Brain最新文献

{"title":"Medial temporal lobe atrophy in Down syndrome along the Alzheimer's disease continuum","authors":"Benjamin J Buehner, Alejandra O Morcillo-Nieto, Sara E Zsadanyi, Mateus Rozalem Aranha, José Enrique Arriola-Infante, Lídia Vaqué-Alcázar, Javier Arranz, Íñigo Rodríguez-Baz, Lucia Maure Blesa, Laura Videla, Isabel Barroeta, Laura Del Hoyo Soriano, Bessy Benejam, Susana Fernández, Aida Sanjuan Hernandez, Nuria Bargalló, Sofía González-Ortiz, Sandra Giménez, Robin de Flores, Paul A Yushkevich, Daniel Alcolea, Olivia Belbin, Alberto Lleó, Maria Carmona-Iragui, Juan Fortea, Alexandre Bejanin","doi":"10.1093/brain/awaf133","DOIUrl":"https://doi.org/10.1093/brain/awaf133","url":null,"abstract":"Medial temporal lobe structures are among the first areas impacted by neurofibrillary tangle pathology, making volumetric changes of these areas promising biomarkers for Alzheimer's disease. To date, little is known about the integrity of these regions in individuals with Down syndrome, a population which almost invariably develops Alzheimer's disease and thus offers a unique opportunity to determine the earliest structural changes related to the disease. We aimed to characterize the sequential involvement of medial temporal lobe structures with Alzheimer's disease progression, explore associations with fluid biomarkers of Alzheimer’s pathology, and assess the utility of regional volumes and cortical thickness in distinguishing Alzheimer’s disease clinical stages in Down syndrome. 138 euploid controls and 259 adults with Down syndrome underwent clinical assessment and MRI scanning, followed by automated segmentation of the medial temporal lobe on T1-weighted images. Parametric statistical tests and local regression models were used to assess the cross-sectional association between regional volumes/cortical thickness and Alzheimer’s disease clinical stage, estimated years of onset, and CSF biomarkers. Additionally, markers were assessed in their ability to distinguish clinical stages using area under the receiver-operating characteristic curves. Results showed a progressive loss of volume and cortical thickness in medial temporal lobe with advancing Alzheimer’s disease stage, showing reduced volume/thickness at the dementia stage in all subregions. The asymptomatic and prodromal groups showed significant differences in the anterior and posterior hippocampus. We identified the entorhinal cortex and posterior hippocampus as the regions showing the earliest loss in Down syndrome, starting 13-15 years before Alzheimer’s disease symptom onset. We observed non-linear structural changes with disease progression, with certain structures (e.g., the parahippocampal cortex) characterized by an initial increase in cortical thickness followed by subsequent thinning. Of all subregions, the hippocampal volumes showed the closest correlation to CSF Aβ42/40, pTau181, and neurofilament light chain levels. Further analyses demonstrated a high predictive value, similar to CSF biomarkers, of the hippocampus in differentiating between individuals with asymptomatic versus prodromal/demented Alzheimer’s disease in Down syndrome. This study provides a novel understanding of the progressive, non-linear volumetric changes of medial temporal lobe structures in relation to Alzheimer’s disease pathology in Down syndrome, which can have important implications for clinical trials monitoring neurodegeneration using MRI. We also show that MRI information can refine the prediction of clinical status in Down syndrome. This is particularly relevant in Down syndrome, where early clinical stages can be challenging to detect due to neurodevelopmental intellectual disability.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"89 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841694","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":"Alterations in dopaminergic innervation and receptors in focal cortical dysplasia.","authors":"Norisa Meli,Katherine Sheran,Julika Pitsch,Sabine Krabbe,Valeri Borger,Tobias Baumgartner,Albert Becker,Sandra Blaess","doi":"10.1093/brain/awaf080","DOIUrl":"https://doi.org/10.1093/brain/awaf080","url":null,"abstract":"Focal cortical dysplasia (FCD) type 2 is the most common malformation of cortical development associated with pharmaco-resistant focal epilepsy and frequently located in the frontal cortex. Neuropathological hallmarks comprise abnormal cortical layering and enlarged, dysmorphic neuronal elements. Fundamentally altered local neuronal activity has been reported in human FCD type 2 epilepsy surgical biopsies. Of note, FCD type 2 emerges during brain development and forms complex connectivity architectures with surrounding neuronal networks. Local cortical microcircuits, particularly in frontal localization, are extensively modulated by monoaminergic axonal projections originating from the brainstem. Previous analysis of monoaminergic modulatory inputs in human FCD type 2 biopsies suggested altered density and distribution of these monoaminergic axons; however, a systematic investigation is still pending. Here, we perform a comprehensive analysis of dopaminergic (DA) innervation, in human FCD type 2 biopsies and in the