Parkinsonism & related disorders最新文献

{"title":"Atypical ADCY5-related movement disorders: Highlighting adolescent/adult-onset cervical dystonia","authors":"Floriane Quazza ,&nbsp;Florence Riant ,&nbsp;Martina Patera ,&nbsp;Antonio Suppa ,&nbsp;Sara Satolli ,&nbsp;Lydie Burglen ,&nbsp;Michael Zech ,&nbsp;Sylvia Boesch ,&nbsp;Elisabetta Indelicato ,&nbsp;Elodie Hainque ,&nbsp;Emmanuelle Apartis ,&nbsp;Diana Rodriguez ,&nbsp;Diane Doummar ,&nbsp;Aurélie Méneret ,&nbsp;Claudia Ravelli","doi":"10.1016/j.parkreldis.2025.107274","DOIUrl":"10.1016/j.parkreldis.2025.107274","url":null,"abstract":"<div><h3>Background</h3><div><em>ADCY5</em>-related movement disorders are typically paroxysmal dyskinesia (PxDs) and/or static hyperkinetic movement disorders. Nocturnal paroxysmal dyskinesia (PxD), facial or perioral dyskinesia are suggestive of this genetic diagnosis. Next generation sequencing has enabled an expansion of the <em>ADCY5</em>- related phenotype.</div></div><div><h3>Objective</h3><div>The aim of our study was to report atypical phenotypes.</div></div><div><h3>Results</h3><div>We describe 13 patients from 8 different families, of which 10 had adolescent/adult-onset head and upper limb tremor followed by static cervical dystonia without PxD. We report three novel <em>ADCY5</em> variants in these patients, located in the catalytic domains, close to previously reported variants. Caffeine was ineffective for the 3 patients who tried the treatment, and botulinum toxin therapy seemed to be the most effective treatment. We also describe 2 patients with spontaneous remission of pediatric-onset PxD before adulthood.</div></div><div><h3>Conclusion</h3><div>We highlight an adolescent/adult-onset phenotype with head tremor and cervical dystonia, widening the genetic spectrum of cervical dystonia. Moreover, we broaden the pediatric <em>ADCY5-</em>PxD phenotype, highlighting previously unreported cases of spontaneous remission.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"132 ","pages":"Article 107274"},"PeriodicalIF":3.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143099993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tardive dyskinesia versus tardive syndrome. What is in a name?","authors":"Karen Frei, Alicia Scott, Stanley N Caroff, Joseph Jankovic, William Ondo, Leslie Citrome, Robert Hauser, Joseph H Friedman, Roongroj Bhidayasiri, Martha Sajatovic, Dennis Alters, Jonathan Meyer, Stuart Factor, E K Tan, G Remington, Ira Glick, Hubert Fernandez, Cynthia Comella, John Kane, Joseph McEvoy, Delwyn Miller, Clement C Zai, J P Lindenmayer, Richard Trosch, Daniel D Truong","doi":"10.1016/j.parkreldis.2025.107295","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107295","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107295"},"PeriodicalIF":3.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional movement disorders in dopa-responsive dystonia","authors":"Feline Hamami ,&nbsp;Jannik Prasuhn ,&nbsp;Leon-Claas van Well ,&nbsp;Katja Lohmann ,&nbsp;Christine Klein ,&nbsp;Norbert Brüggemann ,&nbsp;Tobias Bäumer ,&nbsp;Alexander Münchau ,&nbsp;Anne Weissbach","doi":"10.1016/j.parkreldis.2025.107292","DOIUrl":"10.1016/j.parkreldis.2025.107292","url":null,"abstract":"<div><h3>Background</h3><div>Functional neurological movement disorders are common and disabling. Little is known about their coexistence with other non-functional movement disorders and their impact on the general disease burden.</div></div><div><h3>Objectives</h3><div>Investigating frequency and characteristics of functional movement disorders in <em>GCH1</em>-positive dopa-responsive dystonia patients.</div></div><div><h3>Methods</h3><div>Twenty-one patients underwent a detailed clinical motor examination and completed self-questionnaires evaluating non-motor characteristics.</div></div><div><h3>Results</h3><div>Seven patients (33 %) had comorbid functional movement symptoms, including functional gait disorders (n = 7), balance disturbances (n = 7), and weakness (n = 5), dominating the clinical phenotype and resulting in disability with immobilization. None of them was previously diagnosed with or treated for the functional symptoms. Functional movement symptoms appeared suddenly (on average 18 years after the first dopa-responsive dystonia symptoms) and were unresponsive to L-Dopa. These patients showed significantly higher disability and received unnecessary treatments.