Neurology and Therapy最新文献

{"title":"Navigating the Landscape of Plasma Biomarkers in Alzheimer's Disease: Focus on Past, Present, and Future Clinical Applications.","authors":"Sarrah E Ankeny, Julia R Bacci, Boris Decourt, Marwan N Sabbagh, Michelle M Mielke","doi":"10.1007/s40120-024-00658-x","DOIUrl":"https://doi.org/10.1007/s40120-024-00658-x","url":null,"abstract":"<p><p>As the prevalence of Alzheimer's disease (AD) and its impact on healthcare systems increase, developing tools for accurate diagnosis and monitoring of disease progression is a priority. Recent technological advancements have allowed for the development of blood-based biomarkers (BBMs) to aid in the diagnosis of AD, but many questions remain regarding the clinical implementation of these BBMs. This review outlines the historical timeline of AD BBM development. It highlights key breakthroughs that have transformed the perspective of AD BBMs from theoretically ideal but unattainable markers, to clinically valid and reliable BBMs with potential for implementation in healthcare settings. Technological advancements like single-molecule detection and mass spectrometry methods have significantly improved assay sensitivity and accuracy. High-throughput, fully automated platforms have potential for clinical use. Despite these advancements, however, significant work is needed before AD BBMs can be implemented in widespread clinical practice. Cutpoints must be established, the influence of chronic conditions and medications on BBM levels must be better understood, and guidelines must be created for healthcare providers related to interpreting and communicating information obtained from AD BBMs. Additionally, the development of BBMs for synaptic dysfunction, inflammation, and cerebrovascular disease may provide better precision medicine approaches to treating AD and related dementia. Future research and collaboration between scientists and physicians are essential to addressing these challenges and further advancing AD BBMs, with the goal of integration in clinical practice.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146067","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":"Symptoms of Hereditary Transthyretin Amyloidosis: The Patient and Physician Perspective.","authors":"Michael Lane, Michael Polydefkis","doi":"10.1007/s40120-024-00657-y","DOIUrl":"https://doi.org/10.1007/s40120-024-00657-y","url":null,"abstract":"<p><p>This article has been co-authored by a patient living with hereditary transthyretin (ATTRv) amyloidosis and a neurologist. This rare, progressive disease is associated with impairment of multiple organ systems, including the nerves, heart, and the gastrointestinal tract, forcing patients to live with and adapt to a range of debilitating symptoms. Here, the patient and physician discuss how the symptoms of ATTRv amyloidosis profoundly impact day to day life, the difficulties with identifying the disease, and how this effects the diagnosis experience. In recent years, significant advancements have been made in the treatment and management of ATTRv amyloidosis. However, the authors highlight the urgency of increasing awareness of the disease among the wider medical community, as well as in patients who notice the symptoms, to ensure that earlier diagnosis and appropriate treatment are achieved.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140655","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":"Patient and Physician Perspectives of Treatment Burden in Multiple Sclerosis.","authors":"Barry A Singer, Dawn Morgan, Julie A Stamm, Anita A Williams","doi":"10.1007/s40120-024-00654-1","DOIUrl":"https://doi.org/10.1007/s40120-024-00654-1","url":null,"abstract":"<p><p>The number of disease-modifying therapies (DMTs) approved for the treatment of multiple sclerosis (MS) has greatly increased in recent decades, leading to higher treatment complexity. DMTs can differ in mode and frequency of administration, benefit-risk profile, and associated costs. Patients with MS contend not only with the burden of their chronic disease but also with the treatment burden of their MS therapy. Adhering to dosing schedules and infusion appointments can be difficult for busy, working-age patients or those with limited access to transportation. Patients and healthcare professionals (HCPs) may have differing priorities, concerns, and preferences when selecting treatment, potentially affecting treatment satisfaction and, importantly, adherence. Additionally, patients face direct and indirect costs related to treatment. These factors can all contribute to a high treatment burden on patients, impacting their quality of life and potentially leading to worse patient outcomes. HCPs, patients, and caregivers must work together to alleviate treatment burden through effective communication, shared decision-making, appreciating each other's perspectives, and additional HCP support. Consideration of treatment burden into clinical guidelines is also warranted. In this review, we examine key factors impacting treatment burden for patients with MS, with a focus on the patient perspective as provided by our patient authors, and provide strategies to minimize treatment burden.