Neuromyelitis optica (NMO) spectrum disorder (NMOSD) is a relapsing inflammatory disease of the CNS, characterized by the presence of serum aquaporin 4 (AQP4) autoantibodies (AQP4-IgGs) and core clinical manifestations such as optic neuritis, myelitis, and brain or brainstem syndromes. Some people exhibit clinical characteristics of NMOSD but test negative for AQP4-IgG, and a subset of these individuals are now recognized to have serum autoantibodies against myelin oligodendrocyte glycoprotein (MOG) — a condition termed MOG antibody-associated disease (MOGAD). Therefore, the concept of NMOSD is changing, with a disease spectrum emerging that includes AQP4-IgG-seropositive NMOSD, MOGAD and double-seronegative NMOSD. MOGAD shares features with NMOSD, including optic neuritis and myelitis, but has distinct pathophysiology, clinical profiles, neuroimaging findings (including acute disseminated encephalomyelitis and/or cortical encephalitis) and biomarkers. AQP4-IgG-seronegative NMOSD seems to be a heterogeneous condition and requires further study. MOGAD can manifest as either a monophasic or a relapsing disease, whereas NMOSD is usually relapsing. This Review summarizes the history and current concepts of NMOSD and MOGAD, comparing epidemiology, clinical features, neuroimaging, pathology and immunology. In addition, we discuss new monoclonal antibody therapies for AQP4-IgG-seropositive NMOSD that target complement, B cells or IL-6 receptors, which might be applied to MOGAD in the near future. This Review summarizes the history and current concepts of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), including epidemiology, clinical and neuroimaging features and pathophysiology. It also discusses new molecularly targeted therapies for NMOSD that might be also applied to MOGAD in the future.
{"title":"NMOSD and MOGAD: an evolving disease spectrum","authors":"Akiyuki Uzawa, Frederike Cosima Oertel, Masahiro Mori, Friedemann Paul, Satoshi Kuwabara","doi":"10.1038/s41582-024-01014-1","DOIUrl":"10.1038/s41582-024-01014-1","url":null,"abstract":"Neuromyelitis optica (NMO) spectrum disorder (NMOSD) is a relapsing inflammatory disease of the CNS, characterized by the presence of serum aquaporin 4 (AQP4) autoantibodies (AQP4-IgGs) and core clinical manifestations such as optic neuritis, myelitis, and brain or brainstem syndromes. Some people exhibit clinical characteristics of NMOSD but test negative for AQP4-IgG, and a subset of these individuals are now recognized to have serum autoantibodies against myelin oligodendrocyte glycoprotein (MOG) — a condition termed MOG antibody-associated disease (MOGAD). Therefore, the concept of NMOSD is changing, with a disease spectrum emerging that includes AQP4-IgG-seropositive NMOSD, MOGAD and double-seronegative NMOSD. MOGAD shares features with NMOSD, including optic neuritis and myelitis, but has distinct pathophysiology, clinical profiles, neuroimaging findings (including acute disseminated encephalomyelitis and/or cortical encephalitis) and biomarkers. AQP4-IgG-seronegative NMOSD seems to be a heterogeneous condition and requires further study. MOGAD can manifest as either a monophasic or a relapsing disease, whereas NMOSD is usually relapsing. This Review summarizes the history and current concepts of NMOSD and MOGAD, comparing epidemiology, clinical features, neuroimaging, pathology and immunology. In addition, we discuss new monoclonal antibody therapies for AQP4-IgG-seropositive NMOSD that target complement, B cells or IL-6 receptors, which might be applied to MOGAD in the near future. This Review summarizes the history and current concepts of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), including epidemiology, clinical and neuroimaging features and pathophysiology. It also discusses new molecularly targeted therapies for NMOSD that might be also applied to MOGAD in the future.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"602-619"},"PeriodicalIF":28.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142175002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1038/s41582-024-01017-y
Heather Wood
New research adds to growing evidence of altered tau phosphorylation in multiple sclerosis.
