Neuro-oncology advances最新文献

{"title":"Directionally non-rotating electric field therapy (dnEFT) delivered through implanted electrodes as a glioblastoma treatment platform: a proof-of-principle study","authors":"Jun Ma, Shilpi Singh, Ming Li, Davis Seelig, Gregory F Molnar, Eric T Wong, S. Dhawan, Stefan Kim, Logan Helland, David Chen, Nikos Tapinos, Sean Lawler, Gatikrushna Singh, Clark C Chen","doi":"10.1093/noajnl/vdae121","DOIUrl":"https://doi.org/10.1093/noajnl/vdae121","url":null,"abstract":"\u0000 \u0000 \u0000 While directionally rotating Tumor Treating Fields (TTF) therapy has garnered considerable clinical interest in recent years, there has been comparatively less focus on directionally non-rotating electric field therapy (dnEFT).\u0000 \u0000 \u0000 \u0000 We explored dnEFT generated through customized electrodes as a glioblastoma therapy in in vitro and in vivo pre-clinical models. The effects of dnEFT on tumor apoptosis and microglia/macrophages in the tumor microenvironment were tested using flow-cytometric and qPCR assays.\u0000 \u0000 \u0000 \u0000 In vitro, dnEFT generated using a clinical grade spinal cord stimulator showed anti-neoplastic activity against independent glioblastoma cell lines. In support of the results obtained using the clinical grade electrode, dnEFT delivered through a customized, two-electrode array induced glioblastoma apoptosis. To characterize this effect in vivo, a custom-designed four-electrode array was fabricated such that tumor cells can be implanted into murine cerebrum through a center channel equidistant from the electrodes. After implantation with this array and luciferase expressing murine GL261 glioblastoma cells, mice were randomized to dnEFT or placebo. Relative to placebo treated mice, dnEFT reduced tumor growth (measured by bioluminescence) and prolonged survival (median survival gain of 6.5 days). Analysis of brain sections following dnEFT showed a notable increase in the accumulation of peri-tumoral macrophage/microglia with increased expression of M1 genes (IFNγ, TNFα, IL-6) and decreased expression of M2 genes (CD206, Arg, IL-10) relative to placebo treated tumors.\u0000 \u0000 \u0000 \u0000 Our results suggest therapeutic potential in glioblastoma for dnEFT delivered through implanted electrodes, supporting the development of a proof-of-principle clinical trial using commercially available deep brain stimulator electrodes.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141652004","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":"Glioma oncogenesis in the constitutional mismatch repair deficiency (CMMRD) syndrome","authors":"L. Guerrini-Rousseau, Jane Merlevede, Philippe Denizeau, F. Andreiuolo, Pascale Varlet, S. Puget, K. Beccaria, T. Blauwblomme, O. Cabaret, N. Hamzaoui, Franck Bourdeaut, Cécile Faure-Conter, Martine Muleris, C. Colas, Tiphaine Adam de Beaumais, D. Castel, Etienne Rouleau, L. Brugières, Jacques Grill, Marie-Anne Debily","doi":"10.1093/noajnl/vdae120","DOIUrl":"https://doi.org/10.1093/noajnl/vdae120","url":null,"abstract":"\u0000 \u0000 \u0000 Constitutional Mismatch Repair Deficiency (CMMRD) is a cancer predisposition due to biallelic mutations in one of the mismatch repair (MMR) genes associated with early onset of cancers, especially high-grade gliomas. Our aim was to decipher the molecular specificities of these gliomas.\u0000 \u0000 \u0000 \u0000 Clinical, histopathological and whole exome sequencing data were analyzed in 12 children with genetically proven CMMRD and a high-grade glioma.\u0000 \u0000 \u0000 \u0000 PDL1 expression was present on immunohistochemistry in 50% of the samples. In 9 patients, the glioma harbored an ultra-hypermutated phenotype (104-635 coding single nucleotide variants (SNV) per Mb, median 204). Driver mutations in POLE and POLD1 exonuclease domains were described for 8 and 1 patients respectively and were always present in the mutation burst with the highest variant allele frequency (VAF). The mutational signatures were dominated by MMR-related ones and similar in the different mutation bursts of a same patient without subsequent enrichment of the mutation signatures with POL-driven ones. Median number of coding SNV with VAF above the one of the driving polymerase mutation per Mb was 57 (17-191). Our findings suggest that somatic polymerase alterations does not entirely explain the ultra-hypermutant phenotype. SETD2, TP53, NF1, EPHB2, PRKDC and DICER1 genes were frequently mutated with higher VAF than the deleterious somatic polymerase mutation.\u0000 \u0000 \u0000 \u0000 CMMRD-associated gliomas have a specific oncogenesis that does not involve usual pathways and mutations seen in sporadic pediatric or adult glioblastomas. Frequent alterations in other pathways such as MAPK may suggest the use of other targeted therapies along with PD1 inhibitors.