NPJ Parkinson's Disease最新文献

{"title":"Neural correlates of bradykinesia in Parkinson’s disease: a kinematic and functional MRI study","authors":"Elisabetta Sarasso, Andrea Gardoni, Lucia Zenere, Daniele Emedoli, Roberta Balestrino, Andrea Grassi, Silvia Basaia, Chiara Tripodi, Elisa Canu, Massimo Malcangi, Elisa Pelosin, Maria Antonietta Volontè, Davide Corbetta, Massimo Filippi, Federica Agosta","doi":"10.1038/s41531-024-00783-2","DOIUrl":"https://doi.org/10.1038/s41531-024-00783-2","url":null,"abstract":"<p>Bradykinesia is defined as a “<i>complex</i>” of motor alterations including decreased movement amplitude and/or speed and tendency to reduce them with movement repetition (sequence effect). This study aimed at investigating the neural and kinematic correlates of bradykinesia during hand-tapping in people with Parkinson’s disease (pwPD) relative to healthy controls. Twenty-five pwPD and 25 age- and sex-matched healthy controls underwent brain functional MRI (fMRI) during a hand-tapping task: subjects alternatively opened and closed their right hand as fully and quickly as possible. Hand-tapping kinematic parameters were objectively measured during the fMRI task using an optical fibre glove. During the fMRI task, pwPD showed reduced hand-tapping amplitude (hypokinesia) and a greater sequence effect. PwPD relative to healthy controls showed a reduced activity of fronto-parietal areas, middle cingulum/supplementary motor area (SMA), parahippocampus, pallidum/thalamus and motor cerebellar areas. Moreover, pwPD showed an increased activity of brain cognitive areas such as superior temporal gyrus, posterior cingulum, and cerebellum crus I. The decreased activity of cerebellum IV–V–VI, vermis IV–V, inferior frontal gyrus, and cingulum/SMA correlated with hypokinesia and with the sequence effect. Interestingly, a reduced activity of areas involved in motor planning and timing correlated both with hypokinesia and with the sequence effect in pwPD. This study has the major strength of collecting objective motor parameters and brain activity simultaneously, providing a unique opportunity to investigate the neural correlates of the “bradykinesia complex”.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142615","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":"Calbindin and Girk2/Aldh1a1 define resilient vs vulnerable dopaminergic neurons in a primate Parkinson’s disease model","authors":"Natalia López-González del Rey, Nagore Hernández-Pinedo, Megan Carrillo, María del Cerro, Noelia Esteban-García, Inés Trigo-Damas, Mariana H. G. Monje, José L. Lanciego, Carmen Cavada, José A. Obeso, Javier Blesa","doi":"10.1038/s41531-024-00777-0","DOIUrl":"https://doi.org/10.1038/s41531-024-00777-0","url":null,"abstract":"<p>The differential vulnerability of dopaminergic neurons of the <i>substantia nigra pars compacta</i> (SNc) is a critical and unresolved question in Parkinson´s disease. Studies in mice show diverse susceptibility of subpopulations of nigral dopaminergic neurons to various toxic agents. In the primate midbrain, the molecular phenotypes of dopaminergic neurons and their differential vulnerability are poorly characterized. We performed a detailed histological study to determine the anatomical distribution of different molecular phenotypes within identified midbrain neurons and their selective vulnerability in control and MPTP-treated monkeys. In the ventral tier of the SNc (<i>nigrosome</i>), neurons rich in Aldh1a1 and Girk2 are intermingled, whereas calbindin is the marker that best identifies the most resilient neurons located in the dorsal tier and ventral tegmental area, recapitulating the well-defined dorsoventral axis of susceptibility to degeneration of dopaminergic neurons. In particular, a loss of Aldh1a1+ neurons in the ventral SNc was observed in parallel to the progressive development of parkinsonism. Aldh1a1+ neurons were the main population of vulnerable dopaminergic nigrostriatal-projecting neurons, while Aldh1a1- neurons giving rise to nigropallidal projections remained relatively preserved. Moreover, bundles of entwined Aldh1a1+ dendrites with long trajectories extending towards the <i>substantia nigra pars reticulata</i> emerged from clusters of Aldh1a1+ neurons and colocalized with dense cannabinoid receptor 1 afferent fibers likely representing part of the striatonigral projection that is affected in human disorders, including Parkinson´s disease. In conclusion, vulnerable nigrostriatal-projecting neurons can be identified by using Aldh1a1 and Girk2. Further studies are needed to define the afferent/efferent projection patterns of these most vulnerable neurons.