Neuro-oncology advancesPub Date : 2024-10-29eCollection Date: 2024-01-01DOI: 10.1093/noajnl/vdae163
Elaine R Mardis, Jonathan L Finlay
{"title":"International symposium on inheritable central nervous system (CNS) cancer predisposition: A prologue.","authors":"Elaine R Mardis, Jonathan L Finlay","doi":"10.1093/noajnl/vdae163","DOIUrl":"https://doi.org/10.1093/noajnl/vdae163","url":null,"abstract":"","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549872","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}
Neuro-oncology advancesPub Date : 2024-10-04eCollection Date: 2024-01-01DOI: 10.1093/noajnl/vdae170
Linda Götz, Tananeh Ansafi, Michael Gerken, Monika Klinkhammer-Schalke, Anna Fischl, Markus J Riemenschneider, Martin Proescholdt, Elisabeth Bumes, Oliver Kölbl, Nils Ole Schmidt, Ralf Linker, Peter Hau, Tareq M Haedenkamp
{"title":"Effect of antibiotic drug use on outcome and therapy-related toxicity in patients with glioblastoma-A retrospective cohort study.","authors":"Linda Götz, Tananeh Ansafi, Michael Gerken, Monika Klinkhammer-Schalke, Anna Fischl, Markus J Riemenschneider, Martin Proescholdt, Elisabeth Bumes, Oliver Kölbl, Nils Ole Schmidt, Ralf Linker, Peter Hau, Tareq M Haedenkamp","doi":"10.1093/noajnl/vdae170","DOIUrl":"10.1093/noajnl/vdae170","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GB) is the most frequent malignant brain tumor and has a dismal prognosis. In other cancers, antibiotic use has been associated with severity of chemotherapy-induced toxicity and outcome. We investigated if these mechanisms are also involved in GB.</p><p><strong>Methods: </strong>We selected a cohort of 78 GB patients who received combined radiochemotherapy. We investigated if exposure to prediagnostic antibiotic use is associated with clinical side effects and laboratory changes during adjuvant therapy as well as overall survival (OS) and progression-free survival (PFS) using chi-square test, binary logistic regression, Kaplan-Meyer analysis, and multivariable Cox regression.</p><p><strong>Results: </strong>Seventeen patients (21.8%) received at least one course of prediagnostic antibiotics and 61 (78.2%) received no antibiotics. We found a higher incidence of loss of appetite (23.5% vs. 4.9%; <i>P</i> = .018) and myelosuppression (41.2% vs. 18.0%; <i>P</i> = .045) in the antibiotic group. Multivariable logistic regression analysis revealed antibiotics to be a predictor for nausea (OR = 6.94, 95% CI: 1.09-44.30; <i>P</i> = .041) and myelosuppression (OR = 9.75, 95% CI: 1.55-61.18; <i>P</i> = .015). Furthermore, lymphocytopenia was more frequent in the antibiotic group (90.0% vs. 56.1%, <i>P</i> = .033). There were no significant differences in OS (<i>P</i> = .404) and PFS (<i>P</i> = .844). Multivariable Cox regression showed a trend toward shorter survival time (<i>P</i> = .089) in the antibiotic group.</p><p><strong>Conclusions: </strong>Our study suggests that antibiotic use affects symptoms and lab values in GB patients. Larger prospective studies are required to investigate if prediagnostic antibiotic use could be a prognostic factor in GB patients.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570801","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}
Neuro-oncology advancesPub Date : 2024-10-04eCollection Date: 2024-01-01DOI: 10.1093/noajnl/vdae164
{"title":"Correction to: Effect of bevacizumab on refractory meningiomas: 3D volumetric growth rate versus response assessment in neuro-oncology criteria.","authors":"","doi":"10.1093/noajnl/vdae164","DOIUrl":"https://doi.org/10.1093/noajnl/vdae164","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/noajnl/vdae128.].</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383056","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}
Neuro-oncology advancesPub Date : 2024-10-03eCollection Date: 2024-01-01DOI: 10.1093/noajnl/vdae167
Philipp Lohmann, Johnny Duerinck, Matthijs van der Meulen, Dan Mitrea, Susan Short, Marjolein Geurts
{"title":"Empowering the next generation in neuro-oncology: Introduction of the EANO Career Boost Initiative.","authors":"Philipp Lohmann, Johnny Duerinck, Matthijs van der Meulen, Dan Mitrea, Susan Short, Marjolein Geurts","doi":"10.1093/noajnl/vdae167","DOIUrl":"https://doi.org/10.1093/noajnl/vdae167","url":null,"abstract":"","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515558","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}
