Brain最新文献

{"title":"Harnessing psychedelics for stroke recovery: therapeutic potential and mechanisms.","authors":"Yuefeng Yang, Yibo Wang, Xiaohui Wang","doi":"10.1093/brain/awaf093","DOIUrl":"https://doi.org/10.1093/brain/awaf093","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565933","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}

{"title":"Towards precision MRI biomarkers in epilepsy with normative modelling.","authors":"Remika Mito, James Cole, Sila Genc, Graeme Jackson, Andrew Zalesky","doi":"10.1093/brain/awaf090","DOIUrl":"https://doi.org/10.1093/brain/awaf090","url":null,"abstract":"<p><p>Epilepsy is recognised as one of the leading targets for precision medicine, following on from the successes in cancer therapy, due to its substantial clinical heterogeneity and divergent therapeutic options. To bring personalised care to the epilepsies, there is a need for appropriate precision biomarkers that can identify disease processes or predict treatment outcomes at the individual patient level. Neuroimaging techniques, including magnetic resonance imaging (MRI), have been transformative for clinical practice, particularly in medically refractory focal epilepsies. Advanced MRI techniques have the potential to bring precision medicine clearly into view for epileptology; however, there are challenges that must be overcome before cutting-edge neuroimaging tools can be used in clinical practice. In this Review article, we communicate our view that implementation of normative modelling frameworks will help to deliver robust quantitative MRI biomarkers for individualized prediction. Here, we provide recommendations for researchers and clinicians alike, from careful research design to clinical applications, that will help to identify diagnostic and predictive imaging biomarkers. Such precision markers will be key to delivering personalised medicine for the epilepsies.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565936","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}

{"title":"The presence and prognosis of nerve pathology following whiplash injury: a prospective cohort study.","authors":"Joel Fundaun, Colette Ridehalgh, Soraya Koushesh, Alex Novak, Macarena Tejos-Bravo, Stephen Bremner, Georgios Baskozos, Andrew Dilley, Annina B Schmid","doi":"10.1093/brain/awaf088","DOIUrl":"https://doi.org/10.1093/brain/awaf088","url":null,"abstract":"<p><p>Whiplash Associated Disorders (WAD) affect 20-50 million individuals globally each year, with up to 50% developing persistent pain. WAD grade II (WADII) is the most common type and is characterised by neck symptoms and musculoskeletal signs without apparent nerve injury on routine diagnostic testing. However, emerging evidence suggests nerve pathology may be present in some people with WADII. This longitudinal cohort study aimed to comprehensively investigate the presence, temporal patterns, and prognostic value of nerve pathology and neuropathic pain in acute WADII. A prospective longitudinal cohort study was conducted with 129 acute participants with WADII (median age 36.0 years, 58% female) and 36 healthy controls (median age 39.0 years, 61% female). Participants with WADII were recruited within four weeks of injury from local emergency departments. Data collection included bedside neurological assessments, quantitative sensory testing (QST), intraepidermal nerve fibre density, and serum neurofilament light chain (NfL) concentrations. Follow-up assessments were conducted 6-months after injury. Signs of neuropathic pain were present in 65% (84/129) acutely and persisted in 32% (21/66) 6-months post-injury. Bedside neurological assessment revealed somatosensory loss of function was present in 54% (70/129) acutely reducing to 25% (17/67) 6-months post-injury. QST demonstrated significantly reduced cold, warm, thermal sensory limen, mechanical, and vibration detection thresholds in acute WADII compared to controls (d>0.47). Acute loss of function in at least one QST parameter was present in 67.6% (85/126) of WADII. At 6-months, participants with WADII showed persistent hypoaesthesia to warm, thermal sensory limen, and mechanical detection thresholds, and decreased mechanical pain and pressure pain sensitivity compared to controls (d>0.44). These functional neurological changes were accompanied by elevated serum neurofilament light chain levels in acute WADII compared to controls (d=-0.52 (95% confidence interval -0.94, -0.10). Intraepidermal nerve fibre densities at the index finger were not significantly different between groups. However, dermal MBP+/PGP+ myelinated nerve bundles at the index finger were reduced 6-months post-injury in WADII compared to controls (d=0.69 (0.26, 1.11). Multivariable linear regression suggested bedside tests for hypoaesthesia at the index finger were prognostic for whiplash-related upper quadrant pain 6-months post-injury (r2=0.13, p=0.02). In conclusion, two-thirds of participants with acute WADII initially exhibited signs of neuropathic pain and nerve pathology. At the 6-month follow-up, neuropathic pain persisted in one-third of participants with WADII, while nerve pathology persisted in two-thirds. These findings challenge the traditional musculoskeletal classification of WADII and underscore the need for targeted neurological assessments and treatment.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555865","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}

