Journal of neuroimmunology最新文献

{"title":"Calycosin regulates astrocyte reactivity and astrogliosis after spinal cord injury by targeting STAT3 phosphorylation","authors":"Wenhai Tang ,&nbsp;Aitao Wang ,&nbsp;Shengxing Liu ,&nbsp;Guangyu Wen ,&nbsp;Hao Qi ,&nbsp;Yuntao Gu ,&nbsp;Chunzhao Xu ,&nbsp;Shanwu Ren ,&nbsp;Shunli Zhang ,&nbsp;Yongxiong He","doi":"10.1016/j.jneuroim.2025.578535","DOIUrl":"10.1016/j.jneuroim.2025.578535","url":null,"abstract":"<div><h3>Background</h3><div>Astrocytes are the most populous glial cells in the central nervous system (CNS), which can exert detrimental effects through a process of reactive astrogliosis. Our previous study has indicated the potential effect of Calycosin in preventing spinal cord injury (SCI). This study aims to investigate the mechanism by which calycosin regulates the polarization of A1 astrocytes, a neurotoxic subtype of reactive astrocytes, in SCI models.</div></div><div><h3>Materials and methods</h3><div>The SCI model was induced by applying mechanical compression to the spinal cord using vascular clamps. A1 astrocyte differentiation was induced by treating astrocytes with microglia supernatant obtained after Lipopolysaccharide (LPS) stimulation. Key protein expression levels were analyzed by Western blotting, and astrocyte markers such as CS56, GFAP, C3, S100A10 were assessed through immunofluorescence staining.</div></div><div><h3>Results</h3><div>Calycosin treatment significantly reduced glial scar formation and C3 expression in SCI rats. However, S100A10 expression remained unchanged. Further analysis showed that Calycosin inhibited A1 astrocyte activation, migration, and invasion, which was associated with STAT3 phosphorylation. Calycosin downregulated p-STAT3 levels in both A1 astrocytes and SCI rats. These effects were reversed by Colivelin (a STAT3 activator) in A1 astrocytes.</div></div><div><h3>Conclusion</h3><div>Calycosin treatment can modulate p-STAT3 expression, thereby altering the functionality of astrocytes during the recovery phase and positively impacting the treatment and rehabilitation of SCI.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578535"},"PeriodicalIF":2.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of visual outcome in optic neuropathy of sarcoidosis","authors":"Anudeep Sai Nakirikanti ,&nbsp;Sally El Sammak ,&nbsp;William Tyor ,&nbsp;Spencer K. Hutto","doi":"10.1016/j.jneuroim.2025.578529","DOIUrl":"10.1016/j.jneuroim.2025.578529","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Up to 25 % of patients with neurosarcoidosis develop optic neuropathy, and prior observational studies have demonstrated a sizeable portion of these patients will remain significantly visually impaired. Despite its major influence on future disability, no prognostic factors are available to predict the potential for visual recovery.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To evaluate clinical and paraclinical data for their ability to predict final visual outcomes in sarcoid optic neuropathy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Between 01/2011 and 03/2023, patients with neurosarcoidosis were included if they experienced an inflammatory optic neuropathy as a symptomatic disease manifestation and adequate clinical details were available for retrospective review. The cohort was divided into those with better (visual acuity better than 20/100) and worse (visual acuity 20/100 or worse) final visual outcomes. Presenting clinical features, radiographic findings, results of ancillary testing, and subsequent clinical course were compared between the two groups to identify factors predictive of final visual outcome. Means and proportions were compared between groups using the two-sample &lt;em&gt;t&lt;/em&gt;-test for continuous variables and the Chi-squared test for categorical variables.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;36 cases (36/247 or 14.6 % of the total neurosarcoidosis cohort, 17 patients excluded) were included (mean age of visual onset 46.5 ±11.3 years, 24/36 or 66.7 % female, 28/36 or 80 % Black), of which 20 (55.6 %) and 16 (44.4 %) were observed to have better and worse visual outcomes at last follow-up, respectively. The majority had inflammation along the optic nerves in the orbital apex and optic canals (29/32, 90.6 %), predominantly in a perineural fashion in isolation (14/32, 43.8 %) or with enhancement of the optic nerve intrinsically (10/32, 31.3 %). Inflammation outside of the optic apparatus, neurologically or systemically, was almost always present (35/36, 97.2 %). Predictors of future worse visual outcomes