Brain, Behavior, and Immunity最新文献

{"title":"Multispecies probiotic intake during pregnancy modulates neurodevelopmental trajectories of offspring: Aiming towards precision microbial intervention","authors":"","doi":"10.1016/j.bbi.2024.08.050","DOIUrl":"10.1016/j.bbi.2024.08.050","url":null,"abstract":"<div><p>Recent research highlights the pivotal role of the maternal gut microbiome during pregnancy in shaping offspring neurodevelopment. In this study, we investigated the impact of maternal intake of a multispecies probiotic formulation during a critical prenatal window (from gestational day 6 until birth) on neurodevelopmental trajectories in mice. Our findings demonstrate significant and persistent benefits in emotional behavior, gut microbiota composition, and expression of tight junction-related genes, particularly in male offspring, who exhibited heightened sensitivity to the probiotic intervention compared to females. Additionally, we observed elevated gene expression levels of the anti-inflammatory cytokine <em>IL-10</em> and the oxytocin receptor (<em>Oxtr</em>) in the prefrontal cortex (PFC) of exposed juvenile offspring; however, these changes persisted only in the adult male offspring. Furthermore, the sustained increase in the expression of the proton-coupled oligopeptide transporter 1 (<em>PepT1</em>), which is involved in the transport of bacterial peptidoglycan motifs, in the PFC of exposed male offspring suggests a potential mechanistic pathway underlying the observed sex-dependent effects on behavior and gene expression. These results underscore the potential of prenatal multispecies probiotic interventions to promote long-term neurodevelopmental outcomes, with implications for precision microbial reconstitution aimed at promoting healthy neurodevelopment and behavior.</p></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0889159124005737/pdfft?md5=ab52e66f98f3cf72d3ec2ba2415a5d8d&pid=1-s2.0-S0889159124005737-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of mesenchymal stromal cells in mouse models of Alzheimer’s Disease: The Mediating role of gut microbes and their metabolites via the Microbiome-Gut-Brain axis","authors":"","doi":"10.1016/j.bbi.2024.08.047","DOIUrl":"10.1016/j.bbi.2024.08.047","url":null,"abstract":"<div><p>The intricacy and multifaceted nature of Alzheimer’s disease (AD) necessitate therapies that target multiple aspects of the disease. Mesenchymal stromal cells (MSCs) emerge as potential agents to mitigate AD symptoms; however, whether their therapeutic efficacy involves modulation of gut microbiota and the microbiome-gut-brain axis (MGBA) remains unexplored. In this study, we evaluated the effects of three distinct MSCs types—derived from the umbilical cord (UCMSC), dental pulp (SHED), and adipose tissue (ADSC)—in an APP/PS1 mouse model of AD. In comparison to saline control, MSCs administration resulted in a significant reduction of behavioral disturbances, amyloid plaques, and phosphorylated tau in the hippocampus and frontal cortex, accompanied by an increase in neuronal count and Nissl body density across AD-afflicted brain regions. Through 16S rRNA gene sequencing, we identified partial restoration of gut microbial balance in AD mice post-MSCs treatment, evidenced by the elevation of neuroprotective Akkermansia and reduction of the AD-associated Sphingomonas. To examine whether gut microbiota involved in MSCs efficacy in treating AD, SHED with better anti-inflammatory and gut microbiota recovery effects among three MSCs, and another AD model 5 × FAD mice with earlier and more pathological proteins in brain than APP/PS1, were selected for further studies. Antibiotic-mediated gut microbial inactivation attenuated MSCs efficacy in 5 × FAD mice, implicating the involvement of gut microbiota in the therapeutic mechanism. Functional analysis of altered gut microbiota and targeted bile acid metabolism profiling revealed a significant enhancement in bile acid variety following MSCs therapy. A chief bile acid constituent, taurocholic acid (TCA), was orally administered to AD mice and similarly abated AD symptoms. Nonetheless, the disruption of intestinal neuronal integrity with enterotoxin abrogated the ameliorative impact of both MSCs and TCA treatments. Collectively, our findings substantiate that MSCs confer therapeutic benefits in AD within a paradigm that primarily involves regulation of gut microbiota and their metabolites through the MGBA.