Neuro-oncology advances最新文献

{"title":"A fast protocol for multi-center, multi-parametric quantitative MRI studies in brain tumor patients using vendor sequences","authors":"Dennis C Thomas, Ralf Deichmann, U. Nöth, Christian Langkammer, Mónica Ferreira, Rejane Golbach, Elke Hattingen, K. Wenger","doi":"10.1093/noajnl/vdae117","DOIUrl":"https://doi.org/10.1093/noajnl/vdae117","url":null,"abstract":"\u0000 \u0000 \u0000 Multi-parametric quantitative MRI (mp-qMRI) provides non-invasive, quantitative measurements sensitive to a variety of tissue properties. In brain tumors (BTs), T1, T2*, T2, Water content (H2O) and quantitative susceptibility (χ) give valuable insights into the microenvironment. To generate large multi-center datasets, protocols need to be short and implementable on any scanner. The goal of this work was to develop and validate an 8-minute, 3T mp-qMRI protocol for BT patients solely using generalized pulse sequences (mGRE and EPI).\u0000 \u0000 \u0000 \u0000 A protocol was developed and tested on a multi-compartment phantom, five healthy subjects (mean age: 31.64 yrs), and four BT patients (mean age:39.5 yrs). Phantom and healthy subject T1 maps were compared to those obtained using two reference methods. The five healthy subjects were scanned on 3T MRI scanners at two different sites and the reproducibility between scanners assessed by computing Coefficients of Variance (COV) maps, performing Bland Altman analysis and t-tests. Clinical feasibility was tested on four BT patients.\u0000 \u0000 \u0000 \u0000 T1 values obtained using the proposed mp-qMRI protocol agree with those obtained using the reference methods in volunteers (mean error = 8.94 ms). The qMRI maps (T1, T2*, H2O and χ) of the volunteers showed good reproducibility between scanners with no significant differences for mean WM and GM qMRI values. WM and GM mean qMRI values agreed well with literature values. H2O gave the lowest COV and χ maps the highest.\u0000 \u0000 \u0000 \u0000 The proposed vendor sequence-based 3T mp-qMRI protocol gives high resolution (1 mm isotropic) T1, T2*, H2O and χ maps in 8 minutes acquisition.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141678171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Molecular Glioblastoma: Insights from Advanced Imaging for a Nuanced Understanding of the Molecularly Defined Malignant Biology","authors":"Michael Griessmair, C. Delbridge, Julian Ziegenfeuter, Kirsten Jung, Tobias Mueller, Severin Schramm, Denise Bernhardt, F. Schmidt-Graf, Olivia Kertels, Marie Thomas, Claus Zimmer, Bernhard Meyer, Stephanie E. Combs, Igor Yakushev, B. Wiestler, M. Metz","doi":"10.1093/noajnl/vdae106","DOIUrl":"https://doi.org/10.1093/noajnl/vdae106","url":null,"abstract":"\u0000 \u0000 \u0000 Molecular glioblastoma (molGB) does not exhibit the histologic hallmarks of a grade 4 glioma but is nevertheless diagnosed as glioblastoma when harboring specific molecular markers. MolGB can easily be mistaken for similar-appearing lower-grade astrocytomas. Here, we investigated how advanced imaging could reflect the underlying tumor biology.\u0000 \u0000 \u0000 \u0000 Clinical and imaging data were collected for 7 molGB grade 4, 9 astrocytomas grade 2, and 12 astrocytomas grade 3. Four neuroradiologists performed VASARI-scoring of conventional imaging, and their inter-reader agreement was assessed using Fleiss ϰ coefficient. To evaluate the potential of advanced imaging, two-sample t-test, one-way ANOVA, Mann-Whitney-U, and Kruskal-Wallis-test were performed to test for significant differences between apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) that were extracted fully automatically from the whole tumor volume.\u0000 \u0000 \u0000 \u0000 While conventional VASARI imaging features did not allow for reliable differentiation between glioma entities, rCBV was significantly higher in molGB compared to astrocytomas for the 5th and 95th percentile, mean and median values (p < 0.05). ADC values were significantly lower in molGB than in astrocytomas for mean, median, and the 95th percentile (p < 0.05). Although no molGB showed contrast enhancement initially, we observed enhancement in the short-term follow-up of one patient.\u0000 \u0000 \u0000 \u0000 Quantitative analysis of diffusion and perfusion parameters shows potential in reflecting the malignant tumor biology of molGB. It may increase awareness of molGB in a non-enhancing, \"benign\" appearing tumor. Our results support the emerging hypothesis that molGB might present glioblastoma captured at an early stage of gliomagenesis.