Journal of Neurology最新文献

{"title":"Blood phosphorylated Tau217 distinguishes amyloid-positive from amyloid-negative subjects in the Alzheimer's disease continuum. A systematic review and meta-analysis.","authors":"Annibale Antonioni, Emanuela Maria Raho, Francesco Di Lorenzo, Lamberto Manzoli, Maria Elena Flacco, Giacomo Koch","doi":"10.1007/s00415-025-12996-3","DOIUrl":"10.1007/s00415-025-12996-3","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is the leading cause of dementia worldwide, and cost-effective tools to detect amyloid pathology are urgently needed. Blood-based Tau phosphorylated at threonine 217 (pTau217) seems promising, but its reliability as a proxy for cerebrospinal fluid (CSF) status and ability to identify patients within the AD spectrum remain unclear.</p><p><strong>Methods: </strong>We performed a systematic review and meta-analysis on the potential of blood pTau217 to differentiate amyloid-positive (A+) and amyloid-negative (A-) subjects. We included original studies reporting quantitative data on pTau217 concentrations in both blood and CSF in the AD continuum. The single-group meta-analysis computed the pooled pTau217 levels in blood and in CSF, separately in the A+ and A- groups, while the head-to-head meta-analysis compared the mean pTau217 concentrations in the A+ versus A- subjects, both in blood and CSF, stratifying by assessment method in both cases.</p><p><strong>Results: </strong>Ten studies (819 A+; 1055 A-) were included. The mean pTau217 levels resulted higher in CSF than in blood and, crucially, in A+ individuals than in A- ones, regardless of the laboratory method employed. Most importantly, all laboratory techniques reliably distinguished A+ from A- subjects, whether applied to CSF or blood samples.</p><p><strong>Conclusions: </strong>These results confirm that blood-based pTau217 is a reliable marker of amyloid pathology with significant implications for clinical practice in the AD continuum. Indeed, pTau217 might be a non-invasive, scalable biomarker for early AD detection, reducing the reliance on more invasive, expansive, and less accessible methods.</p><p><strong>Clinical trial registration: </strong>Prospero CRD42024565187.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 3","pages":"252"},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567253","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":"Adrenergic blockers, statins, and non-steroidal anti-inflammatory drugs are associated with later age at onset in Parkinson's disease.","authors":"Camille Malatt, Helia Maghzi, Elliot Hogg, Echo Tan, Ishani Khatiwala, Michele Tagliati","doi":"10.1007/s00415-025-12989-2","DOIUrl":"10.1007/s00415-025-12989-2","url":null,"abstract":"<p><strong>Background: </strong>Several factors have been shown to modify the risk of developing Parkinson's disease (PD), including commonly prescribed medications. However, there is little data describing their correlation with age at onset (AAO) of clinical symptoms. The objective of this study was to evaluate the association of treatment with anti-hypertensives, non-steroidal anti-inflammatories (NSAIDs), statins, as well as smoking and family history of PD with AAO in a large clinical cohort.</p><p><strong>Methods: </strong>A retrospective review of 1201 initial encounters collected information on known risk-modulating factors for PD, including smoking status and family history, anti-hypertensives, statins, NSAIDs, anti-diabetic medications, and beta-agonists. In addition to general exposure, we determined whether medications of interest were started before or after onset of symptoms. Mean AAO was calculated for each set of variables. T-test and multiple regression analyses were used to evaluate association with AAO.</p><p><strong>Results: </strong>Exposure to all studied medications showed a strong correlation with older PD AAO, except for smoking and family history, which correlated with younger AAO. Multiple regression analysis identified exposure to adrenergic blockers (AB) (β = 5.7), statins (β = 5.6), and NSAIDs (β = 4.1) as the strongest independent predictors of older PD AAO (p < 0.001). Patients who were started on AB prior to onset of PD symptoms showed the largest average delay of PD AAO (at 72.3 ± 10.1 years), almost 10 years later as compared with those not on AB (62.7 ± 10.7 years) or those who started taking AB after onset of symptoms (63.0 ± 10.6 years).</p><p><strong>Conclusions: </strong>Multiple common medications are associated with a considerable delay of PD onset.