Investigative ophthalmology & visual science最新文献

{"title":"Using Multi-Layer Perceptron Driven Diagnosis to Compare Biomarkers for Primary Open Angle Glaucoma.","authors":"Nicholas Riina, Alon Harris, Brent A Siesky, Lukas Ritzer, Louis R Pasquale, James C Tsai, James Keller, Barbara Wirostko, Julia Arciero, Brendan Fry, George Eckert, Alice Verticchio Vercellin, Gal Antman, Paul A Sidoti, Giovanna Guidoboni","doi":"10.1167/iovs.65.11.16","DOIUrl":"10.1167/iovs.65.11.16","url":null,"abstract":"<p><strong>Purpose: </strong>To use neural network machine learning (ML) models to identify the most relevant ocular biomarkers for the diagnosis of primary open-angle glaucoma (POAG).</p><p><strong>Methods: </strong>Neural network models, also known as multi-layer perceptrons (MLPs), were trained on a prospectively collected observational dataset comprised of 93 glaucoma patients confirmed by a glaucoma specialist and 113 control subjects. The base model used only intraocular pressure, blood pressure, heart rate, and visual field (VF) parameters to diagnose glaucoma. The following models were given the base parameters in addition to one of the following biomarkers: structural features (optic nerve parameters, retinal nerve fiber layer [RNFL], ganglion cell complex [GCC] and macular thickness), choroidal thickness, and RNFL and GCC thickness only, by optical coherence tomography (OCT); and vascular features by OCT angiography (OCTA).</p><p><strong>Results: </strong>MLPs of three different structures were evaluated with tenfold cross validation. The testing area under the receiver operating characteristic curve (AUC) of the models were compared with independent samples t-tests. The vascular and structural models both had significantly higher accuracies than the base model, with the hemodynamic AUC (0.819) insignificantly outperforming the structural set AUC (0.816). The GCC + RNFL model and the model containing all structural and vascular features were also significantly more accurate than the base model.</p><p><strong>Conclusions: </strong>Neural network models indicate that OCTA optic nerve head vascular biomarkers are equally useful for ML diagnosis of POAG when compared to OCT structural biomarker features alone.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154089","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":"Blue Light-Induced Accelerated Formation of Melanolipofuscin-Like Organelles in Japanese Quail RPE Cells: An Electron Microscopic Study.","authors":"Natalia B Serejnikova, Natalia N Trofimova, Marina A Yakovleva, Alexander E Dontsov, Pavel P Zak, Mikhail A Ostrovsky","doi":"10.1167/iovs.65.11.31","DOIUrl":"10.1167/iovs.65.11.31","url":null,"abstract":"<p><strong>Purpose: </strong>The retinal pigment epithelium (RPE) is a monolayer of epithelial cells essential for photoreceptor function and viability. Quail Coturnix japonica is a convenient experimental animal model for the study of age and pathological retina processes to an accelerated time regime. The three main types of pigment granules present in the RPE are melanin-containing melanosomes, lipofuscin-containing lipofuscin granules, and mixed melanolipofuscin granules containing both melanin and lipofuscin. The purpose of this work was to study the process of melanolipofuscinogenesis during aging and under light exposure.</p><p><strong>Methods: </strong>We examined melanolipofuscin granules in \"macular\" areas, the area of the retina containing oxycarotenoids, as a function of the macula in humans, of the quail retina by transmission electron microscopy in young, middle-aged, and old birds, and in middle-aged birds irradiated with blue LED light (450 nm, 4 J/cm2).</p><p><strong>Results: </strong>It has been shown that during photo-oxidative stress caused by the action of blue light on the quail eye, active fusion of melanosomes and lipofuscin granules occurs with formation of various types, including giant, mixed melanolipofuscin-like granules. Increased accumulation of melanolipofuscin-like granules was also observed in non-irradiated old birds.</p><p><strong>Conclusions: </strong>It is assumed that the decrease in the number of melanosomes in the RPE during aging and photo-oxidative stress is associated with their fusion with lipofuscin granules and subsequent degradation of melanin by reactive oxygen species formed in melanolipofuscin-like granules. The disappearance of melanin deprives the RPE cells of light-filtering and antioxidant protection, and significantly increases the risk of their oxidative stress.