Frontiers in Neuroanatomy最新文献

{"title":"Neuroanatomical mapping of huntingtin-associated protein 1 across the rostral and caudal clusters of mouse raphe nuclei and its immunohistochemical relationships with serotonin.","authors":"Marya Afrin, Md Nabiul Islam, Mirza Mienur Meher, Mir Rubayet Jahan, Kanako Nozaki, Koh-Hei Masumoto, Akie Yanai, Koh Shinoda","doi":"10.3389/fnana.2025.1625793","DOIUrl":"10.3389/fnana.2025.1625793","url":null,"abstract":"<p><p>Huntingtin-associated protein 1 (HAP1) is a crucial component of the stigmoid body (STB) and is recognized as a neuroprotective interactor with causative proteins for several neurodegenerative disorders (NDs). Due to HAP1 protectivity, brain regions rich in STB/HAP1 are typically shielded from neurodegeneration, whereas areas with little or no STB/HAP1 are often affected in NDs. Mounting evidence suggests that serotonin (5-HT) neuron dysfunction contributes to various NDs. While the raphe nuclei denote the origin of 5-HT neurons, HAP1 protectivity has yet to be determined there. To accomplish this, the present study evaluated the expression and detailed neuroanatomical distribution of HAP1 throughout the rostral and caudal clusters of raphe nuclei in adult mice brains and their morphological relationships with 5-HT by employing Western blotting and immunohistochemistry. Our results indicated that in the rostral cluster, HAP1-ir cells were extensively distributed across the caudal linear raphe, median raphe, dorsal raphe, supralemniscal raphe, caudal part of the dorsal raphe, pre-pontine and pontine raphe nuclei. In the caudal cluster, HAP1-ir neurons were disseminated throughout the raphe magnus, raphe obscurus, raphe pallidus, parapyramidal, and raphe interpositus nuclei. Our double-immunofluorescence labeling results confirmed that most of the 5-HT neurons contained HAP1 immunoreactivity throughout the rostral and caudal clusters of the raphe nuclei. These suggest that HAP1 is crucial for modulating/protecting serotonergic functions, plausibly by upholding 5-HT neuronal plasticity/integrity by raising the threshold for neurodegeneration. Our current findings might provide a fundamental basis for further research aimed at elucidating the role of STB/HAP1 in the pathophysiology of serotonin neurons.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"19 ","pages":"1625793"},"PeriodicalIF":2.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relative withdrawal of GFAP-An essential component of brain evolution.","authors":"Mihály Kálmán","doi":"10.3389/fnana.2025.1607603","DOIUrl":"10.3389/fnana.2025.1607603","url":null,"abstract":"<p><p>The glial fibrillary acidic protein (GFAP) is the principal intermediate filament protein and histochemical marker for astroglia. It appears contradictory that there are extended GFAP-poor or even GFAP-free areas in the brains of various vertebrate clades: cartilaginous and ray-finned fishes, and amniotes. The \"Relevant Subsections: Extended GFAP-free areas in various vertebrates\" section in this study reviews our GFAP mapping studies on the brains of 58 species within these clades, as well as mappings from other authors, and demonstrates that these areas appeared independently from one another in the more advanced groups of different clades; it raises the supposition that the lack of GFAP is an apomorphic phenomenon. The GFAP expression has withdrawn mainly relatively: the GFAP-immunonegative areas increased more than the immunopositive ones. Primarily, regions that expanded and increased in complexity during evolution lack GFAP immunopositivity (except for their perivascular glia). The absence of GFAP expression, however, does not indicate the lack of astroglia. In the areas immunonegative to GFAP, astrocytes were visualized using other markers, such as glutamine synthetase or S-100 protein. In birds and mammals, lesions induced GFAP expression in these areas. It shows that the ability to express GFAP is not lost but has become facultative. These data suggest that the lack of GFAP production may provide an evolutionary advantage. The \"Discussion\" section relates the GFAP \"withdrawal\" to other steps of evolution: the increasing complexity and thickening of the brain wall, as well as the appearance of the astrocytes, particularly protoplasmic astrocytes, and then examines the proposed evolutionary advantages and disadvantages of the absence of GFAP. The role of the relative \"withdrawal\" of GFAP expression in brain evolution remains to be definitively answered. The most probable candidates may include the absence of synthesizing an unnecessary protein, improved adaptation of astrocytes to the demands of neurons, and an increased capacity for synaptic plasticity. In contrast, one must consider that the withdrawal of GFAP may not be a primary phenomenon but rather a consequence of the evolution of neural networks.