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 3","pages":"255"},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567248","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":"Cognition in cerebellar disorders: What's in the profile? A systematic review and meta-analysis.","authors":"Stacha F I Reumers, Fleur L P Bongaerts, Frank-Erik de Leeuw, Bart P C van de Warrenburg, Dennis J L G Schutter, Roy P C Kessels","doi":"10.1007/s00415-025-12967-8","DOIUrl":"10.1007/s00415-025-12967-8","url":null,"abstract":"<p><strong>Objective: </strong>This systematic review and meta-analysis aim to examine the profile and extent of cognitive deficits in patients with cerebellar disorders, and to provide a complete overview of the cognitive domains that might be affected in the Cerebellar Cognitive Affective Syndrome (CCAS).</p><p><strong>Methods: </strong>MEDLINE, Embase, PsycINFO, and Web of Science were systematically searched to 17-07-2024. Studies were considered if the participants were adult patients with a clinical diagnosis of cerebellar disorder and were neuropsychological assessed. Outcomes were grouped into the domains of processing speed, language, social cognition, executive function, visuospatial skills, episodic memory, verbal intelligence, attention, and working memory. All aetiologies were included for first evaluation and patients were assigned to one of two groups (focal vs. degenerative) for secondary evaluation. Random-effects models were employed for the meta-analyses.</p><p><strong>Results: </strong>129 studies with a total of 3140 patients with cerebellar disorders were included. Patients performed significantly worse compared to control/standardized data in all domains. Deficits were most pronounced in processing speed, ES [95% CI] = - 0.83 [- 1.04, - 0.63], language, ES [95% CI] = - 0.81 [- 0.94, - 0.67], and social cognition, ES [95% CI] = - 0.81 [- 1.19, - 0.42]. Cognitive impairment varied between patients with focal cerebellar lesions and degenerative cerebellar disorders, but was overall worse in the degenerative group.</p><p><strong>Discussion: </strong>Cerebellar disorders can impact many cognitive domains, extending beyond executive functioning, visuospatial skills, and language. These outcomes contribute to a broader understanding of the cerebellum's role in cognition and sheds light on the cognitive deficits associated with cerebellar disorders.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 3","pages":"250"},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567275","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":"Cerebral foreign body reaction (CFBR) after endovascular treatments is a rare event to be aware of: case series and review of literature.","authors":"Giorgia Atanasio, Salvatore Bertino, Mariano Velo, Agostino Tessitore, Claudio Zaccone, Alessio Masaracchio, Francesca Granata, Sergio Vinci, Antonio Toscano, Olimpia Musumeci","doi":"10.1007/s00415-025-12957-w","DOIUrl":"10.1007/s00415-025-12957-w","url":null,"abstract":"<p><p>Cerebral foreign body reaction (CFBR) due to hydrophilic polymer embolization is a rarely diagnosed complication of cerebral endovascular procedures. Despite the considerable use of endovascular treatment in the literature, few cases of CFBR have been described so far. Our main objective is to describe three patients who were diagnosed at our center with CFBR and provide an overview of the existing literature. In these three cases, cerebral aneurysms were treated with different endovascular techniques as Contour device implantation, coil embolization, and flow diversion stent. Only one patient manifested focal neurological signs characterized by contralateral strength deficit, dysarthria, and headache. In the other two cases, the lesions were asymptomatic and were found at follow-up imaging. Brain MRI showed hyperintense lesions in FLAIR sequences in subcortical white matter without diffusivity restriction on diffusion-weighted imaging (DWI) corresponding to contrast-enhancing foci in T1-weighted images, suggestive of CFBR. Pathophysiology and predisposing factors are still unclear. Corticosteroid therapy led to marked improvement at neuroimaging in all cases and to a clinical remission in the first case. Our data confirm that CFBR is an underestimated complication to be aware of, in both neurological and neuroradiological practice.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 3","pages":"251"},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567257","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":"The deltoid muscle and the pattern of paresis in ALS.","authors":"Albert Ludolph, Veronika Klose, Jens Dreyhaupt, Kelly Del Tredici, Heiko Braak","doi":"10.1007/s00415-025-12949-w","DOIUrl":"10.1007/s00415-025-12949-w","url":null,"abstract":"<p><p>There is neuroanatomical and clinical evidence that the corticospinal tract governs the patterns of pareses in sporadic ALS. These patterns are mirrored by phylogenetically young monosynaptic corticomotor neuronal connections. It is well known that, clinically, dysfunction of the deltoid muscle contributes considerably to the early disability of the ALS patient. In this study, we prospectively compared the degree of pareses of the deltoid muscle with the triceps and biceps brachii in N = 71 patients (426 muscles). We could show that the extent of involvement of the deltoid muscle early in the disease process resembles that of the biceps rather than the triceps brachii. This pattern is consistent with functional data of the corticospinal monosynaptic connectivity of all three muscles.