Yurike Yuliana, Olivia M Tandrasasmita, Raymond R Tjandrawinata
{"title":"Anti-inflammatory Effect of Predimenol, A Bioactive Extract from <i>Phaleria macrocarpa</i>, through the Suppression of NF-κB and COX-2.","authors":"Yurike Yuliana, Olivia M Tandrasasmita, Raymond R Tjandrawinata","doi":"10.2174/2772270816666220119122259","DOIUrl":"10.2174/2772270816666220119122259","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is the response to the reaction of any type of bodily injury by elevating cellular metabolism and releasing soluble mediators. It is also a contributing factor of pain. Predimenol, which has previously been known as DLBS1442, is a bioactive extract from Phaleria macrocarpa (Scheff.) Boerl (Thymelaceae). It can be an alternative treatment for pain relief, especially for long-term use.</p><p><strong>Objective: </strong>The objective of this study is to evaluate the anti-inflammatory activities of predimenol through the evaluation of several parameters involved in the inflammatory pathway.</p><p><strong>Methods: </strong>Cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), and nuclear factor κB (NF-κB) were observed after 24 h exposure of predimenol (0-180 μg/mL) to lipopolysaccharides (LPS)-activated RAW 264.7 cell. The inflammatory markers were measured using nitric oxide (NO) assay and enzyme-linked immunosorbent assay (ELISA) for COX-2 inhibitor assay. The gene expressions of TNF-α, IL-1β, IL-2 and IL-6 were quantified using the polymerase chain reaction (PCR) method. Western blotting was applied to detect phosphorylated IκB kinase (IKK) protein to confirm the activation of NF-κB.</p><p><strong>Results: </strong>Our study showed a similar mechanism with most non-steroidal anti-inflammatory drugs (NSAIDs). Predimenol consistently downregulated the expression of iNOS and inhibited COX-2 activity. Moreover, predimenol significantly inhibited the LPS-induced production of NO, TNF-α, IL-1β, IL-2 and IL-6. Down-regulation of these markers was suggested due to the reduction of NF- κB transcription level and activation by predimenol.</p><p><strong>Conclusion: </strong>Predimenol exhibits anti-inflammatory activities through NF-kB inactivation-mediated COX-2 suppression, which may suggest that predimenol is a potential analgesic and anti-inflammatory agent.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":" ","pages":"99-107"},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39832739","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":"Natural Approach in Osteoarthritis Therapy.","authors":"Alice Grigore, Virginia Vulturescu","doi":"10.2174/2772270816666220331163707","DOIUrl":"https://doi.org/10.2174/2772270816666220331163707","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most common joint disease worldwide, and its rising prevalence is supported by factors such as obesity and sedentariness. At the molecular level, it is considered an inflammatory disease that leads to the destruction of articular cartilage. Effective therapy to end the degenerative process of arthritis remains elusive, and most therapeutic tools prevent the progress or alleviate the symptoms. By now, medicines for OA are available for oral, topical, or intra-articular (IA) therapy and include analgesics, nonsteroidal anti-inflammatory drugs, corticosteroids, and hyaluronic acid. Compared with conventional oral administration, IA therapy has multiple advantages in terms of bioavailability, efficacy, and toxicity. This review aims to study the underlying beneficial effects of herbal medicine in OA therapy and to open new research perspectives. Herbal medicine administered orally or topically exhibits pharmacological properties that could be relevant for their beneficial effect in OA, mainly anti-inflammatory and antioxidant effects. There are few studies regarding IA injections of plant extracts/ compounds and none related to any combination with agents already used in the clinic. Designing natural pharmaceutical formulations with increased bioavailability that are safe, lack side effects, and are specifically tested, would be a plus for research on medicinal plants and a novelty for the clinic.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":"16 1","pages":"26-31"},"PeriodicalIF":0.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10339944","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}
Atul R Chopade, Vijay R Salunkhe, Pramod A Patil, Madhav R Burade, Prakash M Somade, Suraj N Mali, Anima Pandey