Neuro-oncology advancesPub Date : 2024-09-30eCollection Date: 2024-01-01DOI: 10.1093/noajnl/vdae166
Jose Carrillo, Jaya Mini Gill, Charles Redfern, Ivan Babic, Natsuko Nomura, Dhaval K Shah, Sean Carrick, Santosh Kesari
{"title":"A phase 1 dose escalation of pritumumab in patients with refractory or recurrent gliomas or brain metastases.","authors":"Jose Carrillo, Jaya Mini Gill, Charles Redfern, Ivan Babic, Natsuko Nomura, Dhaval K Shah, Sean Carrick, Santosh Kesari","doi":"10.1093/noajnl/vdae166","DOIUrl":"10.1093/noajnl/vdae166","url":null,"abstract":"<p><strong>Background: </strong>This phase 1 (NCT04396717) open-label, multicenter study, evaluated Pritumumab, a IgG1 monoclonal antibody, in patients with gliomas and brain metastases. The primary objective was to evaluate the safety and/or tolerability and to identify a recommended phase 2 dose (RP2D) of Pritumumab.</p><p><strong>Methods: </strong>Adult patients with recurrent gliomas or brain metastases were enrolled in the dose cohort that was open at the time of their consent. Study treatment consisted of pritumumab administered intravenously weekly on days 1, 8, 15, and 22 in 28-day cycles. Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity were evaluated.</p><p><strong>Results: </strong>Fifteen patients received Pritumumab in the recurrent setting. Pritumumab was well tolerated, with no serious adverse events related to Pritumumab reported. The most common drug-related toxicities were constipation and fatigue. There were no dose-limiting toxicities observed, and a maximum tolerable dose was not reached. Thus, the maximum feasible dose and recommended phase 2 dose of Pritumumab was established at 16.2 mg/kg weekly. Out of eleven patients evaluated for efficacy, one patient (9.1%) demonstrated partial response based on response assessment in neuro-oncology criteria, and disease stabilization was seen in 3 patients (27.3%).</p><p><strong>Conclusions: </strong>Pritumumab was well tolerated with no DLTs observed up to 16.2 mg/kg weekly. Further studies are warranted to determine clinical benefit in patients.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515555","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}
Neuro-oncology advancesPub Date : 2024-09-28eCollection Date: 2024-01-01DOI: 10.1093/noajnl/vdae161
Arnaud Lombard, Damla Isci, Gilles Reuter, Emmanuel Di Valentin, Alexandre Hego, Didier Martin, Bernard Rogister, Virginie Neirinckx
{"title":"Development of an intraventricular adeno-associated virus-based labeling strategy for glioblastoma cells nested in the subventricular zone.","authors":"Arnaud Lombard, Damla Isci, Gilles Reuter, Emmanuel Di Valentin, Alexandre Hego, Didier Martin, Bernard Rogister, Virginie Neirinckx","doi":"10.1093/noajnl/vdae161","DOIUrl":"https://doi.org/10.1093/noajnl/vdae161","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is a dreadful brain tumor, with a particular relationship to the adult subventricular zone (SVZ) that has been described as relevant to disease initiation, progression, and recurrence.</p><p><strong>Methods: </strong>We propose a novel strategy for the detection and tracking of xenografted GBM cells that are located in the SVZ, based on an intracerebroventricular (icv) recombinant adeno-associated virus (AAV)-mediated color conversion method. We used different patient-derived GBM stem-like cells (GSCs), which we transduced first with a retroviral vector (LRLG) that included a lox-dsRed-STOP-lox cassette, upstream of the eGFP gene, then with rAAVs expressing the Cre-recombinase. Red and green fluorescence is analyzed in vitro and in vivo using flow cytometry and fluorescence microscopy.</p><p><strong>Results: </strong>After comparing the efficiency of diverse rAAV serotypes, we confirmed that the in vitro transduction of GSC-LRLG with rAAV-Cre induced a switch from red to green fluorescence. In parallel, we verified that rAAV transduction was confined to the walls of the lateral ventricles. We, therefore, applied this conversion approach in 2 patient-derived orthotopic GSC xenograft models and showed that the icv injection of an rAAV-DJ-Cre after GSC-LRLG tumor implantation triggered the conversion of red GSCs to green, in the periventricular region. Green GSCs were also found at distant places, including the migratory tract and the tumor core.</p><p><strong>Conclusions: </strong>This study not only sheds light on the putative outcome of SVZ-nested GBM cells but also shows that icv injection of rAAV vectors allows to transduce and potentially modulate gene expression in hard-to-reach GBM cells of the periventricular area.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515557","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}
