Biomarker Insights最新文献

{"title":"A Comparison of Death Domain-Associated Protein 6 in Different Endometrial Carcinomas Histotypes","authors":"C. Jin, Sean M. Hacking, Miglena K. Komforti, M. Nasim","doi":"10.1177/1177271919864892","DOIUrl":"https://doi.org/10.1177/1177271919864892","url":null,"abstract":"Background: Death domain-associated protein 6 (DAXX) is involved in regulating apoptosis via subcellular localization. The presence of DAXX point mutations correlates well with loss of nuclear expression on immunohistochemistry (IHC). In this study, we sought to determine (1) whether DAXX expression pattern is the same across different uterine carcinoma subtypes, and (2) which uterine carcinomas show loss of nuclear DAXX IHC. Design: We studied 65 uterine carcinomas of the following histologic types: 30 endometrioid (12 FIGO [The International Federation of Gynecology and Obstetrics] grade 1, 12 FIGO grade 2, and 6 FIGO grade 3), 8 serous, 14 clear cell, and 13 undifferentiated/dedifferentiated type (UEC/DDEC). Nuclear DAXX IHC was assessed in each tumor and was graded semi-quantitatively as follows: 0% to 50%, 50% to 75%, and greater than 75% of lesional cells react. Results: A total of 61% (25/41) of high-grade carcinomas (FIGO grade 3, serous, clear cell, and UEC/DDEC]) showed retained DAXX nuclear staining in >75% of lesional cells, compared with only 4.2% (1/24) of the low-grade carcinomas (FIGO grades 1 and 2) (P = .0001), where DAXX expression was cytoplasmic. In addition, in the 11 DDEC cases, all the differentiated components showed loss of nuclear DAXX compared with the undifferentiated components which retained nuclear DAXX expression. Conclusions: We demonstrate that loss of nuclear DAXX is present in low-grade endometrial carcinomas and the differentiated components in UEC/DDEC, but not in high-grade ones, suggesting DAXX’s role in tumor progression and its potential as a therapeutic target in high-grade endometrial carcinomas.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271919864892","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46582065","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":"Peripheral Biomarker for Vascular Disorders.","authors":"Kaneez Fatima Shad,&nbsp;Nazar Luqman,&nbsp;Ann M Simpson,&nbsp;Sara Lal","doi":"10.1177/1177271918812467","DOIUrl":"https://doi.org/10.1177/1177271918812467","url":null,"abstract":"<p><p>Atherosclerosis is the underlying cause of most myocardial infarction (MI) and ischaemic stroke episodes. An early sign of atherosclerosis is hypertrophy of the arterial wall. It is known that increased intima media thickness (IMT) is a non-invasive marker of arterial wall alteration, which can easily be assessed in the carotid arteries by high-resolution B-mode ultrasound. Similarly, the other key element of MI and ischaemic strokes is the N-methyl-D-aspartate (NMDA) receptor which is an ionotropic glutamate receptor that mediates the vast majority of excitatory neurotransmission in the brain. NMDA activation requires the binding of both glutamate and a coagonist like D-serine to its glycine site. A special enzyme, serine racemase (SR), is required for the conversion of L-serine into D-serine, and alterations in SR activities lead to a variety of physiological and pathological conditions ranging from synaptic plasticity to ischemia, MI, and stroke. The amount of D-serine available for the activation of glutamatergic signalling is largely determined by SR and we have developed ways to estimate its levels in human blood samples and correlate it with the IMT. This research based short communication describes our pilot study, which clearly suggests that there is a direct relationship between the SR, D-serine, and IMT. In this article, we will discuss whether the activity of SR can determine the future consequences resulting from vascular pathologies such as MI and stroke.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"13 ","pages":"1177271918812467"},"PeriodicalIF":3.8,"publicationDate":"2018-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271918812467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36768297","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":"Integration of Biomarkers Into a Signature Profile of Persistent Traumatic Brain Injury Involving Autoimmune Processes Following Water Hammer Injury From Repetitive Head Impacts.","authors":"Steven Kornguth, Neal Rutledge","doi":"10.1177/1177271918808216","DOIUrl":"10.1177/1177271918808216","url":null,"abstract":"<p><strong>Objectives: </strong>To assemble an algorithm that will describe a \"Signature\" predictive of an individual's vulnerability to persistent traumatic brain injury (TBI).</p><p><strong>Subjects and methods: </strong>Studies of athletes and warriors who are subjected to repeated head impacts with rapid acceleration/deceleration forces are used to assist in the diagnosis and management of TBI-affected individuals. Data from multiple areas, including clinical, anatomical, magnetic resonance imaging, cognitive function, and biochemical analyses, are integrated to provide a Signature of persistent TBI.