{"title":"Serotonergic dysfunction in patients with impulse control disorders in Parkinson's disease.","authors":"Stéphane Prange, Elise Metereau, Hélène Klinger, Marine Huddlestone, Melinda De Oliveira, Sandra Duperrier, Pierre Courault, Jérôme Redoute, Léon Tremblay, Véronique Sgambato, Sophie Lancelot, Stéphane Thobois","doi":"10.1093/brain/awaf087","DOIUrl":"https://doi.org/10.1093/brain/awaf087","url":null,"abstract":"<p><p>Impulse control disorders (ICDs) are frequent and particularly distressing neuropsychiatric symptoms in patients with Parkinson's disease (PD) which are related to impaired behavioural inhibition. Multiple PET imaging studies indicate that striatal dopaminergic abnormalities contribute to hyperdopaminergic functioning in PD patients with ICD (PDICD+) and to the dysregulation of the limbic fronto-striatal networks which are critical for reward-related decision impulsivity. However, the serotonergic system is central to response inhibition and plays a critical role in neuropsychiatric symptoms in PD, but its role remains undetermined in PDICD. We hypothesized that PDICD+ patients exhibit serotonergic dysfunction within the cortico-striato-pallido-thalamic circuits involved in the inhibitory control of behaviour and decided to investigate the pre- and post-synaptic serotonergic innervation using two highly-specific PET tracers for the serotonin transporter (SERT) using [11C]DASB and the 5-HT2A receptor using [18F]altanserin. In this prospective, case-control, double-tracer PET study, we recruited 15 PDICD+ patients, 15 PDICD- patients and 15 healthy controls, matched for age and sex, and compared the availability of [11C]DASB and [18F]altanserin using permutation-based analysis. PDICD+ patients had one (n=9) or multiple ICDs (n=6), consisting in hypersexuality (n=8), compulsive eating (n=6), compulsive shopping (n=5) and pathological gambling (n=4) and were characterized by greater choice impulsivity (impaired delay discounting for monetary rewards) and greater urgency with more severe depressive and anxious symptoms. We demonstrate that PDICD+ patients had greater [11C]DASB binding in the posterior putamen and pallidum in comparison to PDICD- patients, corresponding to relatively preserved presynaptic SERT availability within the subcortical sensorimotor network involved in response inhibition. In addition, cortical [18F]altanserin binding was greater in PDICD+ patients in the bilateral supplementary motor area, precentral gyrus and right dorsolateral prefrontal cortex, involving the sensorimotor and associative networks which regulate behavioural inhibition. Furthermore, we show that pre- and post-synaptic serotonergic dysfunction subserving action versus decision impulsivity in PD patients specifically followed the distinctive functional organization of the sensorimotor and associative fronto-striatal networks. Altogether, we demonstrate that serotonergic dysfunction related to ICDs in PD specifically involve the sensorimotor and associative cortico-striato-pallido-thalamic circuits involved in inhibitory control. Thus, serotonergic dysfunction contributes to the mechanisms related to the vulnerability and development of ICDs in PD patients, beyond the known dopaminergic abnormalities in the limbic fronto-striatal circuit.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555863","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}