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287409","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":"Erratum in: Metabolic Phenotyping of Healthy and Diseased Human RPE Cells.","authors":"","doi":"10.1167/iovs.65.11.35","DOIUrl":"10.1167/iovs.65.11.35","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287411","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":"Single-Cell Transcriptomic Analysis Reveals Dynamic Cellular Processes in Corneal Epithelium During Wound Healing in Cynomolgus Monkeys.","authors":"Ming Zhou, Zhuo-Xing Shi, Zhong Liu, Shu-Rui Ke, Chao-Yang Wang, Xiao-Lin Liang, Qiu-Ling Hu, Qi-Kai Zhang, Dong-Liang Wang, Li Sun, Yu-Heng Lin, Qi Dai, Ying-Feng Zheng","doi":"10.1167/iovs.65.11.43","DOIUrl":"https://doi.org/10.1167/iovs.65.11.43","url":null,"abstract":"<p><strong>Purpose: </strong>Corneal wounding healing is critical for maintaining clear vision, however, a complete understanding of its dynamic regulatory mechanisms remains elusive. Here, we used single-cell RNA sequencing (scRNA-seq) to analyze the cellular activities and transcriptional changes of corneal limbal epithelial cells at different stages after wound healing in cynomolgus monkeys, which exhibit a closer transcriptomic similarity to humans.</p><p><strong>Methods: </strong>Corneal limbal tissues were collected during uninjured, 1-day and 3-day healing stages, dissociated into single cells, and subjected to scRNA-seq using the 10× Genomics platform. Cell types were clustered by graph-based visualization methods and unbiased computational analysis. Additionally, cell migration assays and immunofluorescent staining were performed on cultured human corneal epithelial cells.</p><p><strong>Results: </strong>We characterized nine cell clusters by scRNA-seq analysis of the cynomolgus monkey corneal epithelium. By comparing heterogeneous transcriptional changes in major cell types during corneal healing, we highlighted the importance of limbal epithelial cells (LEPCs) and basal epithelial cells (BEPCs) in extracellular matrix (ECM) formation and wound healing, as well as suprabasal epithelial cells (SEPCs) in epithelial differentiation during the healing processes. We further identified five different sub-clusters in LEPC, including the transit amplifying cell (TAC) sub-cluster that promotes early healing through the activation of thrombospondin-1 (THBS1) expression.</p><p><strong>Conclusions: </strong>Our study represents the first comprehensive exploration of the detailed transcriptome profile of individual corneal cells during the wound healing process in nonhuman primates. We demonstrate the intricate mechanisms involved in corneal healing and provide a promising avenue for potential therapies in corneal wound healing.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346861","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":"Lens Power and Associated Factors in Nonhuman Primate Subjects: A Cross-sectional Study.","authors":"Yingting Zhu, Rui Xie, Qi Zhang, Yuan Zhang, Guitong Ye, Liangzhi Xu, Simeng Hou, Wei Liu, Zhiwei Huang, Jian Wu, Yehong Zhuo","doi":"10.1167/iovs.65.11.2","DOIUrl":"10.1167/iovs.65.11.2","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to examine the normative profile of crystalline lens power (LP) and its associations with ocular biometric parameters including age, axial length (AL), spherical equivalent refraction (SE), corneal radius (CR), lens thickness, anterior chamber depth, and AL/CR ratio among a cynomolgus monkey colony.</p><p><strong>Methods: </strong>This population-based cross-sectional Non-human Primate Eye Study recruited middle-aged subjects in South China. All included macaques underwent a detailed ophthalmic examination. LP was calculated using the modified Bennett's formula, with biometry data from an autorefractometer and A-scan. SPSS version 25.0 was used for statistical analysis.</p><p><strong>Results: </strong>A total of 301 macaques with an average age of 18.75 ± 2.95 years were collected in this study. The mean LP was 25.40 ± 2.96 D. Greater LP was independently associated with younger age, longer AL, and lower SE (P = 0.028, P = 0.025, and P = 0.034, respectively). LP showed a positive correlation with age, SE, CR, AL, lens thickness, and anterior chamber depth, whereas no correlation was observed between LP and AL/CR ratio.</p><p><strong>Conclusions: </strong>Our results suggested the LP distribution in the nonhuman primate colony and indicated that AL and SE strongly influenced the rate of LP. Therefore, this study contributed to a deeper understanding of the relative significance of the LP on the optics of the crystalline lens study.