Annals of Neurology最新文献

{"title":"Dopamine Transporter Imaging as Objective Monitoring Biomarker in Parkinson's Disease","authors":"Verena Dzialas MSc,&nbsp;Gérard N. Bischof PhD,&nbsp;Kathrin Möllenhoff PhD,&nbsp;Alexander Drzezga MD,&nbsp;Thilo van Eimeren MD","doi":"10.1002/ana.27223","DOIUrl":"10.1002/ana.27223","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Although dopamine transporter (DaT) imaging is a valuable diagnostic biomarker, few studies have investigated its utility in objectively monitoring disease progression in patients with Parkinson's disease (PD). To date, no study has established a longitudinal relationship between the DaT signal decline and the motor symptom increase, potentially due to neglected factors such as brain regions, disease laterality, and symptom subtypes, which this study addresses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cohort study included participants who met the Movement Disorder Society (MDS) criteria for PD, with longitudinal imaging and clinical data from the Parkinson's Progression Markers Initiative Database. Linear mixed model analyses were used to investigate the relationship between the DaT signal decline and the motor symptom severity increase over time. We hypothesized that a decline in putaminal DaT availability in the less affected hemisphere would be associated with increasing contralateral motor symptoms, measured by the Unified Parkinson's Disease Rating Scale (UPDRS). Additional models explored the effects of different brain regions (caudate and putamen), symptom categories (MDS UPDRSIII score with and without tremor items), and disease onset laterality (left or right hemisphere).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 719 participants (443 male patients and 276 female patients; mean age = 62.2 ± 9.5 years) with 1,981 available data points. As hypothesized, we observed a significant association between the decrease in the less affected putaminal DaT signal and motor symptom increase in the contralateral body side, independent of including or excluding tremor scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our findings support the use of repetitive DaT imaging for objectively monitoring PD progression. This could facilitate personalized disease tracking, subtyping, and intervention testing in the future. ANN NEUROL 2025;98:120–135</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 1","pages":"120-135"},"PeriodicalIF":8.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI in Neurology: Everything, Everywhere, All at Once Part 3: Surveillance, Synthesis, Simulation, and Systems.","authors":"Matthew Rizzo","doi":"10.1002/ana.27230","DOIUrl":"https://doi.org/10.1002/ana.27230","url":null,"abstract":"<p><p>This final part 3 review builds on the practical applications discussed in part 2 and explores how artificial intelligence (AI) is transforming data management, neurological education, and neurological care across large healthcare networks and datasets. The review also highlights AI's role in real-world and synthetic data, digital twins, and innovative clinical trial designs, such as in silico and adaptive trials. The review emphasizes AI's ability to drive continuous improvements in care and discovery through comparative effectiveness research and learning health systems. The global healthcare implications discussed here tie back to earlier discussions on human-AI collaboration and precision care, underscoring the neurological sciences' responsibility to adopt AI advances judiciously, while managing their ethical, economic, and environmental impacts. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707922","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":"Neuroimaging Biomarkers for Friedreich Ataxia: A Cross-Sectional Analysis of the TRACK-FA Study.","authors":"Nellie Georgiou-Karistianis, Louise A Corben, Eric F Lock, Helena Bujalka, Isaac Adanyeguh, Manuela Corti, Dinesh K Deelchand, Martin B Delatycki, Imis Dogan, Jennifer Farmer, Marcondes C França, Anthony S Gabay, William Gaetz, Ian H Harding, James Joers, Michelle A Lax, Jiakun Li, David R Lynch, Thomas H Mareci, Alberto R M Martinez, Massimo Pandolfo, Marina Papoutsi, Richard G Parker, Kathrin Reetz, Thiago J R Rezende, Timothy P Roberts, Sandro Romanzetti, David A Rudko, Susmita Saha, Jörg B Schulz, Sub H Subramony, Veena G Supramaniam, Christophe Lenglet, Pierre-Gilles Henry","doi":"10.1002/ana.27237","DOIUrl":"https://doi.org/10.1002/ana.27237","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to quantify differences in the brain and spinal cord between Friedreich ataxia and controls, stratified by age and disease stage, including for the first time in young children.