Frontiers in tuberculosis最新文献

{"title":"A broader evaluation of vaccine-induced T cell immunity against tuberculosis","authors":"P. Ogongo","doi":"10.3389/ftubr.2024.1435344","DOIUrl":"https://doi.org/10.3389/ftubr.2024.1435344","url":null,"abstract":"Although Bacillus Calmette-Guérin (BCG) vaccine, the only licensed vaccine against tuberculosis (TB), is the most widely used vaccine worldwide, TB is the second leading global killer from a single infectious agent responsible for over one million deaths annually. With the increasing threat of the emergence of drug-resistant TB, there is intense research toward better and more efficacious vaccines against TB. Indeed, TB vaccine research has blossomed in recent years: demonstration of sterilizing immunity against Mycobacterium tuberculosis (Mtb) challenge in non-human primates, the potential benefit of BCG revaccination in humans, and a phase IIb vaccine with ~50% efficacy against developing active disease. Consequently, several vaccines are set to begin phase 3 trials in 2024, and new candidates have entered phase 1 including mRNA-based TB vaccines. However, despite the enthusiasm, there are no known correlates of protection against TB, the antigens that induce protective immunity are incompletely defined, and the overreliance on Th1 cytokine production as an “absolute” measure of protection is increasingly debatable. In this perspective, I highlight the recent milestones in TB Vaccine research and the remaining challenges and propose suggestions for future considerations.","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":" 680","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141823528","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}

{"title":"Bridging the gap: evaluating high TB burden country data needs to support the potential introduction of TB vaccines for adolescents and adults: a workshop report.","authors":"Rebecca A Clark, Carly Young, Shaun Palmer, Erick Auma, Shelly Malhotra, Rupali Limaye, Birgitte Giersing, Lewis Schrager, Gerald Voss, Edine Tiemersma, Mike Frick, Ijeoma Edoka, Alemnew F Dagnew, Thokozile Nkhoma, Puck T Pelzer, Richard G White","doi":"10.3389/ftubr.2024.1384036","DOIUrl":"10.3389/ftubr.2024.1384036","url":null,"abstract":"<p><p>High tuberculosis (TB) burden countries (HBCs) need to prepare for TB vaccine implementation alongside licensure, to ensure rapid rollout. WHO policy/implementation frameworks have been created to support this effort. Using WHO frameworks, we convened a workshop to ask HBC experts about what epidemiological, impact, feasibility and acceptability data they anticipated they would need to guide TB vaccine introduction. For required data, we asked HBC and global experts which data were already available, data collection planned, or gaps. HBC experts expressed high demand for epidemiological, impact, feasibility and acceptability data, reported variable availability of existing epidemiological data, and low availability for impact, feasibility, and acceptability data. Global experts reported additional knowledge of existing data on impact, upcoming collection of infection prevalence, acceptability and feasibility data, and potential epidemiological data collection on adolescents, adults, people living with HIV, and underweight individuals. HBC and global experts made key recommendations for: a coordinated data collation, collection, analysis and sharing system; updating existing HBC health and economic impact estimates and extending impact analyses to other HBCs; demand/market forecasting; resource gap mapping; aligning delivery strategies; addressing manufacturing, procurement, delivery, and regulatory barriers; sharing potential vaccine licensure timing; incorporating TB vaccine introduction strategies into NSPs, immunization programs, and health services; collecting vaccine hesitancy, mistrust, and misinformation data; collecting adolescent/adult vaccine demand generation data, and identifying funding. Experts recommended expanding this analysis to other areas of the WHO frameworks, including more HBC stakeholders, and repeating this analysis after country and community advocacy and socialization around different vaccine candidates.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"2 ","pages":"1384036"},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diverse interactions of Mycobacterium tuberculosis infection and of BCG vaccination with SARS-CoV-2","authors":"P. Salgame, S. Pentakota, J. C. M. Malabad, P. Narasimhan, Sheetal Verma, S. Prakash Babu, Vartika Sharma, Sonali Sarkar, Marissa M. Alejandria, Jerrold Ellner","doi":"10.3389/ftubr.2024.1378068","DOIUrl":"https://doi.org/10.3389/ftubr.2024.1378068","url":null,"abstract":"The COVID pandemic and tuberculosis (TB) endemicity is double trouble to much of the world. SARS-CoV-2 and Mycobacterium tuberculosis (Mtb), causative agents of COVID and TB, respectively, are both infectious respiratory pathogens involving close communities