included: diagnostic classification of definite (&lt;em&gt;p&lt;/em&gt; = 0.03), significantly impaired visual acuity at onset (20/100 or worse, &lt;em&gt;p&lt;/em&gt; = 0.001), impaired visual fields at onset (&lt;em&gt;p&lt;/em&gt; = 0.004), dyschromatopsia at onset (&lt;em&gt;p&lt;/em&gt; = 0.01), optic disc pallor or atrophy at initial evaluation (&lt;em&gt;p&lt;/em&gt; = 0.033), and at least one recurrence of inflammatory optic neuropathy over the course of follow-up (&lt;em&gt;p&lt;/em&gt; = 0.038). A pattern of optic perineuritis on MRI (&lt;em&gt;p&lt;/em&gt; = 0.025) and use of azathioprine as the initial disease modifying treatment (&lt;em&gt;p&lt;/em&gt; = 0.027) was predictive of a better visual outcome. Laterality (uni- vs bi-) of visual impairment, inflammatory localization within the visual apparatus (anterior vs posterior, longitudinal extent), associated MRI features (of inflammatory deposits not affecting the visual apparatus), delay in diagnosis, delay in initiation of steroids as an ","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578529"},"PeriodicalIF":2.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphine's role in macrophage polarization: Exploring M1 and M2 dynamics and disease susceptibility","authors":"Jonaid Ahmad Malik,&nbsp;Javed N. Agrewala","doi":"10.1016/j.jneuroim.2025.578534","DOIUrl":"10.1016/j.jneuroim.2025.578534","url":null,"abstract":"<div><div>Morphine is a globally prevalent substance of misuse, renowned for its immunosuppressive effects mediated through opioid receptors expressed on immune cells. Macrophages are crucial antigen-presenting cells that fulfill diverse roles, such as antigen presentation, phagocytosis, wound healing, and disease protection. They are typically classified based on their activation states: M1 (proinflammatory), M2 (anti-inflammatory), and M0 (resting). Morphine significantly modulates immune responses and neuroinflammation, further complicating the landscape of opioid dependency and disease susceptibility. The association of macrophages under the influence of morphine needs to be understood under various diseased conditions. Several studies have been focused on investigating the impact of morphine on macrophage function and its implications in infectious diseases and brain-associated diseases. To light this subject, we have discussed recent advancements in understanding the influences between morphine, macrophage function, polarization, infection, brain tumors, and drug dependency. This article explores the complex relationship between morphine, macrophages, and related pathologies. Consequently, discussing deeper insights into these dynamics could guide effective treatments for substance abuse disorders.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578534"},"PeriodicalIF":2.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting extracellular matrix components to attenuate microglia neuroinflammation: A study of fibulin-2 and CSPGs in a model of multiple sclerosis","authors":"Gurleen Randhawa ,&nbsp;Maryam Mobarakabadi ,&nbsp;Charlotte D’Mello ,&nbsp;Marlene T. Morch ,&nbsp;Ping Zhang ,&nbsp;Chang-Chun Ling ,&nbsp;V. Wee Yong ,&nbsp;Samira Ghorbani","doi":"10.1016/j.jneuroim.2025.578533","DOIUrl":"10.1016/j.jneuroim.2025.578533","url":null,"abstract":"<div><div>The extracellular matrix (ECM) plays an important role in the central nervous system (CNS), shaping tissue structure and functions as well as contributing to the pathology of chronic diseases such as multiple sclerosis (MS). ECM components, including fibulin-2 (FBLN2) and chondroitin sulfate proteoglycans (CSPGs), may impact neuroinflammation and remyelination. We investigated the capacity of FBLN2 to modulate immune responses and evaluated its interaction with CSPGs in experimental autoimmune encephalomyelitis (EAE), a common model for MS. We show that FBLN2 deficiency in EAE mice reduced microglial pro-inflammatory activity, while effects on monocyte-derived macrophages and border-associated macrophages were less pronounced. Targeting FBLN2 and CSPGs individually, using FBLN2^−/− mice and the CSPG-synthesis inhibitor difluorosamine (DIF), respectively, enhanced recovery of disability and reduced neuroinflammation in EAE mice. However, their combined targeting did not result in additive therapeutic effects beyond either alone. This study underscores the complex regulatory roles of ECM components on neuroinflammation and provides insights into potential therapeutic strategies for neuroinflammatory diseases.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578533"},"PeriodicalIF":2.