{"title":"Efficacy of MEDI0618, a pH-dependent monoclonal antibody targeting PAR2, in preclinical models of migraine","authors":"Caroline M Kopruszinski, John E Linley, Peter Thornton, Alison S Walker, Philip Newton, Sadhana Podichetty, Radhey Hemendra Ruparel, Luiz Henrique Moreira de Souza, Edita Navratilova, Guy Meno-Tetang, Ian Gurrell, David W Dodick, Claire Dobson, Tharani Chessell, Frank Porreca, Iain Chessell","doi":"10.1093/brain/awae344","DOIUrl":"https://doi.org/10.1093/brain/awae344","url":null,"abstract":"Protease activated receptor 2 (PAR2) is a G-protein coupled receptor expressed in meningeal neurons, fibroblasts and mast cells that may be targeted to treat migraine. MEDI0618, a fully humanized PAR2 monoclonal antibody, engineered to enhance FcRn-dependent recycling and currently in clinical development, was evaluated in human and rodent in vitro assays, in multiple murine in vivo migraine models and in a model of post-traumatic headache. MEDI0618 bound specifically and with high affinity to cells expressing human PAR2 (hPAR2) and prevented matriptase-induced increase in cytosolic calcium. Similarly, MEDI0618 prevented matriptase-induced calcium in primary fibroblasts and microvascular endothelial cells from human dura mater. MEDI0618 had no effect on hPAR1 receptors. Single-cell calcium imaging of acutely dissociated mouse trigeminal ganglion neurons confirmed expression and functionality of mouse PAR2. Studies in vivo used evoked cutaneous allodynia as a surrogate of headache-like pain and, in some experiments, rearing as a measure of non-evoked headache pain. MEDI0618 was administered subcutaneously to C57BL6/J female mice prior to induction of migraine-like pain with (i) systemic nitroglycerin or compound 48/80 (mast cell degranulator); or (ii) with supradural compound 48/80 or an inflammatory mediator (IM) cocktail. To assess possible efficacy against CGRP receptor (CGRP-R)-independent pain, MEDI0618 was also evaluated in the IM model in animals pretreated with systemic olcegepant (CGRP-R antagonist). Migraine-like pain was also induced by inhalational umbellulone, a TRPA1 agonist, in animals primed with restraint stress in the presence or absence of MEDI0618 as well as in a model of post-traumatic headache pain induced by a mild traumatic brain injury. MEDI0618 prevented cutaneous allodynia elicited by systemic nitroglycerin, compound 48/80 and from supradural compound 48/80 and IM. Systemic olcegepant completely blocked periorbital cutaneous allodynia induced by supradural CGRP but failed to reduce IM-induced cutaneous allodynia. In contrast, MEDI0618 fully prevented IM-induced cutaneous allodynia, regardless of pretreatment with olcegepant. Umbellulone elicited cutaneous allodynia only in restraint stress-primed animals, which was prevented by MEDI0618. MEDI0618 prevented the decrease in rearing behaviour elicited by compound 48/80. However, MEDI0618 did not prevent mild traumatic brain injury-related post-traumatic headache measures. These data indicate that MEDI0618 is a potent and selective inhibitor of PAR2 that is effective in human and rodent in vitro cell systems. Further, blockade of PAR2 with MEDI0618 was effective in all preclinical migraine models studied but not in a model of post-traumatic headache. MEDI0618 may represent a novel therapy for migraine prevention with activity against CGRP-dependent and independent attacks.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"23 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546568","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}

{"title":"Converging and conflicting evidence for left temporal lobe regions in acoustic-phonetic perception","authors":"Liberty Hamilton","doi":"10.1093/brain/awaf083","DOIUrl":"https://doi.org/10.1093/brain/awaf083","url":null,"abstract":"This scientific commentary refers to ‘Lesion correlates of impaired acoustic-phonetic perception after unilateral left hemisphere stroke’ by Binder et al. (https://doi.org/10.1093/brain/awae417).","PeriodicalId":9063,"journal":{"name":"Brain","volume":"13 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546567","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}

{"title":"Preclinical type 2 diabetes mellitus subtypes: new insights into diabetes, depression and dementia","authors":"Sijia Zhao","doi":"10.1093/brain/awaf079","DOIUrl":"https://doi.org/10.1093/brain/awaf079","url":null,"abstract":"This scientific commentary refers to ‘Machine learning reveals connections between preclinical type 2 diabetes subtypes and brain health’ by Yi et al. (https://doi.org/10.1093/brain/awaf057).","PeriodicalId":9063,"journal":{"name":"Brain","volume":"91 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546569","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}

{"title":"Mendelian randomization identifies proteins involved in neurodegenerative diseases","authors":"Lazaros Belbasis, Sam Morris, Cornelia van Duijn, Derrick Bennett, Robin Walters","doi":"10.1093/brain/awaf018","DOIUrl":"https://doi.org/10.1093/brain/awaf018","url":null,"abstract":"Proteins are involved in multiple biological functions. High-throughput technologies have allowed the measurement of thousands of proteins in population biobanks. In this study, we aimed to identify proteins related to Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and amyotrophic lateral sclerosis by leveraging large-scale genetic and proteomic data. We performed a two-sample cis Mendelian randomization study by selecting instrumental variables for the abundance of &amp;gt;2700 proteins measured by either Olink or SomaScan platforms in plasma from the UK Biobank and the deCODE Health Study. We also used the latest publicly available genome-wide association studies for the neurodegenerative diseases of interest. The potentially causal effect of proteins on neurodegenerative diseases was estimated based on the Wald ratio. We tested 13 377 protein–disease associations, identifying 169 associations that were statistically significant (5% false discovery rate). Evidence of co-localization between plasma protein abundance and disease risk (posterior probability &amp;gt; 0.80) was identified for 61 protein–disease pairs, leading to 50 unique protein–disease associations. Notably, 23 of 50 protein–disease associations corresponded to genetic loci not previously reported by genome-wide association studies. The two-sample Mendelian randomization and co-localization analysis also showed that APOE abundance in plasma was associated with three subcortical volumes (hippocampus, amygdala and nucleus accumbens) and white matter hyper-intensities, whereas PILRA and PILRB abundance in plasma was associated with caudate nucleus volume. Our study provided a comprehensive assessment of the effect of the human proteome that is currently measurable through two different platforms on neurodegenerative diseases. The newly associated proteins indicated the involvement of complement (C1S and C1R), microglia (SIRPA, SIGLEC9 and PRSS8) and lysosomes (CLN5) in Alzheimer’s disease; the interleukin-6 pathway (CTF1) in Parkinson’s disease; lysosomes (TPP1), blood–brain barrier integrity (MFAP2) and astrocytes (TNFSF13) in amyotrophic lateral sclerosis; and blood–brain barrier integrity (VEGFB), oligodendrocytes (PARP1), node of Ranvier and dorsal root ganglion (NCS1, FLRT3 and CDH15) and the innate immune system (CR1, AHSG and WARS) in multiple sclerosis. Our study demonstrates how harnessing large-scale genomic and proteomic data can yield new insights into the role of the plasma proteome in the pathogenesis of neurodegenerative diseases.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"7 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546566","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}