</p><p><strong>Methods: </strong>TRACK-FA is the largest prospective, longitudinal, multi-modal neuroimaging study in Friedreich ataxia to date. We assessed individuals with Friedreich ataxia and controls, 5 to 42 years, at 7 sites across 4 continents. The 17 imaging primary outcome measures (POMs) were selected from metrics that showed a significant longitudinal change in previous small-scale studies. These included brain and spinal cord morphometry (structural magnetic resonance imaging [MRI]) and microstructure (diffusion MRI); brain iron levels (quantitative susceptibility mapping); and spinal cord biochemistry (magnetic resonance spectroscopy). This study is registered with ClinicalTrials.gov (NCT04349514).</p><p><strong>Results: </strong>Between February 2021 and August 2023, we assessed 169 individuals with Friedreich ataxia and 95 controls. Compared to controls, individuals with Friedreich ataxia had lower volume of dentate nucleus and superior cerebellar peduncles; smaller cross-sectional area of spinal cord; lower fractional anisotropy and higher diffusivity in spinal cord and superior cerebellar peduncles; and lower total N-acetyl-aspartate/myo-inositol ratio in spinal cord. Morphometric differences in spinal cord and superior cerebellar peduncles increased dramatically with age during childhood, with rapid development in controls, but not in Friedreich ataxia. Many imaging POMs showed significant associations with clinical severity.</p><p><strong>Interpretation: </strong>Our findings provide strong imaging evidence of impaired development of spinal cord and superior cerebellar peduncles during childhood in Friedreich ataxia and open the way for the use of neuroimaging biomarkers in clinical trials. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676687","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":"Neurology in the Twenty-First Century","authors":"John D. England MD,&nbsp;Ann C. Tilton MD,&nbsp;Carlayne E. Jackson MD","doi":"10.1002/ana.27241","DOIUrl":"10.1002/ana.27241","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 1","pages":"1-3"},"PeriodicalIF":8.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676689","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":"Letter on Wine Glass Sign in Bulbar-Onset Amyotrophic Lateral Sclerosis","authors":"Yu Zhu,&nbsp;Menghua Li,&nbsp;Meihong Zhou,&nbsp;Daojun Hong MD, PhD","doi":"10.1002/ana.27239","DOIUrl":"10.1002/ana.27239","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 6","pages":"1222"},"PeriodicalIF":8.1,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672980","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":"A Newly Defined, Common Ophthalmologic Condition Requires Special Neurological Attention","authors":"Kristina K. Hardy PhD,&nbsp;Daofen Chen PhD,&nbsp;Walter J. Koroshetz MD","doi":"10.1002/ana.27236","DOIUrl":"10.1002/ana.27236","url":null,"abstract":"<p>A host of acquired abnormalities in visual function are known to occur in persons who suffer stroke, traumatic brain injury, and neurodegenerative disorders. Cerebral visual impairment occurs in children with early neurological injury or disorders, especially neonatal hypoxic-ischemic injury. With the improved survival of pre-term infants through meticulous neonatal intensive care unit care, cerebral visual impairment in children has become much more common in developed countries. In recent months a number of National Institutes of Health institutes and the American Academy of Pediatrics have brought new attention to this major public health problem, which is highly relevant to child neurologists, neuro-ophthalmologists, as well as the general neurologists who will care for affected individuals as they enter adulthood. ANN NEUROL 2025;97:1019–1021</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 6","pages":"1019-1021"},"PeriodicalIF":8.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Memoriam: Robert B. Daroff, MD (8/3/1936–1/12/2025)","authors":"R. John Leigh,&nbsp;Robert L. Ruff,&nbsp;Michael Devereaux","doi":"10.1002/ana.27232","DOIUrl":"10.1002/ana.27232","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 5","pages":"807-808"},"PeriodicalIF":8.