</div></div><div><h3>Conclusion</h3><div>Functional neurological movement disorders are common in patients with dopa-responsive dystonia and impact the clinical picture and the degree of disability. Diagnosing both disorders in an individual patient has substantial therapeutical implications because increases in L-Dopa dosages to treat functional symptoms should be avoided, and physiotherapy should relocate attention away from the affected body region so that movements in the affected body part can be executed without external control to facilitates automatic movements. Physiotherapy should be complemented by psychoeducation and psychotherapeutic approaches.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"132 ","pages":"Article 107292"},"PeriodicalIF":3.1,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reassessing the hypothesis of essential tremor as a prodromal feature of Parkinson's disease","authors":"Qiu-Han Xu ,&nbsp;Jia-Li Wang ,&nbsp;Yi-Ling Wang,&nbsp;Bao-Rong Zhang,&nbsp;Jun Tian","doi":"10.1016/j.parkreldis.2025.107268","DOIUrl":"10.1016/j.parkreldis.2025.107268","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"132 ","pages":"Article 107268"},"PeriodicalIF":3.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the neuroprotective potential of immunosuppressants in Parkinson's disease","authors":"Huiam M. Mubarak ,&nbsp;Brad A. Racette ,&nbsp;Jordan A. Killion ,&nbsp;Irene M. Faust ,&nbsp;Osvaldo J. Laurido-Soto ,&nbsp;Sai Anmisha Doddamreddy ,&nbsp;Susan Searles Nielsen","doi":"10.1016/j.parkreldis.2025.107294","DOIUrl":"10.1016/j.parkreldis.2025.107294","url":null,"abstract":"<div><h3>Introduction</h3><div>Neuroprotective therapy to slow Parkinson's disease (PD) progression is a critical unmet need. Neuroinflammation likely represents an important pathophysiologic mechanism for disease progression. Medications that target this inflammation, such as immunosuppressants, represent potential disease-modifying therapies for PD. The relation between these medications and PD risk might inform candidate selection.</div></div><div><h3>Methods</h3><div>We conducted a population-based case-control study using Medicare data from the United States. The study included 207,532 incident PD cases and 975,177 controls from 2016 to 2018, age 67–110. We examined the association between PD risk and immunosuppressant use before PD diagnosis/control selection. We considered 37 immunosuppressants, representing &gt;10 medication classes, in Part D prescription claims. We used logistic regression to estimate the relative risk (RR) and 95 % confidence interval (CI) between each medication and PD, while accounting for age, sex, race/ethnicity, smoking, and healthcare utilization. In sensitivity analyses we applied exposure lagging, restricted to immunosuppressant users, and corrected for multiple comparisons.</div></div><div><h3>Results</h3><div>Medicare beneficiaries using the calcineurin inhibitor tacrolimus (RR 0.49, CI 0.40–0.60) and mTOR inhibitors everolimus (RR 0.38, CI 0.26–0.56) and sirolimus (RR 0.59, CI 0.37–0.93) had a lower risk of PD compared to those not taking the medication. The TNF inhibitor certolizumab was also associated with lower PD risk (RR 0.54, CI 0.34–0.84). Tacrolimus and everolimus remained significant after Bonferroni correction. Sensitivity analyses otherwise confirmed results for all four medications.</div></div><div><h3>Conclusion</h3><div>Calcineurin or mTOR inhibition might reduce PD risk. Future studies should examine whether these medications or structurally similar agents might have potential as disease-modifying therapies for PD.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"132 ","pages":"Article 107294"},"PeriodicalIF":3.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Audible tremor: Analysis of the validity of audible information in assessing tremor severity","authors":"Natalie Grill ,&nbsp;Ethan Wainman ,&nbsp;Vibhash D. Sharma ,&nbsp;Padraig O'Suilleabhain ,&nbsp;Elan D. Louis","doi":"10.1016/j.parkreldis.2025.107291","DOIUrl":"10.1016/j.parkreldis.2025.107291","url":null,"abstract":"<div><h3>Introduction</h3><div>Assessing the severity of kinetic tremor is important in clinical and research settings. Archimedes spirals are often used to assess tremor severity. Rating tremor from spirals has been based solely on visual information. However, one can often “hear” tremor.</div></div><div><h3>Objectives</h3><div>We evaluated the type of information that could be gained from hearing tremors and assessed its validity using visualized tremor as a gold standard.</div></div><div><h3>Methods</h3><div>52 essential tremor cases (94 spirals), 11 Parkinson's disease patients and 11 controls (20 spirals each) were enrolled. During videotaping, cases drew Archimedes spirals in a standardized manner. Three experienced movement disorders neurologists first listened to videotaped spiral drawing (no visual) and assigned a tremor severity rating using Washington Heights Inwood Genetic Study of Essential Tremor (WHIGET) ratings (0, 0.5, 1, 1.5, 2, 3). Later, the neurologist rated the physical (i.e., visual) spiral and assigned a WHIGET tremor rating.