{"title":"Antinociceptive Investigations of Niranthin in Complete Freund's Adjuvant- induced Chronic Pain in Mice.","authors":"Atul R Chopade, Vijay R Salunkhe, Pramod A Patil, Madhav R Burade, Prakash M Somade, Suraj N Mali, Anima Pandey","doi":"10.2174/2772270816666220105122956","DOIUrl":"10.2174/2772270816666220105122956","url":null,"abstract":"<p><strong>Objective: </strong>The main objectives of the present work are to determine the clinical effect of niranthin on visceral or somatic inflammatory pain. The study was performed to determine the effects of niranthin on visceral or somatic inflammatory hypersensitivity of adult Swiss albino mice by using complete Freund's adjuvant (CFA) induced pain model.</p><p><strong>Methods: </strong>The effect of CFA injection was determined after 24 hours of injection by using an aesthesiometer such as Von Frey filaments to evaluate tactile acetone-evoked cooling and thermal sensitivity. We used a digital Plethysmometer to measure paw edema. Single dose of niranthin intraperitoneal injection (5 and 10 mg/kg) was injected into mice having CFA-induced mechanical hypersensitivity and after 30 minutes of administration, reduced mechanical hypersensitivity was observed. In addition, niranthin also reduced acetone-evoked hypersensitivity within 4 hours.</p><p><strong>Results: </strong>Compared to DMSO, niranthin was most highly active to reduce CFA-induced paw edema. To reduce mechanical hypersensitivity, multiple doses of niranthin (bis in die (b.i.d.)) from 1st - 5th day and b.i.d. day 9th and 10th) were given and remarkable results were observed such as did not cause tolerance in multiple dosing and significantly reduced in CFA induced hypersensitivity.</p><p><strong>Conclusion: </strong>This work reported niranthin having antinociceptive activity and indicated that niranthin is conventionally active in the management of persistent pain.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":" ","pages":"108-112"},"PeriodicalIF":1.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39876467","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}
Hussein Kadhem Al-Hakeim, Hawraa Kadhem Al-Jassas, Gerwyn Morris, Michael Maes
{"title":"Increased ACE2, sRAGE, and Immune Activation, but Lowered Calcium and Magnesium in COVID-19.","authors":"Hussein Kadhem Al-Hakeim, Hawraa Kadhem Al-Jassas, Gerwyn Morris, Michael Maes","doi":"10.2174/2772270816666220318103929","DOIUrl":"https://doi.org/10.2174/2772270816666220318103929","url":null,"abstract":"<p><strong>Background: </strong>The characterization of new biomarkers that could help externally validate the diagnosis of COVID-19 and optimize treatments is extremely important. Many studies have established changes in immune-inflammatory and antibody levels, but few studies measured the soluble receptor for the advanced glycation end product (sRAGE), angiotensin-converting enzyme 2 (ACE2), calcium, and magnesium in COVID-19.</p><p><strong>Objective: </strong>To evaluate serum advanced glycation end-product receptor (sRAGE) and angiotensin converting enzyme (ACE)2 and peripheral oxygen saturation (SpO2) and chest CT scan abnormalities (CCTA) in COVID-19.</p><p><strong>Methods: </strong>sRAGE, ACE2, interleukin (IL)-6, IL-10, C-reactive protein (CRP), calcium, magnesium, and albumin were measured in 60 COVID-19 patients and 30 healthy controls.</p><p><strong>Results: </strong>COVID-19 is characterized by significantly increased IL-6, CRP, IL-10, sRAGE, ACE2, and lowered SpO2, albumin, magnesium, and calcium. COVID-19 with CCTAs showed lower SpO<sub>2</sub> and albumin. SpO2 was significantly inversely correlated with IL-6, IL-10, CRP, sRAGE, and ACE2, and positively with albumin, magnesium, and calcium. Neural networks showed that a combination of calcium, IL-6, CRP, and sRAGE yielded an accuracy of 100% in detecting COVID-19 patients, with calcium being the most important predictor followed by IL-6 and CRP. Patients with positive IgG results showed a significant elevation in the serum level of IL-6, sRAGE, and ACE2 compared to the negatively IgG patient subgroup.</p><p><strong>Conclusion: </strong>The results show that immune-inflammatory and RAGE pathways biomarkers may be used as an external validating criterion for the diagnosis of COVID-19. Those pathways coupled with lowered SpO2, calcium, and magnesium are drug targets that may help reduce the consequences of COVID-19.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":"16 1","pages":"32-43"},"PeriodicalIF":0.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10450949","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":"Association of Growth Differentiation Factor 15 with Arterial Stiffness and Endothelial Function in Subpopulations of Patients with Coronary Artery Disease: A Proof-of-Concept Study.","authors":"Konstantinos Mourouzis, Gerasimos Siasos, Nikoleta Bozini, Evangelos Oikonomou, Marina Zaromitidou, Vasiliki Tsigkou, Eleni Kokkou, Evanthia Bletsa, Panagiota Stampouloglou, Manolis Vavuranakis, Dimitrios Tousoulis","doi":"10.2174/2772270817666221104120923","DOIUrl":"https://doi.org/10.2174/2772270817666221104120923","url":null,"abstract":"<p><strong>Background: </strong>Growth-differentiation factor-15 (GDF-15) is a biomarker belonging to the transforming growth factor-beta cytokine superfamily, which is linked to many pathological conditions, including inflammation and myocardial injury. Pulse wave velocity (cfPWV) and augmentation index (AIx) are indices of arterial stiffness, which are associated with the severity of coronary artery disease (CAD). Flow-mediated dilatation (FMD) is a well-studied surrogate marker of endothelial-dependent dysfunction and systemic inflammation.