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141678874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant Combination Treatment with Checkpoint Inhibitors, Chemotherapy, and BRAF/MEK Inhibitors for BRAFV600E Glioblastoma Results in Sustained Response: A Case Report","authors":"Naveed Wagle, Akanksha Sharma, Minhdan Nguyen, J. Truong, Tiffany M Juarez, Santosh Kesari","doi":"10.1093/noajnl/vdae110","DOIUrl":"https://doi.org/10.1093/noajnl/vdae110","url":null,"abstract":"\u0000 Radiation’s confounding and adverse effects on tumor microenvironment and normal brain could potentially be delayed by upfront combination treatment. We present a patient with newly diagnosed BRAFV600E-mutant, PD-L1-positive glioblastoma treated with off-label RAF/MEK inhibitors encorafenib/binimetinib after progressing on postoperative immune checkpoint blockade and temozolomide (no radiation administered: NCT03425292). Complete response occurred six months after adding encorafenib/binimetinib, and clinical benefit was sustained for over 20 months. Treatment was well-tolerated with manageable toxicities, with quality of life and cognitive function maintained throughout treatment. Adding encorafenib/binimetinib to immunotherapy and temozolomide conferred favorable and lasting efficacy for our BRAFV600E-mutant glioblastoma patient, justifying future studies.","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141688423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxicity on low-grade canine meningioma with the use of somatostatin analogue (octreotide): an in vitro study","authors":"M. Mandara, A. Tognoloni, Giuseppe Giglia, Massimo Baroni, C. Falzone, Pietro Calò, Elisabetta Chiaradia","doi":"10.1093/noajnl/vdae111","DOIUrl":"https://doi.org/10.1093/noajnl/vdae111","url":null,"abstract":"\u0000 \u0000 \u0000 Meningioma is the most common tumour of the central nervous system of dogs. For this tumour, surgery remains the treatment of choice, either alone or in combination with radiotherapy. Unfortunately, chemotherapeutic strategies are practically absent in dogs and palliative therapies are the only option to surgery. Somatostatin receptor subtype 2 (SSTR2) is expressed in canine meningioma. Since the potent cell-proliferation inhibiting effect of somatostatin (SST), the aim of this study was to investigate in vitro the effects of octreotide, as SST analogue, in the viability of canine meningioma.\u0000 \u0000 \u0000 \u0000 Four surgical canine meningiomas were used in this study to establish cell cultures. Expression of SSTR2 was verified with immunolabelling in PEFF and cell cultures. The effects of octreotide on cell viability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). After 24 hours they were exposed to different concentrations of octreotide (0.1 nM, 1 nM, 10 nM, 100nM) for 24h and 48h.\u0000 \u0000 \u0000 \u0000 All meningiomas consisted in grade I tumours. The cultured neoplastic cells expressed SSTR2 from 80% to 100%. Octreotide significantly increased cell death after 48h of continuous exposure, with 10 nM and 100 nM octreotide doses. The percentage of cell viability was 80.92 ±4.9 and 80.49 ±3.61, compared to the control, respectively, consistent with decreased cell viability of about 20% for both the doses.\u0000 \u0000 \u0000 \u0000 Octreotide reduced the alive neoplastic cultured cells of low-grade canine meningioma in a dose-dependent pattern with continuous exposition for 48h. These results support an alternative systemic treatment of meningioma with octreotide in the dog,\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141684366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Velcrin molecular glues induce apoptosis in glioblastomas with high PDE3A and SLFN12 expression","authors":"Elisa Aquilanti, Silvia Goldoni, Andrew Baker, K. Kotýnková, Sawyer Andersen, Vincent Bozinov, Galen F Gao, Andrew D Cherniack, Martin Lange, Ralf Lesche, Charlotte Kopitz, P. Lienau, Timothy Lewis, Marine Garrido, S. Gradl, Henrik Seidel, Yuen-Yi Tseng, Keith L. Ligon, Patrick Y. Wen, Matthew L Meyerson, H. Greulich","doi":"10.1093/noajnl/vdae115","DOIUrl":"https://doi.org/10.1093/noajnl/vdae115","url":null,"abstract":"\u0000 \u0000 \u0000 Velcrins are molecular glues that kill cells by inducing the formation of a protein complex between the RNase SLFN12 and the phosphodiesterase PDE3A. Formation of the complex activates SLFN12, which cleaves tRNALeu(TAA) and induces apoptosis. Velcrins such as the clinical investigational compound, BAY 2666605, were found to have activity across multiple solid tumors cell lines from the Cancer Cell Line Encyclopedia (CCLE), including glioblastoma cell lines. We therefore aim to characterize velcrins as novel therapeutic agents in glioblastoma.