</p></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between childhood abuse and risk of post-COVID-19 conditions: Results from three large prospective cohort studies","authors":"","doi":"10.1016/j.bbi.2024.08.046","DOIUrl":"10.1016/j.bbi.2024.08.046","url":null,"abstract":"<div><h3>Background</h3><p>Significant early life adversities, such as childhood sexual and physical/emotional abuse, are associated with risk of poor health outcomes but are understudied risk factors for post-COVID-19 conditions. In this prospective study, we examined the associations between combined exposure to sexual and physical/emotional abuse during childhood with risk of post-COVID-19 conditions in adulthood. Additionally, we explored the extent to which lifestyle, health-related and psychological factors explain this association.</p></div><div><h3>Methods</h3><p>We used data from three large, ongoing cohorts: Nurses’ Health Study (NHS)-II, NHS3, and the Growing Up Today Study. Between April 2020 and November 2021, participants responded to periodic COVID-19 surveys. Participants were included if they responded to a questionnaire about childhood abuse, subsequently tested positive for SARS-CoV-2 infection and responded to questions about post-COVID-19 conditions. Childhood sexual abuse was measured before the COVID-19 pandemic with the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scale, and physical/emotional abuse was measured with the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire. Post-COVID-19 conditions, defined as COVID–19–related symptoms lasting 4 weeks or longer (e.g., fatigue, dyspnea), were self-reported in the final COVID-19 questionnaire in November 2021. Sexual abuse and physical/emotional abuse were examined separately and jointly in relation to post-COVID-19 conditions. Data on key lifestyle (e.g., cigarette smoking), health-related (e.g., asthma, diabetes), and psychological factors (e.g., depression and anxiety) were obtained.</p></div><div><h3>Results</h3><p>Of 2851 participants, the mean age (range) was 55.8 (22.0–75.0) years; 2789 (97.8 %) were females, and 2750 (96.5 %) were whites. We observed a dose-dependent relationship between severity of childhood abuse and post-COVID conditions (p-trend:&lt;0.0001); participants with severe versus no childhood abuse had a 42 % higher subsequent risk of post-COVID conditions [relative risk (95 % confidence interval): 1.42 (1.25 to 1.61)]. Key lifestyle, health-related, and psychological factors mediated 25.5 % of this association. Both sexual and physical/emotional abuse, were independently associated with post-COVID conditions.</p></div><div><h3>Conclusions</h3><p>In this prospective study of 2851 participants, childhood abuse was significantly associated with increased risk of post-COVID conditions. Biological pathways connecting childhood abuse with subsequent risk of post-COVID conditions should be investigated.</p></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD8+ T cells exacerbate AD-like symptoms in mouse model of amyloidosis","authors":"","doi":"10.1016/j.bbi.2024.08.045","DOIUrl":"10.1016/j.bbi.2024.08.045","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is linked to toxic Aβ plaques in the brain and activation of innate responses. Recent findings however suggest that the disease may also depend on the adaptive immunity, as B cells exacerbate and CD8⁺ T cells limit AD-like pathology in mouse models of amyloidosis. Here, by artificially blocking or augmenting CD8⁺ T cells in the brain of 5xFAD mice, we provide evidence that AD-like pathology is promoted by pathogenic, proinflammatory cytokines and exhaustion markers expressing CXCR6⁺ CD39⁺CD73^+/- CD8⁺ T_RM-like cells. The CD8⁺ T cells appear to act by targeting disease associated microglia (DAM), as we find them in tight complexes with microglia around Aβ plaques in the brain of mice and humans with AD. We also report that these CD8⁺ T cells are induced by B cells in the periphery, further underscoring the pathogenic importance of the adaptive immunity in AD. We propose that CD8⁺ T cells and B cells should be considered as therapeutic targets for control of AD, as their ablation at the onset of AD is sufficient to decrease CD8⁺ T cells in the brain and block the amyloidosis-linked neurodegeneration.</p></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of social dominance and acute social stress on morphology of microglia and structural integrity of the medial prefrontal cortex","authors":"","doi":"10.1016/j.bbi.2024.08.043","DOIUrl":"10.1016/j.bbi.2024.08.043","url":null,"abstract":"<div><p>Chronic stress increases activity of the brain’s innate immune system and impairs function of the medial prefrontal cortex (mPFC). However, whether acute stress triggers similar neuroimmune mechanisms is poorly understood. Across four studies, we used a Syrian hamster model to investigate whether acute stress drives changes in mPFC microglia in a time-, subregion-, and social status-dependent manner. We found that acute social defeat increased expression of ionized calcium binding adapter molecule 1 (Iba1) in the infralimbic (IL) and