</p><p><strong>Objective: </strong>In this proof-of-concept study, we aimed to investigate the relationship between circulating GDF-15, endothelial dysfunction, and indices of arterial stiffness in different settings of coronary artery disease and myocardial injury.</p><p><strong>Methods: </strong>In this cross-sectional single-center study, we enrolled patients (n = 22) after interventional treatment for acute myocardial infarction (AMI), patients (n = 11) admitted with chest pain and elevated cardiac enzymes but without evidence of obstructing CAD (MI-NOCAD) in percutaneous coronary angiography (CAG), and patients (n = 20) who underwent CAG according to indications without evident obstructive CAD in CAG (NOCAD). FMD was assessed at the brachial artery. AIx of the central aortic pressure and cfPWV were estimated by applanation tonometry at the radial and carotid-femoral site, respectively, with a validated acquisition system (Sphygmo- Cor, AtCor Medical, Sydney (NSW), Australia). ELISA was used to determine circulating GDF- 15 serum levels (R&D Systems, Minneapolis, MN). Clinical and demographic data and values of routine biochemical biomarkers were obtained. The highest high-sensitive cardiac Troponin I (hsTpnI) value during hospitalization was also recorded. Left ventricular ejection fraction (LVEF) was assessed with a transthoracic echocardiogram.</p><p><strong>Results: </strong>Patients with AMI were older, had worse LVEF, higher values of hsTpnI and increased circulating GDF-15 levels. Importantly, AMI patients had increased cfPWV values, deteriorated AIx values, blunted FMD and worse serum creatinine levels compared to MI-NOCAD and NOCAD patients, respectively, whereas MI-NOCAD and NOCAD did not differ from each other significantly on these biomarkers. Both AMI and MI-NOCAD patients presented a higher but comparable white blood cell count than NOCAD patients. A strong linear correlation between GDF-15 and cfPWV, hsTpnI, AIx, white blood cell count and creatinine but not with FMD was demonstrated in the general study population.</p><p><strong>Conclusion: </strong>This proof-of-concept study showed that higher circulating levels of GDF-15, an inflammatory biomarker, were associated significantly with increased arterial stiffness only in AMI patients, whereas elevated GDF-15 demonstrated a linear relationship with the severity of the myocardial injury.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":"16 2","pages":"107-115"},"PeriodicalIF":0.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10754885","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":"GDF15 in Vascular and Liver Metabolic Disorders: A Novel Therapeutic Target.","authors":"Stefano Fiorucci, Ginevra Urbani","doi":"10.2174/277227081602221221113442","DOIUrl":"https://doi.org/10.2174/277227081602221221113442","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":"16 2","pages":"55-59"},"PeriodicalIF":0.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10634749","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":"Role of mRAGEs and ACE2 in SARS-CoV-2-Related Inflammation.","authors":"Stefano Fiorucci, Ginevra Urbani","doi":"10.2174/277227081601221018140453","DOIUrl":"https://doi.org/10.2174/277227081601221018140453","url":null,"abstract":"","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":"16 1","pages":"2-4"},"PeriodicalIF":0.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10403346","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}
Shahrzad Hassani, Jalil Tavakol Afshari, Fahimeh Jafarnezhad-Ansariha, Abbas Mirshafiey
{"title":"The Evaluation of Safety Property and Apoptotic Efficacy of α-L-Guluronic Acid (G2013), as a Novel NSAID, Under <i>In Vitro</i> Examination on L929 and Hepatocellular Carcinoma Cell Lines.","authors":"Shahrzad Hassani, Jalil Tavakol Afshari, Fahimeh Jafarnezhad-Ansariha, Abbas Mirshafiey","doi":"10.2174/2772434416666210909111912","DOIUrl":"https://doi.org/10.2174/2772434416666210909111912","url":null,"abstract":"<p><strong>Background: </strong>Many investigations have expanded this concept that liver chronic inflammation has an essential role in persistent cell damages along with altering the liver microenvironment leading to fibrosis, cirrhosis, and finally, hepatocellular carcinoma (HCC). To reduce inflammation and relieve symptoms, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly used; however, their long-term usage can lead to severe adverse events on vital organs like the liver. Interestingly, the α-L-Guluronic Acid (G2013), as a novel NSAID with immunomodulatory properties, has shown the inhibitory effects on inflammation and metastasis in experimental models.