Exploration of targeted anti-tumor therapy最新文献

{"title":"Clinical relevance of circulating tumor DNA in ovarian cancer: current issues and future opportunities.","authors":"Elena Trevisi, Cristiana Sessa, Ilaria Colombo","doi":"10.37349/etat.2024.00239","DOIUrl":"10.37349/etat.2024.00239","url":null,"abstract":"<p><p>Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide. Due to the lack of effective screening and early detection strategies, many patients with OC are diagnosed with advanced disease, where treatment is rarely curative. Moreover, OC is characterized by high intratumor heterogeneity, which represents a major barrier to the development of effective treatments. Conventional tumor biopsy and blood-based biomarkers, such as cancer antigen 125 (CA125), have different limitations. Liquid biopsy has recently emerged as an attractive and promising area of investigation in oncology, due to its minimally invasive, safe, comprehensive, and real-time dynamic nature. Preliminary evidence suggests a potential role of liquid biopsy to refine OC management, by improving screening, early diagnosis, assessment of response to treatment, detection, and profiling of drug resistance. The current knowledge and the potential clinical value of liquid biopsy in OC is discussed in this review to provide an overview of the clinical settings in which its use might support and improve diagnosis and treatment.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"627-640"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536155","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":"Evaluation of antitumor potential of an anti-glypican-1 monoclonal antibody in preclinical lung cancer models reveals a distinct mechanism of action.","authors":"Minghua Li, Yanhong Wang, Xiaoyang Lin, Haiqiang Yang, Xiaolin Zhang, Yun Bai, Xiankun Li, Lulu Zhang, Feng Cheng, Chuanhai Cao, Qingyu Zhou","doi":"10.37349/etat.2024.00238","DOIUrl":"10.37349/etat.2024.00238","url":null,"abstract":"<p><strong>Aim: </strong>The main objective of this study was to investigate the antitumor effect of a mouse anti-human glypican-1 (GPC1) monoclonal antibody (mAb) on non-small cell lung carcinoma (NSCLC) and associated molecular mechanisms.</p><p><strong>Methods: </strong>The anti-proliferative and anti-migratory activities of anti-GPC1 mAb were examined in A549 and H460 NSCLC cells and LL97A lung fibroblasts. The inhibitory effect of anti-GPC1 mAb on tumor growth was evaluated in an orthotopic lung tumor model.</p><p><strong>Results: </strong>The in vitro study showed that anti-GPC1 mAb profoundly inhibited the anchorage-independent growth of A549 and H460 NSCLC cells and exhibited relatively high cytotoxic activities towards LL97A lung fibroblasts, A549/LL97A and H460/LL97A coculture spheroids. Moreover, anti-GPC1 mAb significantly decreased the expression of phospho-Src (p-Src; Tyr416), p-Akt (Ser473) and β-catenin in the co-cultured LL97A lung fibroblasts, and the expression of phospho-mitogen-activated protein kinase kinase (p-MEK; Ser217/221) and phospho-90 kDa ribosomal s6 kinase (p-p90RSK; Ser380) in co-cultured A549 cells. When anti-GPC1 mAb was administered to tumor-bearing mice, the inhibitory effect of anti-GPC1 mAb on the orthotopic lung tumor growth was not statistically significant. Nonetheless, results of Western blot analysis showed significant decrease in the phosphorylation of fibroblast growth factor receptor 1 (FGFR1) at Tyr766, Src at Tyr416, extracellular signal-regulated kinase (ERK) at Thr202/Tyr204, 90 kDa ribosomal S6 kinase (RSK) at Ser380, glycogen synthase kinases 3α (GSK3α) at Ser21 and GSK3β at Ser9 in tumor tissues. These data implicate that anti-GPC1 mAb treatment impairs the interaction between tumor cells and tumor associated fibroblasts by attenuating the paracrine FGFR signal transduction.</p><p><strong>Conclusions: </strong>The relatively potent cytotoxicity of anti-GPC1 mAb in lung fibroblasts and its potential inhibitory effect on the paracrine FGFR signal transduction warrant further studies on the combined use of this mAb with targeted therapeutics to improve therapeutic outcomes in lung cancer.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"600-626"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536158","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":"Imaging of supratentorial ependymomas with radio-pathological correlation.","authors":"Arpita Sahu, Aditi Venkatesh, Aman Snehil, Abhishek Mahajan, Amit Janu, Ayushi Sahay, Epari Sridhar","doi":"10.37349/etat.2024.00245","DOIUrl":"10.37349/etat.2024.00245","url":null,"abstract":"<p><strong>Aim: </strong>Supratentorial ependymoma (STE) is a rare tumor with distinct genetic alterations, whose imaging features have been scarcely studied. This study aims to review the computed tomography (CT) and magnetic resonance imaging (MRI) features of a cohort of histopathologically proven STE to identify the distinguishing features of STE, and look for specific signs of zinc finger translocation associated (ZFTA) fused STEs.