</p><p><strong>Results: </strong>Studies to date indicate that susceptibility to TBI results from an interaction between host genetic and structural vulnerability factors and force and torque of impact on the head and torso. The host factors include molecular markers affecting immune and inflammatory responses to stress/insult as well as anatomical features such as the degree of transcortical fiber projections and vascular malformations. The host response to forceful impact includes the release of intracellular neural proteins and nucleic acids into the cerebrospinal fluid and vascular compartment as well as mobilization of cytokines and macrophages into the central nervous system with subsequent activation of microglia and inflammatory responses including autoimmune processes. Maximum impact to the base of the sulci via a \"water hammer effect\" is consistent with the localization of microvascular and inflammatory responses in the affected brain region.</p><p><strong>Conclusions: </strong>An assessment of an individuals' predisposition to persistent TBI with delayed cognitive deficits and behavioral changes requires an understanding of host vulnerability (genetic factors and brain structure) and external stressors (force and torque of impact as well as repetitive head injury and time interval between impacts). An algorithm that has utility in predicting vulnerability to TBI will include qualitative and quantitative measures of the host factors weighted against post impact markers of neural injury. Implementation of the resulting \"Signature\" of vulnerability at early stages of injury will help inform athletes and warriors, along with commanders and management, of the risk/benefit approaches that will markedly diminish health care costs to the nation and suffering to this population. This report attempts to define a strategy to create such an algorithm.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"13 ","pages":"1177271918808216"},"PeriodicalIF":3.8,"publicationDate":"2018-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/68/f7/10.1177_1177271918808216.PMC6207974.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36697326","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":"MicroRNAs as Biomarkers of B-cell Lymphoma.","authors":"Carla Solé,&nbsp;Esther Arnaiz,&nbsp;Charles H Lawrie","doi":"10.1177/1177271918806840","DOIUrl":"https://doi.org/10.1177/1177271918806840","url":null,"abstract":"<p><p>B-cell lymphomas represent a diverse group of neoplasms classified primarily by histopatholgy and are often challenging to accurately diagnose. Despite having been recognized less than 20 years ago, microRNAs (miRNAs) have emerged as one of the most promising class of cancer molecular biomarkers and are particularly attractive as they can be readily detected in formalin-fixed paraffin-embedded biopsy material and biological fluids such as blood. Many of the identified B-cell lymphoma miRNA biomarkers also play crucial regulatory roles in normal B-cell development. Below we consider the identity, function, and biomarker potential of miRNAs in B-cell lymphoma and most importantly the barriers that remain to be overcome if they are really to become part of routine clinical practice.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"13 ","pages":"1177271918806840"},"PeriodicalIF":3.8,"publicationDate":"2018-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271918806840","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36651004","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":"Identifying Reliable Diagnostic/Predictive Biomarkers for Rheumatoid Arthritis.","authors":"Leroy Shervington,&nbsp;Ashish Darekar,&nbsp;Murassa Shaikh,&nbsp;Roshini Mathews,&nbsp;Amal Shervington","doi":"10.1177/1177271918801005","DOIUrl":"https://doi.org/10.1177/1177271918801005","url":null,"abstract":"<p><strong>Introduction and objective: </strong>Elevated C-reactive protein is usually a good indicator of rheumatoid arthritis (RA); however, there are limitations that compromise its specificity and therefore there is an urgent need to identify more reliable diagnostic biomarkers to detect early stages of RA. In addition, identifying the correct therapeutic biomarker for the treatment of RA using methotrexate (MTX) would greatly increase the benefits experienced by the patients.</p><p><strong>Materials and methods: </strong>Primary normal synoviocytes human fibroblast-like synoviocytes (HFLS) and its phenotype rheumatic HFLS-RA cells were chosen for this study. The HFLS-RA-untreated and MTX-treated cells were subjected to microarray analysis.</p><p><strong>Results: </strong>Microarray data identified 74 differentially expressed genes. These genes were mapped against an RA inflammatory pathway, shortlisting 10 candidate genes. Gene expression profiling of the 10 genes were studied. Fold change (FC) was calculated to determine the differential expression of the samples.</p><p><strong>Discussion: </strong>The transcription profiles of the 10 candidate genes were highly induced in HFLS-RA cells compared with HFLS cells. However, on treating the HFLS-RA cells with MTX, the transcription profiles of these genes were highly downregulated. The most significant expression FC difference between HFLS and HFLS-RA (treated and untreated) was observed with <i>HSPA6, MMP1, MMP13</i>, and <i>TNFSF10</i> genes.