prelimbic (PL) and altered the morphology Iba1+ cells 1, 2, and 7 days after social defeat. We also investigated whether acute defeat induced tissue degeneration and reductions of synaptic plasticity 2 days post-defeat. We found that while social defeat increased deposition of cellular debris and reduced synaptophysin immunoreactivity in the PL and IL, treatment with minocycline protected against these cellular changes. Finally, we tested whether a reduced conditioned defeat response in dominant compared to subordinate hamsters was associated with changes in microglia reactivity in the IL and PL. We found that while subordinate hamsters and those without an established dominance relationships showed defeat-induced changes in morphology of Iba1+ cells and cellular degeneration, dominant hamsters showed resistance to these effects of social defeat. Taken together, these findings indicate that acute social defeat alters microglial morphology, increases markers of tissue degradation, and impairs structural integrity in the IL and PL, and that experience winning competitive interactions can specifically protect the IL and reduce stress vulnerability.</p></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking severe traumatic brain injury to pulmonary Infections: Translocation of intestinal bacteria mediated by nociceptor neurons","authors":"","doi":"10.1016/j.bbi.2024.08.041","DOIUrl":"10.1016/j.bbi.2024.08.041","url":null,"abstract":"<div><p>The prevalence of bacterial infections significantly increases among patients with severe traumatic brain injury (STBI), leading to a notable rise in mortality rates. While immune dysfunctions are linked to the incidence of pneumonia, our observations indicate that endogenous pathogens manifest in the lungs post-STBI due to the migration of gut commensal bacteria. This translocation involves gut-innervating nociceptor sensory neurons, which are crucial for host defense. Following STBI, the expression of transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons significantly decreases, despite an initial brief increase. The timing of TRPV1 defects coincides with the occurrence of pulmonary infections post-STBI. This alteration in TRPV1⁺ neurons diminishes their ability to signal bacterial injuries, weakens defense mechanisms against intestinal bacteria, and increases susceptibility to pulmonary infections via bacterial translocation. Experimental evidence demonstrates that pulmonary infections can be successfully replicated through the chemical ablation and gene interference of TRPV1⁺ nociceptors, and that these infections can be mitigated by TRPV1 activation, thereby confirming the crucial role of nociceptor neurons in controlling intestinal bacterial migration. Furthermore, TRPV1⁺ nociceptors regulate the immune response of microfold cells by releasing calcitonin gene-related peptide (CGRP), thereby influencing the translocation of gut bacteria to the lungs. Our study elucidates how changes in nociceptive neurons post-STBI impact intestinal pathogen defense. This new understanding of endogenous risk factors within STBI pathology offers novel insights for preventing and treating pulmonary infections.</p></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Intrathecal non-viral interleukin-10 gene therapy ameliorates neuropathic pain as measured by both classical static allodynia and a novel supra-spinally mediated pain assay, the Two-Arm Rodent Somatosensory (TARS) task” [Brain Behav. Immun. 111 (2023) 177–185]","authors":"","doi":"10.1016/j.bbi.2024.08.020","DOIUrl":"10.1016/j.bbi.2024.08.020","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0889159124005427/pdfft?md5=4364ed678082f4afb8d3ccf0f3d3f8d0&pid=1-s2.0-S0889159124005427-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “DNA binding protein HMGB1 secreted by activated microglia promotes the apoptosis of hippocampal neurons in diabetes complicated with OSA” [Brain Behav. Immun. 73 (2018) 482–492]","authors":"","doi":"10.1016/j.bbi.2024.08.031","DOIUrl":"10.1016/j.bbi.2024.08.031","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0889159124005543/pdfft?md5=f2ac994d9aaf05911e0ae6593554a1cf&pid=1-s2.0-S0889159124005543-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exogenous PD-L1 binds to PD-1 to alleviate and prevent autism-like behaviors in maternal immune activation-induced male offspring mice","authors":"","doi":"10.1016/j.bbi.2024.08.042","DOIUrl":"10.1016/j.bbi.2024.08.042","url":null,"abstract":"<div><p>Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder caused by the interaction of multiple pathogenic factors. Epidemiological studies and animal experiments indicate that maternal immune activation (MIA) is closely related to the development of ASD in offspring. A large number of pro-inflammatory