{"title":"Enhancing detection and monitoring of circulating tumor cells: Integrative approaches in liquid biopsy advances","authors":"Thanmayi Velpula, Viswanath Buddolla","doi":"10.1016/j.jlb.2025.100297","DOIUrl":"10.1016/j.jlb.2025.100297","url":null,"abstract":"<div><div>Liquid biopsy offers a minimally invasive method for detecting and monitoring cancer, with key biomarkers including circulating tumor cells (CTCs), cell-free DNA (cfDNA), and extracellular vesicles (EVs). Among these, CTCs provide dynamic insights into tumor heterogeneity, metastatic potential, and therapeutic resistance through molecular profiling and single-cell analysis. This review examines recent advancements in technologies such as microfluidics, nanotechnology, and next-generation sequencing (NGS), which have improved the accuracy and clinical use of CTC detection. A comparative analysis of liquid biopsy techniques highlights the strengths and limitations of key platforms, including NGS, digital PCR (ddPCR), and quantitative PCR (qPCR), providing insights into diagnostic accuracy and clinical significance. Combining genomic, transcriptomic, and proteomic analyses with artificial intelligence (AI) tools has enhanced tumor profiling and supports personalized treatment decisions in precision oncology. Despite notable progress, issues like assay standardization, sample variability, regulatory complexity, and data integration still limit widespread clinical use. Future directions emphasize interdisciplinary innovation, clinical validation, and robust bioinformatics frameworks to facilitate the seamless incorporation of CTC-based liquid biopsy into standard oncology practice. Overcoming these challenges may allow liquid biopsy to become a standard tool for early cancer detection, ongoing monitoring, and individualized treatment.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"8 ","pages":"Article 100297"},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898771","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}
Annunziata Gaetana Cicatiello , Michele Musone , Silvestro Imperatore , Carlo Giulioni , Roberto La Rocca , Angelo Cafarelli , Francesco Del Giudice , Monica Dentice , Felice Crocetto
{"title":"Circulating miRNAs in genitourinary cancer: pioneering advances in early detection and diagnosis","authors":"Annunziata Gaetana Cicatiello , Michele Musone , Silvestro Imperatore , Carlo Giulioni , Roberto La Rocca , Angelo Cafarelli , Francesco Del Giudice , Monica Dentice , Felice Crocetto","doi":"10.1016/j.jlb.2025.100296","DOIUrl":"10.1016/j.jlb.2025.100296","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are noncoding, single-stranded RNAs molecules modulating gene expression thanks to their ability to bind mRNAs. Indeed, they regulate key processes for the proper functioning of the organism and affect the course of human pathologies. Altered expression of individual miRNAs has been shown in most human cancers, endowed with oncogenic or suppressor potential. Additionally, miRNAs have shown a promising potential as cancer markers. Not only miRNAs are present in various body fluids, such as serum and plasma, they also have high biological stability of miRNAs that in turn facilitates their detection. For these reasons, the use of miRNAs detection as non-invasive prognostic and predictive biomarkers in cancer provides new perspectives and strategies for personalized medicine and cancer therapy.</div><div>This review summarizes the current knowledge supporting the utility of miRNAs as novel early diagnostic and prognostic tool, with a special focus on the effectiveness of miRNAs of the liquid biopsies in the diagnosis of urogenital cancers. In conclusion, we rightly state that circulating miRNAs and therefore liquid biopsy have the potential to revolutionize the diagnosis, monitoring and even treatment of urological tumors, entering clinical practice as a more accurate, less invasive and more suitable diagnostic tool for patient follow-up compared to current methodologies. With the progress of scientific research and the implementation of advanced technologies that also exploit artificial intelligence, the future of oncological diagnosis, especially for urological tumors, could be increasingly oriented towards less invasive approaches and based on precision medicine, tailored for the specific patient.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"8 ","pages":"Article 100296"},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887424","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":"Circulating tumor DNA monitoring in advanced mutated melanoma (LIQUID-MEL)","authors":"Martines Gianmarco , Palazzi Carolina , Monica Gregorio , Verzè Michela , Pluchino Monica , Giudice Giulia Claire , Maffezzoli Michele , Mazzaschi Giulia , Manuguerra Roberta , Azzoni Cinzia , Bottarelli Lorena , Tiseo Marcello , Perrone Fabiana , Minari Roberta","doi":"10.1016/j.jlb.2025.100295","DOIUrl":"10.1016/j.jlb.2025.100295","url":null,"abstract":"<div><h3>Introduction</h3><div>Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic melanoma, but a percentage of patients did not show benefit. Circulating tumor DNA (ctDNA) has emerged as a potential non-invasive tool for monitoring disease evolution and treatment response. The present study aimed to evaluate the clinical utility of ctDNA dynamics in patients with metastatic melanoma receiving ICIs, while exploring its role in the oncological course.