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119813","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":"In Vivo Visualization of Intravascular Patrolling Immune Cells in the Primate Eye.","authors":"Drew Ashbery,Hector C Baez,Rye E Kanarr,Karteek Kunala,Derek Power,Colin J Chu,Jesse Schallek,Juliette E McGregor","doi":"10.1167/iovs.65.11.23","DOIUrl":"https://doi.org/10.1167/iovs.65.11.23","url":null,"abstract":"PurposeInsight into the immune status of the living eye is essential as we seek to understand ocular disease and develop new treatments. The nonhuman primate (NHP) is the gold standard preclinical model for therapeutic development in ophthalmology, owing to the similar visual system and immune landscape in the NHP relative to the human. Here, we demonstrate the utility of phase-contrast adaptive optics scanning light ophthalmoscope (AOSLO) to visualize immune cell dynamics on the cellular scale, label-free in the NHP.MethodsPhase-contrast AOSLO was used to image preselected areas of retinal vasculature in five NHP eyes. Images were registered to correct for eye motion, temporally averaged, and analyzed for immune cell activity. Cell counts, dimensions, velocities, and frequency per vessel were determined manually and compared between retinal arterioles and venules. Based on cell appearance and circularity index, cells were divided into three morphologies: ovoid, semicircular, and flattened.ResultsImmune cells were observed migrating along vascular endothelium with and against blood flow. Cell velocity did not significantly differ between morphology or vessel type and was independent of blow flood. Venules had a significantly higher cell frequency than arterioles. A higher proportion of cells resembled \"flattened\" morphology in arterioles. Based on cell speeds, morphologies, and behaviors, we identified these cells as nonclassical patrolling monocytes (NCPMs).ConclusionsPhase-contrast AOSLO has the potential to reveal the once hidden behaviors of single immune cells in retinal circulation and can do so without the requirement of added contrast agents that may disrupt immune cell behavior.","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249911","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":"iPSC-Derived LCHADD Retinal Pigment Epithelial Cells Are Susceptible to Lipid Peroxidation and Rescued by Transfection of a Wildtype AAV-HADHA Vector.","authors":"Tiffany DeVine,Gabriela Elizondo,Garen Gaston,Shannon J Babcock,Dietrich Matern,Mikhail S Shchepinov,Mark E Pennesi,Cary O Harding,Melanie B Gillingham","doi":"10.1167/iovs.65.11.22","DOIUrl":"https://doi.org/10.1167/iovs.65.11.22","url":null,"abstract":"PurposeProgressive choroid and retinal pigment epithelial (RPE) degeneration causing vision loss is a unique characteristic of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), a fatty acid oxidation disorder caused by a common c.1528G>C pathogenic variant in HADHA, the α subunit of the mitochondrial trifunctional protein (TFP). We established and characterized an induced pluripotent stem cell (iPSC)-derived RPE cell model from cultured skin fibroblasts of patients with LCHADD and tested whether addition of wildtype (WT) HAHDA could rescue the phenotypes identified in LCHADD-RPE.MethodsWe constructed an rAAV expression vector containing 3' 3xFLAG-tagged human HADHA cDNA under the transcriptional control of the cytomegalovirus (CMV) enhancer-chicken beta actin (CAG) promoter (CAG-HADHA-3XFLAG). LCHADD-RPE were cultured, matured, and transduced with either AAV-GFP (control) or AAV-HADHA-3XFLAG.ResultsLCHADD-RPE express TFP subunits and accumulate 3-hydroxy-acylcarnitines, cannot oxidize palmitate, and release fewer ketones than WT-RPE. When LCHADD-RPE are exposed to docosahexaenoic acid (DHA), they have increased oxidative stress, lipid peroxidation, decreased viability, and are rescued by antioxidant agents potentially explaining the pathologic mechanism of RPE loss in LCHADD. Transduced LCHADD-RPE expressing a WT copy of TFPα incorporated TFPα-FLAG into the TFP complex in the mitochondria and accumulated significantly less 3-hydroxy-acylcarnitines, released more ketones in response to palmitate, and were more resistant to oxidative stress following DHA exposure than control.ConclusionsiPSC-derived LCHADD-RPE are susceptible to lipid peroxidation mediated cell death and are rescued by exogenous HADHA delivered with rAAV. These results are promising for AAV-HADHA gene addition therapy as a possible treatment for chorioretinopathy in patients with