Brain Sciences最新文献

{"title":"Towards a New Dawn for Neuro-Oncology: Nanomedicine at the Service of Drug Delivery for Primary and Secondary Brain Tumours.","authors":"Smita Khilar, Antonina Dembinska-Kenner, Helen Hall, Nikolaos Syrmos, Gianfranco K I Ligarotti, Puneet Plaha, Vasileios Apostolopoulos, Salvatore Chibbaro, Giuseppe Maria Vincenzo Barbagallo, Mario Ganau","doi":"10.3390/brainsci15020136","DOIUrl":"10.3390/brainsci15020136","url":null,"abstract":"<p><p>(1) Background/Objectives: Primary and secondary brain tumours often hold devastating prognoses and low survival rates despite the application of maximal neurosurgical resection, and state-of-the-art radiotherapy and chemotherapy. One limiting factor in their management is that several antineoplastic agents are unable to cross the blood-brain barrier (BBB) to reach the tumour microenvironment. Nanomedicine could hold the potential to become an effective means of drug delivery to overcome previous hurdles towards effective neuro-oncological treatments. (2) Methods: A scoping review following the PRISMA-ScR guidelines and checklist was conducted using key terms input into PubMed to find articles that reflect emerging trends in the utilisation of nanomedicine in drug delivery for primary and secondary brain tumours. (3) Results: The review highlights various strategies by which different nanoparticles can be exploited to bypass the BBB; we provide a synthesis of the literature on the ongoing contributions to therapeutic protocols based on chemotherapy, immunotherapy, focused ultrasound, radiotherapy/radiosurgery, and radio-immunotherapy. (4) Conclusions: The emerging trends summarised in this scoping review indicate encouraging advantageous properties of nanoparticles as potential effective drug delivery mechanisms; however, there are still nanotoxicity issues that largely remain to be addressed before the translation of these innovations from laboratory to clinical practice.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling ALS with Patient-Derived iPSCs: Recent Advances and Future Potentials.","authors":"Ladan Dawoody Nejad, Erik P Pioro","doi":"10.3390/brainsci15020134","DOIUrl":"10.3390/brainsci15020134","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a terminal complex neurodegenerative disease, with 10-15% of cases being familial and the majority being sporadic with no known cause. There are no animal models for the 85-90% of sporadic ALS cases. More creative, sophisticated models of ALS disease are required to unravel the mysteries of this complicated disease. While ALS patients urgently require new medications and treatments, suitable preclinical <i>in vitro</i> models for drug screening are lacking. Therefore, human-derived induced pluripotent stem cell (hiPSC) technology offers the opportunity to model diverse and unreachable cell types in a culture dish. In this review, we focus on recent hiPSC-derived ALS neuronal and non-neuronal models to examine the research progress of current ALS 2D monocultures, co-cultures, and more complex 3D-model organoids. Despite the challenges inherent to hiPSC-based models, their application to preclinical drug studies is enormous.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Source of Drugs Targeting Central Nervous System Tumors-Focus on NAD(P)H Oxidoreductase 1 (NQO1) Activity.","authors":"Nikola M Stojanovic, Milica Mitić, Jovan Ilić, Milica Radić, Miša Radisavljević, Marko Baralić, Miljan Krstić","doi":"10.3390/brainsci15020132","DOIUrl":"10.3390/brainsci15020132","url":null,"abstract":"<p><p>Central nervous system (CNS) tumors involve a large and diverse group of malignancies that arise from various cell types within the brain tissue. Although there are advances in treatments, CNS tumors still remain challenging, due to their complex biology and the delicate nature of the surrounding tissue. NAD(P)H O=oxidoreductase 1 (NQO1) is an enzyme that plays a critical role in the detoxification of quinones, protecting cells from oxidative stress. In CNS tumors this enzyme is often overexpressed, which contributes to the resistance of tumor cells to chemotherapy by enhancing their antioxidant defenses. NQO1 influences the progression of CNS tumors by affecting downstream signaling pathways, such as those involving the transcription factor SNAIL, as well as others that are associated with tumor behavior. Plants represent a valuable source of numerous constituents with different chemical structures known to affect different molecular signaling pathways associated with different pathologies.