Acta Neuropathologica Communications最新文献

{"title":"Distinct subcellular localization of tau and alpha-synuclein in lewy body disease.","authors":"D Luke Fischer, Marissa Menard, Omar Z Abdelaziz, Nicholas M Kanaan, Virginia G Cobbs, Richard E Kennedy, Geidy E Serrano, Thomas G Beach, Laura A Volpicelli-Daley","doi":"10.1186/s40478-024-01913-w","DOIUrl":"10.1186/s40478-024-01913-w","url":null,"abstract":"<p><p>Lewy bodies and neurofibrillary tangles, composed of α-synuclein (α-syn) and tau, respectively, often are found together in the same brain and correlate with worsening cognition. Human postmortem studies show colocalization of α-syn and tau occurs in Lewy bodies, but with limited effort to quantify colocalization. In this study, postmortem middle temporal gyrus tissue from decedents (n = 9) without temporal lobe disease (control) or with Lewy body disease (LBD) was immunofluorescently labeled with antibodies to phosphorylated α-syn (p-α-syn), tau phosphorylated at Ser202/Thr205 (p-tau), or exposure of tau's phosphatase-activating domain (PAD-tau) as a marker of early tau aggregates. Immunofluorescence for major-histocompatibility complex class 2 (MHCII) and ionized calcium binding adaptor molecule 1 (Iba1) also was performed because inflammation is an additional pathological hallmark of LBDs, and they were a positive control for two markers known to colocalize. The abundance of p-α-syn, p-tau, and MHCII was significantly associated with diagnosis of LBD. Quantification of colocalization showed that MHCII and Iba1 colocalized, demonstrating activated immune cells are mostly microglia. However, p-α-syn rarely colocalized with p-tau or PAD-tau, although the overlap of p-α-syn with PAD-tau was significantly associated with LBD. In the rare cases pathologic α-syn and pathologic tau were found in the same Lewy body or Lewy neurite, tau appeared to surround α-syn but did not colocalize within the same structure. The relationship between tau and α-syn copathology is important for explaining clinical symptoms, severity, and progression, but there is no evidence for frequent, direct protein-protein interactions in the middle temporal gyrus.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"14"},"PeriodicalIF":6.2,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998208","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":"Recursive seed amplification detects distinct α-synuclein strains in cerebrospinal fluid of patients with Parkinson's disease.","authors":"Stefan Bräuer, Iñaki Schniewind, Elisabeth Dinter, Björn H Falkenburger","doi":"10.1186/s40478-024-01923-8","DOIUrl":"10.1186/s40478-024-01923-8","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with a wide range of clinical phenotypes. Pathologically, it is characterized by neuronal inclusions containing misfolded, fibrillar alpha-synuclein (aSyn). Prion-like properties of aSyn contribute to the spread of aSyn pathology throughout the nervous system as the disease progresses. Utilizing these properties, seed amplification assays (SAA) enable the detection of aSyn pathology in living patients. We hypothesized that structurally distinct aSyn aggregates, or strains, may underlie the clinical heterogeneity of PD. To test this hypothesis, we recursively amplified aSyn fibrils from the cerebrospinal fluid (CSF) of 54 patients (34 people with PD and 20 controls). These fibrils were then characterized regarding SAA kinetic properties and detergent resistance. In addition, cultured cells were transfected with SAA products, and the extent of seeded aSyn pathology was quantified by staining for phosphorylated aSyn followed by automated high-throughput microscopy and image analysis. We found that fibrils, amplified from CSF by recursive SAA, exhibit two types of distinct biophysical properties and have different seeding capacities in cells. These properties are associated with clinical parameters and may therefore help explain the clinical heterogeneity in PD. Measuring aSyn strains may be relevant for prognosis and for therapies targeting aSyn pathology.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"13"},"PeriodicalIF":6.