新的研究补充了越来越多的证据，表明多发性硬化症患者的 tau 磷酸化发生了改变。
{"title":"Tau phosphorylation correlates with multiple sclerosis disease course","authors":"Heather Wood","doi":"10.1038/s41582-024-01017-y","DOIUrl":"10.1038/s41582-024-01017-y","url":null,"abstract":"New research adds to growing evidence of altered tau phosphorylation in multiple sclerosis.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"569-569"},"PeriodicalIF":28.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1038/s41582-024-01011-4
Håkan Ashina, Rune H. Christensen, Debbie L. Hay, Amynah A. Pradhan, Jan Hoffmann, Dora Reglodi, Andrew F. Russo, Messoud Ashina
Migraine is a disabling neurological disorder that affects more than one billion people worldwide. The clinical presentation is characterized by recurrent headache attacks, which are often accompanied by photophobia, phonophobia, nausea and vomiting. Although the pathogenesis of migraine remains incompletely understood, mounting evidence suggests that specific signalling molecules are involved in the initiation and modulation of migraine attacks. These signalling molecules include pituitary adenylate cyclase-activating polypeptide (PACAP), a vasoactive peptide that is known to induce migraine attacks when administered by intravenous infusion to people with migraine. Discoveries linking PACAP to migraine pathogenesis have led to the development of drugs that target PACAP signalling, and a phase II trial has provided evidence that a monoclonal antibody against PACAP is effective for migraine prevention. In this Review, we explore the molecular and cellular mechanisms of PACAP signalling, shedding light on its role in the trigeminovascular system and migraine pathogenesis. We then discuss emerging therapeutic strategies that target PACAP signalling for the treatment of migraine and consider the research needed to translate the current knowledge into a treatment for migraine in the clinic. Pituitary adenylate cyclase-activating polypeptide signalling has been linked to migraine pathogenesis. In this Review, Ashina and co-workers explore the molecular and cellular mechanisms of pituitary adenylate cyclase-activating polypeptide signalling and discuss emerging therapeutic strategies to target this pathway for migraine treatment.
{"title":"Pituitary adenylate cyclase-activating polypeptide signalling as a therapeutic target in migraine","authors":"Håkan Ashina, Rune H. Christensen, Debbie L. Hay, Amynah A. Pradhan, Jan Hoffmann, Dora Reglodi, Andrew F. Russo, Messoud Ashina","doi":"10.1038/s41582-024-01011-4","DOIUrl":"10.1038/s41582-024-01011-4","url":null,"abstract":"Migraine is a disabling neurological disorder that affects more than one billion people worldwide. The clinical presentation is characterized by recurrent headache attacks, which are often accompanied by photophobia, phonophobia, nausea and vomiting. Although the pathogenesis of migraine remains incompletely understood, mounting evidence suggests that specific signalling molecules are involved in the initiation and modulation of migraine attacks. These signalling molecules include pituitary adenylate cyclase-activating polypeptide (PACAP), a vasoactive peptide that is known to induce migraine attacks when administered by intravenous infusion to people with migraine. Discoveries linking PACAP to migraine pathogenesis have led to the development of drugs that target PACAP signalling, and a phase II trial has provided evidence that a monoclonal antibody against PACAP is effective for migraine prevention. In this Review, we explore the molecular and cellular mechanisms of PACAP signalling, shedding light on its role in the trigeminovascular system and migraine pathogenesis. We then discuss emerging therapeutic strategies that target PACAP signalling for the treatment of migraine and consider the research needed to translate the current knowledge into a treatment for migraine in the clinic. Pituitary adenylate cyclase-activating polypeptide signalling has been linked to migraine pathogenesis. In this Review, Ashina and co-workers explore the molecular and cellular mechanisms of pituitary adenylate cyclase-activating polypeptide signalling and discuss emerging therapeutic strategies to target this pathway for migraine treatment.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 11","pages":"660-670"},"PeriodicalIF":28.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1038/s41582-024-01006-1