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum NfL predicts outcome and secondary autoimmunity in herpes-simplex encephalitis","authors":"Kim Kristin Falk ,&nbsp;Ligia Abrante Cabrera ,&nbsp;Ralf Junker ,&nbsp;Frank Leypoldt ,&nbsp;Michael P. Malter ,&nbsp;Robert Markewitz ,&nbsp;Makbule Senel ,&nbsp;Hayrettin Tumani ,&nbsp;Klaus-Peter Wandinger ,&nbsp;Uwe K. Zettl ,&nbsp;Justina Dargvainiene","doi":"10.1016/j.jneuroim.2025.578528","DOIUrl":"10.1016/j.jneuroim.2025.578528","url":null,"abstract":"<div><h3>Objectives</h3><div>Herpes simplex virus 1 encephalitis (HSE) is the most common infectious encephalitis in developed countries. We aimed to evaluate the association of serum neurofilament light chain (sNfL) with disease severity, outcome and secondary anti-neuronal autoantibodies in a retrospective cohort study.</div></div><div><h3>Methods</h3><div>We retrospectively identified 30 patients with HSE and 132 controls (bacterial meningoencephalitis BM <em>n</em> = 27, non-bacterial meningitis NBM <em>n</em> = 33, healthy controls = 72). sNfL concentration was tested in all available samples (<em>N</em> = 231) using single molecule array (SiMoA) technology. Screening for secondary anti-neuronal autoantibodies was performed using rat brain immunohistochemistry, cell-based assays for anti-neuronal surface antibodies and indirect immunofluorescence with non-permeabilized rat hippocampal neuronal cultures.</div></div><div><h3>Results</h3><div>Patients with HSE and BM had higher sNfL levels than NBM and healthy controls. Within the HSE group, higher onset sNfL levels were associated with need for mechanical ventilation and poorer outcome measured by modified Rankin Scale. Increased sNFL levels in follow-up samples (24 days after HSE onset, 95 % CI 15–33) were associated with development of secondary anti-neuronal autoantibodies.</div></div><div><h3>Discussion</h3><div>Our results suggest sNfL as a potential biomarker of neuroaxonal damage in HSE with the potential to identify patients at risk of developing secondary anti-neuronal autoantibodies, which might lead to secondary autoimmunity of central nervous system. Future studies are needed to evaluate diagnostic values and establish suitable cut-offs.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578528"},"PeriodicalIF":2.9,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of serum and brain cytokine levels following prolonged binge-like methamphetamine self-administration and cued methamphetamine seeking","authors":"Amanda M. Acuña ,&nbsp;Erin K. Nagy ,&nbsp;Justin L. Legg ,&nbsp;Serena E. Rodarte ,&nbsp;M. Foster Olive","doi":"10.1016/j.jneuroim.2025.578530","DOIUrl":"10.1016/j.jneuroim.2025.578530","url":null,"abstract":"<div><div>Methamphetamine (METH) use is associated with peripheral and brain inflammation that can contribute to METH-associated toxicity and heightened cue reactivity. However, the persistence of these phenomena, especially with regards to changes in brain proinflammatory cytokine levels, is not yet clear. In this study, we determined the effects of repeated binge-like METH self-administration (96-h/week for 3 weeks) followed by cued drug seeking for up to 60 days into abstinence in male and female rats. Serum cytokine levels were assessed prior to cued drug seeking tests on days 21 and 60 of abstinence, and cytokine levels in the prefrontal cortex (PFC) and dorsal striatum (DStr) were assessed on the day following that last cued seeking test. We observed robust levels of METH intake in both sexes as well as a gradual increase in magnitude of METH seeking across abstinence that did not differ between sexes. Magnitude of METH seeking on days 10 and 60 were positively correlated with prior total drug intake. Sex- and region-dependent changes in various chemokines and interleukins were observed in the PFC and DStr, as were sex- and time-dependent changes in serum cytokine levels, with the largest number of cytokines altered on day 60 in male animals. Serum levels of IL-6 were positively correlated with brain levels of this cytokine, but serum levels of this and other cytokines did not correlate with the magnitude of METH seeking. These findings suggest that binge-like METH intake produces persistent yet divergent central and peripheral immune responses that extend well into abstinence.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578530"},"PeriodicalIF":2.