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141655635","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":"Comprehensive multimodal deep learning survival prediction enabled by a transformer architecture: A multicenter study in glioblastoma.","authors":"Ahmed Gomaa, Yixing Huang, Amr Hagag, Charlotte Schmitter, Daniel Höfler, Thomas Weissmann, Katharina Breininger, Manuel Schmidt, Jenny Stritzelberger, Daniel Delev, Roland Coras, Arnd Dörfler, Oliver Schnell, Benjamin Frey, Udo S Gaipl, Sabine Semrau, Christoph Bert, Peter Hau, Rainer Fietkau, Florian Putz","doi":"10.1093/noajnl/vdae122","DOIUrl":"10.1093/noajnl/vdae122","url":null,"abstract":"<p><strong>Background: </strong>This research aims to improve glioblastoma survival prediction by integrating MR images, clinical, and molecular-pathologic data in a transformer-based deep learning model, addressing data heterogeneity and performance generalizability.</p><p><strong>Methods: </strong>We propose and evaluate a transformer-based nonlinear and nonproportional survival prediction model. The model employs self-supervised learning techniques to effectively encode the high-dimensional MRI input for integration with nonimaging data using cross-attention. To demonstrate model generalizability, the model is assessed with the time-dependent concordance index (Cdt) in 2 training setups using 3 independent public test sets: UPenn-GBM, UCSF-PDGM, and Rio Hortega University Hospital (RHUH)-GBM, each comprising 378, 366, and 36 cases, respectively.</p><p><strong>Results: </strong>The proposed transformer model achieved a promising performance for imaging as well as nonimaging data, effectively integrating both modalities for enhanced performance (UCSF-PDGM test-set, imaging Cdt 0.578, multimodal Cdt 0.672) while outperforming state-of-the-art late-fusion 3D-CNN-based models. Consistent performance was observed across the 3 independent multicenter test sets with Cdt values of 0.707 (UPenn-GBM, internal test set), 0.672 (UCSF-PDGM, first external test set), and 0.618 (RHUH-GBM, second external test set). The model achieved significant discrimination between patients with favorable and unfavorable survival for all 3 datasets (log-rank <i>P</i> 1.9 × 10^-8, 9.7 × 10^-3, and 1.2 × 10^-2). Comparable results were obtained in the second setup using UCSF-PDGM for training/internal testing and UPenn-GBM and RHUH-GBM for external testing (Cdt 0.670, 0.638, and 0.621).</p><p><strong>Conclusions: </strong>The proposed transformer-based survival prediction model integrates complementary information from diverse input modalities, contributing to improved glioblastoma survival prediction compared to state-of-the-art methods. Consistent performance was observed across institutions supporting model generalizability.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001606","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":"Neuro-oncology access in Sub-Saharan Africa: A literature review of challenges and opportunities.","authors":"W Elorm Yevudza, Vincent Buckman, Kwadwo Darko, Mabel Banson, Teddy Totimeh","doi":"10.1093/noajnl/vdae057","DOIUrl":"10.1093/noajnl/vdae057","url":null,"abstract":"<p><strong>Background: </strong>Ensuring equitable access to treatments and therapies in the constantly evolving field of neuro-oncology is an imperative global health issue. With its unique demographic, cultural, socioeconomic, and infrastructure characteristics, Sub-Saharan Africa faces distinct challenges. This literature review highlights specific barriers to neuro-oncology care in the region and explores potential opportunities for enhancing access.</p><p><strong>Methods: </strong>Predetermined keyword searches were employed to screen titles and abstracts using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework. Inclusion criteria were studies published between January 1, 2003, and June 20, 2023, specifically addressing the capacity and challenges of neuro-oncology in the Sub-Saharan African region. The data sources queried were PubMed and Google Scholar. Systematic reviews and meta-analyses were deliberately excluded. All authors conducted independent screening and structured data extraction meticulously.</p><p><strong>Results: </strong>Our paper identified multiple challenges that impede access to quality treatment for brain tumors. These include constrained resources, insufficient training of healthcare professionals, certain cultural beliefs, and a general lack of awareness about brain tumors, all contributing to delayed diagnosis and treatment. Furthermore, the lack of detailed data on the incidence and prevalence of primary central nervous system tumors impairs the accurate assessment of disease burden and precise identification of areas requiring improvement. However, we discovered that ongoing research, advocacy, enhanced training, mentorship, and collaborative efforts present valuable opportunities for substantial progress in neuro-oncology access.