Journal of Neurology最新文献

{"title":"Leo G. Abood (1922–1998)","authors":"Lazaros C. Triarhou","doi":"10.1007/s00415-024-12685-7","DOIUrl":"https://doi.org/10.1007/s00415-024-12685-7","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between blood-based protein biomarkers and brain MRI in the Alzheimer’s disease continuum: a systematic review","authors":"Micaela Mitolo, Gemma Lombardi, Riccardo Manca, Benedetta Nacmias, Annalena Venneri","doi":"10.1007/s00415-024-12674-w","DOIUrl":"https://doi.org/10.1007/s00415-024-12674-w","url":null,"abstract":"<p>Blood-based biomarkers (BBM) are becoming easily detectable tools to reveal pathological changes in Alzheimer’s disease (AD). A comprehensive and up-to-date overview of the association between BBM and brain MRI parameters is not available. This systematic review aimed to summarize the literature on the associations between the main BBM and MRI markers across the clinical AD continuum. A systematic literature search was carried out on PubMed and Web of Science and a total of 33 articles were included. Hippocampal volume was positively correlated with Aβ42 and Aβ42/Aβ40 and negatively with Aβ40 plasma levels. P-tau181 and p-tau217 concentrations were negatively correlated with temporal grey matter volume and cortical thickness. NfL levels were negatively correlated with white matter microstructural integrity, whereas GFAP levels were positively correlated with myo-inositol values in the posterior cingulate cortex/precuneus. These findings highlight consistent associations between various BBM and brain MRI markers even in the pre-clinical and prodromal stages of AD. This suggests a possible advantage in combining multiple AD-related markers to improve accuracy of early diagnosis, prognosis, progression monitoring and treatment response.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting multiple sclerosis disease progression and outcomes with machine learning and MRI-based biomarkers: a review","authors":"Hibba Yousef, Brigitta Malagurski Tortei, Filippo Castiglione","doi":"10.1007/s00415-024-12651-3","DOIUrl":"https://doi.org/10.1007/s00415-024-12651-3","url":null,"abstract":"<p>Multiple sclerosis (MS) is a demyelinating neurological disorder with a highly heterogeneous clinical presentation and course of progression. Disease-modifying therapies are the only available treatment, as there is no known cure for the disease. Careful selection of suitable therapies is necessary, as they can be accompanied by serious risks and adverse effects such as infection. Magnetic resonance imaging (MRI) plays a central role in the diagnosis and management of MS, though MRI lesions have displayed only moderate associations with MS clinical outcomes, known as the clinico-radiological paradox. With the advent of machine learning (ML) in healthcare, the predictive power of MRI can be improved by leveraging both traditional and advanced ML algorithms capable of analyzing increasingly complex patterns within neuroimaging data. The purpose of this review was to examine the application of MRI-based ML for prediction of MS disease progression. Studies were divided into five main categories: predicting the conversion of clinically isolated syndrome to MS, cognitive outcome, EDSS-related disability, motor disability and disease activity. The performance of ML models is discussed along with highlighting the influential MRI-derived biomarkers. Overall, MRI-based ML presents a promising avenue for MS prognosis. However, integration of imaging biomarkers with other multimodal patient data shows great potential for advancing personalized healthcare approaches in MS.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenomics of clinical response to Natalizumab in multiple sclerosis: a genome-wide multi-centric association study","authors":"Ferdinando Clarelli, Andrea Corona, Kimmo Pääkkönen, Melissa Sorosina, Alen Zollo, Fredrik Piehl, Tomas Olsson, Pernilla Stridh, Maja Jagodic, Bernhard Hemmer, Christiane Gasperi, Adil Harroud, Klementy Shchetynsky, Alessandra Mingione, Elisabetta Mascia, Kaalindi Misra, Antonino Giordano, Maria Laura Terzi Mazzieri, Alberto Priori, Janna Saarela, Ingrid Kockum, Massimo Filippi, Federica Esposito, Filippo Giovanni Martinelli Boneschi","doi":"10.1007/s00415-024-12608-6","DOIUrl":"https://doi.org/10.1007/s00415-024-12608-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Inter-individual differences in treatment response are marked in multiple sclerosis (MS). This is true for Natalizumab (NTZ), to which a subset of patients displays sub-optimal treatment response. We conducted a multi-centric genome-wide association study (GWAS), with additional pathway and network analysis to identify genetic predictors of response to NTZ.