</div></div><div><h3>Results</h3><div>The Spearman's correlation coefficient (visual vs. auditory rating) was 0.721 (p &lt; 0.001) and the weighted kappa statistic was 0.674, a level of agreement that is considered good.</div></div><div><h3>Conclusions</h3><div>Auditory information provides <em>in-time synchronous corroboration</em> of what the rater is seeing. That is, it informs the visual data and provides construct validity. The results of this study have ramifications for observational and experimental therapeutic studies, which commonly rely on videotaped tremor examinations. Additional corroborative information is available if the sound is left on. Regardless of the decision to present sound to the rater or not, clear instructions and a standardized practice within the study are imperative.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"132 ","pages":"Article 107291"},"PeriodicalIF":3.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vibro-tactile stimulation of the neck induces head righting in people with cervical dystonia","authors":"Laura Avanzino ,&nbsp;Jiapeng Xu ,&nbsp;Davide Martino ,&nbsp;Antonella Conte ,&nbsp;Stephanie Standal ,&nbsp;Parisa Salehi ,&nbsp;Sara Terranova ,&nbsp;Gaia Bonassi ,&nbsp;Parisa Alizadeh ,&nbsp;Janet Adesewa Adeoti ,&nbsp;Daniele Belvisi ,&nbsp;Matteo Costanzo ,&nbsp;Jinseok Oh ,&nbsp;Jürgen Konczak","doi":"10.1016/j.parkreldis.2025.107263","DOIUrl":"10.1016/j.parkreldis.2025.107263","url":null,"abstract":"<div><h3>Introduction</h3><div>Cervical dystonia (CD) is characterized by involuntary neck muscle spasms that lead to abnormal head movements or postures. It is associated with somatosensory (tactile and proprioceptive) dysfunction. Here we tested whether vibro-tactile stimulation (VTS) of the cervical muscles constitutes a non-invasive form of neuromodulation of the somatosensory system that can provide temporary symptom relief for people with CD.</div></div><div><h3>Material and method</h3><div>In a multi-centre study, 67 CD patients (44 female) received VTS to sternocleidomastoid and/or trapezius muscles for up to 45 min under 9 different stimulation conditions. Retention was assessed 1, 5 and 20 min past VTS. Head angles and neck muscle EMG were recorded. The primary outcome measure was a head angle index (HAI), a composite measure reflecting the head deviation across the three axes of the head.</div></div><div><h3>Results</h3><div>After identifying the most effective VTS condition for each participant, analysis showed that 85 % (57/67) of participants experienced an improvement in HAI of at least 10 % during the application of VTS. HAI improved by 50 % or higher in 26/67 of participants. For those responding to VTS, the effects tended to decay within 20 min. For the different CD phenotypes several stimulation sites could induce similarly large relative improvements in head posture.</div></div><div><h3>Conclusion</h3><div>The study provides first systematic evidence that cervical VTS can induce fast-acting improvements in abnormal head posture in patients with CD. It demonstrates that a stimulation of somatosensory afferent networks modulates the innervation of dystonic muscles. It highlights the potential of cervical VTS as an adjuvant, non-invasive neuromodulation treatment in CD.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"132 ","pages":"Article 107263"},"PeriodicalIF":3.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term, continuous, subcutaneous levodopa/carbidopa infusion with ND0612 in Parkinson's disease: 3-year outcomes from the open-label BeyoND study","authors":"Aaron L. Ellenbogen ,&nbsp;Werner Poewe ,&nbsp;Alberto J. Espay ,&nbsp;Tanya Simuni ,&nbsp;Tanya Gurevich ,&nbsp;Tami Yardeni ,&nbsp;Nelson Lopes ,&nbsp;Nissim Sasson ,&nbsp;Ryan Case ,&nbsp;Fabrizio Stocchi","doi":"10.1016/j.parkreldis.2025.107293","DOIUrl":"10.1016/j.parkreldis.2025.107293","url":null,"abstract":"<div><h3>Introduction</h3><div>ND0612 is being investigated as a continuous, subcutaneous levodopa/carbidopa infusion, in combination with oral levodopa/carbidopa, for motor fluctuations in Parkinson's disease (PD). One-year data from the ongoing BeyoND study (NCT02726386) showed that the ND0612 regimen was safe and well tolerated and provided a sustained ≥2-h improvement in daily Good ON-time through 12 months of treatment.