{"title":"Myopathic aggregation-prone variants in the TDP-43 prion-like domain: genetics paving the way","authors":"Pedro Ervilha Pereira, Jan L De Bleecker, Elke Bogaert, Bart Dermaut","doi":"10.1093/brain/awaf076","DOIUrl":"https://doi.org/10.1093/brain/awaf076","url":null,"abstract":"While neuropathological and genetic studies have established the crucial involvement of TDP-43 proteinopathy in the pathogenesis of ALS (Amyotrophic Lateral Sclerosis), FTD (Frontotemporal Dementia) and related neurodegenerative disorders, multiple studies have described the presence of TDP-43 inclusions in muscular disorders, including inclusion body myositis but also other related rimmed vacuole myopathies. In addition, TDP-43 has been reported to be essential in normal muscle physiology as it is implicated in the formation of so-called amyloid-like myogranules during normal muscle regeneration after injury. However, genetic evidence supporting a primary role for TDP-43 proteinopathy in muscle disease has been missing. In the present review we highlight recent landmark discoveries linking novel pathogenic TDP-43 variants [p.(W385IfsX10) and p.(G376V)] within the prion-like domain with unusual aggregation-propensity and muscle rather than neuronal pathology. We discuss these studies in the context of known TDP-43-related pathways in ALS/FTD pathogenesis and show how they challenge some widely accepted views such as ALS as a pure neurogenic presynaptic neuromuscular disease and the direct correlation between TDP-43 aggregation-propensity and neurotoxicity. Finally, we discuss TDP-43 as part of a growing list of RNA-binding proteins including hnRNPA2B1 and hnRNPA1 as genetic causes of myopathies and relate this to the idea of ‘multisystem proteinopathy’.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"1 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546603","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}

{"title":"Post-mortem validation of in vivo TSPO PET as a microglial biomarker","authors":"Sasvi S Wijesinghe, James B Rowe, Hannah D Mason, Kieren S J Allinson, Reuben Thomas, Davi S Vontobel, Tim D Fryer, Young T Hong, Mehtap Bacioglu, Maria Grazia Spillantini, Jelle van den Ameele, John T O’Brien, Sanne Kaalund, Maura Malpetti, Annelies Quaegebeur","doi":"10.1093/brain/awaf078","DOIUrl":"https://doi.org/10.1093/brain/awaf078","url":null,"abstract":"Neuroinflammation is a feature of many neurodegenerative diseases, and is quantified in vivo by PET imaging with radioligands for the translocator protein (TSPO, e.g. [11C]-PK11195). TSPO radioligand binding correlates with clinical severity and predicts clinical progression. However, the cellular substrate of altered TSPO binding is controversial and requires neuropathological validation. We used progressive supranuclear palsy (PSP) as a demonstrator condition, to test the hypothesis that [11C]-PK11195 PET reflects microglial changes. We included people with PSP-Richardson’s syndrome who had undergone [11C]-PK11195 PET in life (n=8). In post-mortem brain tissue from the same participants, we characterised cell-type specific TSPO expression and quantified microgliosis in eight cortical and eleven subcortical regions. Double-immunofluorescence labelling for TSPO and cell markers showed TSPO expression in microglia, astrocytes, and endothelial cells. Microglial (and not astrocytic) TSPO levels were higher in donors with PSP compared to controls (n=3), and correlated with changes in microglial density. There was a significant positive correlation between regional [11C]-PK11195 binding potential ante-mortem and the density of post-mortem CD68+ phagocytic microglia, as well as microglial TSPO levels. We conclude that in vivo disease-related changes in [11C]-PK11195 binding is largely driven by microglia and can be interpreted as a biomarker of microglia-mediated neuroinflammation in tauopathies.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"131 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546564","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}