</div></div><div><h3>Materials and methods</h3><div>The LIQUID-MEL study is a prospective, single-centre pilot study including patients with <em>BRAF/NRAS</em>-mutant metastatic melanoma. ctDNA was quantified using digital droplet PCR (ddPCR) at four different time points. Uni- and multivariable Cox regression models were used to assess the correlation between shedding and progression-free survival (PFS), and overall survival (OS).</div></div><div><h3>Results</h3><div>Overall, 23 patients were included. At baseline, ctDNA was detectable in 5/23 (21.7 %) cases. Baseline ctDNA shedding was associated with shorter PFS (3.88 months <em>vs</em>. 0.69 months, <em>p=</em>0.012). A strong numerical trend was observed also in OS (12.66 months <em>vs</em>. 2.53 months, <em>p=</em>0.287). Shedding at baseline did not demonstrate independent prognostic or predictive value in the uni- and multivariable analysis. The longitudinal analysis revealed intriguing patterns of ctDNA shedding in individual patients.</div></div><div><h3>Conclusion</h3><div>ctDNA detectability and its dynamic changes during treatment may have potential clinical utility in patients with metastatic melanoma, offering a valuable non-invasive tool for monitoring disease and treatment response. The small sample size limited the statistical power of the analysis. Further studies with larger cohorts are needed to validate its role in routine clinical practice.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"8 ","pages":"Article 100295"},"PeriodicalIF":0.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828398","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":"The growing field of liquid biopsy and its Snowball effect on reshaping cancer management","authors":"Roberto Borea , Carolina Reduzzi","doi":"10.1016/j.jlb.2025.100293","DOIUrl":"10.1016/j.jlb.2025.100293","url":null,"abstract":"<div><div>Liquid biopsy (LB) has emerged as a transformative tool in oncology, providing a minimally invasive approach for tumor detection, molecular characterization, and real-time treatment monitoring. By analyzing circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), extracellular vesicles (EVs), and microRNA (miRNA), LB enables comprehensive tumor profiling without the need for traditional tissue biopsies. Over the past decade, research in this field has expanded exponentially, leading to the integration of LB into clinical practice for specific cancer types, including lung and breast cancer. In 2024, the Journal of Liquid Biopsy (JLB) published innovative studies exploring the latest advancements in LB technologies, biomarkers, and their applications for cancer detection, minimal residual disease (MRD) monitoring, and therapy response assessment. This review synthesizes recent findings on the role of LB in cancer treatment and monitoring across different biomarkers, with a particular focus on newly published studies and their context within translational research. Additionally, it highlights emerging techniques such as fragmentomics, artificial intelligence, and multiomics, paving the way for more precise, personalized treatment decisions. Despite these advancements, challenges remain in standardizing methodologies, optimizing clinical validation, and integrating LB into routine oncological workflows. This mini-review highlights the evolving landscape of LB research and its potential to revolutionize cancer diagnosis, treatment monitoring, and therapeutic decision-making, ushering in a new era of precision oncology.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"8 ","pages":"Article 100293"},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791973","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":"Smoking induces different expression of miR-320b and miR-10b-5p in plasma extracellular vesicles of non-small cell lung cancer patients","authors":"Markus Yovian Widjaja Lomanto , Septelia Inawati Wanandi , Achmad Mulawarman Jayusman , Donny Lukmanto , Yuniar Harris Prayitno , Noorwati Sutandyo","doi":"10.1016/j.jlb.2025.100291","DOIUrl":"10.1016/j.jlb.2025.100291","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies found that cigarette smoke (CS) exposure could induce NSCLC malignancy and miRNA dysregulation. Yet, the association of CS-induced miRNA dysregulation and NSCLC malignancy has not been clearly understood. This study aimed to evaluate the effect of CS exposure in smokers on the expression of miR-10b-5p and miR-320b in extracellular vesicles (EVs) from NSCLC patients.</div></div><div><h3>Material and methods</h3><div>Bioinformatic analysis was conducted to validate miRNA candidates. Blood and tissue samples were collected from NSCLC patients (n = 21) with smoking and non-smoking history. EVs were isolated from plasma and miRNAs were extracted from the isolated EVs. The miRNAs relative expression was analyzed and compared.