and individuals. Both pathogens can cause lung disease, involving unbalanced inflammatory cell immune responses that can lead to a syndemic impact. Moreover, dual infection is common in certain settings. In low- and middle- income countries, most individuals with SARS-CoV-2 infection or COVID-19, in fact, will have been exposed to or infected with Mtb and some will develop active TB. Here we review the literature examining the diverse interactions of M. tuberculosis infection and of BCG vaccination with SARS-CoV-2. We discuss areas in which contradictory results have been published and conclude that there are still several unresolved issues that warrant further study on the co-pathogenesis of SARS-CoV-2 and Mtb and BCG- mediated heterologous protection against COVID-19.","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"6 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140667691","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}

{"title":"Case report: Congenital multidrug-resistant tuberculosis","authors":"Hongyi Zhang, Lu Xia, Peize Zhang","doi":"10.3389/ftubr.2024.1343217","DOIUrl":"https://doi.org/10.3389/ftubr.2024.1343217","url":null,"abstract":"Congenital multidrug-resistant tuberculosis (MDR-TB) is a rare disease with high mortality. We report a case of a neonate girl with congenital MDR-TB. The infant's mother underwent in vitro fertilization–embryo transfer and did not show any symptoms prior to delivery. After the 14th day of life, the infant had a fever and worsening difficulty breathing despite antibiotic treatment. She was then confirmed to have congenital MDR-TB and received ventilation and anti-TB treatment. When the infant's TB was diagnosed, her mother was screened for TB and found to have MDR-TB, affecting both her lungs and reproductive system. They both recovered and were discharged from the hospital, with anti-TB treatment ongoing.","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"76 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140726507","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}

{"title":"Exposure of <i>Mycobacterium tuberculosis</i> to human alveolar lining fluid shows temporal and strain-specific adaptation to the lung environment.","authors":"Anna Allué-Guardia, Andreu Garcia-Vilanova, Alyssa M Schami, Angélica M Olmo-Fontánez, Amberlee Hicks, Jay Peters, Diego J Maselli, Mark D Wewers, Yufeng Wang, Jordi B Torrelles","doi":"10.3389/ftubr.2024.1352806","DOIUrl":"10.3389/ftubr.2024.1352806","url":null,"abstract":"<p><p>Upon infection, <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>) reaches the alveolar space and comes in close contact with the lung mucosa or human alveolar lining fluid (ALF) for an uncertain period of time prior to its encounter with alveolar cells. We showed that homeostatic ALF hydrolytic enzymes modify the <i>M.tb</i> cell envelope, driving <i>M.tb</i>-host cell interactions. Still, the contribution of ALF during <i>M.tb</i> infection is poorly understood. Here, we exposed 4 <i>M.tb</i> strains with different levels of virulence, transmissibility, and drug resistance (DR) to physiological concentrations of human ALF for 15-min and 12-h, and performed RNA sequencing. Gene expression analysis showed a temporal and strain-specific adaptation to human ALF. Differential expression (DE) of ALF-exposed <i>vs</i>. unexposed <i>M.tb</i> revealed a total of 397 DE genes associated with lipid metabolism, cell envelope and processes, intermediary metabolism and respiration, and regulatory proteins, among others. Most DE genes were detected at 12-h post-ALF exposure, with DR-<i>M.tb</i> strain W-7642 having the highest number of DE genes. Interestingly, genes from the KstR2 regulon, which controls the degradation of cholesterol C and D rings, were significantly upregulated in all strains post-ALF exposure. These results indicate that <i>M.tb</i>-ALF contact drives initial bacterial metabolic and physiologic changes, which may have implications in the early events of <i>M.tb</i> infection.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"2 ","pages":"1352806"},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Test and treat approach for tuberculosis infection amongst household contacts of drug-susceptible pulmonary tuberculosis, Mumbai, India.","authors":"Daksha Shah, Sampada Bhide, Rajesh Deshmukh, Jonathan P Smith, Satish Kaiplyawar, Varsha Puri, Vijay Yeldandi, Anand Date, Melissa Nyendak, Christine S Ho, Patrick K Moonan","doi":"10.3389/ftubr.2024.1454277","DOIUrl":"10.3389/ftubr.2024.1454277","url":null,"abstract":"<p><strong>Background: </strong>Mumbai is one of the most densely populated areas in the world and is a major contributor to the tuberculosis (TB) epidemic in India. A test and treat approach for TB infection (TBI) amongst household contacts (HHC) is part of the national policy for TB preventive treatment (TPT). However, in practice, the use of interferon-gamma release assay (IGRA) tests for infection are limited, and prevalence of TBI in Mumbai is not known.