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118058","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":"Exploring causal effects of sarcopenia on risk and progression of Parkinson disease by Mendelian randomization","authors":"Tao Wang, Jiaquan Geng, Xi Zeng, Ruijiang Han, Young Eun Huh, Jiajie Peng","doi":"10.1038/s41531-024-00782-3","DOIUrl":"https://doi.org/10.1038/s41531-024-00782-3","url":null,"abstract":"<p>Previous observational studies suggested that sarcopenia is associated with Parkinson disease (PD), but it is unclear whether this association is causal. The objective of this study was to examine causal associations between sarcopenia-related traits and the risk or progression of PD using a Mendelian randomization (MR) approach. Two-sample bidirectional MR analyses were conducted to evaluate causal relationships. Genome-wide association study (GWAS) summary statistics for sarcopenia-related traits, including right handgrip strength (<i>n</i> = 461,089), left handgrip strength (<i>n</i> = 461,026), and appendicular lean mass (<i>n</i> = 450,243), were retrieved from the IEU OpenGWAS database. GWAS data for the risk of PD were derived from the FinnGen database (4235 cases; 373,042 controls). Summary-level data for progression of PD, including progression to Hoehn and Yahr stage 3, progression to dementia, and development of levodopa-induced dyskinesia, were obtained from a recent GWAS publication on progression of PD in 4093 patients from 12 longitudinal cohorts. Significant causal associations identified in MR analysis were verified through a polygenic score (PGS)-based approach and pathway enrichment analysis using genotype data from the Parkinson’s Progression Markers Initiative. MR results supported a significant causal influence of right handgrip strength (odds ratio [OR] = 0.152, 95% confidence interval [CI] = 0.055–0.423, adjusted <i>P</i> = 0.0036) and appendicular lean mass (OR = 0.597, 95% CI = 0.440–0.810, adjusted <i>P</i> = 0.0111) on development of levodopa-induced dyskinesia. In Cox proportional hazard analysis, higher PGSs for right handgrip strength (hazard ratio [HR] = 0.225, 95% CI = 0.095–0.530, adjusted <i>P</i> = 0.0019) and left handgrip strength (HR = 0.303, 95% CI = 0.121–0.59, adjusted <i>P</i> = 0.0323) were significantly associated with a lower risk of developing levodopa-induced dyskinesia, after adjusting for covariates. Pathway enrichment analysis revealed that genome-wide significant single-nucleotide polymorphisms for right handgrip strength were substantially enriched in biological pathways involved in the control of synaptic plasticity. This study provides genetic evidence of the protective role of handgrip strength or appendicular lean mass on the development of levodopa-induced dyskinesia in PD. Sarcopenia-related traits can be promising prognostic markers for levodopa-induced dyskinesia and potential therapeutic targets for preventing levodopa-induced dyskinesia in patients with PD.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085624","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":"Advancing age and the rs6265 BDNF SNP are permissive to graft-induced dyskinesias in parkinsonian rats","authors":"Natosha M. Mercado, Carlye Szarowicz, Jennifer A. Stancati, Caryl E. Sortwell, Samuel A. Boezwinkle, Timothy J. Collier, Margaret E. Caulfield, Kathy Steece-Collier","doi":"10.1038/s41531-024-00771-6","DOIUrl":"https://doi.org/10.1038/s41531-024-00771-6","url":null,"abstract":"<p>The rs6265 single nucleotide polymorphism (SNP) in the gene for brain-derived neurotrophic factor is a common variant that alters therapeutic outcomes for individuals with Parkinson’s disease (PD). We previously investigated the effects of this SNP on the experimental therapeutic approach of neural grafting, demonstrating that young adult parkinsonian rats carrying the variant Met allele exhibited enhanced graft function compared to wild-type rats and also exclusively developed aberrant graft-induced dyskinesias (GID). Aging is the primary risk factor for PD and reduces graft efficacy. Here we investigated whether aging interacts with this SNP to further alter cell transplantation outcomes. We hypothesized that aging would reduce enhancement of graft function associated with this genetic variant and exacerbate GID in all grafted subjects. Unexpectedly, beneficial graft function was maintained in aged rs6265 subjects. However, aging was permissive to GID induction, regardless of genotype, with the greatest incidence and severity found in rs6265-expressing animals.