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126276","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":"Effectiveness of Nusinersen in Adolescents and Adults with Spinal Muscular Atrophy: Systematic Review and Meta-analysis.","authors":"Tim Hagenacker, Lorenzo Maggi, Giorgia Coratti, Bora Youn, Stephanie Raynaud, Angela D Paradis, Eugenio Mercuri","doi":"10.1007/s40120-024-00653-2","DOIUrl":"https://doi.org/10.1007/s40120-024-00653-2","url":null,"abstract":"<p><strong>Introduction: </strong>Nusinersen clinical trials have limited data on adolescents and adults with 5q-associated spinal muscular atrophy (SMA). We conducted a systematic literature review (SLR) and meta-analysis to assess effectiveness of nusinersen in adolescents and adults with SMA in clinical practice.</p><p><strong>Methods: </strong>Our search included papers published 12/23/2016 through 07/01/2022 with ≥ 5 individuals ≥ 13 years of age and with ≥ 6 months' data on ≥ 1 selected motor function outcomes [Hammersmith Functional Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM), and Six-Minute Walk Test (6MWT)]. For meta-analysis, effect sizes were pooled using random-effects models. To understand treatment effects by disease severity, subgroup meta-analysis by SMA type and ambulatory status was conducted.</p><p><strong>Results: </strong>Fourteen publications including 539 patients followed up to 24 months met inclusion criteria for the SLR. Patients were age 13-72 years and most (99%) had SMA Type II or III. Modest improvement or stability in motor function was consistently observed at the group level. Significant mean increases from baseline were observed in HFMSE [2.3 points (95% CI 1.3-3.3)] with 32.1% (21.7-44.6) of patients demonstrating a clinically meaningful increase (≥ 3 points) at 18 months. Significant increases in RULM were consistently found, with a mean increase of 1.1 points (0.7-1.4) and 38.3% (30.3-47.1) showing a clinically meaningful improvement (≥ 2 points) at 14 months. Among ambulatory patients, there was a significant increase in mean 6MWT distance of 25.0 m (8.9-41.2) with 50.9% (33.4-68.2) demonstrating a clinically meaningful improvement (≥ 30 m) at 14 months. The increases in HFMSE were greater for less severely affected patients, whereas more severely affected patients showed greater improvement in RULM.</p><p><strong>Conclusions: </strong>Findings provide consolidated evidence that nusinersen is effective in improving or stabilizing motor function in many adolescents and adults with a broad spectrum of SMA.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109932","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":"Presurgical Use of Cenobamate for Adult and Pediatric Patients Referred for Epilepsy Surgery: Expert Panel Recommendations.","authors":"Kenneth D Laxer, Christopher J Elder, Giancarlo Di Gennaro, Louis Ferrari, Gregory L Krauss, Jacob Pellinen, William E Rosenfeld, Vicente Villanueva","doi":"10.1007/s40120-024-00651-4","DOIUrl":"https://doi.org/10.1007/s40120-024-00651-4","url":null,"abstract":"<p><p>Cenobamate has demonstrated efficacy in patients with treatment-resistant epilepsy, including patients who continued to have seizures after epilepsy surgery. This article provides recommendations for cenobamate use in patients referred for epilepsy surgery evaluation. A panel of six senior epileptologists from the United States and Europe with experience in presurgical evaluation of patients with epilepsy and in the use of antiseizure medications (ASMs) was convened to provide consensus recommendations for the use of cenobamate in patients referred for epilepsy surgery evaluation. Many patients referred for surgical evaluation may benefit from ASM optimization; both ASM and surgical treatment should be individualized. Based on previous clinical studies and the authors' clinical experience with cenobamate, a substantial proportion of patients with treatment-resistant epilepsy can become seizure-free with cenobamate. We recommend a cenobamate trial and ASM optimization in parallel with presurgical evaluations. Cenobamate can be started before phase two monitoring, especially in patients who are found to be suboptimal surgery candidates. As neurostimulation therapies are generally palliative, we recommend trying cenobamate before vagus nerve stimulation (VNS), deep brain stimulation, or responsive neurostimulation (RNS). In surgically remediable cases (mesial temporal sclerosis, benign discrete lesion in non-eloquent cortex, cavernous angioma, etc.), cenobamate use should not delay imminent surgery; however, a patient may decide to defer or even cancel surgery should they achieve sustained seizure freedom with cenobamate. This decision should be made on an individual, case-by-case basis based on seizure etiology, patient preferences, potential surgical risks (mortality and morbidity), and likely surgical outcome. The addition of cenobamate after unsuccessful surgery or palliative neuromodulation may also be associated with better outcomes.