</p><p><strong>Methods: </strong>We conducted a cross-sectional study among HHCs exposed to persons with microbiologically-confirmed, drug-susceptible pulmonary TB that were notified for antituberculosis treatment in Mumbai, India during September-December, 2021. Community-based field workers made home visits and offered IGRA (QuantiFERON-TB^® Gold In-Tube Plus) tests to HHC aged 5 years and older. After ruling out active TB disease, HHC with IGRA-positive test results were referred for TPT. All HHC were monitored for at least 24 months for progression to active TB disease.</p><p><strong>Results: </strong>Among 502 HHCs tested, 273 (54%) had IGRA-positive results. A total of 254 (93%) were classified as TBI and were eligible for TPT, of which 215 (85%) initiated TPT, and 194 (90%) completed TPT successfully. There was substantial variation in rates of TBI per household. In 32% of households, all HHC (100%) were IGRA positive and in 64% of households >50% of HHC were infected. In all, 22 HHCs (4%; 22/558) were diagnosed with TB disease; of these, five HHC were diagnosed during follow up, of which three were IGRA positive and had no evidence of disease at initial screening but chose not to initiate TPT.</p><p><strong>Conclusion: </strong>A test and treat strategy for HHC resulted in the detection of a substantial proportion of TBI and secondary TB cases. Home-based IGRA testing led to high participation rates, clinical evaluations, TPT initiation, and early diagnoses of additional secondary cases. A community-focused, test and treat approach was feasible in this population and could be considered for broader implementation.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Mycobacterial</i> PE/PPE proteins function as \"personal protective equipment\" against host defenses.","authors":"Carlos Resstel, Bala T S A Madduri, Samantha L Bell","doi":"10.3389/ftubr.2024.1458105","DOIUrl":"10.3389/ftubr.2024.1458105","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) is the deadliest bacterial infection worldwide, but many molecular details of how it interacts with the innate immune system remain obscure. In particular, although <i>Mtb</i> secretes a large number of putative effector proteins, a relatively small number have assigned functions in facilitating host-pathogen interactions. One particularly large family of secreted mycobacterial proteins that remains poorly understood is the PE/PPE proteins. Despite numerous lines of evidence for potential roles in virulence and in mediating host-pathogen interactions, only a small fraction of these 170+ proteins have been well characterized. However, this large family of proteins is likely key for understanding how <i>Mtb</i> subverts immune responses, manipulates host cell biology, and establishes a successful infection. Here, we highlight examples of PE/PPEs that have well-defined effects on cell intrinsic pathways in macrophages during mycobacterial infection. Examples include PPE2, which blunts production of reactive oxygen species and nitric oxide; PE_PGRS33, which facilitates bacterial uptake; PE_PGRS29, which directly binds ubiquitin to promote host autophagy and limit pathologic inflammation; MirA, which facilitates actin tail formation to promote cell-to-cell spread; and others. Understanding the full spectrum of PE/PPE functions is critical for understanding <i>Mtb</i> pathogenesis and for developing new strategies to combat the worldwide TB pandemic. Advancing the lagging research efforts characterizing this mysterious family of effector proteins is critical for the TB field.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Mycobacterium abscessus</i> pulmonary infection and associated respiratory function in cystic fibrosis-like βENaC mice.","authors":"Camron M Pearce, Timothy D Shaw, Brendan Podell, Mary Jackson, Marcela Henao-Tamayo, Andres Obregon-Henao, Ha Lam, Ilham M Alshiraihi, Wanda O'Neal, Alessandra Livraghi-Butrico, Anthony J Hickey, Bernd Meibohm, Mercedes Gonzalez-Juarrero","doi":"10.3389/ftubr.2024.1473341","DOIUrl":"10.3389/ftubr.2024.1473341","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic pulmonary infection with <i>Mycobacterium abscessus</i> (<i>M. abscessus</i>) is a significant cause of morbidity and mortality in people with cystic fibrosis (CF). Developing an animal model of <i>M. abscessus</i> pulmonary infection, especially under CF conditions, is essential to understanding clinical pulmonary <i>M. abscessus</i> infection. βENaC transgenic mice are known to develop spontaneous CF-like disease characterized by airway mucus obstruction and inflammation. The aim of this study was to evaluate the suitability of βENaC mice as a preclinical model and characterize their respiratory function during <i>M. abscessus</i> lung infection.