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998264","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":"Discontiguous recurrences of IDH-wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutated.","authors":"Malcolm F McDonald, Sricharan Gopakumar, Tareq A Juratli, Ilker Y Eyüpoglu, Ganesh Rao, Jacob J Mandel, Ali Jalali","doi":"10.1186/s40478-024-01900-1","DOIUrl":"https://doi.org/10.1186/s40478-024-01900-1","url":null,"abstract":"<p><p>Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences. In our institutional database, we identified 22 patients with targeted exome sequencing of pairs of initial and recurrent IDH-wildtype glioblastoma. Recurrences were classified as contiguous or discontiguous based on the presence or absence of T2 FLAIR signal connection to the initial site of disease on MRI. Exome analysis revealed shared driver and passenger mutations between discontiguous recurrences and initial tumors, supporting a common origin. Discontiguous recurrences were more likely to be hypermutated compared to contiguous recurrences (p = 0.038). Analysis of 2 glioblastoma cases with discontiguous recurrence at a collaborating institution also exhibited hypermutation. In conclusion, discontiguous glioblastoma recurrences share a common origin with the initial tumor and are more likely to be hypermutated than contiguous recurrences.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"9"},"PeriodicalIF":6.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998227","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":"Pediatric high-grade gliomas with concomitant RB1 and SETD2 alterations and Li-Fraumeni syndrome.","authors":"Arnault Tauziède-Espariat, Marie Simbozel, Philipp Sievers, Volodia Dangouloff-Ros, Lelio Guida, Thomas Blauwblomme, Kévin Beccaria, Raphael Saffroy, Lauren Hasty, Alice Métais, Jacques Grill, Léa Guerrini-Rousseau, Pascale Varlet","doi":"10.1186/s40478-024-01885-x","DOIUrl":"https://doi.org/10.1186/s40478-024-01885-x","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"8"},"PeriodicalIF":6.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998209","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":"Unraveling calcium dysregulation and autoimmunity in immune mediated rippling muscle disease.","authors":"Samir R Nath, Aneesha Dasgupta, Divyanshu Dubey, Eileen Kokesh, Grayson Beecher, Numrah Fadra, Teerin Liewuck, Sean Pittock, Jason D Doles, William Litchy, Margherita Milone","doi":"10.1186/s40478-025-01926-z","DOIUrl":"https://doi.org/10.1186/s40478-025-01926-z","url":null,"abstract":"<p><p>Rippling Muscle Disease (RMD) is a rare skeletal myopathy characterized by abnormal muscular excitability manifesting with wave-like muscle contractions and percussion-induced muscle mounding. Hereditary RMD is associated with caveolin-3 or cavin-1 mutations. Recently, we identified cavin 4 autoantibodies as a biomarker of immune-mediated RMD (iRMD), though the underlying disease-mechanisms remain poorly understood. Transcriptomic studies were performed on muscle biopsies of 8 patients (5 males; 3 females; ages 26-to-80) with iRMD. Subsequent pathway analysis compared iRMD to human non-disease control and disease control (dermatomyositis) muscle samples. Transcriptomic studies demonstrated changes in key pathways of muscle contraction and development. All iRMD samples had significantly upregulated cavin-4 expression compared to controls, likely compensatory for autoantibody-mediated protein degradation. Proteins involved in muscle relaxation (including SERCA1, PMCA and PLN) were significantly increased in iRMD compared to controls. Comparison of iRMD to dermatomyositis transcriptomics demonstrated significant overlap in immune pathways, and the IL-6 signaling pathway was markedly increased in all iRMD patient muscle biopsies and increased in the majority of iRMD patients' serum. This study represents the first muscle transcriptomic analysis of iRMD patients and dissects underlying disease mechanisms. Increase of sarcolemmal and cellular calcium channels as well as PLN, an inhibitor of the SERCA pump for calcium into the sarcoplasm, likely alters the calcium dynamics in iRMD. These changes in crucial components of muscle relaxation may underlie rippling by altering calcium flux. Our findings provide crucial insights into the differential expression of genes regulating muscle relaxation and highlight potential disease pathomechanisms.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"11"},"PeriodicalIF":6.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998266","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":"An exceptionally rare case of a diffuse midline glioma with concomitant H3.1 K27M and G34R mutations in the HIST1H3C (H3C3) gene.","authors":"Zita Reisz, Rita Pereira, Smitha Nevis, Alan Mackay, Leena Bhaw, Yura Grabovska, Ross Laxton, Valeria Molinari, Anna Burford, Barnaby Clark, Cristina Bleil, Bassel Zebian, Erika Pace, Annette Weiser, Fernando Carceller, Lynley Marshall, Andrew King, Istvan Bodi, Safa Al-Sarraj, Chris Jones, Matthew Clarke","doi":"10.1186/s40478-024-01899-5","DOIUrl":"https://doi.org/10.1186/s40478-024-01899-5","url":null,"abstract":"<p><p>Histone mutations (H3 K27M, H3 G34R/V) are