</p><p><strong>Methods: </strong>Ethical clearance was obtained from the institutional ethics committee. The magnetic resonance (MR) images, CT images when available, clinical details, and pathological reports of 25 patients from a single institute with histopathologically proven STE were retrospectively reviewed. Imaging features, demographic details, pathological and molecular features, and type of surgical resection were described and tabulated. Relevant associations with imaging features were computed and tabulated.</p><p><strong>Results: </strong>The study showed that STEs are common in the pediatric population with no sex predilection. The periventricular location was the most common. A significant association between periventricular location and the presence of a cystic component (<i>P</i> value = 0.023) and the presence of the periwinkle sign/stellate sign (<i>P</i> value = 0.045) was found. Common features of ZFTA fused STEs included periventricular or intraventricular location, cystic component, necrosis, and the periwinkle sign. A significant association was found between ZFTA fusion and cystic component (<i>P</i> value = 0.048).</p><p><strong>Conclusions: </strong>This study attempts to identify the imaging features of STEs and their associations with molecular pathology and surgical outcome, and the distinguishing features of ZFTA fused STEs.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"766-779"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536159","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":"Landscape of targeted therapies for advanced urothelial carcinoma.","authors":"Shihao Shang, Lei Zhang, Kepu Liu, Maoxin Lv, Jie Zhang, Dongen Ju, Di Wei, Zelong Sun, Pinxiao Wang, Jianlin Yuan, Zheng Zhu","doi":"10.37349/etat.2024.00240","DOIUrl":"10.37349/etat.2024.00240","url":null,"abstract":"<p><p>Bladder cancer (BC) is the tenth most common malignancy globally. Urothelial carcinoma (UC) is a major type of BC, and advanced UC (aUC) is associated with poor clinical outcomes and limited survival rates. Current options for aUC treatment mainly include chemotherapy and immunotherapy. These options have moderate efficacy and modest impact on overall survival and thus highlight the need for novel therapeutic approaches. aUC patients harbor a high tumor mutation burden and abundant molecular alterations, which are the basis for targeted therapies. Erdafitinib is currently the only Food and Drug Administration (FDA)-approved targeted therapy for aUC. Many potential targeted therapeutics aiming at other molecular alterations are under investigation. This review summarizes the current understanding of molecular alterations associated with aUC targeted therapy. It also comprehensively discusses the related interventions for treatment in clinical research and the potential of using novel targeted drugs in combination therapy.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"641-677"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536160","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":"Conceptual breakthroughs of the long noncoding RNA functional system and its endogenous regulatory role in the cancerous regime.","authors":"Anyou Wang","doi":"10.37349/etat.2024.00211","DOIUrl":"10.37349/etat.2024.00211","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) derived from noncoding regions in the human genome were once regarded as junks with no biological significance, but recent studies have shown that these molecules are highly functional, prompting an explosion of studies on their biology. However, these recent efforts have only begun to recognize the biological significance of a small fraction (< 1%) of the lncRNAs. The basic concept of these lncRNA functions remains controversial. This controversy arises primarily from conventional biased observations based on limited datasets. Fortunately, emerging big data provides a promising path to circumvent conventional bias to understand an unbiased big picture of lncRNA biology and advance the fundamental principles of lncRNA biology. This review focuses on big data studies that break through the critical concepts of the lncRNA functional system and its endogenous regulatory roles in all cancers. lncRNAs have unique functional systems distinct from proteins, such as transcriptional initiation and regulation, and they abundantly interact with mitochondria and consume less energy. lncRNAs, rather than proteins as traditionally thought, function as the most critical endogenous regulators of all cancers. lncRNAs regulate the cancer regulatory regime by governing the endogenous regulatory network of all cancers. This is accomplished by dominating the regulatory network module and serving as a key hub and top inducer. These critical conceptual breakthroughs lay a blueprint for a comprehensive functional picture of the human genome. They also lay a blueprint for combating human diseases that are regulated by lncRNAs.