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"19 ","pages":"1607603"},"PeriodicalIF":2.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The orca (<i>Orcinus orca</i>) pituitary gland: an anatomical, immunohistochemical and ultrastructural analysis.","authors":"Paula Alonso-Almorox, Alfonso Blanco, Carla Fiorito, Jose C Gómez-Villamandos, M A Risalde, Javier Almunia, Antonio Fernández","doi":"10.3389/fnana.2025.1626079","DOIUrl":"10.3389/fnana.2025.1626079","url":null,"abstract":"<p><p>The pituitary gland is central to endocrine regulation in vertebrates, coordinating key physiological processes such as growth, reproduction, and stress responses. In cetaceans, and particularly in large odontocetes like orcas (Orcinus orca), understanding pituitary structure is essential for advancing neuroendocrine research and informing welfare and health assessments. Despite their ecological, cognitive, and conservation significance, detailed morphological studies of the orca pituitary gland remain scarce. In this study, we conducted a comprehensive structural and ultrastructural analysis of the orca pituitary gland using postmortem samples from four captive individuals. We combined computed tomography, histology, immunohistochemistry, and transmission electron microscopy to examine the gland's anatomical organization and cellular composition. Our results reveal features consistent with other cetaceans as well as species-specific characteristics, including the distribution and morphology of endocrine cells within the adenohypophysis and neurohypophysis. These findings provide the first integrated anatomical and ultrastructural reference for the orca pituitary gland, offering valuable insights into cetacean neuroendocrinology and supporting improved species-specific welfare evaluation, health monitoring, and management practices for orcas under human care.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"19 ","pages":"1626079"},"PeriodicalIF":2.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution and morphological features of astrocytes and Purkinje cells in the human cerebellum.","authors":"Christa Hercher, Kristin Ellerbeck, Louise Toutée, Xinyu Ye, Refilwe Mpai, Claudia Belliveau, Maria Antonietta Davoli, W Todd Farmer, Alanna J Watt, Keith K Murai, Gustavo Turecki, Naguib Mechawar","doi":"10.3389/fnana.2025.1592671","DOIUrl":"10.3389/fnana.2025.1592671","url":null,"abstract":"<p><strong>Introduction: </strong>The cerebellar cortex is now recognized as a functionally heterogeneous brain region involved not only in traditional motor functioning but also in higher-level emotional and cognitive processing. Similarly, cerebellar astrocytes also display a high degree of morphological and functional diversity based on their location. Yet, the morphological features and distribution of cerebellar astrocytes have yet to be quantified in the human brain.</p><p><strong>Methods: </strong>To address this, we performed a comprehensive postmortem examination of cerebellar astrocytes in the healthy human brain using microscopy-based techniques. Purkinje cells (PCs) were also quantified due to their close relationship with Bergmann glia (BG). Using canonical astrocyte markers glial fibrillary acidic protein (GFAP) and aldehyde dehydrogenase-1 family member L1 (ALDH1L1), we first mapped astrocytes within a complete cerebellar hemisphere.</p><p><strong>Results: </strong>Astrocytes were observed to be differentially distributed across cerebellar layers with their processes displaying known morphological features unique to humans. Stereological quantifications in three functionally distinct lobules demonstrated that the vermis lobule VIIA, folium displayed the lowest densities of ALDH1L1+ astrocytes compared with lobule III and crus I. Assessing cerebellar layers showed that the PC layer had the highest ALDH1L1+ densities while GFAP+ densities and astrocytes colocalizing (ALDH1L1+ GFAP+) were highest in the granule cell layer yet displayed the smallest GFAP-defined territories. PC parameters revealed subtle differences across lobules, with vermis folium VIIA having the lowest PC densities while a trend for the highest BG:PC ratio was observed in the cognitive lobule crus I. Lastly, to determine if these features differ from those of cerebellar astrocytes and PCs in species used to model human illnesses, we performed comparative analyses in mice and macaques showing both divergence and commonalities across species.</p><p><strong>Discussion: </strong>The present study highlights the heterogeneity of astrocytes in the human cerebellum and serves as a valuable resource on cerebellar astrocyte and PC properties in the healthy human brain.