\u0000 \u0000 \u0000 \u0000 PDE3A and SLFN12 expression levels were measured in glioblastoma cell lines, TCGA tumor samples and tumor neurospheres. Velcrin-treated cells were assayed for viability, induction of apoptosis, cell cycle phases, and global changes in translation. Transcriptional profiling of the cells was obtained. Xenograft-harboring mice treated with velcrins were also monitored for survival.\u0000 \u0000 \u0000 \u0000 We identified several velcrin-sensitive glioblastoma cell lines and four velcrin-sensitive glioblastoma patient-derived models. We determined that BAY 2666605 crosses the blood brain barrier and elicits full tumor regression in an orthotopic xenograft model of GB1 cells. We also determined that the velcrins BAY 2666605 and BRD3800 induce tumor regression in subcutaneous glioblastoma PDX models.\u0000 \u0000 \u0000 \u0000 Velcrins have anti-tumor activity in preclinical models of glioblastoma, warranting further investigation as potential therapeutic agents.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141693753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling glioblastoma diversity: Insights into methylation subtypes and spatial relationships.","authors":"Martha Foltyn-Dumitru, Haidar Alzaid, Aditya Rastogi, Ulf Neuberger, Felix Sahm, Tobias Kessler, Wolfgang Wick, Martin Bendszus, Philipp Vollmuth, Marianne Schell","doi":"10.1093/noajnl/vdae112","DOIUrl":"10.1093/noajnl/vdae112","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this study was to elucidate the relationship between distinct brain regions and molecular subtypes in glioblastoma (GB), focusing on integrating modern statistical tools and molecular profiling to better understand the heterogeneity of Isocitrate Dehydrogenase wild-type (IDH-wt) gliomas.</p><p><strong>Methods: </strong>This retrospective study comprised 441 patients diagnosed with new IDH-wt glioma between 2009 and 2020 at Heidelberg University Hospital. The diagnostic process included preoperative magnetic resonance imaging and molecular characterization, encompassing IDH-status determination and subclassification, through DNA-methylation profiling. To discern and map distinct brain regions associated with specific methylation subtypes, a support-vector regression-based lesion-symptom mapping (SVR-LSM) was employed. Lesion maps were adjusted to 2 mm³ resolution. Significance was assessed with beta maps, using a threshold of <i>P</i> < .005, with 10 000 permutations and a cluster size minimum of 100 voxels.</p><p><strong>Results: </strong>Of 441 initially screened glioma patients, 423 (95.9%) met the inclusion criteria. Following DNA-methylation profiling, patients were classified into RTK II (40.7%), MES (33.8%), RTK I (18%), and other methylation subclasses (7.6%). Between molecular subtypes, there was no difference in tumor volume. Using SVR-LSM, distinct brain regions correlated with each subclass were identified: MES subtypes were associated with left-hemispheric regions involving the superior temporal gyrus and insula cortex, RTK I with right frontal regions, and RTK II with 3 clusters in the left hemisphere.</p><p><strong>Conclusions: </strong>This study linked molecular diversity and spatial features in glioblastomas using SVR-LSM. Future studies should validate these findings in larger, independent cohorts to confirm the observed patterns.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early prognostication of overall survival for pediatric diffuse midline gliomas using MRI radiomics and machine learning: A two-center study.","authors":"Xinyang Liu, Zhifan Jiang, Holger R Roth, Syed Muhammad Anwar, Erin R Bonner, Aria Mahtabfar, Roger J Packer, Anahita Fathi Kazerooni, Miriam Bornhorst, Marius George Linguraru","doi":"10.1093/noajnl/vdae108","DOIUrl":"10.1093/noajnl/vdae108","url":null,"abstract":"<p><strong>Background: </strong>Diffuse midline gliomas (DMG) are aggressive pediatric brain tumors that are diagnosed and monitored through MRI. We developed an automatic pipeline to segment subregions of DMG and select radiomic features that predict patient overall survival (OS).</p><p><strong>Methods: </strong>We acquired diagnostic and post-radiation therapy (RT) multisequence MRI (T1, T1ce, T2, and T2 FLAIR) and manual segmentations from 2 centers: 53 from 1 center formed the internal cohort and 16 from the other center formed the external cohort. We pretrained a deep learning model on a public adult brain tumor data set (BraTS 2021), and finetuned it to automatically segment tumor core (TC) and whole tumor (WT) volumes. PyRadiomics and sequential feature selection were used for feature extraction and selection based on the segmented volumes. Two machine learning models were trained on our internal cohort to predict patient 12-month survival from diagnosis. One model used only data obtained at diagnosis prior to any therapy (baseline study) and the other used data at both diagnosis and post-RT (post-RT study).