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"170-186"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095213","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":"Efficacy of metformin and electrical pulses in breast cancer MDA-MB-231 cells.","authors":"Praveen Sahu, Ignacio G Camarillo, Raji Sundararajan","doi":"10.37349/etat.2024.00204","DOIUrl":"10.37349/etat.2024.00204","url":null,"abstract":"<p><strong>Aim: </strong>Triple-negative breast cancer (TNBC) is a very aggressive subset of breast cancer, with limited treatment options, due to the lack of three commonly targeted receptors, which merits the need for novel treatments for TNBC. Towards this need, the use of metformin (Met), the most widely used type-2 diabetes drug worldwide, was explored as a repurposed anticancer agent. Cancer being a metabolic disease, the modulation of two crucial metabolites, glucose, and reactive oxygen species (ROS), is studied in MDA-MB-231 TNBC cells, using Met in the presence of electrical pulses (EP) to enhance the drug efficacy.</p><p><strong>Methods: </strong>MDA-MB-231, human TNBC cells were treated with Met in the presence of EP, with various concentrations Met of 1 mmol/L, 2.5 mmol/L, 5 mmol/L, and 10 mmol/L. EP of 500 V/cm, 800 V/cm, and 1,000 V/cm (with a pulse width of 100 µs at 1 s intervals) were applied to TNBC and the impact of these two treatments was studied. Various assays, including cell viability, microscopic inspection, glucose, ROS, and wound healing assay, were performed to characterize the response of the cells to the combination treatment.</p><p><strong>Results: </strong>Combining 1,000 V/cm with 5 mmol/L Met yielded cell viability as low as 42.6% at 24 h. The glucose level was reduced by 5.60-fold and the ROS levels were increased by 9.56-fold compared to the control, leading to apoptotic cell death.</p><p><strong>Conclusions: </strong>The results indicate the enhanced anticancer effect of Met in the presence of electric pulses. The cell growth is inhibited by suppressing glucose levels and elevated ROS. This shows a synergistic interplay between electroporation, Met, glucose, and ROS metabolic alterations. The results show promises for combinational therapy in TNBC patients.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"54-73"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095216","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":"Therapy resistance in prostate cancer: mechanism, signaling and reversal strategies.","authors":"Neha Thakur, Pallavi Singh, Aditi Bagri, Saumya Srivastava, Vinay Dwivedi, Asha Singh, Sunil Kumar Jaiswal, Sunny Dholpuria","doi":"10.37349/etat.2024.00266","DOIUrl":"10.37349/etat.2024.00266","url":null,"abstract":"<p><p>Prostate cancer (PC) depicts a major health challenge all over the globe due to its complexities in the treatment and diverse clinical trajectories. Even in the advances in the modern treatment strategies, the spectrum of resistance to the therapies continues to be a significant challenge. This review comprehensively examines the underlying mechanisms of the therapy resistance occurred in PC, focusing on both the tumor microenvironment and the signaling pathways implicated in the resistance. Tumor microenvironment comprises of stromal and epithelial cells, which influences tumor growth, response to therapy and progression. Mechanisms such as microenvironmental epithelial-mesenchymal transition (EMT), anoikis suppression and stimulation of angiogenesis results in therapy resistance. Moreover, dysregulation of signaling pathways including androgen receptor (AR), mammalian target of rapamycin/phosphoinositide 3 kinase/AKT (mTOR/PI3K/AKT), DNA damage repair and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways drive therapy resistance by promoting tumor survival and proliferation. Understanding these molecular pathways is important for developing targeted therapeutic interventions which overcomes resistance. In conclusion, a complete grasp of mechanisms and pathways underlying medication resistance in PC is important for the development of individualized treatment plans and enhancements of clinical outcomes. By studying and understanding the complex mechanisms of signaling pathways and microenvironmental factors contributing to therapy resistance, this study focuses and aims to guide the development of innovative therapeutic approaches to effectively overcome the PC progression and improve the survival rate of patients.