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 3","pages":"253"},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567279","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":"Antibody-positive paraneoplastic neurological syndromes associated with immune checkpoint inhibitors: a systematic review.","authors":"Le Zhang, Siyuan Fan, Jiawei Wang, Haitao Ren, Hongzhi Guan","doi":"10.1007/s00415-025-12992-7","DOIUrl":"10.1007/s00415-025-12992-7","url":null,"abstract":"<p><strong>Background and objectives: </strong>This study aimed to describe the clinical and prognostic characteristics of antibody-positive paraneoplastic neurological syndrome (PNS) associated with immune checkpoint inhibitors (ICIs).</p><p><strong>Methods: </strong>We conducted a systematic review of relevant publications in PubMed and Embase from inception to December 2023. Patients with positive anti-neuronal antibodies who had a definite, probable, or possible diagnosis of PNS based on the 2021 PNS-Care Score criteria were included.</p><p><strong>Results: </strong>A total of 76 records with 108 antibody-positive ICI-PNS patients were included in this systematic review. According to the updated 2021 criteria, 60.2% of patients were classified as definite PNS, 29.6% as probable PNS, and 10.2% as possible PNS. The median age was 66 years (range: 26-82), and 56.5% of patients were male. The most frequently associated tumors included lung cancer, melanoma, and Merkel cell carcinoma, and 72.2% of patients developed neurological symptoms within 6 months after ICIs treatment. The most common clinical phenotypes were limbic encephalitis (35.2%), rapidly progressive cerebellar syndrome (19.4%), and Lambert-Eaton myasthenic syndrome (13.0%), while the most common autoantibodies were anti-Hu (34.3%), anti-Ma2 (16.7%), and anti-P/Q VGCC (14.8%) antibodies. CSF inflammation was observed in 63.0% patients, predominantly lymphocytic. Corticosteroids were the mainstay of immunotherapy (90.9%), followed by intravenous immunoglobulin (IVIG) and plasma exchange. Outcome information was reported for 103 patients. The median follow-up was 4 months (IQR: 2, 10), and 56.3% of patients showed improvement, while 37.0% of patients died at the last follow-up. Patients with anti-Hu or  anti-Ma2 antibodies had a higher proportion of deterioration and mortality (P < 0.05).</p><p><strong>Conclusion: </strong>Limbic encephalitis and anti-Hu antibody are relatively common in antibody-positive ICI-PNS, and most patients present with CSF inflammation. Discontinuation of ICIs and corticosteroids are the main treatments. High-risk antibodies may be a risk factor for an unfavorable prognosis, particularly anti-Hu and anti-Ma2 antibodies.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 3","pages":"249"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557224","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":"Separation of stroke from vestibular neuritis using the video head impulse test: machine learning models versus expert clinicians.","authors":"Chao Wang, Jeevan Sreerama, Benjamin Nham, Nicole Reid, Nese Ozalp, James O Thomas, Cecilia Cappelen-Smith, Zeljka Calic, Andrew P Bradshaw, Sally M Rosengren, Gülden Akdal, G Michael Halmagyi, Deborah A Black, David Burke, Mukesh Prasad, Gnana K Bharathy, Miriam S Welgampola","doi":"10.1007/s00415-025-12918-3","DOIUrl":"10.1007/s00415-025-12918-3","url":null,"abstract":"<p><strong>Background: </strong>Acute vestibular syndrome usually represents either vestibular neuritis (VN), an innocuous viral illness, or posterior circulation stroke (PCS), a potentially life-threatening event. The video head impulse test (VHIT) is a quantitative measure of the vestibulo-ocular reflex that can distinguish between these two diagnoses. It can be rapidly performed at the bedside by any trained healthcare professional but requires interpretation by an expert clinician. We developed machine learning models to differentiate between PCS and VN using only the VHIT.</p><p><strong>Methods: </strong>We trained machine learning classification models using unedited head- and eye-velocity data from acute VHIT performed in an Emergency Room on patients presenting with acute vestibular syndrome and whose final diagnosis was VN or PCS. The models were validated using an independent test dataset collected at a second institution. We compared the performance of the models against expert clinicians as well as a widely used VHIT metric: the gain cutoff value.