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996207","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":"Quantitative Analysis of White Matter Hyperintensities as a Predictor of 1-Year Risk for Ischemic Stroke Recurrence.","authors":"Yi Sun, Wenping Xia, Ran Wei, Zedong Dai, Xilin Sun, Jie Zhu, Bin Song, Hao Wang","doi":"10.1007/s40120-024-00652-3","DOIUrl":"https://doi.org/10.1007/s40120-024-00652-3","url":null,"abstract":"<p><strong>Introduction: </strong>This study evaluates the role of quantitative characteristics of white matter hyperintensities (WMHs) in predicting the 1-year recurrence risk of ischemic stroke.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 1061 patients with ischemic stroke from January 2018 to April 2021. WMHs were automatically segmented using a cluster-based method to quantify their volume and number of clusters (NoC). Additionally, two radiologists independently rated periventricular and deep WMHs using the Fazekas scale. The cohort was divided into a training set (70%) and a testing set (30%). We employed Cox proportional hazards models to develop predictors based on quantitative WMH characteristics, Fazekas scores, and clinical factors, and compared their performance using the concordance index (C-index).</p><p><strong>Results: </strong>A total of 180 quantitative variables related to WMHs were extracted. A higher NoC in deep white matter and brainstem, advanced age (> 90 years old), specific stroke subtypes, and absence of discharge antiplatelets showed stronger associations with the risk of ischemic stroke recurrence within 1 year. The nomogram incorporating quantitative WMHs data showed superior discrimination compared to those based on the Fazekas scale or clinical factors alone, with C-index values of 0.709 versus 0.647 and 0.648, respectively, in the testing set. Notably, a combined model including both WMHs and clinical factors achieved the highest predictive accuracy, with a C-index of 0.735 in the testing set.</p><p><strong>Conclusion: </strong>Quantitative assessment of WMHs provides a valuable neuro-imaging tool for enhancing the prediction of ischemic stroke recurrence risk.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971574","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":"Population Pharmacokinetic Modeling and Simulation for Dose Optimization of GB-5001, a Long-Acting Intramuscular Injection of Donepezil, in Healthy Participants.","authors":"Juyoung Khwarg, Heeyong Lee, Kyung-Sang Yu, Eunyoung Seol, Jae-Yong Chung","doi":"10.1007/s40120-024-00643-4","DOIUrl":"https://doi.org/10.1007/s40120-024-00643-4","url":null,"abstract":"<p><strong>Introduction: </strong>GB-5001 is an intramuscular (IM) formulation of donepezil under development for the treatment of Alzheimer's disease. The objective of this study was to develop a population pharmacokinetic (PK) model for donepezil in both IM and oral formulations, and to optimize the IM dosage of GB-5001 using bioequivalence (BE) simulation.</p><p><strong>Methods: </strong>A population PK model of donepezil was developed using NONMEM. It was based on plasma concentration data from a Phase 1 dose escalation study, which involved a single administration of donepezil IM formulation at doses of 70, 140, and 280 mg, and the oral formulation at 10 mg. The model was evaluated based on goodness-of-fit plots, conditional weighted residuals, visual predictive checks, and bootstrapping. BE simulations were conducted using a parallel design between various doses of the IM formulation and the 10-mg dose of oral formulation.</p><p><strong>Results: </strong>The PKs of donepezil were best described by a two-compartment model, which incorporated distinct absorption compartments for the IM (dual first-order absorption and simultaneous zero-order absorption with lag time) and oral (first-order absorption with lag time) formulations. Based on the simulation results, an IM dosage range of 210-215 mg in a sample size of over 92 was estimated to achieve a success rate of approximately 80% for BE.</p><p><strong>Conclusion: </strong>The population PK model well explained the PKs of donepezil following administration of both the IM and oral formulations. This model could be applied for the design and dose selection of future BE trials.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT05525780.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913410","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":"Systemic Inflammatory Response Index and the Short-Term Functional Outcome of Patients with Acute Ischemic Stroke: A Meta-analysis.","authors":"Ying Han, Nan Lin","doi":"10.1007/s40120-024-00645-2","DOIUrl":"https://doi.org/10.1007/s40120-024-00645-2","url":null,"abstract":"<p><strong>Introduction: </strong>The systemic inflammatory response index (SIRI) is a novel indicator of systemic inflammation derived from the absolute counts of neutrophils, monocytes, and lymphocytes. The aim of this meta-analysis was to evaluate the association between SIRI and functional outcome in patients with acute ischemic stroke (AIS).