to intact virion particles and leads to limited lytic gene expression in infected cells yet does not produce additional infectious particles. Prime-boost vaccination of mice with RDV-50.stop elicited virus-specific neutralizing antibody and effector T cell responses in the lung and spleen. In contrast to vaccination with heat-inactivated WT MHV68, vaccination with RDV-50.stop resulted in a near complete abolishment of virus replication in the lung 7 days post-challenge and reduction of latency establishment in the spleen 16 days post-challenge with WT MHV68. Ifnar1^-/- mice, which lack the type I interferon receptor, exhibit severe disease and high mortality upon infection with WT MHV68. RDV-50.stop vaccination of Ifnar1^-/- mice prevented wasting and mortality upon challenge with WT MHV68. These results demonstrate that prime-boost vaccination with a gammaherpesvirus that is unable to undergo lytic replication offers protection against acute replication, impairs the establishment of latency, and prevents severe disease upon the WT virus challenge. Our study also reveals that the ability of a gammaherpesvirus to persist in vivo despite potent pre-existing immunity is an obstacle to obtaining sterilizing immunity.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T cell independent antibody responses with class switch and memory using peptides anchored on liposomes.","authors":"Ásdís Hjálmsdóttir, Fabio Hasler, Ying Waeckerle-Men, Agathe Duda, María Pilar López-Deber, Maria Pihlgren, Marija Vukicevic, Thomas M Kündig, Pål Johansen","doi":"10.1038/s41541-024-00902-3","DOIUrl":"10.1038/s41541-024-00902-3","url":null,"abstract":"<p><p>Vaccines generally require T lymphocytes for B-cell activation and immunoglobulin class switching in response to peptide or protein antigens. In the absence of T cells, limited IgG class switch takes place, germinal centers are short-lived, and the B cells lack memory. Here, immunization of mice with liposomes containing 15mer peptides and monophosphoryl lipid A (MPLA) as adjuvant, induced T-cell independent (TI) IgG class switch within three days, as well as germinal center formation. The antibody responses were long-lived, strictly dependent on Toll-like receptor 4 (TLR4) signaling, partly dependent on Bruton's tyrosine kinase (BTK) signal transmission, and independent of signaling through T-cell receptors, MHC class II and inflammasome. The antibody response showed characteristics of both TI type 1 and TI type 2. All IgG subclasses could be boosted months after primary immunization, and the biological function of the secreted antibodies was demonstrated in murine models of allergic anaphylaxis and of bacterial infection. Moreover, antibody responses after immunization with peptide- and MPLA-loaded liposomes could be triggered in neonatal mice and in mice receiving immune-suppressants. This study demonstrates T-cell independent endogenous B-cell memory and recall responses in vivo using a peptide antigen. The stimulation of these antibody responses required a correct and dense assembly and administration of peptide and adjuvant on the surface of liposomes. In the future, TI vaccines may prove beneficial in pathological conditions in which T-cell immunity is compromised through disease or medicines or when rapid, antibody-mediated immune protection is needed.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcifediol boosts efficacy of ChAdOx1 nCoV-19 vaccine by upregulating genes promoting memory T cell responses.","authors":"Himanshu Singh Saroha, Swati Bhat, Liza Das, Pinaki Dutta, Michael F Holick, Naresh Sachdeva, Raman Kumar Marwaha","doi":"10.1038/s41541-024-00909-w","DOIUrl":"10.1038/s41541-024-00909-w","url":null,"abstract":"<p><p>The ChAdOx1 nCoV-19 (COVISHIELD) vaccine has emerged as a pivotal tool in the global fight against the COVID-19 pandemic. In our previous study eligible subjects were supplemented with calcifediol, a direct precursor to the biologically active form of vitamin D, calcitriol with an objective to enhance the immunogenicity of the COVISHIELD vaccine. Herein we investigated the effects of calcifediol supplementation on gene expression profiles in individuals who received the COVISHIELD vaccine. Peripheral blood mononuclear cells were isolated from vaccinated individuals with and without calcifediol supplementation at baseline, 3rd and 6th month, and the gene expression profiles were analyzed using high-throughput sequencing. The results revealed distinct patterns of gene expression associated with calcifediol supplementation, suggesting potential molecular mechanisms underlying the beneficial effects of calcifediol in improving the efficacy of COVISHIELD vaccine via augmentation of T cell activation, proliferation and T cell memory responses. Additionally, there was upregulation of NOD like receptor, JAK/STAT and TGF beta signaling pathways. Calcifediol supplementation in vaccinated individuals also downregulated the pathways related to the Coronavirus disease. Taken together, our findings provide valuable insights into the interplay between vitamin D receptor (VDR) signaling and vaccine-induced immune responses and offer another approach in improving vaccination induced antiviral responses.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11190216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}