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142045643","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":"Neuroprotection of low dose carbon monoxide in Parkinson’s disease models commensurate with the reduced risk of Parkinson’s among smokers","authors":"K. N. Rose, M. Zorlu, A. Fassini, H. Lee, W. Cai, X. Xue, S. Lin, P. Kivisakk, M. A. Schwarzschild, X. Chen, S. N. Gomperts","doi":"10.1038/s41531-024-00763-6","DOIUrl":"https://doi.org/10.1038/s41531-024-00763-6","url":null,"abstract":"<p>Paradoxically, cigarette smoking is associated with a reduced risk of Parkinson’s Disease (PD). This led us to hypothesize that carbon monoxide (CO) levels, which are constitutively but modestly elevated in smokers, might contribute to neuroprotection. Using rodent models of PD based on α-synuclein (αSyn) accumulation and oxidative stress, we show that low-dose CO mitigates neurodegeneration and reduces αSyn pathology. Oral CO administration activated signaling cascades mediated by heme oxygenase-1 (HO-1), which have been implicated in limiting oxidative stress, and in promoting αSyn degradation, thereby conferring neuroprotection. Consistent with the neuroprotective effect of smoking, HO-1 levels in cerebrospinal fluid were higher in human smokers compared to nonsmokers. Moreover, in PD brain samples, HO-1 levels were higher in neurons without αSyn pathology. Thus, CO in rodent PD models reduces pathology and increases oxidative stress responses, phenocopying possible protective effects of smoking evident in PD patients. These data highlight the potential for low-dose CO-modulated pathways to slow symptom onset and limit pathology in PD patients.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142021960","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":"Serum neurofilament light at diagnosis: a prognostic indicator for accelerated disease progression in Parkinson's Disease.","authors":"Camilla Christina Pedersen, Anastasia Ushakova, Guido Alves, Ole-Bjørn Tysnes, Kaj Blennow, Henrik Zetterberg, Jodi Maple-Grødem, Johannes Lange","doi":"10.1038/s41531-024-00768-1","DOIUrl":"10.1038/s41531-024-00768-1","url":null,"abstract":"<p><p>Neurofilament light chain (NFL) is elevated in neurodegenerative diseases, including Parkinson's disease (PD). This study aimed to investigate serum NFL in newly diagnosed PD and its association with cognitive and motor decline over 10 years. Serum NFL levels were measured in PD patients and controls from the ParkWest study at diagnosis (baseline) and after 3 and 5 years. Mixed-effects regression analyzed changes in NFL and the association with annual changes in MMSE and UPDRS-III scores over 10 years. PD patients had elevated serum NFL at all visits and a faster annual increase over 5 years compared to controls (0.09 pg/mL per year; p = 0.029). Higher baseline NFL predicted faster cognitive decline β -0.77 transformed MMSE; p = 0.010), and a 40% NFL increase predicted future motor decline (β 0.28 UPDRS-III; p = 0.004). Elevated serum NFL in early PD is linked to faster cognitive and motor impairment, suggesting its prognostic value in PD biomarker panels.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009150","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":"Assessing the clinical utility of inertial sensors for home monitoring in Parkinson's disease: a comprehensive review.","authors":"Stefano Sapienza, Olena Tsurkalenko, Marijus Giraitis, Alan Castro Mejia, Gelani Zelimkhanov, Isabel Schwaninger, Jochen Klucken","doi":"10.1038/s41531-024-00755-6","DOIUrl":"10.1038/s41531-024-00755-6","url":null,"abstract":"<p><p>This review screened 296 articles on wearable sensors for home monitoring of people with Parkinson's Disease within the PubMed Database, from January 2017 to May 2023. A three-level maturity framework was applied for classifying the aims of 59 studies included: demonstrating technical efficacy, diagnostic sensitivity, or clinical utility. As secondary analysis, user experience (usability and patient adherence) was evaluated. The evidences provided by the studies were categorized and stratified according to the level of maturity. Our results indicate that approximately 75% of articles investigated diagnostic sensitivity, i.e. correlation of sensor-data with clinical parameters. Evidence of clinical utility, defined as improvement on health outcomes or clinical decisions after the use of the wearables, was found only in nine papers. A third of the articles included reported evidence of user experience. Future research should focus more on clinical utility, to facilitate the translation of research results within the management of Parkinson's Disease.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009149","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":"A systematic exploration of unexploited genes for oxidative stress in Parkinson's disease.","authors":"Takayuki Suzuki, Hidemasa Bono","doi":"10.1038/s41531-024-00776-1","DOIUrl":"10.1038/s41531-024-00776-1","url":null,"abstract":"<p><p>Human disease-associated gene data are accessible through databases, including the Open Targets Platform, DisGeNET, miRTex, RNADisease, and PubChem. However, missing data entries in such databases are anticipated because of curational errors, biases, and text-mining failures. Additionally, the extensive research on human diseases has led to challenges in registering comprehensive data. The lack of essential data in databases hinders knowledge sharing and should be addressed. Therefore, we propose an analysis pipeline to explore missing entries of unexploited genes in the human disease-associated gene databases. Using this pipeline for genes in Parkinson's disease with oxidative stress revealed two unexploited genes: nuclear protein 1 (NUPR1) and ubiquitin-like with PHD and ring finger domains 2 (UHRF2). This methodology enhances the identification of underrepresented disease-associated genes, facilitating easier access to potential human disease-related functional genes. This study aims to identify unexploited genes for further research and does not include independent experimental validation.