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"19 ","pages":"1592671"},"PeriodicalIF":2.1,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: 15 years of frontiers in neuroanatomy: the origin of Parkinson's disease.","authors":"Barbara Falquetto, Cristina Nombela, Luiz R G Britto","doi":"10.3389/fnana.2025.1649700","DOIUrl":"10.3389/fnana.2025.1649700","url":null,"abstract":"","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"19 ","pages":"1649700"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered dendritic morphology of MEC II pyramidal and stellate cells in Rett syndrome mice.","authors":"Manigandan Krishnan, Ayishal B Mydeen, Mohammed M Nakhal, Marwa F Ibrahim, Richard L Jayaraj, Milos R Ljubisavljevic, Mohammad I K Hamad, Fatima Y Ismail","doi":"10.3389/fnana.2025.1580435","DOIUrl":"10.3389/fnana.2025.1580435","url":null,"abstract":"<p><strong>Introduction: </strong>Mutations in the methyl-CpG-binding protein-2 gene (<i>MECP2</i>), which cause Rett syndrome (RTT), disrupt neuronal activity; however, the impact of the <i>MECP2</i> loss-of-function on the cytoarchitecture of medial entorhinal cortex layer II (MECII) neurons-crucial for spatial memory and learning-remains poorly understood.</p><p><strong>Methods: </strong>In this study, we utilized Golgi staining and neuron tracing in the <i>Mecp</i>2^+/- mouse model of RTT to investigate the pyramidal and stellate cell alterations in MECII.</p><p><strong>Results and discussion: </strong>Our findings revealed that pyramidal cells displayed a significant reduction in apical dendritic length, soma size, and spine density, while basal dendrites showed increased dendritic complexity and branching. On the other hand, stellate cells exhibited dendritic hypertrophy along with increased soma size, primary dendrites, and localized increase in dendritic intersections, despite an overall reduction in total dendritic length and spine density. These findings underscore the notion that <i>MECP2</i> loss-of-function can disrupt MECII pyramidal and stellate cell cytoarchitecture in a cell-type-specific manner, emphasizing its critical role in maintaining proper dendritic morphology in circuits, which is crucial for learning and memory.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"19 ","pages":"1580435"},"PeriodicalIF":2.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Neuroanatomical and molecular biomarkers for multiple sclerosis progression and therapeutic response.","authors":"Ignacio Casanova, María Inmaculada Domínguez-Mozo, Roberto Álvarez-Lafuente","doi":"10.3389/fnana.2025.1640594","DOIUrl":"https://doi.org/10.3389/fnana.2025.1640594","url":null,"abstract":"","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"19 ","pages":"1640594"},"PeriodicalIF":2.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A domain-based framework for cognitive profile identification in Parkinson's disease across diverse samples.","authors":"Elvira Andújar-Castillo, Carla Carrillo-Molina, Fernando Alonso, Clara Villanueva-Iza, Gustavo Fernández-Pajarín, Angel Sesar, Isabel Jiménez-Martín, Juan Francisco Martín-Rodriguez, Maria Jesús Lama, Pablo Mir, Elena Perez-Hernandez, Cristina Nombela Otero","doi":"10.3389/fnana.2025.1566835","DOIUrl":"10.3389/fnana.2025.1566835","url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms and heterogeneous cognitive impairments influenced by factors such as age, disease duration, and severity. Traditional neuropsychological assessments often fall short in capturing the multifaceted nature of PD-related cognitive dysfunction due to their reliance on single test metrics. This study provides empirical support for the implementation of domain-based cognitive assessments, structured in line with Movement Disorder Society recommendations, to provide a multidimensional evaluation of cognitive profiles in PD patients.</p><p><strong>Methods: </strong>Neuropsychological and clinical data were analyzed from 316 PD patients recruited from three Spanish hospitals-Hospital Clínico San Carlos (Madrid), the University Complejo Universitario de Santiago de Compostela (Galicia), and Hospital Virgen del Rocío (Sevilla)- and a control group of 96 older individuals, whose age difference from the PD group was statistically significant. Five cognitive domains were constructed, addressing attention/working memory, executive functions, memory, visuospatial abilities, and language, using composite z-scores derived from standardized neuropsychological tests.</p><p><strong>Results: </strong>Latent Cluster Analysis identified three distinct cognitive profiles: (1) a fronto-striatal profile characterized by mild deficits in executive and attention functions and intact visuospatial abilities, (2) a posterior cortical profile marked by severe memory and visuospatial impairments but strong language performance, and (3) a preserved profile displaying mild deficits across multiple domains. Comparisons between PD clusters and controls revealed significant differences in cognitive trajectories, emphasizing the value of a domain-based approach for differentiating neurodegenerative patterns from normal aging.