</p><p><strong>Conclusions: </strong>The data from this study suggest the use of <i>HSPA6, MMP1, MMP13</i>, and <i>TNFSF10</i> gene expression profiles as potential diagnostic biomarkers. In addition, these gene profiles can help in predicting the therapeutic efficacy of MTX.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"13 ","pages":"1177271918801005"},"PeriodicalIF":3.8,"publicationDate":"2018-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271918801005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36531647","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":"Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma.","authors":"Maria Åström,&nbsp;Walid Tajeddinn,&nbsp;Mats G Karlsson,&nbsp;Olle Linder,&nbsp;Jan Palmblad,&nbsp;Per Lindblad","doi":"10.1177/1177271918792246","DOIUrl":"https://doi.org/10.1177/1177271918792246","url":null,"abstract":"<p><strong>Background: </strong>Various paraneoplastic syndromes are encountered in renal cell carcinomas. This case report illustrates that a paraneoplastic leukemoid reaction may precede the diagnosis of renal cell carcinoma and be explained by cytokine production from the cancer cells.</p><p><strong>Case presentations: </strong>A 64-year-old man was referred for hematology workup due to pronounced leukocytosis. While being evaluated for a possible hematologic malignancy as the cause, he was found to have a metastasized renal cell carcinoma, and hyperleukocytosis was classified as a leukemoid reaction. A multiplex panel for measurement of 25 serum cytokines/chemokines showed highly elevated levels of granulocyte colony-stimulating factor (G-CSF) and CXCL8 (C-X-C-motif chemokine ligand 8, previously known as interleukin [IL]-8). By immunohistochemistry it was shown that the renal carcinoma cells expressed both these cytokines. Two additional, consecutive patients with renal cell carcinoma with paraneoplastic leukocytosis also showed elevated serum levels of CXCL8, but not of G-CSF. Nonparametric statistical evaluation showed significantly higher serum concentrations of CXCL8, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor, but lower interferon gamma (IFN-γ) and IL-1α, for the 3 renal cell carcinoma cases compared with healthy blood donors.</p><p><strong>Conclusions: </strong>In suspected paraneoplastic leukocytosis, multiplex serum cytokine analyses may facilitate diagnosis and provide an understanding of the mechanisms for the reaction. In the index patient, combined G-CSF and CXCL8 protein expression by renal carcinoma cells was uniquely documented. A rapidly fatal course was detected in all 3 cases, congruent with the concept that autocrine/paracrine growth signaling in renal carcinoma cells may induce an aggressive tumor phenotype. Immune profiling studies could improve our understanding for possible targets when choosing therapies for patients with metastatic renal cell carcinoma.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"13 ","pages":"1177271918792246"},"PeriodicalIF":3.8,"publicationDate":"2018-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271918792246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36429119","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":"Is Procalcitonin Useful in Pediatric Critical Care Patients?","authors":"Sara Bobillo-Perez, Javier Rodríguez-Fanjul, Iolanda Jordan Garcia","doi":"10.1177/1177271918792244","DOIUrl":"10.1177/1177271918792244","url":null,"abstract":"<p><p>This review examines the use of procalcitonin in different clinical situations in the pediatric patient, with special emphasis on those requiring intensive care. We review the latest articles on its potency as a biomarker in both infectious processes at diagnosis and on the response to treatment.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"13 ","pages":"1177271918792244"},"PeriodicalIF":3.8,"publicationDate":"2018-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c0/be/10.1177_1177271918792244.PMC6081751.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36382303","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":"Development of a Novel Proteomic Risk-Classifier for Prognostication of Patients With Early-Stage Hormone Receptor-Positive Breast Cancer.","authors":"Charusheila Ramkumar,&nbsp;Ljubomir Buturovic,&nbsp;Sukriti Malpani,&nbsp;Arun Kumar Attuluri,&nbsp;Chetana Basavaraj,&nbsp;Chandra Prakash,&nbsp;Lekshmi Madhav,&nbsp;Dinesh Chandra Doval,&nbsp;Anurag Mehta,&nbsp;Manjiri M Bakre","doi":"10.1177/1177271918789100","DOIUrl":"https://doi.org/10.1177/1177271918789100","url":null,"abstract":"<p><p>Use of proteomic strategies to identify a risk classifier that estimates probability of distant recurrence in early-stage hormone receptor (HR)-positive breast cancer is relevant to physiological cellular function and therefore to intrinsic tumor biology. We used a 298-sample retrospective training set to develop an immunohistochemistry-based novel risk classifier called CanAssist-Breast (CAB) which combines 5 prognostically relevant biomarkers and 3 clinico-pathological parameters to arrive at probability of distant recurrence within 5 years from diagnosis. Five selected biomarkers, namely, CD44, ABCC4, ABCC11, N-cadherin, and pan-cadherin, were chosen based on their role in tumor metastasis. The chosen biomarkers represent the hallmarks of cancer and are distinct from other proliferation and gene expression-based prognostic signatures. The 