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emotional Availability in Autism Intervention: A Mother-Father Comparative Analysis.","authors":"Silvia Perzolli, Giulio Bertamini, Paola Venuti, Arianna Bentenuto","doi":"10.3390/brainsci15020133","DOIUrl":"10.3390/brainsci15020133","url":null,"abstract":"<p><strong>Background/objectives: </strong>The literature highlights the importance of parental involvement in autism treatment. However, much research has predominantly focused on child outcomes and cognitive dimensions. This study explores the impact of an early intensive intervention with parental involvement, focusing on changes in parents' affective exchanges. Notably, given the paucity of studies on fathers in the intervention context, this study examines the comparative trajectory of change considering both caregivers.</p><p><strong>Methods: </strong>Twenty autistic preschoolers were monitored for one year during a parental-based intervention. Child-mother and child-father play interactions were coded with the Emotional Availability Scales at baseline and at 12 months. Repeated measures linear mixed-effect models were employed to investigate time and caregiver effects and their interaction.</p><p><strong>Results: </strong>Results highlighted both similarities and differences in change trajectories between caregivers. Parental sensitivity, structuring, and non-intrusiveness significantly increased for both parents with fathers showing more prominent gains in structuring the interaction while being non-intrusive. Child responsiveness and involvement significantly increased, showing similar trajectories with both caregivers. Children were generally more involved while interacting with their fathers.</p><p><strong>Conclusion: </strong>Parent-child interactions with caregivers evolved toward more adaptive exchanges regarding emotional availability for children's and parents' dimensions. Fathers appeared to be particularly receptive regarding acquiring structuring abilities and non-intrusive behaviors. Our results underscore the importance of investigating parental features as well as the importance of actively involving caregivers to support distal outcomes and generalization.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Computational Analysis of the Effect of Hard Choices on the Individuation of Values.","authors":"Norberto M Grzywacz","doi":"10.3390/brainsci15020131","DOIUrl":"10.3390/brainsci15020131","url":null,"abstract":"<p><strong>Background/objectives: </strong>Experimental studies show that when an individual makes choices, they affect future decisions. Future choices tend to be consistent with past ones. This tendency matters in the context of ambivalent situations because they may not lead to clear choices, often leading people to make \"arbitrary\" decisions. Thus, because of choice consistency with the past, people's decision-making values diverge. Thus, hard choices may contribute to the individuation of values.</p><p><strong>Methods: </strong>Here, we develop a Bayesian framework for the effects of cognitive choice consistency on decision-making. This framework thus extends earlier cognitive-science Bayesian theories, which focus on other tasks, such as inference. The minimization of total surprisals considering the history of stimuli and chosen actions implements choice consistency in our framework. We then use a computational model based on this framework to study the effect of hard choices on decision-making values.</p><p><strong>Results: </strong>The results for action selection based on sensory stimuli show that hard choices can cause the spontaneous symmetry breaking of the decision-making space. This spontaneous symmetry breaking is different across individuals, leading to individuation. If in addition, rewards are given to certain choices, then the direction of the symmetry breaking can be guided by these incentives. Finally, we explore the effects of the parametric complexity of the model, the number of choices, and the length of choice memory.</p><p><strong>Conclusions: </strong>Considering the brain's mechanism of choice consistency and the number of hard choices made in life, we hypothesize that they contribute to individuality. We assess this hypothesis by placing our study in the context of the cognition-of-individuality literature and proposing experimental tests of our computational results.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Dysfunction Correlates with Brain Amyloid Binding, Memory, and Executive Function in Down Syndrome: Implications for Alzheimer's Disease in Down Syndrome.","authors":"Jessica A Beresford-Webb, Catherine J McAllister, Alison Sleigh, Madeleine J Walpert, Anthony J Holland, Shahid H Zaman","doi":"10.3390/brainsci15020130","DOIUrl":"10.3390/brainsci15020130","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Mitochondrial dysfunction is increasingly recognized as a central contributor to neurodegenerative diseases and age-related cognitive decline. Individuals with Down syndrome (DS) are at high risk of neurodegeneration due to Alzheimer's disease (AD). This study aims to explore the relationship between mitochondrial dysfunction, brain amyloid-beta (Aβ) deposition, and cognitive decline in this population. <b>Methods:</b> We investigated mitochondrial function, brain amyloid-beta burden, and cognitive performance in a pilot study of a cohort of 10 eligible adults with DS selected from a sample of 28 individuals with DS. Phosphorus-31 magnetic resonance spectroscopy (³¹P-MRS) was used to assess mitochondrial function in skeletal muscle using a post-exercise paradigm, while positron emission tomography using ¹¹C-Pittsburgh compound B (PiB-PET) measured brain Aβ deposition. Cognitive performance was evaluated using the Cambridge Cognitive Examination adapted for individuals with Down syndrome (CAMCOG-DS) and executive function batteries. <b>Results:</b> Significant correlations were observed between slowed phosphocreatine (PCr) recovery in muscle and increased Aβ deposition in key brain regions, particularly the striatum. Cognitive performance inversely correlated with mitochondrial function, with pronounced deficits in memory and executive function tasks. Notably, an individual carrying the APOE-ε4 allele exhibited the poorest mitochondrial function, highest Aβ burden, and most severe cognitive impairment, suggesting a potential interaction between genetic risk and mitochondrial health. <b>Conclusions:</b> These findings highlight the role of mitochondrial dysfunction in DS-associated AD (DSAD) and its impact on cognition in adults. The results support targeting mitochondrial pathways as a potential therapeutic strategy to mitigate AD progression in DS populations. Further research with larger cohorts and longitudinal designs is needed to clarify causative mechanisms and develop effective interventions.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Competition on Left Prefrontal and Temporal Cortex During Conceptual Comparison of Brand-Name Product Pictures: Analysis of fNIRS Using Tensor Decomposition.","authors":"Terrence M Barnhardt, Jasmine Y Chan, Behnaz Ghoraani, Teresa Wilcox","doi":"10.3390/brainsci15020127","DOIUrl":"10.3390/brainsci15020127","url":null,"abstract":"<p><strong>Background/objectives: </strong>Recent theories of the neurocognitive architecture of semantic memory have included a distinction between semantic control in the left inferior frontal gyrus (LIFG) and semantic representation in the left anterior temporal lobe (LATL). Support for this distinction has been found both in tasks in which high semantic selection demands have been instantiated and in tasks in which previous presentations of semantic information that compete with target information have been instantiated.</p><p><strong>Methods: </strong>In the current study, these manipulations were combined in a novel manner into a single task in which brand-name product pictures were used. Functional near-infrared spectroscopy (fNIRS) was used to measure hemodynamic activity and tensor decomposition, in addition to grand averaging, was used to analyze the fNIRS output.</p><p><strong>Results: </strong>Both analytic methods converged on the same set of findings. That is, in line with past studies, greater activity in the LIFG was observed in the competitive condition than in a repeated condition. However, unlike past studies, greater activity in the competitive condition was also observed in both the left and right anterior temporal lobes (ATLs).</p><p><strong>Conclusions: </strong>While it was possible that the novel combination of high selection and competition into a single task unlocked a semantic selection mechanism in the bilateral ATL, a number of other post-hoc explanations were offered for this unusual finding, including a re-interpretation of the high-selection task as an ad hoc categorization task. Finally, the convergence of the tensor decomposition and grand averaging approaches on the same set of findings supported tensor decomposition as a viable approach to the analysis of fNIRS data.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minocycline Ameliorates <i>Staphylococcus aureus</i>-Induced Neuroinflammation and Anxiety-like Behaviors by Regulating the TLR2 and STAT3 Pathways in Microglia.","authors":"Jiao Zou, Junwei Gao, Weilong Shang, Xiaotang Fan","doi":"10.3390/brainsci15020128","DOIUrl":"10.3390/brainsci15020128","url":null,"abstract":"<p><p><b>Background:</b> Anxiety disorders are the most common mental illnesses. <i>S. aureus</i> is a Gram-positive opportunistic pathogen most commonly associated with anxiety-like behaviors. Minocycline ameliorates Gram-negative bacterial LPS-induced anxiety-like behaviors by suppressing microglia activation. However, the effects of minocycline on anxiety-like behaviors caused by <i>S. aureus</i> infections have received little attention. In this study, we aimed to investigate the molecular mechanism and effect of minocycline on anxiety-like behaviors caused by <i>S. aureus</i> infection. <b>Methods:</b> BV2 and N9 microglial cells