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646623","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":"Amyloid PET in Sporadic Early- Versus Late-Onset Alzheimer's Disease: Comparison of the LEADS and ADNI Cohorts.","authors":"Julien Lagarde, Piyush Maiti, Daniel R Schonhaut, Ganna Blazhenets, Jiaxiuxiu Zhang, Ani Eloyan, Maryanne Thangarajah, Alexander Taurone, Isabel Elaine Allen, David N Soleimani-Meigooni, Ehud Zeltzer, Charles Windon, Maison Abu Raya, Agathe Vrillon, Karen Smith, Ranjani Shankar, Alinda Amuiri, Salma Rocha, Dustin B Hammers, Jeffrey L Dage, Kelly N Nudelman, Kala Kirby, Paul Aisen, Robert Koeppe, Susan M Landau, Maria C Carrillo, Alexandra Touroutoglou, Michael Brickhouse, Prashanthi Vemuri, Laurel Beckett, Rema Raman, Alireza Atri, Gregory S Day, Ranjan Duara, Neill R Graff-Radford, Lawrence S Honig, David T Jones, Joseph C Masdeu, Mario F Mendez, Kyle Womack, Erik Musiek, Chiadi U Onyike, Meghan Riddle, Ian M Grant, Emily Rogalski, Erik C B Johnson, Stephen Salloway, Sharon Sha, R Scott Turner, Thomas S Wingo, David A Wolk, Bradford C Dickerson, Liana G Apostolova, Renaud La Joie, Gil D Rabinovici","doi":"10.1002/ana.27233","DOIUrl":"10.1002/ana.27233","url":null,"abstract":"<p><strong>Objective: </strong>Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) differ in many respects. Here, we address the issue of possible differences in fibrillar amyloid pathology as measured by positron emission tomography (PET), which remains unresolved due to the lack of large-scale comparative studies.</p><p><strong>Methods: </strong>Three hundred ninety-nine cognitively impaired participants younger than 65 years of age from the multicenter Longitudinal Early-onset Alzheimer's Disease Study (LEADS) and 450 cognitively impaired participants older than 65 years from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent clinical assessment, brain magnetic resonance imaging (MRI), and amyloid PET and were included in this study. We compared amyloid PET outcomes (positivity rate based on visual read and quantified tracer uptake expressed as Centiloids [CLs]) between the 2 cohorts and studied their association with age, sex, APOE genotype, and cognition.</p><p><strong>Results: </strong>The amyloid positivity rate was higher in LEADS (78%, 95% confidence interval [CI] = 74-82) than in ADNI (71%, 95% CI = 67-75, p = 0.02). Lower Mini-Mental State Examination (MMSE) and APOE4 genotype increased the odds of amyloid positivity in both cohorts. Visually positive scans had higher CLs in LEADS (EOAD, mean = 95.3 ± 26.1) than in ADNI (LOAD, mean = 80.9 ± 36.8, p < 0.0001), predominantly in parietal cortex/precuneus, superior temporal, and frontal cortices. In amyloid-positive patients, (1) CLs were higher in female patients in both cohorts; (2) APOE4 carriership was associated with lower CLs in EOAD, which was not observed in LOAD; and (3) correlations between CLs and MMSE scores were significantly stronger in EOAD than in LOAD.</p><p><strong>Interpretation: </strong>Differences in the burden of amyloid pathology may contribute to differences in clinical and anatomic patterns in sporadic EOAD and LOAD, and have implications for optimizing therapeutic strategies in each group. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646617","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":"Regional Brain Metabolism across the Alzheimer's Disease Continuum in Down Syndrome","authors":"José Enrique Arriola-Infante MD,&nbsp;Alejandra O. Morcillo-Nieto MSc,&nbsp;Sara E. Zsadanyi MSc,&nbsp;María Franquesa-Mullerat Msc,&nbsp;Lídia Vaqué-Alcázar PhD,&nbsp;Mateus Rozalem-Aranha MD, PhD,&nbsp;Javier Arranz MD,&nbsp;Íñigo Rodríguez-Baz MD, PhD,&nbsp;Lucia Maure-Blesa MD,&nbsp;Laura Videla PhD,&nbsp;Isabel Barroeta MD, PhD,&nbsp;Laura Del Hoyo Soriano PhD,&nbsp;Bessy Benejam PhD,&nbsp;Susana Fernández MD,&nbsp;Aida Sanjuan-Hernández BSc,&nbsp;Sandra Giménez MD, PhD,&nbsp;Daniel Alcolea MD, PhD,&nbsp;Olivia Belbin PhD,&nbsp;Albert Flotats MD, PhD,&nbsp;Valle Camacho MD, PhD,&nbsp;Alberto Lleó MD, PhD,&nbsp;María Carmona-Iragui MD, PhD,&nbsp;Juan Fortea MD, PhD,&nbsp;Alexandre Bejanin PhD","doi":"10.1002/ana.27226","DOIUrl":"10.1002/ana.27226","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The goal was to examine the effect of sociodemographic