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>MS patients from three different centers were included. Response to NTZ was dichotomized, nominating responders (R) relapse-free patients and non-responders (NR) all the others, over a follow-up of 4 years. Association analysis on ~ 4.7 M imputed autosomal common single-nucleotide polymorphisms (SNPs) was performed fitting logistic regression models, adjusted for baseline covariates, followed by meta-analysis at SNP and gene level. Finally, these signals were projected onto STRING interactome, to elicit modules and hub genes linked to response.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Overall, 1834 patients were included: 119 from Italy (R = 94, NR = 25), 81 from Germany (R = 61, NR = 20), and 1634 from Sweden (R = 1349, NR = 285). The top-associated variant was rs11132400_T (<i>p</i> = 1.33 × 10^–6, OR = 0.58), affecting expression of several genes in the locus, like <i>KLKB1</i>. The interactome analysis implicated a module of 135 genes, with over-representation of terms like <i>canonical WNT signaling pathway</i> (<i>p</i>_adjust = 7.08 × 10^–6). Response-associated genes like <i>GRB2</i> and <i>LRP6</i>, already implicated in MS pathogenesis<i>,</i> were topologically prioritized within the module.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This GWAS, the largest pharmacogenomic study of response to NTZ, suggested MS-implicated genes and Wnt/β-catenin signaling pathway, an essential component for blood–brain barrier formation and maintenance, to be related to treatment response.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jean Aicardi (1926–2015)","authors":"Alisha Huang, Saba Jafarpour, Nicole A. Nishimori, Lilia Kazerooni, Jonathan D. Santoro","doi":"10.1007/s00415-024-12684-8","DOIUrl":"https://doi.org/10.1007/s00415-024-12684-8","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GFAP and NfL as fluid biomarkers for clinical disease severity and disease progression in multiple system atrophy (MSA)","authors":"Sabrina Katzdobler, Georg Nübling, Martin Klietz, Urban M. Fietzek, Carla Palleis, Alexander M. Bernhardt, Florian Wegner, Meret Huber, Sophia Rogozinski, Luisa-Sophie Schneider, Eike Jakob Spruth, Aline Beyle, Ina R. Vogt, Moritz Brandt, Niels Hansen, Wenzel Glanz, Kathrin Brockmann, Annika Spottke, Daniel C. Hoffmann, Oliver Peters, Josef Priller, Jens Wiltfang, Emrah Düzel, Anja Schneider, Björn Falkenburger, Thomas Klockgether, Thomas Gasser, Brigitte Nuscher, Christian Haass, Günter Höglinger, Johannes Levin","doi":"10.1007/s00415-024-12647-z","DOIUrl":"https://doi.org/10.1007/s00415-024-12647-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Multiple system atrophy (MSA), an atypical parkinsonian syndrome, is a rapidly progressive neurodegenerative disease with currently no established fluid biomarkers available. MSA is characterized by an oligodendroglial α-synucleinopathy, progressive neuronal cell loss and concomitant astrocytosis. Here, we investigate glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as fluid biomarkers for differential diagnosis, assessment of clinical disease severity and prediction of disease progression in MSA.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>GFAP and NfL levels were analyzed in plasma and CSF samples of 47 MSA patients as well as 24 Parkinson’s disease (PD) and 25 healthy controls (HC) as reference cohorts. In MSA, biomarker levels were correlated to baseline and longitudinal clinical disease severity (UMSARS scores).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In MSA, GFAP levels in CSF and plasma predicted baseline clinical disease severity as indicated by UMSARS scores, while NfL levels predicted clinical disease progression as indicated by longitudinal changes in UMSARS scores. Cross-sectionally, NfL levels in CSF and plasma were significantly elevated in MSA compared to both PD and HC. Receiver operating curves (ROC) indicated high diagnostic accuracy of NfL for distinguishing MSA from PD (CSF: AUC = 0.97, 95% CI 0.90–1.00; plasma: AUC = 0.90, 95% CI 0.81–1.00).