</p><p><strong>Conclusions: </strong>While we provide a glimpse of the current state, we hope these results will help stimulate dialogue and catalyze initiatives to surmount highlighted obstacles and improve neuro-oncology outcomes across Sub-Saharan Africa.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592475","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":"Frequent Alzheimer’s disease neuropathological change in patients with glioblastoma","authors":"L. Greutter, Y. Miller-Michlits, Sigrid Klotz, R. Reimann, K. Nenning, Stephan Platzek, Elena Krause, B. Kiesel, Georg Widhalm, Georg Langs, B. Baumann, A. Woehrer","doi":"10.1093/noajnl/vdae118","DOIUrl":"https://doi.org/10.1093/noajnl/vdae118","url":null,"abstract":"\u0000 \u0000 \u0000 The incidence of brain cancer and neurodegenerative diseases is increasing with a demographic shift towards aging populations. Biological parallels have been observed between glioblastoma and Alzheimer’s disease (AD), which converge on accelerated brain aging. Here, we aimed to map the co-occurrence of AD neuropathological change (ADNC) in the tumor-adjacent cortex of patients with glioblastoma.\u0000 \u0000 \u0000 \u0000 Immunohistochemical screening of AD markers amyloid beta (Abeta), amyloid precursor protein (APP) and hyperphosphorylated tau (pTau) was conducted in 420 tumor samples of 205 patients. For each cortex area we quantified ADNC, neurons, tumor cells, and microglia.\u0000 \u0000 \u0000 \u0000 Fifty-two percent of patients (N=106/205) showed ADNC (Abeta and pTau, Abeta or pTau) in the tumor-adjacent cortex, with histological patterns widely consistent with AD. ADNC was positively correlated with patient age and varied spatially according to Thal phases and Braak stages. It decreased with increasing tumor cell infiltration (p<0.0001) and was independent from frequent expression of APP in neuronal cell bodies (N=182/205) and in tumor necrosis-related axonal spheroids (N=195/205; p=0.46). Microglia response was most present in tumor cell infiltration plus ADNC, being further modulated by patient age and sex. ADNC did not impact patient survival in the present cohort.\u0000 \u0000 \u0000 \u0000 Our findings highlight frequent presence of ADNC in the glioblastoma vicinity, which was linked to patient age and tumor location. The co-occurrence of AD and glioblastoma seemed stochastic without clear spatial relation. ADNC did not impact patient survival in our cohort.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141665019","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":"Correction to: Recurrent fibroblast growth factor receptor3 fusion glioblastoma treated with pemigatinib: A case report and review of the literature.","authors":"","doi":"10.1093/noajnl/vdae116","DOIUrl":"https://doi.org/10.1093/noajnl/vdae116","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/noajnl/vdae072.].</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560661","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":"Predicting Prognosis Outcomes of Primary Central Nervous System Lymphoma with High-Dose Methotrexate-Based Chemotherapeutic Treatment Using Lipidomics","authors":"Yi Zhong, Liying Zhou, Jingshen Xu, He Huang","doi":"10.1093/noajnl/vdae119","DOIUrl":"https://doi.org/10.1093/noajnl/vdae119","url":null,"abstract":"\u0000 \u0000 \u0000 Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy which is commonly treated with high-dose methotrexate (HD-MTX)-based chemotherapy. However, the prognosis outcome of HD-MTX-based treatment cannot be accurately predicted using the current prognostic scoring systems, such as the Memorial Sloan Kettering Cancer Center (MSKCC) score.\u0000 \u0000 \u0000 \u0000 We studied two cohorts of patients with PCNSL and applied lipidomic analysis on their cerebrospinal fluid (CSF) samples. After removing the batch effects and features engineering, we applied and compared several classic machine-learning models based on lipidomic data of CSF to predict the relapse of PCNSL in patients who were treated with HD-MTX-based chemotherapy.\u0000 \u0000 \u0000 \u0000 We managed to remove the batch effects and got the optimum features of each model. Finally, we found that Cox regression had the best prediction performance (AUC = 0.711) on prognosis outcome.\u0000 \u0000 \u0000 \u0000 We developed a Cox regression model based on lipidomic data, which could effectively predict PCNSL patient prognosis before the HD-MTX-based chemotherapy treatments.