molecular features defining subtypes of paediatric-type diffuse high-grade gliomas (HGG) (diffuse midline glioma (DMG), H3 K27-altered, diffuse hemispheric glioma (DHG), H3 G34-mutant). The WHO classification recognises in exceptional cases, these mutations co-occur. We report one such case of a 2-year-old female presenting with neurological symptoms; MRI imaging identified a brainstem lesion which was biopsied. Histology showed diffusely infiltrating pleomorphic astrocytes, multinucleated cells, and conspicuous mitotic activity; the diagnosis was DMG, H3 K27-altered (immunohistochemistry: H3K27me3 loss, H3K27M positivity). DNA methylation profiling (Illumina EPIC BeadArrays, brain tumour classifier (MNP v12.5 R package)) classified the tumour as 'DMG, H3 K27-altered' (calibrated score = 0.99). Further molecular studies (whole exome, whole genome sequencing) revealed concurrent H3.1 K27M and G34R mutations (clonal, in the same reads) of H3C3, FGF11 and PIK3CA somatic variants, and a pathogenic germline NBN variant. The RNAseq profile clustered with H3K27M-mutant tumours. A patient-derived cell culture was established enabling unbiased in vitro drug screening; no selective sensitivities were identified. Chromatin immunoprecipitation assays with sequencing (ChIP-seq; H3K27ac, H3K27me3, H3K36me3, RNApol2 marks) showed features in keeping with DMG H3 K27M-mutant tumours (H3K27ac loci including OLIG2, IRX1/2, PKDCC). The patient was treated with adjuvant radiotherapy, but progressed and passed away 13 months post-diagnosis. This case is an exceptionally rare, complex variant of histone-mutant paediatric HGG, illustrating that the H3.1 K27M mutation demonstrates a dominance over the molecular and clinical profiles compared to G34R, and highlights the importance of broad molecular profiling to identify such examples for further study.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"7"},"PeriodicalIF":6.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998226","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":"Transcriptome analysis of novel B16 melanoma metastatic variants generated by serial intracarotid artery injection.","authors":"Jenny C Kienzler, Erick M Contreras, Janet Treger, Linda M Liau, Geoffrey C Owens, Robert M Prins","doi":"10.1186/s40478-025-01924-1","DOIUrl":"https://doi.org/10.1186/s40478-025-01924-1","url":null,"abstract":"<p><p>The incidence of brain metastases (BrM) in patients with metastatic melanoma is reported to be 30-50% and constitutes the third most frequent BrM after breast and renal cancers. Treatment strategies including surgical resection, stereotactic radiation, and immunotherapy have improved clinical response rates and overall survival, but the changes that occur in circulating melanoma cells to promote invasion of the brain are not fully understood. To investigate brain tropism, we generated new variants of the B16 mouse melanoma model by serially passaging B16 cells through the brain of immune competent syngeneic C57BL/6 mice. Cells were injected into the right carotid artery and recovered from the brain after the mice had reached the study endpoint due to tumor burden, then expanded in vitro and reinjected. We compared the transcriptomes of 4th generation B16 cell populations from separate lineages with the founder B16-F0 cells. Gene set enrichment analysis (GSEA) of differentially expressed protein coding genes revealed that cells isolated from the brain as well as from the lung and meninges expressed higher levels of genes associated with an epithelial to mesenchymal transition (EMT), upregulation of the KRAS signaling pathway, and a metastasis aggressiveness gene signature associated with poor survival in melanoma patients. Principal component analysis of differentially expressed genes showed that 4th generation melanoma cells isolated from the brain, lung and meninges from one lineage were distinct from those of the other three lineages. Among the differentially expressed genes, transcript levels of several genes, including Itgb2, Rftn2, and Kcnn4, were significantly higher in all cell populations that comprised this lineage compared with all cell populations from the other three lineages. In conclusion, we have derived an aggressive, highly brain metastatic B16 variant associated with leptomeningeal disease by serially passaging cells in vivo.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"10"},"PeriodicalIF":6.