</p><p><strong>Results: </strong>Overall survival prediction accuracy was 77% and 81% for the baseline study, and 85% and 78% for the post-RT study, for internal and external cohorts, respectively. Homogeneous WT intensity in baseline T2 FLAIR and larger post-RT TC/WT volume ratio indicate shorter OS.</p><p><strong>Conclusions: </strong>Machine learning analysis of MRI radiomics has potential to accurately and noninvasively predict which pediatric patients with DMG will survive less than 12 months from the time of diagnosis to provide patient stratification and guide therapy.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Effect of food on selumetinib pharmacokinetics and gastrointestinal tolerability in adolescents with neurofibromatosis type 1-related plexiform neurofibromas.","authors":"","doi":"10.1093/noajnl/vdae100","DOIUrl":"https://doi.org/10.1093/noajnl/vdae100","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/noajnl/vdae036.].</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11200133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From bench to bedside: Advancing towards therapeutic treatment of vestibular schwannomas.","authors":"Shaolei Guo, Xuan Zheng, Wenli Chen, Umar Raza, Ailiang Zeng, Farhana Akter, Quan Huang, Shun Yao","doi":"10.1093/noajnl/vdae107","DOIUrl":"10.1093/noajnl/vdae107","url":null,"abstract":"<p><p>Vestibular schwannomas are rare intracranial tumors originating from Schwann cells of the vestibular nerve. Despite their benign nature, these tumors can exert significant mass effects and debilitating symptoms, including gradual hearing loss, vertigo, facial nerve dysfunction, and headaches. Current clinical management options encompass wait-and-scan, surgery, radiation therapy, and off-label medication. However, each approach exhibits its own challenges and harbors limitations that underscore the urgent need for therapeutic treatments. Over the past 2 decades, extensive elucidation of the molecular underpinnings of vestibular schwannomas has unraveled genetic anomalies, dysregulated signaling pathways, downstream of receptor tyrosine kinases, disrupted extracellular matrix, inflammatory tumor microenvironment, and altered cerebrospinal fluid composition as integral factors in driving the development and progression of the disease. Armed with this knowledge, novel therapeutic interventions tailored to the unique molecular characteristics of those conditions are actively being pursued. This review underscores the urgency of addressing the dearth of Food and Drug Administration-approved drugs for vestibular schwannoma, highlighting the key molecular discoveries and their potential translation into therapeutics. It provides an in-depth exploration of the evolving landscape of therapeutic development, which is currently advancing from bench to bedside. These ongoing efforts hold the promise of significantly transforming the lives of vestibular schwannoma patients in the future.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathways to hypermutation in high-grade gliomas: Mechanisms, syndromes, and opportunities for immunotherapy.","authors":"Tuesday Haynes, Mark R Gilbert, Kevin Breen, Chunzhang Yang","doi":"10.1093/noajnl/vdae105","DOIUrl":"10.1093/noajnl/vdae105","url":null,"abstract":"<p><p>Despite rapid advances in the field of immunotherapy, including the success of immune checkpoint inhibition in treating multiple cancer types, clinical response in high-grade gliomas (HGGs) has been disappointing. This has been in part attributed to the low tumor mutational burden (TMB) of the majority of HGGs. Hypermutation is a recently characterized glioma signature that occurs in a small subset of cases, which may open an avenue to immunotherapy. The substantially elevated TMB of these tumors most commonly results from alterations in the DNA mismatch repair pathway in the setting of extensive exposure to temozolomide or, less frequently, from inherited cancer predisposition syndromes. In this review, we discuss the genetics and etiology of hypermutation in HGGs, with an emphasis on the resulting genomic signatures, and the state and future directions of immuno-oncology research in these patient populations.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}