</p><h3 data-test=\"abstract-sub-heading\">Discussion</h3><p>In MSA, GFAP shows promise as novel biomarker for assessing current clinical disease severity, while NfL might serve as biomarker for prediction of disease progression and differential diagnosis of MSA against PD.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Takotsubo syndrome in a Sardinian amyotrophic lateral sclerosis cohort","authors":"A. Maccabeo, M. I. Pateri, F. Pili, S. Pilotto, V. Pierri, A. Muroni, T. Ercoli, R. Montisci, M. F. Marchetti, A. Martis, L. Fazzini, G. Defazio, M. Puligheddu, G. Borghero","doi":"10.1007/s00415-024-12681-x","DOIUrl":"https://doi.org/10.1007/s00415-024-12681-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Amyotrophic lateral sclerosis (ALS) is known to be associated with varying degrees of autonomic and cardiovascular dysfunction. Recent case reports showed that ALS may be linked to Takotsubo syndrome (TTS). We assessed the frequency of TTS in an incident ALS cohort from Sardinia, Italy, and investigated the relationship of TTS with ALS course.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We retrospectively examined a 10-year (2010–2019) incident cohort of ALS patients of Sardinian ancestry, reported TTS frequency and patients’ clinical characteristics. Following, we checked for TTS among patients with ALS onset after 2019 and focused on the same features as for the incident cohort.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Our incident cohort included 344 ALS patients and 5 of them (1.45%) developed TTS. All were female and their median onset age was 71.5 years (IQR 62.75–77). Two patients had spinal and three bulbar onset, though all patients had bulbar involvement and were at an advanced stage of disease (ALSFRS ≤ 25, King’s ≥ 3) at TTS diagnosis. We identified a potential TTS trigger in three patients (hospitalization for PEG placement, pneumonia). Among patients who had ALS onset after 2019, we identified a further TTS case and described it.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>TTS is not a rare condition in ALS. Female sex, bulbar involvement, and later age of disease onset may be important risk factors for developing this cardiac condition and a physical or psychological trigger is often observed. Despite autonomic dysfunction in ALS has been already demonstrated, the precise physiopathological mechanism underlying TTS needs to be further clarified.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid differentiation of MOGAD and MS after a single optic neuritis.","authors":"T Pakeerathan, J Havla, C Schwake, A Salmen, M Ringelstein, O Aktas, M Weise, J A Gernert, B Kornek, G Bsteh, A-K Pröbstel, A Papadopoulou, L Kulsvehagen, A B Ayroza Galvão Ribeiro Gomes, N Cerdá-Fuertes, F C Oertel, A S Duchow, F Paul, J P Stellmann, N Stolowy, K Hellwig, C Schneider-Gold, T Kümpfel, R Gold, P Albrecht, I Ayzenberg","doi":"10.1007/s00415-024-12666-w","DOIUrl":"https://doi.org/10.1007/s00415-024-12666-w","url":null,"abstract":"<p><strong>Background: </strong>Optic neuritis (ON) is a common manifestation of multiple sclerosis (MS) and myelin-oligodendrocyte-glycoprotein IgG-associated disease (MOGAD). This study evaluated the applicability of optical coherence tomography (OCT) for differentiating between both diseases in two independent cohorts.</p><p><strong>Methods: </strong>One hundred sixty two patients from seven sites underwent standard OCT and high-contrast visual acuity (HCVA) testing at least 6 months after first ON. Of these, 100 patients (32 MOGAD, 68 MS) comprised the primary investigational cohort, while 62 patients (31 MOGAD, 31 MS) formed a validation cohort. A composite score distinguishing between MOGAD and MS was developed using multivariate logistic regression.</p><p><strong>Results: </strong>Bilateral simultaneous ON occurred more frequently in MOGAD compared to MS (46.9 vs. 11.8%, p < 0.001). OCT revealed more peripapillary retinal nerve fiber layer (pRNFL) atrophy in all segments in MOGAD compared to predominantly temporal pRNFL atrophy in MS (p < 0.001). HCVA was better preserved in MS (p = 0.007). pRNFL thickness in all except for temporal segments was suitable for differentiating MOGAD and MS. Simultaneous bilateral ON and critical atrophy in nasal (< 58.5 µm) and temporal superior (< 105.5 µm) segments were included into the composite score as three independent predictors for MOGAD. The composite score distinguished MOGAD from MS with 75% sensitivity and 90% specificity in the investigational cohort, and 68% sensitivity and 87% specificity in the validation cohort.