</p><p><strong>Methods: </strong>Mice received an intrapulmonary aerosol of <i>M. abscessus</i> using a high-pressure syringe device (Penn-Century) for subsequent characterization of disease progression and respiratory function. Whole body unrestrained plethysmography (WBP) data was collected to monitor lung function and endpoints determined organ bacterial burden and associated pathology.</p><p><strong>Results: </strong>Endpoint CFU data in the lung and spleen showed that there was no significant difference in bacterial clearance between βENaC and WT mice. WBP data showed an impairment in overall respiratory function during and after <i>M. abscessus</i> infection in both strains of mice. Interestingly, even in wildtype control mice, lung dysfunction persisted after bacterial clearance.</p><p><strong>Discussion: </strong>Even with CF-like features, the βENaC transgenic mice cleared <i>M. abscessus</i> at a similar rate than WT mice, however, the associated respiratory monitoring revealed that there are long-term implications of <i>M. abscessus</i> lung exposure. The clear decline in respiratory function, even after <i>M. abscessus</i> clearance, suggests that WBP coupled animal modeling provides important insight that is relevant to disease burden and treatment efficacy. The <i>M. abscessus</i> clearance in the βENaC mice may help improve the fields understanding of CF-modulated immune deficiencies in <i>M. abscessus</i> pulmonary infection.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the bacillary load and host interaction to design a point-of-care test to diagnose tuberculosis","authors":"P. Cardona","doi":"10.3389/ftubr.2023.1243479","DOIUrl":"https://doi.org/10.3389/ftubr.2023.1243479","url":null,"abstract":"Designing of a Point-of-care test to diagnose tuberculosis (TB) is not an easy task. This viewpoint stems from the dichotomous diagnostic approach, based on the bacillary load estimated in latent tuberculosis infection (LTBI), thanks to the isoniazid chemoprophylaxis strategy, as well as the importance of imaging to differentiate between LTBI and TB. It integrates the “TB spectrum” elucidated through positron emission tomography-computed tomography scan (PET-CT) to highlight the dynamic nature of TB lesions. Additionally, it emphasizes the relevance of animal models that support this perspective, including the drainage of bacilli through foamy macrophages, which aids in understanding LTBI and its chemoprophylaxis, and the significance of lung anatomy in TB induction. Especially the role of interlobular septa and the encapsulation process and its role in lung lobe predilection impact disease progression. Moreover, it acknowledges the gender bias in TB, as its incidence is significantly higher in men across various socioeconomic circumstances, suggesting an unidentified biological mechanism. For a comprehensive approach, the impact of stress and cortisol levels is suggested as a new parameter to be considered, given their association with poverty, and social inequity, and their tendency to be higher in men. All this information has to be contemplated when designing an accurate point-of-care test. The test should encompass the complexity of TB and necessarily integrate both bacillary and host response parameters. It also should cover the diagnosis of extrapulmonary TB, and pay attention to immunosuppressed and pediatric population.","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121527039","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}

{"title":"Atg8ylation as a host-protective mechanism against <i>Mycobacterium tuberculosis</i>.","authors":"Vojo Deretic","doi":"10.3389/ftubr.2023.1275882","DOIUrl":"10.3389/ftubr.2023.1275882","url":null,"abstract":"<p><p>Nearly two decades have passed since the first report on autophagy acting as a cell-autonomous defense against <i>Mycobacterium tuberculosis</i>. This helped usher a new area of research within the field of host-pathogen interactions and led to the recognition of autophagy as an immunological mechanism. Interest grew in the fundamental mechanisms of antimicrobial autophagy and in the prophylactic and therapeutic potential for tuberculosis. However, puzzling in vivo data have begun to emerge in murine models of <i>M. tuberculosis</i> infection. The control of infection in mice affirmed the effects of certain autophagy genes, specifically ATG5, but not of other ATGs. Recent studies with a more complete inactivation of ATG genes now show that multiple ATG genes are indeed necessary for protection against <i>M. tuberculosis</i>. These particular ATG genes are involved in the process of membrane atg8ylation. Atg8ylation in mammalian cells is a broad response to membrane stress, damage and remodeling of which canonical autophagy is one of the multiple downstream outputs. The current developments clarify the controversies and open new avenues for both fundamental and translational studies.</p>","PeriodicalId":101354,"journal":{"name":"Frontiers in tuberculosis","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71416495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}