Giancarlo Comi, Gloria Dalla Costa, Bruno Stankoff, Hans-Peter Hartung, Per Soelberg Sørensen, Patrick Vermersch, Letizia Leocani
Progressive multiple sclerosis poses a considerable challenge in the evaluation of disease progression and treatment response owing to its multifaceted pathophysiology. Traditional clinical measures such as the Expanded Disability Status Scale are limited in capturing the full scope of disease and treatment effects. Advanced imaging techniques, including MRI and PET scans, have emerged as valuable tools for the assessment of neurodegenerative processes, including the respective role of adaptive and innate immunity, detailed insights into brain and spinal cord atrophy, lesion dynamics and grey matter damage. The potential of cerebrospinal fluid and blood biomarkers is increasingly recognized, with neurofilament light chain levels being a notable indicator of neuro-axonal damage. Moreover, patient-reported outcomes are crucial for reflecting the subjective experience of disease progression and treatment efficacy, covering aspects such as fatigue, cognitive function and overall quality of life. The future incorporation of digital technologies and wearable devices in research and clinical practice promises to enhance our understanding of functional impairments and disease progression. This Review offers a comprehensive examination of these diverse evaluation tools, highlighting their combined use in accurately assessing disease progression and treatment efficacy in progressive multiple sclerosis, thereby guiding more effective therapeutic strategies. The approval of therapies for progressive multiple sclerosis has heightened the need for thorough assessment of disease progression and treatment response. This Review provides a comprehensive summary of available and emerging techniques, including advanced imaging, fluid biomarkers and patient-reported outcomes, highlighting their combined use for the accurate assessment of disease.
进展期多发性硬化症的病理生理学具有多面性，因此对疾病进展和治疗反应的评估提出了巨大挑战。传统的临床测量方法，如 "残疾状况扩展量表"（Expanded Disability Status Scale），在全面反映疾病和治疗效果方面存在局限性。先进的成像技术，包括核磁共振成像和正电子发射计算机断层扫描，已成为评估神经退行性病变过程的重要工具，包括适应性免疫和先天性免疫各自的作用、大脑和脊髓萎缩的详细情况、病变动态和灰质损伤。脑脊液和血液生物标志物的潜力日益得到认可，其中神经丝轻链水平是神经轴损伤的一个显著指标。此外，患者报告的结果对于反映疾病进展和治疗效果的主观感受至关重要，包括疲劳、认知功能和整体生活质量等方面。未来，数字技术和可穿戴设备在研究和临床实践中的应用有望增强我们对功能障碍和疾病进展的了解。本综述全面探讨了这些不同的评估工具，重点介绍了它们在准确评估进展期多发性硬化症的疾病进展和治疗效果方面的综合应用，从而为更有效的治疗策略提供指导。
{"title":"Assessing disease progression and treatment response in progressive multiple sclerosis","authors":"Giancarlo Comi, Gloria Dalla Costa, Bruno Stankoff, Hans-Peter Hartung, Per Soelberg Sørensen, Patrick Vermersch, Letizia Leocani","doi":"10.1038/s41582-024-01006-1","DOIUrl":"10.1038/s41582-024-01006-1","url":null,"abstract":"Progressive multiple sclerosis poses a considerable challenge in the evaluation of disease progression and treatment response owing to its multifaceted pathophysiology. Traditional clinical measures such as the Expanded Disability Status Scale are limited in capturing the full scope of disease and treatment effects. Advanced imaging techniques, including MRI and PET scans, have emerged as valuable tools for the assessment of neurodegenerative processes, including the respective role of adaptive and innate immunity, detailed insights into brain and spinal cord atrophy, lesion dynamics and grey matter damage. The potential of cerebrospinal fluid and blood biomarkers is increasingly recognized, with neurofilament light chain levels being a notable indicator of neuro-axonal damage. Moreover, patient-reported outcomes are crucial for reflecting the subjective experience of disease progression and treatment efficacy, covering aspects such as fatigue, cognitive function and overall quality of life. The future incorporation of digital technologies and wearable devices in research and clinical practice promises to enhance our understanding of functional impairments and disease progression. This Review offers a comprehensive examination of these diverse evaluation tools, highlighting their combined use in accurately assessing disease progression and treatment efficacy in progressive multiple sclerosis, thereby guiding more effective therapeutic strategies. The approval of therapies for progressive multiple sclerosis has heightened the need for thorough assessment of disease progression and treatment response. This Review provides a comprehensive summary of available and emerging techniques, including advanced imaging, fluid biomarkers and patient-reported outcomes, highlighting their combined use for the accurate assessment of disease.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"573-586"},"PeriodicalIF":28.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03DOI: 10.1038/s41582-024-01012-3