3 clinico-pathological parameters integrated into the machine learning-based CAB algorithm are tumor size, tumor grade, and node status. These features are used to calculate a \"CAB risk score\" that classifies patients into low- or high-risk groups and predicts probability of distant recurrence in 5 years. Independent clinical validation of CAB in a retrospective study comprising 196 patients indicated that distant metastasis-free survival (DMFS) was significantly different in the 2 risk groups. The difference in DMFS between the low- and high-risk categories was 19% in the validation cohort (<i>P</i> = .0002). In multivariate analysis, CAB risk score was the most significant independent predictor of distant recurrence with a hazard ratio of 4.3 (<i>P</i> = .0003). CanAssist-Breast is a precise and unique machine learning-based proteomic risk-classifier that can assist in risk stratification of patients with early-stage HR+ breast cancer.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"13 ","pages":"1177271918789100"},"PeriodicalIF":3.8,"publicationDate":"2018-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271918789100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36374039","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":"Heart Rate Variability as a Biomarker for Predicting Stroke, Post-stroke Complications and Functionality.","authors":"Ty Lees,&nbsp;Fatima Shad-Kaneez,&nbsp;Ann M Simpson,&nbsp;Najah T Nassif,&nbsp;Yiguang Lin,&nbsp;Sara Lal","doi":"10.1177/1177271918786931","DOIUrl":"https://doi.org/10.1177/1177271918786931","url":null,"abstract":"<p><strong>Background: </strong>Heart rate variability (HRV) is a non-invasive measure of the function of the autonomic nervous system, and its dynamic nature may provide a means through which stroke and its associated complications may be predicted, monitored, and managed.</p><p><strong>Objective: </strong>The objective of this review is to identify and provide a critique on the most recent uses of HRV in stroke diagnosis/management and highlight areas that warrant further research.</p><p><strong>Methods: </strong>The MEDLINE, CINAHL, and OVID MEDLINE databases were canvassed using a systematic search strategy, for articles investigating the use of HRV in stroke diagnosis and management. Initial paper selections were based on title alone, and final paper inclusion was informed by a full-text critical appraisal.</p><p><strong>Results: </strong>The systematic search returned 98 records, of which 51 were unique. Following screening, 22 records were included in the final systematic review. The included papers provided some information regarding predicting incident stroke, which largely seems to be best predicted by time- and frequency-domain HRV parameters. Furthermore, post-stroke complications and functionality are similarly predicted by time- and frequency-domain parameters, as well as non-linear parameters in some instances.</p><p><strong>Conclusions: </strong>Current research provides good evidence that HRV parameters may have utility as a biomarker for stroke and for post-stroke complications and/or functionality. Future research would benefit from the integration of non-linear, and novel parameters, the hybridisation of HRV parameters, and the expansion of the utilisation of predictive regression and hazard modelling.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"13 ","pages":"1177271918786931"},"PeriodicalIF":3.8,"publicationDate":"2018-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271918786931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36338422","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":"Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases.","authors":"Hongjie Chen,&nbsp;Eileen M McGowan,&nbsp;Nina Ren,&nbsp;Sara Lal,&nbsp;Najah Nassif,&nbsp;Fatima Shad-Kaneez,&nbsp;Xianqin Qu,&nbsp;Yiguang Lin","doi":"10.1177/1177271918785130","DOIUrl":"https://doi.org/10.1177/1177271918785130","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) is the leading cause of death in the world and our approach to the control and management of CVD mortality is limited. Nattokinase (NK), the most active ingredient of natto, possesses a variety of favourable cardiovascular effects and the consumption of Natto has been linked to a reduction in CVD mortality. Recent research has demonstrated that NK has potent fibrinolytic activity, antihypertensive, anti-atherosclerotic, and lipid-lowering, antiplatelet, and neuroprotective effects. This review covers the major pharmacologic effects of NK with a focus on its clinical relevance to CVD. It outlines the advantages of NK and the outstanding issues pertaining to NK pharmacokinetics. Available evidence suggests that NK is a unique natural compound that possesses several key cardiovascular beneficial effects for patients with CVD and is therefore an ideal drug candidate for the prevention and treatment of CVD. Nattokinase is a promising alternative in the management of CVD.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"13 ","pages":"1177271918785130"},"PeriodicalIF":3.8,"publicationDate":"2018-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177271918785130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36315648","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}