</p><p><strong>Results: </strong>The training and test datasets comprised 252 and 49 patients, respectively. In the test dataset, the best machine learning model identified VN with 87.8% (95% CI 77.6%-95.9%) accuracy. Model performance was not significantly different (p = 0.56) from that of blinded expert clinicians who achieved 85.7% accuracy (75.5%-93.9%) and was superior (p = 0.01) to that of the optimal gain cutoff value (75.5% accuracy (63.8%-85.7%)).</p><p><strong>Conclusion: </strong>Machine learning models can effectively differentiate PCS from VN using only VHIT data, with comparable accuracy to expert clinicians. They hold promise as a tool to assist Emergency Room clinicians evaluating patients with acute vestibular syndrome.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 3","pages":"248"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557167","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":"Heterogeneity of cognitive progression and clinical predictors in Parkinson's disease-subjective cognitive decline.","authors":"Jon Rodríguez-Antigüedad, Saül Martínez-Horta, Arnau Puig-Davi, Andrea Horta-Barba, Javier Pagonabarraga, Teresa de Deus Fonticoba, Silvia Jesús, Marina Cosgaya, Juan García Caldentey, María Asunción Ávila-Rivera, Nuria Caballol, Inés Legarda, Jorge Hernández Vara, Iria Cabo, Lydia López Manzanares, Isabel González Aramburu, Víctor Gómez Mayordomo, Jessica González Ardura, Julio Dotor García-Soto, Carmen Borrué, Berta Solano Vila, María Álvarez Sauco, Lydia Vela, Sonia Escalante, Esther Cubo, Zebenzui Mendoza, Isabel Pareés, Pilar Sánchez Alonso, María G Alonso Losada, Nuria López Ariztegui, Itziar Gastón, Javier Ruíz Martínez, María Teresa Buongiorno, Carlos Ordás, Caridad Valero, Víctor Puente, Mónica Kurtis, Marta Blázquez Estrada, Pablo Martínez-Martín, Pablo Mir, Diego Santos-García, Jaime Kulisevsky","doi":"10.1007/s00415-024-12808-0","DOIUrl":"10.1007/s00415-024-12808-0","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 3","pages":"246"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557243","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":"Overlapping presence of β-amyloid, tau, p-tau, and α-synuclein in skin nerve fibers in Alzheimer's disease.","authors":"Emilie Buchholz, Marie-Luise Machule, Maria Buthut, Leon Stefanovski, Rosa Rössling, Harald Prüss","doi":"10.1007/s00415-025-12994-5","DOIUrl":"10.1007/s00415-025-12994-5","url":null,"abstract":"<p><strong>Objective: </strong>Skin nerve fiber deposition of proteins can be strongly associated with neurodegenerative diseases, such as phosphorylated α-synuclein (p-SN) in synucleinopathies. Little is known about other neurodegenerative proteins, such as tau or β-amyloid, in skin nerve fibers of patients with Alzheimer's disease (AD) and their link to underlying neurodegeneration. We therefore aimed for describing the presence and distribution of these proteins in the skin of patients with AD and non-AD controls.</p><p><strong>Methods: </strong>Skin biopsies were taken from 45 patients with AD (n = 23) and non-AD controls (n = 22). Nerve fibers were identified using antibodies against protein gene product 9.5 (PGP9.5), and protein deposits were evaluated with double-immunostaining of β-amyloid 1-42 (Aβ1-42), p-SN, tau, and phospho-tau (p-tau).</p><p><strong>Results: </strong>Skin nerve fiber Aβ1-42 was present in 7/23 (30.4%) patients with AD and 7/22 (31.8%) controls. p-tau was detected in 12/23 (52.2%) patients with AD and 9/22 (40.9%) controls. Tau was present in 19/23 (82.6%) patients with AD and 16/22 (72.7%) controls. p-SN was detected in 12/23 (52.2%) patients with AD and 8/22 (36.4%) controls. Frequencies of deposits were not significantly different between groups and protein frequency did not correlate with severity of cognitive impairment.</p><p><strong>Interpretation: </strong>Deposits of β-amyloid 1-42, p-SN, tau, and p-tau were detected in skin nerve fibers in both patient groups; however, qualitative assessment did not discriminate between AD and non-AD patients at this sample size. Future analyses of protein distribution and spreading in peripheral nerves may give new insights into the pathophysiology of neurodegenerative diseases, but may require quantitative detection.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 3","pages":"247"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557248","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":"Ultralong-term EEG: a loop recorder for the brain.","authors":"Earshad Mia, Khalid Hamandi","doi":"10.1007/s00415-025-12985-6","DOIUrl":"10.1007/s00415-025-12985-6","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 3","pages":"245"},"PeriodicalIF":4.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542351","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}