Marinos C. Dalakas
Stiff-person syndrome (SPS) is the prototypical and most common autoimmune neuronal hyperexcitability disorder. It presents with stiffness in the limbs and axial muscles, stiff gait with uncontrolled falls, and episodic painful muscle spasms triggered by anxiety, task-specific phobias and startle responses, collectively leading to disability. Increased awareness of SPS among patients and physicians has created concerns about diagnosis, misdiagnosis and treatment. This Review addresses the evolving diagnostic challenges in SPS and overlapping glutamic acid decarboxylase (GAD) antibody spectrum disorders, highlighting the growing number of overdiagnoses and focusing on the progress made in our understanding of SPS pathophysiology, antibodies against GAD and other inhibitory synaptic antigens, and the fundamentals of neuronal hyperexcitability. It considers the role of impaired GABAergic or glycinergic inhibition in the cortex and at multiple levels in the neuraxis; the underlying autoimmunity and involvement of GAD antibodies; immunopathogenic mechanisms beyond antibodies, including environmental triggers; familial and immunogenetic susceptibility; and potential T cell cytotoxicity. Finally, the mechanistic rationale for target-specific therapeutic interventions is presented along with the available therapeutic approaches, including enhancers of GABA signalling drugs and immunotherapies. Stiff-person syndrome is an autoimmune neuronal hyperexcitability disorder that causes limb stiffness, painful spasms and falls, and increased awareness of the disease is creating diagnostic and management challenges. In this Review, Dalakas provides an overview of the current clinical and mechanistic understanding of stiff-person syndrome and related disorders and discusses current and emerging therapeutic interventions.
{"title":"Stiff-person syndrome and related disorders — diagnosis, mechanisms and therapies","authors":"Marinos C. Dalakas","doi":"10.1038/s41582-024-01012-3","DOIUrl":"10.1038/s41582-024-01012-3","url":null,"abstract":"Stiff-person syndrome (SPS) is the prototypical and most common autoimmune neuronal hyperexcitability disorder. It presents with stiffness in the limbs and axial muscles, stiff gait with uncontrolled falls, and episodic painful muscle spasms triggered by anxiety, task-specific phobias and startle responses, collectively leading to disability. Increased awareness of SPS among patients and physicians has created concerns about diagnosis, misdiagnosis and treatment. This Review addresses the evolving diagnostic challenges in SPS and overlapping glutamic acid decarboxylase (GAD) antibody spectrum disorders, highlighting the growing number of overdiagnoses and focusing on the progress made in our understanding of SPS pathophysiology, antibodies against GAD and other inhibitory synaptic antigens, and the fundamentals of neuronal hyperexcitability. It considers the role of impaired GABAergic or glycinergic inhibition in the cortex and at multiple levels in the neuraxis; the underlying autoimmunity and involvement of GAD antibodies; immunopathogenic mechanisms beyond antibodies, including environmental triggers; familial and immunogenetic susceptibility; and potential T cell cytotoxicity. Finally, the mechanistic rationale for target-specific therapeutic interventions is presented along with the available therapeutic approaches, including enhancers of GABA signalling drugs and immunotherapies. Stiff-person syndrome is an autoimmune neuronal hyperexcitability disorder that causes limb stiffness, painful spasms and falls, and increased awareness of the disease is creating diagnostic and management challenges. In this Review, Dalakas provides an overview of the current clinical and mechanistic understanding of stiff-person syndrome and related disorders and discusses current and emerging therapeutic interventions.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"587-601"},"PeriodicalIF":28.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03DOI: 10.1038/s41582-024-01005-2