medial prefrontal cortex (mPFC) of an FCD type 2 mouse model [mechanistic target of rapamyin (mTOR) hyperactivation model] during adolescent and adult stages. In addition, we analyse the expression of dopamine receptor transcripts via multiplex fluorescent RNA in situ hybridization in human specimens and the mPFC of this mouse model. In the mTOR hyperactivation mouse model, we observe a transient alteration of DA innervation density during adolescence and a trend towards decreased innervation in adulthood. In human FCD type 2 areas, the overall DA innervation density is decreased in adult patients compared with control areas from these patients. Moreover, the DA innervation shows an altered lamination pattern in the FCD type 2 area compared with the control area. Dopamine receptors 1 and 2 appear to be differentially expressed in the dysmorphic neurons in human samples and mTOR-mutant cells in mice compared with normally developed neurons. Intriguingly, our results suggest complex molecular and structural alterations putatively inducing impaired DA neurotransmission in FCD type 2. We hypothesize that this may have important implications for the development of these malformations and the manifestation of seizures.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"37 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841062","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":"What's left to explain and what's right to conclude about the neurocognition of deductive reasoning?","authors":"Carlo Reverberi,Giosuè Baggio,Paolo Cherubini","doi":"10.1093/brain/awaf117","DOIUrl":"https://doi.org/10.1093/brain/awaf117","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"4 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841123","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":"Cognitive and neuropsychiatric profiles distinguish atypical parkinsonian syndromes","authors":"Michele T Hu, Agustin Querejeta Coma, James B Rowe, Tanja Zerenner, Alistair Church, Riona Fumi, Alyssa Constantini, Edwin Jabbari, Marte T Jensen, Alexander Gerhard, Nicola Pavese, Christopher Kobylecki, P Nigel Leigh, Ivan Koychev, Huw Morris, Sanjay G Manohar","doi":"10.1093/brain/awaf132","DOIUrl":"https://doi.org/10.1093/brain/awaf132","url":null,"abstract":"Atypical parkinsonian syndromes are distinguished from Parkinson’s disease by additional neurological signs and characteristic underlying neuropathology. However, they can be diagnostically challenging, rapidly progressive, and are often diagnosed late in disease course. Their different demographic features and prognoses are well studied, but the accompanying cognitive and psychiatric features may also facilitate diagnosis. Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) may cause cognitive and behavioural manifestations that overlap with frontotemporal dementia, including non-fluent aphasia, apathy and impulsivity. Clinical diagnostic criteria have limited sensitivity, with pathologically confirmed PSP often having presented an initial clinical syndrome other than PSP-Richardson’s syndrome. Here we integrate cross-sectional multi-centre baseline data from the PROSPECT and Oxford Discovery cohorts. This allowed us to compare cognitive and psychiatric features across a total of 1138 people with PSP, CBS, multiple-system atrophy (MSA), and idiopathic Parkinson’s disease (PD). Data from the different cohorts were harmonised and compared using multiple linear regression. There were five key results. 1. Different syndromes showed distinctive cognitive profiles, using readily applicable ‘bedside’ screening tools. Frontal executive dysfunction was most evident in PSP, visuospatial deficits in CBS, with milder deficits in memory and executive function in MSA, as compared with PD. 2. The most prevalent neuropsychiatric features were depression and anxiety in CBS, apathy in PSP, with sleep disturbances common in PD. As expected, apathy correlated positively with impulsivity across all disorders. Neuropsychiatric features were generally better at discriminating between atypical parkinsonian syndromes than were the cognitive domains. 3. Both cognitive function and motor severity declined with disease duration, and motor function predicted cognition in PSP, CBS and PD but not in MSA, suggesting that in MSA cognitive and motor dysfunction are decoupled. 4. Plasma neurofilament light chain (NFL) levels, measured in a subset of patients, correlated with cognitive deficits in PSP, but not motor deficits. 5. Cognitive deficits contributed to the impairment in activities of daily living after controlling for motor severity, with every two points on the MoCA worsening the Schwab and England score by one point. In anticipation of future neuroprotective therapies, we present a classifier to improve diagnostic accuracy for atypical parkinsonian syndromes in vivo. Longitudinal cohort studies with resources for neuropathological gold-standard diagnosis remain important to validate better diagnostic tools for people with PSP, CBD, MSA and atypical parkinsonism.