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Balo concentric sclerosis, an emerging variant of multiple sclerosis: A case-series and literature review","authors":"Masoud Etemadifar ,&nbsp;Amirhossein Aghili ,&nbsp;Saba Shojaei ,&nbsp;Seyyed-Ali Alaei ,&nbsp;Mehri Salari ,&nbsp;Mahdi Norouzi","doi":"10.1016/j.jneuroim.2025.578527","DOIUrl":"10.1016/j.jneuroim.2025.578527","url":null,"abstract":"<div><h3>Introduction</h3><div>Balo concentric sclerosis (BCS) is a rare demyelinating disease. This study aims to follow up on patients initially diagnosed with BCS and MS or presented with BCS in the context of MS.</div></div><div><h3>Methods</h3><div>This study was conducted at an MS clinic center in Isfahan, monitoring 2600 MS patients, among which 10 cases were related to BCS. These 10 patients were assessed clinically and radiologically during 2013–2024, with consecutive MRIs and periodic clinical examinations.</div></div><div><h3>Results</h3><div>Among the 10 patients, BCS was either the inaugural presentation of MS or occurred in the context of the disease. The most common Symptoms included limb weakness and paresthesia. All patients exhibited characteristic onion-like lesions in the periventricular white matter, with two showing tumefactive demyelination. CSF analysis was abnormal in all patients, revealing positive oligoclonal bands (OCB), which were categorized as type 2 in all patients. Treatment mainly involved rituximab, which indicated plausible results.</div></div><div><h3>Conclusion</h3><div>Our study highlights the variability in BCS clinical presentations and supports its classification as a variant of MS due to overlapping characteristics. Additionally, our findings contribute to understanding BCS's distinct clinical and radiologic profiles and emphasize the importance of further investigation into its pathophysiology and treatment.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578527"},"PeriodicalIF":2.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Pathogenic Th17 cells are a potential therapeutic target for tacrolimus in AChR-myasthenia gravis patients” [Journal of Neuroimmunology. 2024 Nov 15:396:578464].","authors":"Yingkai Li ,&nbsp;Pei Chen ,&nbsp;Xin Huang ,&nbsp;Hao Huang ,&nbsp;Qian Ma ,&nbsp;Zhongqiang Lin ,&nbsp;Li Qui ,&nbsp;Changyi Ou ,&nbsp;Weibin Liu","doi":"10.1016/j.jneuroim.2025.578526","DOIUrl":"10.1016/j.jneuroim.2025.578526","url":null,"abstract":"","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578526"},"PeriodicalIF":2.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D imaging and pathological analysis of microglia in LPS-treated mice with light-sheet fluorescence microscopy","authors":"Renjie Liu ,&nbsp;Jianbo Xiu","doi":"10.1016/j.jneuroim.2025.578525","DOIUrl":"10.1016/j.jneuroim.2025.578525","url":null,"abstract":"<div><div>Although two-dimensional (2D) histology and immunohistochemistry techniques have long been established and successfully applied to obtain structural information from tissues, recent advances in tissue clearing and expansion approaches combined with light sheet microscopy have led to the realization of three-dimensional (3D) nondestructive pathology, which may revolutionize our knowledge of the morphology of an organ or the whole body in its true state. Employing these 3D technologies, we obtained imaging data of microglia in whole hippocampus of mice. We established a simple procedure to analyze the 3D structures of microglia using the commercial software Amira. Major 3D structural parameters, including the volume of the whole cell, volume of the cell body, Feret's maximum/minimum diameter, number of total branches, fractal dimension, convex hull, and number of intersections,were measured. We found that lipopolysaccharide administration markedly changed multiple 3D morphological parameters of microglia. 3D analysis of microglial structures provides a more comprehensive evaluation than 2D analysis, which can be applied in future neuroscience research.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"399 ","pages":"Article 578525"},"PeriodicalIF":2.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence: Electroconvulsive therapy in N-methyl-D-aspartate receptor encephalitis","authors":"Jonathan Reed Komisar ,&nbsp;Sohag Sanghani ,&nbsp;Grace Thrall ,&nbsp;Leonardo V. Lopez ,&nbsp;Khyati Brahmbhatt ,&nbsp;Stanley Brewer ,&nbsp;Jacob Feigal ,&nbsp;James Luccarelli ,&nbsp;Nasuh Malas ,&nbsp;Dennis Popeo ,&nbsp;Joshua Ryan Smith ,&nbsp;Chase Samsel ,&nbsp;D. Catherine Fuchs ,&nbsp;GenaLynne C. Mooneyham","doi":"10.1016/j.jneuroim.2024.578404","DOIUrl":"10.1016/j.jneuroim.2024.578404","url":null,"abstract":"","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"398 ","pages":"Article 578404"},"PeriodicalIF":2.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}