Ruth Geraldes, Georgina Arrambide, Brenda Banwell, Àlex Rovira, Rosa Cortese, Hans Lassmann, Silvia Messina, Mara Assunta Rocca, Patrick Waters, Declan Chard, Claudio Gasperini, Yael Hacohen, Romina Mariano, Friedemann Paul, Gabriele C. DeLuca, Christian Enzinger, Ludwig Kappos, M. Isabel Leite, Jaume Sastre-Garriga, Tarek Yousry, Olga Ciccarelli, Massimo Filippi, Frederik Barkhof, Jacqueline Palace, MAGNIMS Study Group
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that are an essential component of MOGAD diagnosis are not standardized. Accurate diagnosis of MOGAD is crucial because the treatments and long-term prognosis differ from those for MS. This Expert Recommendation summarizes the outcomes from a Magnetic Resonance Imaging in MS workshop held in Oxford, UK in May 2022, in which MS and MOGAD experts reflected on the pathology and clinical features of these disorders, the contributions of MRI to their diagnosis and the clinical use of the MOG antibody assay. We also critically reviewed the literature to assess the validity of distinctive imaging features in the current MS and MOGAD criteria. We conclude that dedicated orbital and spinal cord imaging (with axial slices) can inform MOGAD diagnosis and also illuminate differential diagnoses. We provide practical guidance to neurologists and neuroradiologists on how to navigate the current MOGAD and MS criteria. We suggest a strategy that includes useful imaging discriminators on standard clinical MRI and discuss imaging features detected by non-conventional MRI sequences that demonstrate promise in differentiating these two disorders. Myelin oligodendrocyte glycoprotein antibody-associated disease is an immune-mediated demyelinating disease that is distinct from multiple sclerosis but shares some of its characteristics. This Expert Recommendation, based on a Magnetic Resonance Imaging in MS workshop, proposes a diagnostic algorithm for the differential diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease and multiple sclerosis, using serological, imaging and clinical features.
{"title":"The influence of MOGAD on diagnosis of multiple sclerosis using MRI","authors":"Ruth Geraldes, Georgina Arrambide, Brenda Banwell, Àlex Rovira, Rosa Cortese, Hans Lassmann, Silvia Messina, Mara Assunta Rocca, Patrick Waters, Declan Chard, Claudio Gasperini, Yael Hacohen, Romina Mariano, Friedemann Paul, Gabriele C. DeLuca, Christian Enzinger, Ludwig Kappos, M. Isabel Leite, Jaume Sastre-Garriga, Tarek Yousry, Olga Ciccarelli, Massimo Filippi, Frederik Barkhof, Jacqueline Palace, MAGNIMS Study Group","doi":"10.1038/s41582-024-01005-2","DOIUrl":"10.1038/s41582-024-01005-2","url":null,"abstract":"Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that are an essential component of MOGAD diagnosis are not standardized. Accurate diagnosis of MOGAD is crucial because the treatments and long-term prognosis differ from those for MS. This Expert Recommendation summarizes the outcomes from a Magnetic Resonance Imaging in MS workshop held in Oxford, UK in May 2022, in which MS and MOGAD experts reflected on the pathology and clinical features of these disorders, the contributions of MRI to their diagnosis and the clinical use of the MOG antibody assay. We also critically reviewed the literature to assess the validity of distinctive imaging features in the current MS and MOGAD criteria. We conclude that dedicated orbital and spinal cord imaging (with axial slices) can inform MOGAD diagnosis and also illuminate differential diagnoses. We provide practical guidance to neurologists and neuroradiologists on how to navigate the current MOGAD and MS criteria. We suggest a strategy that includes useful imaging discriminators on standard clinical MRI and discuss imaging features detected by non-conventional MRI sequences that demonstrate promise in differentiating these two disorders. Myelin oligodendrocyte glycoprotein antibody-associated disease is an immune-mediated demyelinating disease that is distinct from multiple sclerosis but shares some of its characteristics. This Expert Recommendation, based on a Magnetic Resonance Imaging in MS workshop, proposes a diagnostic algorithm for the differential diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease and multiple sclerosis, using serological, imaging and clinical features.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"620-635"},"PeriodicalIF":28.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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