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"17 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841695","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":"Intronic FGF14 GAA repeat expansions impact progression and survival in multiple system atrophy","authors":"Viorica Chelban, David Pellerin, Nirosen Vijiaratnam, Hamin Lee, Yen Yee Goh, Lauren Brown, Sara Sambin, Danielle Seilhean, Stephane Lehericy, Pablo Iruzubieta, Rahema Mohammad, Eleanor Self, Annarita Scardamaglia, Cameron Lee, Miriama Ostrozovicova, Marie-Josée Dicaire, Christine Girges, Emil K Gustavsson, David Murphy, Toby Curless, Joshua Laβ, Joanne Trinh, Timothy Rittman, James B Rowe, Marios Hadjivassiliou, Neil Archibald, Matt C Danzi, Catherine Ashton, Virginie Roth, Marion Wandzel, Warren A Cheung, Djordje O Gveric, Bart De Vil, Jordan Follett, P Nigel Leigh, Lukas Beichert, Tomi Pastinen, Céline Bonnet, Mathilde Renaud, Wassilios G Meissner, Anne Sieben, David Crosiers, Patrick Cras, Stephan Zuchner, Jean-Christophe Corvol, Matthew J Farrer, Matthis Synofzik, Bernard Brais, Tom Warner, Huw R Morris, Zane Jaunmuktane, Tom Foltynie, Henry Houlden","doi":"10.1093/brain/awaf134","DOIUrl":"https://doi.org/10.1093/brain/awaf134","url":null,"abstract":"Partial phenotypic overlap has been suggested between multiple system atrophy (MSA) and spinocerebellar ataxia 27B, the autosomal dominant ataxia caused by an intronic GAA•TTC repeat expansion in FGF14. This study investigated the frequency of FGF14 GAA•TTC repeat expansion in clinically diagnosed and pathologically confirmed multiple system atrophy cases. We screened 657 multiple system atrophy cases (193 clinically diagnosed and 464 pathologically confirmed) and 1,003 controls. The FGF14 repeat locus was genotyped using long-range PCR and bidirectional repeat-primed PCRs, and expansions were confirmed with targeted long-read Oxford Nanopore Technologies sequencing. We identified 19 multiple system atrophy cases carrying an FGF14 GAA≥250 expansion (2.89%, n=19/657), a significantly higher frequency than in controls (1.40%, n=12/1,003) (p=0.04). Long-read Oxford Nanopore Technologies sequencing confirmed repeat sizes and polymorphisms detected by PCR, with high concordance (Pearson’s r=0.99, p<0.0001). Seven multiple system atrophy patients had a pathogenic FGF14 GAA≥300 expansion (five pathologically confirmed and two clinically diagnosed) and 12 had intermediate GAA250-299 expansion (six pathologically confirmed and six clinically diagnosed). A similar proportion of cerebellar-predominant and parkinsonism-predominant multiple system atrophy cases had FGF14 expansions. multiple system atrophy patients carrying an FGF14 GAA≥250 expansion exhibited severe gait ataxia, autonomic dysfunction and parkinsonism in keeping with a MSA phenotype, with a faster progression to falls (p=0.03) and regular wheelchair use (p=0.02) compared to the multiple system atrophy cases without FGF14 GAA expansion. The length of the GAA•TTC repeat expansion lengths inversely correlated with survival in multiple system atrophy patients (r = −0.67; p=0.02), but not with age of onset. Therefore, screening for FGF14 GAA•TTC repeat expansion should be considered for multiple system atrophy patients with rapid loss of mobility and for complete diagnostic accuracy at inclusion in disease-modifying multiple system atrophy drug trials.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"35 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841698","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 right frontal network for analogical and deductive reasoning","authors":"Joseph Mole, James K Ruffle, Amy Nelson, Edgar Chan, Tim Shallice, Parashkev Nachev, Lisa Cipolotti","doi":"10.1093/brain/awaf062","DOIUrl":"https://doi.org/10.1093/brain/awaf062","url":null,"abstract":"Two of the most well-studied types of reasoning are analogical reasoning (AR) and deductive reasoning (DR). Yet, our understanding of the relationship between reasoning abilities and their neuroanatomical basis remains surprisingly limited. We aimed to conduct fine-grained anatomical mapping of performance on tests of AR, DR and fluid intelligence (Gf), in a large sample of patients with unilateral focal frontal or posterior lesions and healthy controls. We assessed 247 prospectively recruited patients using two new tests: the Analogical Reasoning Test (ART) and the Deductive Reasoning Test (DRT); and the best-established measure of Gf: Raven’s Advanced Progressive Matrices (RAPM). Non-parametric Bayesian stochastic block modelling was used to reveal the community structure of lesion deficit networks, disentangling functional from confounding pathological distributed effects. ART and DRT performance was significantly impaired in patients with frontal lesions [ART: F(2,238) = 18.93; P < 0.001; Frontal group worse than Posterior group and healthy controls, both P < 0.001; DRT: F(2,387) = 18.491; P < 0.001; Frontal group worse than healthy controls, P < 0.01]. Right frontal effects were evident on both tests. Thus, on the ART, right frontal patients were more impaired than left (P < 0.05). On the DRT, right frontal patients were more impaired than left frontal patients on questions with indeterminate solutions (P < 0.05) but not on questions with determinate ones. Non-parametric Bayesian stochastic block modelling implicated a right frontal network in ART and DRT performance. Strikingly, we found that this network was also implicated in performance on RAPM. Our study represents the most robust investigation of AR and DR in the focally injured brain. Our findings imply that a right frontal network is critical. The ART and DRT appear to be promising new clinical tests, capable of evaluating reasoning abilities and identifying right frontal lobe dysfunction.