Neuro-oncology advancesPub Date : 2024-09-24eCollection Date: 2024-01-01DOI: 10.1093/noajnl/vdae165
Kasper Amund Henriksen, Thomas Van Overeem Hansen, Karin Wadt, Kjeld Schmiegelow, Jon Foss-Skiftesvik, Ulrik Kristoffer Stoltze
{"title":"Evolutionary evidence precludes <i>ELP1</i> as a high-penetrance pediatric cancer predisposition syndrome gene.","authors":"Kasper Amund Henriksen, Thomas Van Overeem Hansen, Karin Wadt, Kjeld Schmiegelow, Jon Foss-Skiftesvik, Ulrik Kristoffer Stoltze","doi":"10.1093/noajnl/vdae165","DOIUrl":"https://doi.org/10.1093/noajnl/vdae165","url":null,"abstract":"","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515559","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}
Neuro-oncology advancesPub Date : 2024-09-23eCollection Date: 2024-01-01DOI: 10.1093/noajnl/vdae162
Laura Huhtala, Goktug Karabiyik, Kirsi J Rautajoki
{"title":"Development and epigenetic regulation of Atypical teratoid/rhabdoid tumors in the context of cell-of-origin and halted cell differentiation.","authors":"Laura Huhtala, Goktug Karabiyik, Kirsi J Rautajoki","doi":"10.1093/noajnl/vdae162","DOIUrl":"10.1093/noajnl/vdae162","url":null,"abstract":"<p><p>Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive brain tumors primarily observed in infants. The only characteristic, recurrent genetic aberration of AT/RTs is biallelic inactivation of SMARCB1 (or SMARCA4). These genes are members of the mSWI/SNF chromatin-remodeling complex, which regulates various developmental processes, including neural differentiation. This review explores AT/RT subgroups regarding their distinct SMARCB1 loss-of-function mechanisms, molecular features, and patient characteristics. Additionally, it addresses the ongoing debate about the oncogenic relevance of cell-of-origin, examining the influence of developmental stage and lineage commitment of the seeding cell on tumor malignancy and other characteristics. Epigenetic dysregulation, particularly through the regulation of histone modifications and DNA hypermethylation, has been shown to play an integral role in AT/RTs' malignancy and differentiation blockage, maintaining cells in a poorly differentiated state via the insufficient activation of differentiation-related genes. Here, the differentiation blockage and its contribution to malignancy are also explored in a cellular context. Understanding these mechanisms and AT/RT heterogeneity is crucial for therapeutic improvements against AT/RTs.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515556","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}
Neuro-oncology advancesPub Date : 2024-09-21eCollection Date: 2024-01-01DOI: 10.1093/noajnl/vdae160
Maximilian Y Deng, Sophie Rauh, Günes Anil, Jonathan W Lischalk, Laura Hahnemann, Tanja Eichkorn, Juliane Hörner-Rieber, Angela Paul, Elisabetta Sandrini, Philipp Hoegen-Sassmannshausen, Thomas Held, Sebastian Regnery, Lukas Bauer, Felix Sahm, Andreas von Deimling, Antje Wick, Wolfgang Wick, Christine Jungk, Sandro M Krieg, Klaus Herfarth, Jürgen Debus, Laila König
{"title":"Analysis of safety and efficacy of proton radiotherapy for optic nerve sheath meningioma.","authors":"Maximilian Y Deng, Sophie Rauh, Günes Anil, Jonathan W Lischalk, Laura Hahnemann, Tanja Eichkorn, Juliane Hörner-Rieber, Angela Paul, Elisabetta Sandrini, Philipp Hoegen-Sassmannshausen, Thomas Held, Sebastian Regnery, Lukas Bauer, Felix Sahm, Andreas von Deimling, Antje Wick, Wolfgang Wick, Christine Jungk, Sandro M Krieg, Klaus Herfarth, Jürgen Debus, Laila König","doi":"10.1093/noajnl/vdae160","DOIUrl":"10.1093/noajnl/vdae160","url":null,"abstract":"<p><strong>Background: </strong>Primary optic nerve sheath meningiomas (ONSMs) represent a group of benign tumors originating from the optic nerve sheath, typically causing painless, gradual onset monocular visual loss, which can result in blindness if left untreated. Radiation therapy represents an important treatment option for patients with ONSM, allowing for preservation and potential improvement in visual function. In particular, proton radiotherapy may enable a reduction of the side effects due to its physical advantage of an inverted dose profile with a steep dose gradient. The study investigates the visual acuity, local tumor control, and treatment-related toxicities following proton beam radiotherapy with a single institutional cohort comprising 32 patients treated for ONSM.