</p><p><strong>Methods: </strong>The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in this meta-analysis. Relevant cohort studies were retrieved by a search of electronic databases including PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure from database inception to February 9, 2024. A poor functional outcome was defined as a modified Rankin Scale ≥ 3 within 3 months after disease onset. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. The protocol of the meta-analysis was not prospectively registered in PROSPERO.</p><p><strong>Results: </strong>Fourteen cohort studies were included. Pooled results showed that a high SIRI at admission was associated with increased risk of poor functional outcome within 3 months (odds ratio [OR]: 1.57, 95% confidence interval: 1.39 to 1.78, p < 0.001; I² = 0%). Results of the meta-regression analysis suggested that the cutoff for defining a high SIRI was positively related to the OR for the association between SIRI and the risk of poor functional outcome (coefficient = 0.13, p = 0.03), while other variables including sample size, mean age, severity of stroke at admission, percentage of men, current smokers, or patients with diabetes did not significantly modify the results. Subgroup analyses according to study design, main treatments, and study quality scores showed similar results.</p><p><strong>Conclusion: </strong>A high SIRI may be associated with a poor functional outcome in patients after AIS.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907273","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":"Correction to: Assessing the Long-Term (48-Week) Effectiveness, Safety, and Tolerability of Fremanezumab in Migraine in Real Life: Insights from the Multicenter, Prospective, FRIEND3 Study.","authors":"Piero Barbanti, Gabriella Egeo, Stefania Proietti, Florindo d'Onofrio, Cinzia Aurilia, Cinzia Finocchi, Laura Di Clemente, Maurizio Zucco, Alberto Doretti, Stefano Messina, Massimo Autunno, Angelo Ranieri, Antonio Carnevale, Bruno Colombo, Massimo Filippi, Miriam Tasillo, Steno Rinalduzzi, Pietro Querzani, Giuliano Sette, Lorenzo Forino, Francesco Zoroddu, Micaela Robotti, Alessandro Valenza, Cecilia Camarda, Laura Borrello, Marco Aguggia, Giovanna Viticchi, Carlo Tomino, Giulia Fiorentini, Bianca Orlando, Stefano Bonassi, Paola Torelli","doi":"10.1007/s40120-024-00648-z","DOIUrl":"https://doi.org/10.1007/s40120-024-00648-z","url":null,"abstract":"","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893923","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":"Practical Recommendations from the Gulf Region on the Therapeutic Use of Cladribine Tablets for the Management of Relapsing Multiple Sclerosis: Impact of the Latest Real-World Evidence on Clinical Practice.","authors":"Bassem Yamout, Raed Alroughani, Jihad Inshasi, Samar Farouk, Fatema Abdulla, Namareq Y Al-Jarki, Abdulla Alasmi, Sarmad Al Fahad, Jaber Alkhabouri, Khalid Al-Saffar, Beatrice Benedetti, Beatriz Canibano, Dirk Deleu, Ali Hassan, Pournamy Sarathchandran, Ahmed Shatila, Mohammad Abouelnaga, Mona Thakre, Miklos Szolics, Amir Boshra","doi":"10.1007/s40120-024-00650-5","DOIUrl":"https://doi.org/10.1007/s40120-024-00650-5","url":null,"abstract":"<p><p>Cladribine tablets (CladT), like alemtuzumab, acts as an immune reconstitution therapy. However, CladT is administered orally (alemtuzumab is given by infusion) and without the potential for serious side effects that limit the therapeutic use of alemtuzumab in multiple sclerosis (MS). Treatment with CladT, given initially as short courses of treatment 1 year apart, provides years of freedom from MS disease activity in responders to treatment. The appearance of mild or moderate MS disease activity after the initial 2 years of treatment may prompt careful follow-up or a further course of CladT, depending on the nature of the activity and individual circumstances. The appearance of severe MS disease activity requires a switch to an alternative high-efficacy disease-modifying treatment (DMT). The accumulating data from CladT-treated people with MS in real-world studies, including those with follow-up durations extending for years beyond the initial treatment, have demonstrated long-term freedom from MS disease activity in a good proportion of patients. This clinical experience has also confirmed that treatment with CladT is generally safe and well tolerated. The best time to prescribe a high-efficacy DMT is the subject of debate, with evidence that earlier versus later use of such agents may provide more effective long-term protection from disability progression. High-efficacy DMTs have traditionally been reserved for use in people with MS and high disease activity on presentation or breakthrough disease on one or more DMTs, as per the current product labels. The latest evidence from real-world studies suggests that CladT is effective and safe in DMT-naïve patients, including those with shorter disease duration.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889843","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}