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 5","pages":"1110-1134"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333760","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":"Exploring the therapeutic potential of lipid-based nanoparticles in the management of oral squamous cell carcinoma.","authors":"Anis Ahmad Chaudhary, Mohammad Fareed, Salah-Ud-Din Khan, Lina M Alneghery, Mohammed Aslam, Arockia Alex, Md Rizwanullah","doi":"10.37349/etat.2024.00272","DOIUrl":"10.37349/etat.2024.00272","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a highly malignant and invasive tumor with significant mortality and morbidity. Current treatment modalities such as surgery, radiotherapy, and chemotherapy encounter significant limitations, such as poor targeting, systemic toxicity, and drug resistance. There is an urgent need for novel therapeutic strategies that offer targeted delivery, enhanced efficacy, and reduced side effects. The advent of lipid-based nanoparticles (LNPs) offers a promising tool for OSCC therapy, potentially overcoming the limitations of current therapeutic approaches. LNPs are composed of biodegradable and biocompatible lipids, which minimize the risk of toxicity and adverse effects. LNPs can encapsulate hydrophobic drugs, improving their solubility and stability in the biological environment, thereby enhancing their bioavailability. LNPs demonstrate significantly higher ability to encapsulate lipophilic drugs than other nanoparticle types. LNPs offer excellent storage stability, minimal drug leakage, and controlled drug release, making them highly effective nanoplatforms for the delivery of chemotherapeutic agents. Additionally, LNPs can be modified by complexing them with specific target ligands on their surface. This surface modification allows the active targeting of LNPs to the tumors in addition to the passive targeting mechanism. Furthermore, the PEGylation of LNPs improves their hydrophilicity and enhances their biological half-life by reducing clearance by the reticuloendothelial system. This review aims to discuss current treatment approaches and their limitations, as well as recent advancements in LNPs for better management of OSCC.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 6","pages":"1223-1246"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514107","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":"A case of immunotherapy-induced thyroiditis.","authors":"George Pears, Abhishek Mahajan, Anna Olsson-Brown, Joseph Sacco","doi":"10.37349/etat.2024.00214","DOIUrl":"10.37349/etat.2024.00214","url":null,"abstract":"<p><p>Immunotherapy treatments for cancer are known to cause adverse thyroid events which present a diagnostic challenge to clinicians and radiologists. This case report highlights the importance of a high clinical index of suspicion and careful assessment of the thyroid on serial imaging studies to make the diagnosis. The case involves a 65-year-old male with malignant melanoma who was started on immunotherapy as part of a clinical trial. He developed thyroid dysfunction followed by an attack of acute neck pain. Ultrasound of his thyroid was performed which showed significant atrophy. A review of previous imaging was undertaken which confirmed the patient had suffered from thyroiditis and subsequent atrophy. Following this, the diagnosis of immunotherapy-induced thyroid dysfunction was made. Thyroxine supplementation and steroid dose were then adjusted causing his thyroid function and symptoms to improve. Immunotherapy agents for cancers are becoming more and more common. As the case report shows, physicians and radiologists will need to be vigilant to diagnose and treat any adverse events.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"225-231"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095586","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":"Response to trametinib, hydroxychloroquine, and bevacizumab in a young woman with <i>NRAS</i>-mutated metastatic intrahepatic cholangiocarcinoma: a case report.","authors":"Aram A Musaelyan, Ekaterina M Anokhina, Alina I Turdubaeva, Natalia V Mitiushkina, Anastasia N Ershova, Anna D Shestakova, Aigul R Venina, Evgeny N Imyanitov, Sergey V Orlov","doi":"10.37349/etat.2024.00246","DOIUrl":"10.37349/etat.2024.00246","url":null,"abstract":"<p><p>Systemic chemotherapy is the main treatment option for patients with advanced intrahepatic cholangiocarcinoma (iCCA), however, its efficacy is limited. Herein, we report a young patient with <i>NRAS</i>-mutated chemoresistant metastatic iCCA, who received second-line therapy with a combination of trametinib (MEK1/2 inhibitor), hydroxychloroquine (autophagy inhibitor), and bevacizumab (angiogenesis inhibitor). A significant response was achieved during therapy, resulting in a 25% decrease in the size of tumor lesions after 2 months of treatment and an improvement in the patient's condition. The duration of this response was 4 months, but the patient died 10 months after the initiation of this triple therapy. This case report and the analysis of other available studies warrant further investigations on combined MEK and autophagy inhibition in <i>RAS</i>-mutated tumors.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"780-788"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536131","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}