</p><p><strong>Methods: </strong>Patients with primary ONSM, either histologically (16/32) or radiologically confirmed (16/32), which were treated at the Department of Radiation Oncology at the University Hospital Heidelberg (Germany) were assessed in regard to their visual outcomes, treatment toxicity, and local tumor control following radiotherapy according to response assessment in neuro-oncology criteria.</p><p><strong>Results: </strong>After a median follow-up time of 39.5 months, the 5-year local progression-free survival was estimated at 100%, with 84.4% of patients reporting improvement or stability in visual acuity during their last follow-up. Radiation-induced optic neuropathy (RION) was encountered in 9.4%.</p><p><strong>Conclusions: </strong>Our study demonstrates proton beam therapy as a safe and effective treatment alternative in the therapeutic management of ONSMs. RION represents a rare but dreaded complication after treatment. Future head-to-head comparisons with photon radiotherapy in a prospective setting are required to demonstrate a potential, additional clinical benefit.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484588","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}
Neuro-oncology advancesPub Date : 2024-09-16eCollection Date: 2024-01-01DOI: 10.1093/noajnl/vdae154
Dror Limon, Alexandra Amiel, Shaked Even Haim, Noa Gordon, Roi Tschernichovsky, Salomon Stemmer, Omer Gal, Yosef Laviv, Andrew Kanner, Tali Siegal, Shlomit Yust-Katz
{"title":"A phase II, open-label, single-arm trial of pembrolizumab for recurrent meningioma and solitary fibrous tumor.","authors":"Dror Limon, Alexandra Amiel, Shaked Even Haim, Noa Gordon, Roi Tschernichovsky, Salomon Stemmer, Omer Gal, Yosef Laviv, Andrew Kanner, Tali Siegal, Shlomit Yust-Katz","doi":"10.1093/noajnl/vdae154","DOIUrl":"10.1093/noajnl/vdae154","url":null,"abstract":"<p><strong>Background: </strong>Atypical and anaplastic meningiomas account for 20% of all meningioma cases. Solitary fibrous tumor (SFT) is a type of soft tissue sarcoma with similar attributes to meningioma. For patients with refractory or recurrent disease after previous surgery or radiotherapy, there is no effective treatment. Pembrolizumab, an anti-programmed cell death 1 (PD-1) antibody, is an effective treatment for various solid tumors. PD-1 ligand is highly expressed in aggressive meningiomas. We aimed to assess the effectiveness of pembrolizumab in treating meningioma and SFT recurrence after surgery and radiation therapy.</p><p><strong>Methods: </strong>This prospective single-arm phase II trial comprised 15 patients with recurrent meningioma and 3 with anaplastic SFT, treated at a single institution during 2018 to 2022. The study was terminated due to a lack of efficacy and slow accrual. The primary endpoint was 6-month progression-free survival (PFS-6).</p><p><strong>Results: </strong>Median progression-free survival (PFS) was 2.6 months, and median overall survival (OS) was 40 months. The 6- and 12-month PFS were both 11.1%. The 6- and 12-month OS were 94.4% and 61.1%, respectively. According to the Response Assessment in Neuro-Oncology (RANO) criteria, the overall response rate was 11%, with 2 patients achieving stable disease and 2 with partial response. Three patients (16.7%) developed grade 3 toxicity.</p><p><strong>Conclusions: </strong>Our results showed that pembrolizumab failed to improve PFS-6 in patients with aggressive meningioma or anaplastic SFT. However, two patients, one with atypical meningioma and one with anaplastic SFT, achieved a partial response. More clinical studies are needed to identify which subset of patients may benefit from this treatment.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484587","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}