LCHADD.","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249909","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":"Erratum in: Frequency and Genetic Spectrum of Inherited Retinal Dystrophies in a Large Dutch Pediatric Cohort: The RD5000 Consortium.","authors":"","doi":"10.1167/iovs.65.11.26","DOIUrl":"10.1167/iovs.65.11.26","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287410","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":"Quantitative Evaluation of Type 1 and Type 2 Choroidal Neovascularization Components Under Treatment With Projection-Resolved OCT Angiography.","authors":"Kotaro Tsuboi, Qi Sheng You, Jie Wang, Yukun Guo, Christina J Flaxel, Thomas S Hwang, David Huang, Yali Jia, Steven T Bailey","doi":"10.1167/iovs.65.11.32","DOIUrl":"10.1167/iovs.65.11.32","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the response of type 1 and type 2 macular neovascularization (MNV) components under anti-vascular endothelial growth factor (VEGF) treatment in age-related macular degeneration (AMD) using projection-resolved optical coherence tomography angiography (PR-OCTA).</p><p><strong>Methods: </strong>This retrospective study included eyes with treatment-naïve exudative AMD treated with anti-VEGF injections under a pro re nata (PRN) protocol over 1 year. Two-dimensional MNV areas and three-dimensional MNV volumes were derived from macular PR-OCTA scans using an automated convolutional neural network. MNV was detected as flow signal within the outer retinal slab. Type 1 components and type 2 components were analyzed separately.</p><p><strong>Results: </strong>Of 17 enrolled eyes, 12 eyes were pure type 1 MNV and five eyes were type 2 MNV. In eyes with pure type 1, the total (sum of type 1 and type 2 components) MNV area and volume did not change from baseline to 6 months or 12 months (P > 0.05). In eyes with type 2 MNV, the total MNV area significantly decreased from the baseline to 6 months (P = 0.0074) and 12 months (P = 0.014). The total type 2 MNV volume also decreased from baseline visit to visits at 6 months and at 12 months, nearing statistical signifiicance (P = 0.061 and P = 0.074). In eyes with type 2 MNV, the type 1 component increased from 0.093 mm2 to 0.30 mm2 (P = 0.058), and the type 2 component decreased from 0.37 mm2 at 6 months to 0 at 12 months (P = 0.0087).</p><p><strong>Conclusions: </strong>Type 1 and type 2 MNV may have different response under PRN anti-VEGF treatment over 1 year.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287413","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":"Zebrafish Optical Development Requires Regulated Water Permeability by Aquaporin 0.","authors":"Olga Safrina, Irene Vorontsova, Paul J Donaldson, Thomas F Schilling","doi":"10.1167/iovs.65.11.42","DOIUrl":"https://doi.org/10.1167/iovs.65.11.42","url":null,"abstract":"<p><strong>Purpose: </strong>Optical development of the zebrafish eye relies on the movement of the highly refractive lens nucleus from an anterior to a central location in the optical axis during development. We have shown that this mechanism in turn depends on the function of Aquaporin 0a (Aqp0a), a multifunctional and extremely abundant protein in lens fiber cell membranes. Here, we probe the specific cellular functions necessary for rescuing lens nucleus centralization defects in aqp0a-/- null mutants by stable overexpression of an Aqp0 orthologue from a killifish, MIPfun.</p><p><strong>Methods: </strong>We test in vivo requirements for lens transparency and nucleus centralization of MIPfun for auto-adhesion, water permeability (Pf), and Pf sensitivity to regulation by Ca2+ or pH by overexpression of MIPfun mutants previously shown to have defects in these functions in vitro or in silico.</p><p><strong>Results: </strong>Water permeability of MIPfun is essential for rescuing lens transparency and nucleus centralization defects, whereas auto-adhesion is not. Furthermore, water permeability regulation by Ca2+ and pH appear residue-dependent, because some Ca2+-insensitive mutants fail to rescue, and pH-insensitive mutants only partially rescue defects. MIPfun lacking Pf sensitivity to both, Ca2+ and pH, also fails to rescue lens nucleus centralization.</p><p><strong>Conclusion: </strong>This study shows that regulation of water permeability by Aqp0 plays a key role in the centralization of the zebrafish lens nucleus, providing the first direct evidence for water transport in this aspect of optical development.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346862","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}