cytokines are transferred from the placenta to the fetal brain during MIA, which impedes fetal neurodevelopment and is accompanied by activation of immune cells and microglia. Programmed cell death protein 1 (PD-1) can be highly expressed on the surface of various activated immune cells, when combined with programmed cell death-ligand 1 (PD-L1), it can activate the PD-1/PD-L1 pathway and exert powerful immunosuppressive effects, suggesting that this immune checkpoint may have the potential to treat MIA-induced ASD. This study combined bioinformatics analysis and experimental validation to explore the efficacy of Fc-fused PD-L1 (PD-L1-Fc) in treating MIA-induced ASD. Bioinformatics analysis results showed that in human placental inflammation, IL-6 was upregulated, T cells proliferated significantly, and the PD-1/PD-L1 pathway was significantly enriched. The experimental results showed that intraperitoneal injection of poly(I:C) induced MIA in pregnant mice resulted in significant expression of IL-6 in their serum, placenta, and fetal brain. At the same time, the expression of PD-1 and PD-L1 in the placenta and fetal brain increased, CD4⁺ T cells in the spleen were significantly activated, and PD-1 expression increased. Their offspring mice exhibited typical ASD-like behaviors. <em>In vitro</em> experiments on primary microglia of offspring mice have confirmed that the expression of IL-6, PD-1, and PD-L1 is significantly increased, and PD-L1-Fc effectively reduced their expression levels. In the prefrontal cortex of MIA offspring mice, there was an increase in the expression of IL-6, PD-1, and PD-L1; activation of microglial cells, and colocalization with PD-1. Then we administered brain stereotaxic injections of PD-L1-Fc to MIA offspring mice and intraperitoneal injections to MIA pregnant mice. The results indicated that PD-L1-Fc effectively suppressed neuroinflammation in the frontal cortex of offspring mice and partially ameliorated ASD-like behaviors; MIA in pregnant mice was significantly alleviated, and the offspring mice they produced did not exhibit neuroinflammation or ASD-like behaviors. In summary, we have demonstrated the therapeutic ability of PD-L1-Fc for MIA-induced ASD, aiming to provide new strategies and insights for the treatment of ASD.</p></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting CNS myeloid infiltrates provides neuroprotection in a progressive multiple sclerosis model","authors":"","doi":"10.1016/j.bbi.2024.08.032","DOIUrl":"10.1016/j.bbi.2024.08.032","url":null,"abstract":"<div><p>Demyelination and axonal injury in chronic-progressive Multiple Sclerosis (MS) are presumed to be driven by a neurotoxic bystander effect of meningeal-based myeloid infiltrates. There is an unmet clinical need to attenuate disease progression in such forms of CNS-compartmentalized MS. The failure of systemic immune suppressive treatments has highlighted the need for neuroprotective and repair-inducing strategies. Here, we examined whether direct targeting of CNS myeloid cells and modulating their toxicity may prevent irreversible tissue injury in chronic immune-mediated demyelinating disease. To that end, we utilized the experimental autoimmune encephalomyelitis (EAE) model in Biozzi mice, a clinically relevant MS model. We continuously delivered intracerebroventricularly (ICV) a retinoic acid receptor alpha agonist (RARα), as a potent regulator of myeloid cells, in the chronic phase of EAE. We assessed disease severity and performed pathological evaluations, functional analyses of immune cells, and single-cell RNA sequencing on isolated spinal CD11b+ cells. Although initiating treatment in the chronic phase of the disease, the RARα agonist successfully improved clinical outcomes and prevented axonal loss. ICV RARα agonist treatment inhibited pro-inflammatory pathways and shifted CNS myeloid cells toward neuroprotective phenotypes without affecting peripheral infiltrating myeloid cell phenotypes, or peripheral immunity. The treatment regulated cell-death pathways across multiple myeloid cell populations and suppressed apoptosis, resulting in paradoxically marked increased neuroinflammatory infiltrates, consisting mainly of microglia and CNS / border-associated macrophages. This work establishes the notion of bystander neurotoxicity by CNS immune infiltrates in chronic demyelinating disease. Furthermore, it shows that targeting compartmentalized neuroinflammation by selective regulation of CNS myeloid cell toxicity and survival reduces irreversible tissue injury, and may serve as a novel disease-modifying approach.</p></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0889159124005579/pdfft?md5=9ac23478b426ef4f1bcefd35d6132970&pid=1-s2.0-S0889159124005579-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}