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141672380","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":"Diffuse glioma molecular profiling with Arterial Spin Labeling and Dynamic Susceptibility Contrast perfusion MRI: a comparative study","authors":"Yeva Prysiazhniuk, A. Server, H. Leske, Øystein Bech-Aase, E. Helseth, R. Eijgelaar, E. Fuster-García, P. Brandal, A. Bjørnerud, Jakub Otáhal, Jan Petr, W. Nordhøy","doi":"10.1093/noajnl/vdae113","DOIUrl":"https://doi.org/10.1093/noajnl/vdae113","url":null,"abstract":"\u0000 \u0000 \u0000 Evaluation of molecular markers (IDH, pTERT, 1p/19q co-deletion, and MGMT) in adult diffuse gliomas is crucial for accurate diagnosis and optimal treatment planning. Dynamic Susceptibility Contrast (DSC) and Arterial Spin Labeling (ASL) perfusion MRI techniques have both shown good performance in classifying molecular markers, however, their performance has not been compared side-by-side.\u0000 \u0000 \u0000 \u0000 Pre-treatment MRI data from ninety patients diagnosed with diffuse glioma (54 men/36 female, 53.1 ± 15.5 years, grades 2-4) were retrospectively analyzed. DSC-derived normalized cerebral blood flow/volume (nCBF/nCBV) and ASL-derived nCBF in tumor and perifocal edema were analyzed in patients with available IDH–mutation (n=67), pTERT–mutation (n=39), 1p/19q co-deletion (n=33), and MGMT promoter methylation (n=31) status. Cross-validated uni- and multivariate logistic regression models assessed perfusion parameters’ performance in molecular marker detection.\u0000 \u0000 \u0000 \u0000 ASL and DSC perfusion parameters in tumor and edema distinguished IDH-wildtype (wt) and pTERT-wt tumors from mutated ones. Univariate classification performance was comparable for ASL-nCBF and DSC-nCBV in IDH (maximum AUROCC 0.82 and 0.83, respectively) and pTERT (maximum AUROCC 0.70 and 0.81, respectively) status differentiation. The multivariate approach improved IDH (DSC-nCBV AUROCC 0.89) and pTERT (ASL-nCBF AUROCC 0.8, DSC-nCBV AUROCC 0.86) classification. However, ASL and DSC parameters could not differentiate 1p/19q co-deletion or MGMT promoter methylation status. Positive correlations were found between ASL-nCBF and DSC-nCBV/-nCBF in tumor and edema.\u0000 \u0000 \u0000 \u0000 ASL is a viable gadolinium-free replacement for DSC for molecular characterization of adult diffuse gliomas.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141673198","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":"Marrow-ablative Consolidation Chemotherapy and Molecular Targeted Therapy Delivered in a Risk-adapted Manner for Newly Diagnosed Children with Choroid Plexus Carcinoma: A Work in Progress","authors":"Maxim Yankelevich, W. Zaky, L. Lafay-Cousin, Diana Osorio, Jenny K Adamski, U. Kordes, Jonathan L Finlay, Michael Prados, Sabine Mueller","doi":"10.1093/noajnl/vdae109","DOIUrl":"https://doi.org/10.1093/noajnl/vdae109","url":null,"abstract":"\u0000 Choroid plexus carcinomas (CPC) are early childhood cancers characterized by loss of TP53 function and poor survival. We are analyzing data on TP53 status, survival and second cancers from the largest cohort of CPC receiving chemotherapy followed by consolidation with marrow-ablative chemotherapy (HDCx). Additionally, we discuss the rationale for targeted therapies for CPC patients. Currently, eight of 13 with Li-Fraumeni Syndrome (LFS)-associated CPC were treated and continued CPC-free, indicating that HDCx improves CPC-free survival in young children with TP53-mutated CPC. These data justify the inclusion of HDCx in the planned prospective international trial for children with TP53-mutated CPC.","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141673643","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":"Molecular genetics and diversity of choroid plexus tumors","authors":"Christian Thomas, M. Hasselblatt","doi":"10.1093/noajnl/vdae101","DOIUrl":"https://doi.org/10.1093/noajnl/vdae101","url":null,"abstract":"\u0000 Choroid plexus tumors are rare intraventricular brain tumors predominantly arising in children but also affecting adults. Chromosome-wide copy-number alterations and TP53 mutations do occur, but in most choroid plexus tumors, driver mutations have not been identified. Here we give a brief overview on the histopathological and clinical diversity of choroid plexus tumors and their genetic and epigenetic heterogeneity. Preliminary data indicate that choroid plexus carcinomas comprise at least two epigenetic subgroups, one of which is associated with TP53 mutation status. These findings strongly encourage us to further investigate the genetic and epigenetic heterogeneity in a larger cohort and to align molecular subgroup status with clinical annotations, in order to identify prognostic markers that may also aid stratification within future international trials.","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":"141679118","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}