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"26 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837039","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":"Reply: Understanding and misunderstanding cell counts of the human brain: the crux of biological variation.","authors":"Alain Goriely","doi":"10.1093/brain/awaf137","DOIUrl":"https://doi.org/10.1093/brain/awaf137","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"22 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841132","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":"Understanding and misunderstanding cell counts of the human brain: the crux of biological variation.","authors":"Christopher S von Bartheld","doi":"10.1093/brain/awaf136","DOIUrl":"https://doi.org/10.1093/brain/awaf136","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":"8 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841114","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":"Midbrain cytotoxic T cells as a distinct neuropathological feature of progressive supranuclear palsy","authors":"Blas Couto, Shelley L Forrest, Conor Fearon, Seojin Lee, Samantha Knott, Jun Li, Susan H Fox, Maria Carmela Tartaglia, Anthony E Lang, Gabor G Kovacs","doi":"10.1093/brain/awaf135","DOIUrl":"https://doi.org/10.1093/brain/awaf135","url":null,"abstract":"Progressive supranuclear palsy (PSP) is a neurodegenerative disorder with 4-repeat (R) tau protein deposition. The substantia nigra (SN) and midbrain tegmentum nuclei (MBT) are consistently affected. Lymphocyte infiltrates are scarce in the brain of neurodegenerative diseases, although a few reports have described this feature in brains with the α-synucleinopathy, Parkinson’s disease (PD). To evaluate cytotoxic T-cell response, serial sections spanning 120 microns of the SN were consecutively immunostained for phosphorylated tau (AT8) or α-synuclein, cytotoxic T-cell marker, and microglia marker HLA-DR. Sections were analyzed with stereology software in 9 patients with PSP, 10 with PD, and 6 healthy controls. We semiquantitatively scored CD8-positive cells in further brain regions. CD8 lymphocyte cell counts, and microglial activation were increased in the SN of PSP compared to PD and controls. T-cell/neuron contact was observed in PSP. In multivariate models, CD8 counts were not predicted by disease duration, younger age at death, and by the amount of p-tau pathology. SN and midbrain tegmentum showed more CD8 cells than the cortex. The presence of more prominent nigral cytotoxic T-cell response in PSP than in PD supports the notion that the common p-tau neuropathology in PSP might have potential relationships with autoimmune mechanisms.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"108 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837042","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":"Single-cell dissection of the genotype-immunophenotype relationship in glioblastoma","authors":"Nishant Soni, Kavita Rawat, Zhihong Chen, Angela DiMauro, Bruno Giotti, Dolores Hambardzumyan, Alexander M Tsankov","doi":"10.1093/brain/awaf129","DOIUrl":"https://doi.org/10.1093/brain/awaf129","url":null,"abstract":"Glioblastoma (GBM) is the most aggressive and lethal adult brain tumor. The cellular heterogeneity within the tumor microenvironment (TME) plays a critical role in the complexity of treatment and poor survival. GBM is typically classified into 3 molecular subtypes—Classical, Mesenchymal, and Proneural—associated with EGFR, NF1, and PDGFRA genetic drivers, respectively. Yet, the role of these driver mutations on the GBM TME is not fully understood. Here, we utilized single-cell RNA-sequencing of genetically engineered mouse GBM models incorporating human-relevant EGFRvIII, PDGFB, and NF1 driver mutations to systematically characterize the genotype-immunophenotype relationship of the three GBM subtypes. Murine genetic GBM models at the single-cell level effectively mimic the inter- and intra-tumor heterogeneity found in human counterparts. Our analysis revealed that PDGFB-driven tumors were more proliferative and enriched for Wnt signaling interactions, while EGFRvIII-driven tumors showed an elevated interferon signaling response. Moreover, Nf1-silenced tumors displayed higher myeloid abundance, myeloid immunosuppressive interactions involving Osteopontin, Treg infiltration, and expression of immune checkpoint molecule Ctla4. Overall, we established a human-mouse analytical platform for genotype-aware target discovery and validation, which offers promising new avenues for more effective, personalized treatments in GBM.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"108 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822495","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}