</div></div><div><h3>Methods</h3><div>We describe 3-year safety and efficacy outcomes for participants who completed 12 months of ND0612 treatment in the core study period and entered the extension phase.</div></div><div><h3>Results</h3><div>Of the 214 enrolled participants, 120 completed the core 1-year period, and 114 participants continued into the extension phase. Of these, 95/114 (83.3 %) completed 2 years and 77/114 (67.5 %) completed 3 years of study treatment. Key reasons for discontinuation were treatment-emergent adverse events (TEAEs) (n = 5 and n = 11 after 2 and 3 years, respectively) and withdrawal of consent (n = 9 and n = 5, respectively). TEAEs were reported by 105/114 (92.1 %) participants in Year 1, 77/114 (67.5 %) in Year 2, and 73/95 (76.8 %) in Year 3. While most participants experienced infusion site reactions, these led to discontinuation in only five participants during this extension. At Month 36, the mean reduction in OFF-time from baseline was 2.81 h and the increase in Good ON-time was 2.79 h.</div></div><div><h3>Conclusions</h3><div>Three-year results from this open-label study support the long-term safety, tolerability, and efficacy of ND0612. For participants who entered the extension phase, the high rate of retention supports a favorable benefit-risk ratio of the ND0612 regimen for patients with PD experiencing motor fluctuations.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"132 ","pages":"Article 107293"},"PeriodicalIF":3.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling distinct clinical manifestations of primary familial brain calcifications in Asian and European patients: A study based on 10-year individual-level data","authors":"Dehao Yang ,&nbsp;Honghao Huang ,&nbsp;Tian Zeng ,&nbsp;Lebo Wang ,&nbsp;Chenxin Ying ,&nbsp;Xinhui Chen ,&nbsp;Xinbo Zhou ,&nbsp;Fangyue Sun ,&nbsp;Yilin Chen ,&nbsp;Shengqi Li ,&nbsp;Bo Wang ,&nbsp;Sheng Wu ,&nbsp;Fei Xie ,&nbsp;Zhidong Cen ,&nbsp;Wei Luo","doi":"10.1016/j.parkreldis.2025.107290","DOIUrl":"10.1016/j.parkreldis.2025.107290","url":null,"abstract":"<div><h3>Background</h3><div>Primary Familial Brain Calcification (PFBC) can manifest clinically with a complex and heterogeneous array of symptoms, including parkinsonism, dysarthria, and cognitive impairment. However, the distinct presentations of PFBC in Asian and European populations remain unclear.</div></div><div><h3>Methods</h3><div>We conducted a systematic search of PubMed for studies involving genetically confirmed PFBC patients. Demographic data, genetic information, radiological examinations, and clinical characteristics were extracted for each case.</div></div><div><h3>Results</h3><div>The study included 120 publications and 564 genetically confirmed PFBC patients. Asian and European PFBC populations represented 54 % and 37 % of global patients, respectively. While calcification patterns showed no significant differences between Asian and European PFBC patients, European autosomal dominant PFBC variant carriers were more likely to exhibit clinical symptoms compared to their Asian counterparts (OR = 2.90, 95 % CI 1.55–5.60) and had an earlier estimated age of onset (median age 42 vs 58).</div></div><div><h3>Conclusion</h3><div>The interaction between regional differences and genetically determined calcification severity may collectively influence PFBC symptom progression. Future research should further explore the potential roles of gene modifiers, ethnic background, socioeconomic and environmental exposure factors underlying regional differences in PFBC progression.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"132 ","pages":"Article 107290"},"PeriodicalIF":3.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency of anti-IgLON5 disease in patients with a typical clinical presentation of progressive supranuclear palsy/corticobasal syndrome.","authors":"Yoya Ono, Hiroshi Takigawa, Akira Takekoshi, Nobuaki Yoshikura, Ikuko Aiba, Ritsuko Hanajima, Hisanori Kowa, Masato Kanazawa, Takahiko Tokuda, Aya Midori Tokumaru, Mitsuya Morita, Kazuko Hasegawa, Kenji Nakashima, Takeshi Ikeuchi, Akio Kimura, Takayoshi Shimohata","doi":"10.1016/j.parkreldis.2025.107289","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107289","url":null,"abstract":"<p><p>Serum anti-IgLON5 antibodies, which were tested in 223 patients meeting the diagnostic criteria for progressive supranuclear palsy/corticobasal syndrome (PSP/CBS), were negative in all patients. Our study suggests that the frequency of anti-IgLON5 disease is extremely rare in patients with typical presentation of PSP/CBS.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107289"},"PeriodicalIF":3.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}