</div></div><div><h3>Results</h3><div>In silico analysis identified miR-320b and miR-10b-5p as potential biomarkers for diagnosing NSCLC in smokers. Experimental analysis revealed differential expression of EVs-associated miRNAs in NSCLC patients with smoking and non-smoking histories. EVs-associated miR-10b-5p was significantly overexpressed in smoker NSCLC patients (p = 0.000), while miR-320b expression was significantly lower in this group (p = 0.018). Additionally, smoking intensity influenced miRNA expression, with higher smoking intensity correlating with increased miR-10b-5p expression and decreased miR-320b expression. ROC analysis demonstrated that EVs were a superior source of miRNAs compared to plasma for NSCLC diagnostics. miR-10b-5p and miR-320b in EVs showed higher diagnostic performance (AUC 0.878; 0.739) compared to plasma (AUC 0.628; 0.559).</div></div><div><h3>Conclusion</h3><div>CS exposure induces different expression of miR-10b-5p and miR-320b in EVs of NSCLC patients with smoking history. EV-related miR-10b-5p and miR-320b showed potential to be utilized as prognostic biomarker for smokers NSCLC patients.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"8 ","pages":"Article 100291"},"PeriodicalIF":0.0,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687872","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}
Huei-Ying Li , Chun-Chuan Chang , Yu-Hsuan Yang , Chi-Yuan Yao , Jason Chia-Hsun Hsieh , Shao-Hsuan Chang
{"title":"The prospects and limitations of liquid biopsy utilization for clinical practice in Taiwan","authors":"Huei-Ying Li , Chun-Chuan Chang , Yu-Hsuan Yang , Chi-Yuan Yao , Jason Chia-Hsun Hsieh , Shao-Hsuan Chang","doi":"10.1016/j.jlb.2025.100290","DOIUrl":"10.1016/j.jlb.2025.100290","url":null,"abstract":"<div><h3>Objective</h3><div>Liquid biopsy is a promising, non-invasive diagnostic tool for cancer, offering rapid and cost-effective genomic analysis. It provides a less invasive alternative to traditional tissue biopsies, with potential benefits in monitoring disease progression and detecting minimal residual disease (MRD). However, its clinical integration faces challenges, including utility assessment and workflow adaptation. This study evaluates the value of liquid biopsy in Taiwan from a clinical physician's perspective.</div></div><div><h3>Methods</h3><div>A survey was conducted with 16 physicians specializing in thoracic medicine and hematologic oncology. Participants responded to a 5-point Likert scale to evaluate the timing of liquid biopsy adoption, willingness to incorporate it into clinical practice, and agreement on its role in managing specific clinical conditions.</div></div><div><h3>Results</h3><div>Forty percent of physicians preferred liquid biopsy when tissue samples were unavailable. The inclusion of liquid biopsy under National Health Insurance (NHI) was a key factor in its adoption. Hematologic oncologists showed a stronger preference for liquid biopsy, particularly for MRD testing, compared to their counterparts in thoracic medicine (hematologic oncology vs. thoracic medicine: 4.2 ± 0.83 vs. 3.1 ± 0.60; p value = 0.01). Younger physicians valued turnaround time, while senior physicians prioritized test brand, with a focus on report speed.</div></div><div><h3>Conclusion</h3><div>Physicians are generally less inclined to replace tissue biopsies with liquid biopsy, but hematologic oncologists show more flexibility. Test brand plays a role in physician decision-making, and the inclusion of liquid biopsy under NHI coverage is vital for its broader adoption in Taiwan.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"7 ","pages":"Article 100290"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619510","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":"Clonal hematopoiesis: A challenge or opportunity in liquid biopsy?","authors":"Veronica Aran","doi":"10.1016/j.jlb.2025.100292","DOIUrl":"10.1016/j.jlb.2025.100292","url":null,"abstract":"","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"7 ","pages":"Article 100292"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687650","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}
Jessica Gasparello , Carlotta Ceccon , Valentina Angerilli , Tatiane Comunello , Marianna Sabbadin , Felipe D'Almeida Costa , Antonio Antico , Claudio Luchini , Paola Parente , Francesca Bergamo , Sara Lonardi , Matteo Fassan
{"title":"Liquid biopsy in gastric cancer: A snapshot of the current state of the art","authors":"Jessica Gasparello , Carlotta Ceccon , Valentina Angerilli , Tatiane Comunello , Marianna Sabbadin , Felipe D'Almeida Costa , Antonio Antico , Claudio Luchini , Paola Parente , Francesca Bergamo , Sara Lonardi , Matteo Fassan","doi":"10.1016/j.jlb.2025.100288","DOIUrl":"10.1016/j.jlb.2025.100288","url":null,"abstract":"<div><div>Circulating tumor DNA (ctDNA) is nowadays considered a robust source to search for druggable tumoral genetic alterations, and in some specific settings liquid biopsy (LB) is already part of the diagnostics scenario and it has successfully implemented in the everyday practice. Three strengths make LB an extraordinary tool: i) to represent the complex molecular mosaicism that characterizes spatially heterogeneous malignancies; ii) to monitor in real-time the tumoral molecular landscape (i.e. to depict the longitudinal/temporal tumor evolution); iii) to ensure molecular profiling even in those cases in which tissue sampling is not feasible or not adequate. This review provides a snapshot of the current state of the art concerning ctDNA assay utility in gastric cancer (GC), testing its robustness as marker and seeking to understand the reasons for the delay in its application in clinical practice.