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998265","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":"Personalising glioblastoma medicine: explant organoid applications, challenges and future perspectives.","authors":"Niclas Skarne, Rochelle C J D'Souza, Helen M Palethorpe, Kylah A Bradbrook, Guillermo A Gomez, Bryan W Day","doi":"10.1186/s40478-025-01928-x","DOIUrl":"10.1186/s40478-025-01928-x","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a highly aggressive adult brain cancer, characterised by poor prognosis and a dismal five-year survival rate. Despite significant knowledge gains in tumour biology, meaningful advances in patient survival remain elusive. The field of neuro-oncology faces many disease obstacles, one being the paucity of faithful models to advance preclinical research and guide personalised medicine approaches. Recent technological developments have permitted the maintenance, expansion and cryopreservation of GBM explant organoid (GBO) tissue. GBOs represent a translational leap forward and are currently the state-of-the-art in 3D in vitro culture system, retaining brain cancer heterogeneity, and transiently maintaining the immune infiltrate and tumour microenvironment (TME). Here, we provide a review of existing brain cancer organoid technologies, in vivo xenograft approaches, evaluate in-detail the key advantages and limitations of this rapidly emerging technology, and consider solutions to overcome these difficulties. GBOs currently hold significant promise, with the potential to emerge as the key translational tool to synergise and enhance next-generation omics efforts and guide personalised medicine approaches for brain cancer patients into the future.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"6"},"PeriodicalIF":6.2,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969238","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":"Correction: Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice.","authors":"Elena Niccolai, Leandro Di Gloria, Maria Chiara Trolese, Paola Fabbrizio, Simone Baldi, Giulia Nannini, Cassandra Margotta, Claudia Nastasi, Matteo Ramazzotti, Gianluca Bartolucci, Caterina Bendotti, Giovanni Nardo, Amedeo Amedei","doi":"10.1186/s40478-024-01910-z","DOIUrl":"10.1186/s40478-024-01910-z","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"5"},"PeriodicalIF":6.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963536","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":"Biglycan-driven risk stratification in ZFTA-RELA fusion supratentorial ependymomas through transcriptome profiling.","authors":"Konstantin Okonechnikov, David R Ghasemi, Daniel Schrimpf, Svenja Tonn, Martin Mynarek, Jan Koster, Till Milde, Tuyu Zheng, Philipp Sievers, Felix Sahm, David T W Jones, Andreas von Deimling, Stefan M Pfister, Marcel Kool, Kristian W Pajtler, Andrey Korshunov","doi":"10.1186/s40478-024-01921-w","DOIUrl":"https://doi.org/10.1186/s40478-024-01921-w","url":null,"abstract":"<p><p>Recent genomic studies have allowed the subdivision of intracranial ependymomas into molecularly distinct groups with highly specific clinical features and outcomes. The majority of supratentorial ependymomas (ST-EPN) harbor ZFTA-RELA fusions which were designated, in general, as an intermediate risk tumor variant. However, molecular prognosticators within ST-EPN ZFTA-RELA have not been determined yet. Here, we performed methylation-based DNA profiling and transcriptome RNA sequencing analysis of 80 ST-EPN ZFTA-RELA investigating the clinical significance of various molecular patterns. The principal types of ZFTA-RELA fusions, based on breakpoint location, demonstrated no significant correlations with clinical outcomes. Multigene analysis disclosed 1892 survival-associated genes, and a metagene set of 100 genes subdivided ST-EPN ZFTA-RELA into favorable and unfavorable transcriptome subtypes composed of different cell subpopulations as detected by deconvolution analysis. BGN (biglycan) was identified as the top-ranked survival-associated gene and high BGN expression levels were associated with poor survival (Hazard Ratio 17.85 for PFS and 45.48 for OS; log-rank; p-value < 0.01). Furthermore, BGN immunopositivity was identified as a strong prognostic indicator of poor survival in ST-EPN, and this finding was confirmed in an independent validation set of 56 samples. Our results indicate that integrating BGN expression (at mRNA and/or protein level) into risk stratification models may improve ST-EPN ZFTA-RELA outcome prediction. Therefore, gene and/or protein expression analyses for this molecular marker could be adopted for ST-EPN ZFTA-RELA prognostication and may help assign patients to optimal therapies in prospective clinical trials.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"13 1","pages":"4"},"PeriodicalIF":6.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942316","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}