</p><p><strong>Conclusion: </strong>Following a single ON-episode, MOGAD exhibits more pronounced global pRNFL atrophy and lower visual acuity after ON compared to MS. The introduced OCT-based composite score enabled differentiation between the two entities across both cohorts.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving prediction models of amyotrophic lateral sclerosis (ALS) using polygenic, pre-existing conditions, and survey-based risk scores in the UK Biobank.","authors":"Weijia Jin, Jonathan Boss, Kelly M Bakulski, Stephen A Goutman, Eva L Feldman, Lars G Fritsche, Bhramar Mukherjee","doi":"10.1007/s00415-024-12644-2","DOIUrl":"https://doi.org/10.1007/s00415-024-12644-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>Amyotrophic lateral sclerosis (ALS) causes profound impairments in neurological function, and a cure for this devastating disease remains elusive. This study aimed to identify pre-disposing genetic, phenotypic, and exposure-related factors for amyotrophic lateral sclerosis using multi-modal data and assess their joint predictive potential.</p><p><strong>Methods: </strong>Utilizing data from the UK (United Kingdom) Biobank, we analyzed an unrelated set of 292 ALS cases and 408,831 controls of European descent. Two polygenic risk scores (PRS) are constructed: \"GWAS Hits PRS\" and \"PRS-CS,\" reflecting oligogenic and polygenic ALS risk profiles, respectively. Time-restricted phenome-wide association studies (PheWAS) were performed to identify pre-existing conditions increasing ALS risk, integrated into phenotypic risk scores (PheRS). A poly-exposure score (\"PXS\") captures the influence of environmental exposures measured through survey questionnaires. We evaluate the performance of these scores for predicting ALS incidence and stratifying risk, adjusting for baseline demographic covariates.</p><p><strong>Results: </strong>Both PRSs modestly predicted ALS diagnosis but with increased predictive power when combined (covariate-adjusted receiver operating characteristic [AAUC] = 0.584 [0.525, 0.639]). PheRS incorporated diagnoses 1 year before ALS onset (PheRS1) modestly discriminated cases from controls (AAUC = 0.515 [0.472, 0.564]). The \"PXS\" did not significantly predict ALS. However, a model incorporating PRSs and PheRS1 improved the prediction of ALS (AAUC = 0.604 [0.547, 0.667]), outperforming a model combining all risk scores. This combined risk score identified the top 10% of risk score distribution with a fourfold higher ALS risk (95% CI [2.04, 7.73]) versus those in the 40%-60% range.</p><p><strong>Discussion: </strong>By leveraging UK Biobank data, our study uncovers pre-disposing ALS factors, highlighting the improved effectiveness of multi-factorial prediction models to identify individuals at highest risk for ALS.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma NfL, GFAP, amyloid, and p-tau species as Prognostic biomarkers in Parkinson's disease.","authors":"Andrea Pilotto, Nicholas J Ashton, Alessandro Lupini, Beatrice Battaglio, Cinzia Zatti, Chiara Trasciatti, Stefano Gipponi, Elisabetta Cottini, Ilaria Grossi, Alessandro Salvi, Giuseppina de Petro, Marina Pizzi, Antonio Canale, Kaj Blennow, Henrik Zetterberg, Alessandro Padovani","doi":"10.1007/s00415-024-12669-7","DOIUrl":"https://doi.org/10.1007/s00415-024-12669-7","url":null,"abstract":"<p><strong>Introduction: </strong>The prognostic role of plasma neurofilament light chain (NfL), phospho-tau, beta-amyloid, and GFAP is still debated in Parkinson's disease (PD).</p><p><strong>Methods: </strong>Plasma p-tau181, p-tau231, Aβ1-40, Aβ1-42, GFAP, and NfL were measured by SIMOA in 136 PD with 2.9 + 1.7 years of follow-up and 76 controls. Differences in plasma levels between controls and PD and their correlation with clinical severity and progression rates were evaluated using linear regression analyses.</p><p><strong>Results: </strong>Patients exhibited similar distribution of plasma biomarkers but higher P-tau181, P-tau231 and lower Aβ1-42 compared with controls. NfL and GFAP correlated with baseline motor and non-motor severity measures. At follow-up, NfL emerged as the best predictor of progression with marginal effect of GFAP and p-tau181 adjusting for age, sex, disease duration, and baseline motor severity.</p><p><strong>Conclusion: </strong>The present findings confirmed plasma NfL as best predictor of progression in PD, with a marginal role of p-tau181 and GFAP.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}