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"7 ","pages":"Article 100288"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143095520","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":"Potential applications of gene expression profiles obtained from circulating extracellular vesicles in breast cancer","authors":"Aritra Gupta , Siddharth Bhardwaj , Sayan Ghorai , Rosina Ahmed , Sanjit Agarwal , Geetashree Mukherjee , Kartiki V. Desai","doi":"10.1016/j.jlb.2025.100287","DOIUrl":"10.1016/j.jlb.2025.100287","url":null,"abstract":"<div><h3>Background</h3><div>Liquid biopsy-based biomarkers offer several advantages since they are minimally invasive, can be useful in longitudinal monitoring of the disease and have higher patient compliance. We describe a protocol using minimal volumes of archival and prospective serum/plasma samples to define the RNA contents of EVs and discuss its benefits and limitations.</div></div><div><h3>Methods</h3><div>RNA-seq analysis of matched tumor biopsy, circulating EVs from breast cancer patients (EV-C, n = 26) and healthy donors (EV-H, n = 4) was performed and differentially expressed genes were validated by RT-PCR in a separate series of samples (EV-C, n = 32 and EV-H, n = 22). A total of 84 samples were studied.</div></div><div><h3>Results</h3><div>RNA-seq data from 500 μl serum samples yielded more than 17000 genes, of which 320 were DEGs (adjusted p value ≤ 0.05) between EV-C and EV-H samples. Pathways for Myc V1, reactive oxygen species, angiogenesis, allograft rejection and Interferon regulated genes were over-represented in EV-C samples. Computational deconvolution algorithms for cell signatures identified immune cells such as Th1 and memory T-cells, endothelial cells, and osteoblasts from the stromal compartment as significant. Top 6 genes were validated by qRT-PCR in all samples (n = 84) and they consistently and correctly classified cancer and healthy groups. An independent set of 374 and 640 DEGs could segregate ER positive/ER negative and non-metastatic versus metastatic samples, respectively. EVs from metastatic samples had higher variability in gene expression patterns whereas those from non-metastatic samples showed a better correlation.</div></div><div><h3>Conclusion</h3><div>By using low serum amounts successfully for EV transcriptomics, we demonstrate that a minimally invasive technique could be converted to a microinvasive format. These data lay the foundation for EV RNA based biomarker discovery for segregating breast cancers.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"7 ","pages":"Article 100287"},"PeriodicalIF":0.0,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143157404","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":"PADI4 expression in baseline circulating tumour cells acts as a prognostic biomarker in oral squamous cell carcinoma","authors":"Anshika Chauhan , Geeta S. Boora , Arindam Maitra , Rijuneeta Gupta , Jaimanti Bakshi , Sushmita Ghoshal , Arnab Pal","doi":"10.1016/j.jlb.2025.100289","DOIUrl":"10.1016/j.jlb.2025.100289","url":null,"abstract":"<div><div>Oral Squamous Cell Carcinoma (OSCC), one of the most prevalent cancers in developing countries. It is associated with poor prognosis due to relapse in a significant number of patients. Circulating tumour cells (CTCs) are precursors for metastasis and thought to be key players in early relapse in various cancers including OSCC. Though CTC enumeration has been associated with disease outcome, in-depth molecular analysis of CTCs remained minimal as the techniques for CTC isolation and analysis are challenging. While exploring gene expression in CTCs, we performed whole transcriptome analysis of paired primary tumour and CTCs isolated from Oral Squamous Cell Carcinoma (OSCC) patients. Various genes were found to be differentially expressed in CTCs. We found PADI4 gene was significantly upregulated in CTCs. PADI4 gene encodes for an enzyme that converts arginine to citrulline.</div><div>PADI4 expression in primary tumours was previously observed to be associated with metastasis. Here, we are reporting PADI4 expression for the first time in CTCs and its association with relapse. Interestingly in our data, PADI4 expression was more seen in CTCs with EMT (epithelial to mesenchymal transition)-phenotype than with CTCs only epithelial-phenotype. In conclusion, this is the first study presenting the potential prognostic utility of PADI4 expression in CTCs isolated from OSCC patients.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"7 ","pages":"Article 100289"},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143095521","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}