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996292","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":"MRI subtypes in Parkinson’s disease across diverse populations and clustering approaches","authors":"Anna Inguanzo, Rosaleena Mohanty, Konstantinos Poulakis, Daniel Ferreira, Barbara Segura, Franziska Albrecht, J-Sebastian Muehlboeck, Tobias Granberg, Henrik Sjöström, Per Svenningsson, Erika Franzén, Carme Junqué, Eric Westman","doi":"10.1038/s41531-024-00759-2","DOIUrl":"https://doi.org/10.1038/s41531-024-00759-2","url":null,"abstract":"<p>Parkinson’s disease (PD) is clinically heterogeneous, which suggests the existence of subtypes; however, there has been no consensus regarding their characteristics. This study included 633 PD individuals across distinct cohorts: unmedicated de novo PD, medicated PD, mild-moderate PD, and a cohort based on diagnostic work-up in clinical practice. Additionally, 233 controls were included. Clustering based on cortical and subcortical gray matter measures was conducted with and without adjusting for global atrophy in the entire PD sample and validated within each cohort. Subtypes were characterized using baseline and longitudinal demographic and clinical data. Unadjusted results identified three clusters showing a gradient of neurodegeneration and symptom severity across the entire sample and the individual cohorts. When adjusting for global atrophy eight clusters were identified in the entire sample, lacking consistency in individual cohorts. This study identified atrophy-based subtypes in PD, emphasizing the significant impact of global atrophy on subtype number, patterns, and interpretation in cross-sectional analyses.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992007","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":"Risk willingness in multiple system atrophy and Parkinson’s disease understanding patient preferences","authors":"Alexander Maximilian Bernhardt, Marc Oeller, Isabel Friedrich, Emre Kocakavuk, Eliana Nachman, Kevin Peikert, Malte Roderigo, Andreas Rossmann, Tabea Schröter, Lea Olivia Wilhelm, Tino Prell, Christoph van Riesen, Johanna Nieweler, Sabrina Katzdobler, Markus Weiler, Heike Jacobi, Tobias Warnecke, Inga Claus, Carla Palleis, Stephan Breimann, Björn Falkenburger, Moritz Brandt, Andreas Hermann, Jost-Julian Rumpf, Joseph Claßen, Günter Höglinger, Florin Gandor, Johannes Levin, Armin Giese, Annette Janzen, Wolfgang Hermann Oertel","doi":"10.1038/s41531-024-00764-5","DOIUrl":"https://doi.org/10.1038/s41531-024-00764-5","url":null,"abstract":"<p>Disease-modifying therapeutics in the α-synucleinopathies multiple system atrophy (MSA) and Parkinson’s Disease (PD) are in early phases of clinical testing. Involving patients’ preferences including therapy-associated risk willingness in initial stages of therapy development has been increasingly pursued in regulatory approval processes. In our study with 49 MSA and 38 PD patients, therapy-associated risk willingness was quantified using validated standard gamble scenarios for varying severities of potential drug or surgical side effects. Demonstrating a non-gaussian distribution, risk willingness varied markedly within, and between groups. MSA patients accepted a median 1% risk [interquartile range: 0.001–25%] of sudden death for a 99% [interquartile range: 99.999–75%] chance of cure, while PD patients reported a median 0.055% risk [interquartile range: 0.001–5%]. Contrary to our hypothesis, a considerable proportion of MSA patients, despite their substantially impaired quality of life, were not willing to accept increased therapy-associated risks. Satisfaction with life situation, emotional, and nonmotor disease burden were associated with MSA patients’ risk willingness in contrast to PD patients, for whom age, and disease duration were associated factors. An individual approach towards MSA and PD patients is crucial as direct inference from disease (stage) to therapy-associated risk willingness is not feasible. Such studies may be considered by regulatory agencies in their approval processes assisting with the weighting of safety aspects in a patient-centric manner. A systematic quantitative assessment of patients’ risk willingness and associated features may assist physicians in conducting individual consultations with patients who have MSA or PD by facilitating communication of risks and benefits of a treatment option.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986361","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}