were treated in vitro. The effects of minocycline on lipoteichoic acid (LTA)-stimulated inflammatory responses, STAT3 activation, and GLS1 expression were assessed using Western blotting, and cytokine secretion was determined using an ELISA. A mouse model was used to evaluate the capacity of minocycline to ameliorate anxiety-like behaviors caused by <i>S. aureus</i> infection. <b>Results:</b> We found that ≥100 μmol/L of minocycline remarkably attenuated LTA-induced TLR2 signaling pathway activation and proinflammatory cytokine expression in microglial cells. Minocycline prevented LTA-stimulated STAT3 activation and GLS1 expression in vitro. LTA-induced TLR2, TNF-α, IL-6, and GLS1 expression was markedly reduced by the inhibition of STAT3 phosphorylation. Mice were pretreated with 50 mg/kg of minocycline, significantly attenuating microglial activation and neuroinflammation. Minocycline also effectively alleviated the anxiety-like behaviors induced by <i>S. aureus</i> infection. <b>Conclusions:</b> Our findings indicate that minocycline alleviates <i>S. aureus</i> infection-induced anxiety-like behaviors by suppressing microglia activation.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MSEI-ENet: A Multi-Scale EEG-Inception Integrated Encoder Network for Motor Imagery EEG Decoding.","authors":"Pengcheng Wu, Keling Fei, Baohong Chen, Lizheng Pan","doi":"10.3390/brainsci15020129","DOIUrl":"10.3390/brainsci15020129","url":null,"abstract":"<p><strong>Background: </strong>Due to complex signal characteristics and distinct individual differences, the decoding of a motor imagery electroencephalogram (MI-EEG) is limited by the unsatisfactory performance of suboptimal traditional models.</p><p><strong>Methods: </strong>A subject-independent model named MSEI-ENet is proposed for multiple-task MI-EEG decoding. It employs a specially designed multi-scale structure EEG-inception module (MSEI) for comprehensive feature learning. The encoder module further helps to detect discriminative information by its multi-head self-attention layer with a larger receptive field, which enhances feature representation and improves recognition efficacy.</p><p><strong>Results: </strong>The experimental results on Competition IV dataset 2a showed that our proposed model yielded an overall accuracy of 94.30%, MF1 score of 94.31%, and Kappa of 0.92.</p><p><strong>Conclusions: </strong>A performance comparison with state-of-the-art methods demonstrated the effectiveness and generalizability of the proposed model on challenging multi-task MI-EEG decoding.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLTNet: A Hybrid Deep Learning Model for Motor Imagery Classification.","authors":"He Gu, Tingwei Chen, Xiao Ma, Mengyuan Zhang, Yan Sun, Jian Zhao","doi":"10.3390/brainsci15020124","DOIUrl":"10.3390/brainsci15020124","url":null,"abstract":"<p><strong>Background: </strong>Brain-computer interface (BCI) technology opens up new avenues for human-machine interaction and rehabilitation by connecting the brain to machines. Electroencephalography (EEG)-based motor imagery (MI) classification is a key component of BCI technology, which is capable of translating neural activity in the brain into commands for controlling external devices. Despite the great potential of BCI technology, the challenges of extracting and decoding brain signals limit its wide application.</p><p><strong>Methods: </strong>To address this challenge, this study proposes a novel hybrid deep learning model, CLTNet, which focuses on solving the feature extraction problem to improve the classification of MI-EEG signals. In the preliminary feature extraction stage, CLTNet uses a convolutional neural network (CNN) to extract time series, channel, and spatial features of EEG signals to obtain important local information. In the deep feature extraction stage, the model combines the long short-term memory (LSTM) network and the Transformer module to capture time-series data and global dependencies in the EEG. The LSTM explains the dynamics of the brain activity, while the Transformer's self-attention mechanism reveals the global features of the time series. Ultimately, the CLTNet model classifies motor imagery EEG signals through a fully connected layer.</p><p><strong>Results: </strong>The model achieved an average accuracy of 83.02% and a Kappa value of 0.77 on the BCI IV 2a dataset, and 87.11% and a Kappa value of 0.74 on the BCI IV 2b dataset, both of which outperformed the traditional methods.</p><p><strong>Conclusions: </strong>The innovation of the CLTNet model is that it integrates multiple network architectures, which offers a more comprehensive understanding of the characteristics of the EEG signals during motor imagery, providing a more comprehensive perspective and establishing a new benchmark for future research in this area.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}