</p><p><strong>Discussion: </strong>The findings highlight the potential of domain-based assessments to unify data across diverse samples, fostering standardized cross-cohort comparisons and facilitating large-scale research initiatives. By enabling methodological consistency, this approach provides a robust framework for advancing the understanding of cognitive dysfunctions in PD and improving clinical decision-making.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"19 ","pages":"1566835"},"PeriodicalIF":2.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential for flexible lactate shuttling between astrocytes and neurons to mitigate against diving-induced hypoxia.","authors":"Chiara Ciccone, Sari Elena Dötterer, Sigrid Vold Jensen, Cornelia Geßner, Alexander C West, Shona H Wood, David G Hazlerigg, Lars P Folkow","doi":"10.3389/fnana.2025.1607396","DOIUrl":"10.3389/fnana.2025.1607396","url":null,"abstract":"<p><p>For most non-diving mammals, lack of O₂ (hypoxia) has detrimental effects on brain function. Seals, however, display a series of systemic, cellular, and molecular adaptations that enable them to tolerate repeated episodes of severe hypoxia. One as yet unresolved question is whether seal neurons in part employ anaerobic metabolism during diving: the \"reverse astrocyte-neuron lactate shuttle\" (rANLS) hypothesis postulates that seal neurons, by shuttling lactate to the astrocytes, may be relieved (1) from the lactate burden and (2) from subsequent ROS-production as lactate is oxidized by astrocytes upon re-oxygenation after the dive. Here, we have investigated this possibility, through histological and functional comparisons of the metabolic characteristics of neocortical neurons and astrocytes from the deep-diving hooded seal (<i>Cystophora cristata</i>), using mice (<i>Mus musculus</i>) as a non-diving control. We found that seal astrocytes have higher mitochondrial density and larger mitochondria than seal neurons, and that seal neurons have an atypical and significantly higher representation of the monocarboxylate lactate exporter MCT4 compared to mouse neurons. Also, measurements of mitochondrial O₂ consumption suggest that the aerobic capacity of primary seal astrocytes is at least equal to that of primary seal neurons. Transcriptomics data from seals vs. mice suggest that specific adaptations to the electron transport system in seals may contribute to enhance hypoxia tolerance. These observations are consistent with the rANLS hypothesis.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"19 ","pages":"1607396"},"PeriodicalIF":2.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two patterns in apical dendrite extensions of projection neurons within cerebral cortex of reeler mutant mice.","authors":"Ryoichi Ichikawa","doi":"10.3389/fnana.2025.1560972","DOIUrl":"10.3389/fnana.2025.1560972","url":null,"abstract":"<p><strong>Introduction: </strong>Pyramidal-like projection neurons in the cerebral cortex exhibit layer-specific positioning of their cell bodies and target specific cortical regions with their apical dendrites. Reeler mutant mice, which lack the gene for the reelin protein gene secreted by Cajal-Retzius cells and have their projection neurons scattered throughout the cortex, display relatively intact global and local neuronal network connections compared with wild-type mice. The irregular morphologies of these cells, which extend their apical dendrites in a neuron-disoriented direction, are thought to compensate for the malposition of the neurons. I aimed to investigate the projection target-specific regulation of this apical dendrite extension pattern in reeler mice.</p><p><strong>Methods: </strong>To this end, three types of projection neurons-corticospinal (CS), corticothalamic (CT), and corticocallosal (CC) neurons-were evaluated using retrograde labeling techniques.</p><p><strong>Results and discussion: </strong>Reeler CS neurons displayed a congregation pattern of apical dendritic terminal tips in a specific upper cortical zone, whereas reeler CC neurons exhibited a dispersed pattern of scattered tips throughout the cortex. However, reeler CT neurons showed a hybrid pattern, exhibiting characteristics of both congregation- and dispersion-type neurons. Moreover, apical dendrite extension of these projection neurons follows either a congregation or dispersion mode from postnatal day 0 (P0), which subsequently defines their terminal tip positioning by P8. Thus, this early patterning of apical dendrite arborization in reeler projection neurons likely contributes to the formation of projection target-specific neuronal connections during the first two postnatal weeks.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"19 ","pages":"1560972"},"PeriodicalIF":2.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}