variables, Alzheimer's disease (AD) clinical stages and pathology on brain metabolism in Down syndrome (DS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 71 euploid healthy controls (HC) and 105 adults with DS (67 asymptomatic, 12 prodromal, and 26 with dementia) from the Down-Alzheimer Barcelona Neuroimaging Initiative. Participants underwent [18F]fluorodeoxyglucose positron emission tomography, 3 Tmagnetic resonance imaging, and lumbar puncture to measure cerebrospinal fluid (CSF) biomarkers (ratio beween amyloid β peptide 42 and 40, phosphorylated tau 181, and neurofilament light chain [NfL]). Voxel-wise analyses in SPM12 examined the effects of age, sex, intellectual disability, Alzheimer's clinical stage, and CSF biomarkers on brain metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In HC, brain metabolism decreased with age primarily in the frontal lobe. By contrast, a more distributed pattern of metabolic loss was observed in DS with age, predominating in temporoparietal regions. Compared to asymptomatic DS participants, those at the prodromal stage exhibited medial parietal hypometabolism, which later extended to other temporoparietal and frontal regions at the dementia stage. In asymptomatic individuals, we observed a widespread hypometabolism compared to HC, mainly in medial frontal and parietal regions. All CSF biomarkers were closely associated with hypometabolism in regions affected by the disease, with the strongest association observed for NfL in medial parietal structures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The brain metabolic decline in DS with age reflects Alzheimer's pathological processes and involves temporoparietal regions in a similar pattern to that found in other forms of AD. Hypometabolism is more tightly related to CSF NfL levels than to core AD biomarkers. ANN NEUROL 2025;98:163–173</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 1","pages":"163-173"},"PeriodicalIF":8.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622869","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":"Cerebral Edema Progression and Outcomes in Large Infarct Patients Undergoing Endovascular Thrombectomy.","authors":"Ximing Nie, Jinjie Liu, Bernard Yan, Felix C Ng, Sibo Liu, Yongle Wang, Mengxing Wang, Lina Zheng, Zan Wang, Yuying Wang, Yuesong Pan, Xiaochuan Huo, Zhongrong Miao, Stephen M Davis, Liping Liu","doi":"10.1002/ana.27235","DOIUrl":"https://doi.org/10.1002/ana.27235","url":null,"abstract":"<p><strong>Objective: </strong>The goal was to analyze the progression of cerebral edema post-endovascular thrombectomy (EVT) in large infarcts and its association with functional outcomes.</p><p><strong>Methods: </strong>A secondary analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core trial was conducted in patients with large ischemic cores randomized to receive either EVT or medical management (MM) alone. Patients who had follow-up imaging within 7 days post-randomization were involved. The primary outcome was midline shift (MLS). Mediation analysis was performed with EVT as the independent variable, MLS as the mediator, and modified Rankin scale scores at 90 days served as the endpoint. An exploratory analysis was conducted on the progression of net water uptake (ΔNWU).</p><p><strong>Results: </strong>Of 434 patients, median age was 66.0 years (standard deviation [SD], 9.9), with 61.3% (266) being males. EVT was associated with an early increase in MLS at 24 (±12) hours after randomization (mean [SD], 3.0 [4.2] vs 2.4 [3.6]mm; p = 0.03) compared with the MM group, partially mediating poorer functional outcomes post-EVT (mediation proportion, -25%; 95% CI, -46.54 to -4.10), but did not negate the overall efficacy of thrombectomy. The progression of NWU remained slower after EVT throughout 7 days, inconsistent with MLS.</p><p><strong>Interpretation: </strong>In patients with large infarct cores, EVT was associated with an early increased mass effect compared with MM, potentially mediating poorer functional outcomes. Despite the evident overall benefits from thrombectomy, accurate prediction and effective anti-edema interventions for the early mass effect post-EVT may further improve outcomes. The complex relationship between NWU and cerebral edema progression warrants further investigation. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595937","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}