</p><p><strong>Objective: </strong>This study was conducted to determine the effects of G2013 on cytotoxicity and induction of apoptosis, as a new therapeutic target for cancer therapy, in the HepG2 cell line and the mouse fibroblast cell line L929, as a control.</p><p><strong>Methods: </strong>MTT assay and flow cytometry method were carried out using the different concentrations of G2013 (5, 15, 25, 50, 100, 200 and 400 μg/ml) in 3 distinct incubation times.</p><p><strong>Results: </strong>Our data showed that treatment of HepG2 cells with high concentration (400μg/mL) of G2013 could effectively cause a decrease in cell viability, so that they were statistically different after 72 hours compared to other concentrations (5 to 200 μg/ml) (p<0.05 and p<0.01, respectively). Moreover, the proportion of apoptosis of HepG2 cells at the dose of 200μg/mL considerably increased, suggesting that the induction of apoptosis by G2013 in HepG2 cells is dose- and time-dependent, which could promote its anticancer properties.</p><p><strong>Conclusion: </strong>The present study revealed that G2013 could induce apoptosis in the liver cancer model. Therefore, based on these findings, G2013 might be considered as a therapeutic option in cancer therapy.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":"15 1","pages":"9-15"},"PeriodicalIF":0.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39402456","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}
Lorenzo Schiavoni, Alessia Mattei, Giuseppe Pascarella, Alessandro Strumia, Antonio Nenna, Massimo Chello, Felice E Agrò
{"title":"Linezolid Intoxication with Extreme Lactate Blood Levels Successfully Treated with Dialytic Treatment in ICU: A Case Report.","authors":"Lorenzo Schiavoni, Alessia Mattei, Giuseppe Pascarella, Alessandro Strumia, Antonio Nenna, Massimo Chello, Felice E Agrò","doi":"10.2174/2772270816666220606111049","DOIUrl":"https://doi.org/10.2174/2772270816666220606111049","url":null,"abstract":"<p><strong>Introduction: </strong>Lactic acidosis is a rare but life-threatening complication associated with prolonged linezolid therapy. No specific treatment is suggested, except for antibiotic therapy interruption.</p><p><strong>Case report: </strong>A 70-years-old woman faced severe linezolid intoxication after antibiotics therapy initiation for infection of a surgical sternal wound. The patient suffered from a severe increment of blood lactate and thrombocytopenia. She was admitted to ICU twice, and due to dialytic treatment, linezolid and lactate serum levels came back to normality.</p><p><strong>Conclusion: </strong>More studies should be conducted to evaluate the human tissue storage sites of linezolid and the influence of various factors on its clearance and plasma concentrations in critically ill patients.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":"16 1","pages":"50-53"},"PeriodicalIF":0.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10684725","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":"Major Histocompatibility Complex Class II <i>HLA-DRB1</i> Allelic Epitopes in Fibromyalgia.","authors":"Basant K Puri, Gary S Lee, Armin Schwarzbach","doi":"10.2174/2772270816666220321162802","DOIUrl":"https://doi.org/10.2174/2772270816666220321162802","url":null,"abstract":"<p><strong>Background: </strong>Preliminary evidence has pointed an association of the gene HLA-DRB1 with fibromyalgia. HLA-DRB1 alleles carrying the shared or susceptibility epitope encoding the five-amino acid motif QKRAA, QRRAA or RRRAA in positions 70 to 74 of the major histocompatibility complex class II DRβ chain are associated with several autoimmune diseases.</p><p><strong>Objective: </strong>The objective of this study was to test the hypothesis that susceptibility epitope-encoding HLA-DRB1 alleles are associated with fibromyalgia.</p><p><strong>Methods: </strong>Using a case-control design, the prevalence of susceptibility epitope-encoding HLADRB1 alleles in 27 white Caucasian patients fulfilling the revised diagnostic criteria for fibromyalgia of the American College of Rheumatology was compared with that in 27 white Caucasian ageand sex-matched healthy controls.</p><p><strong>Results: </strong>13 (48%) of the fibromyalgia patients had susceptibility epitope-coding HLA-DRB1 alleles compared with 15 (56%) of the controls (P = 0.785). The DRB1*01 allele encoding the protective epitope 70-DERAA-74 motif was found in one of the control subjects; none of the fibromyalgia patients had such a protective epitope.</p><p><strong>Conclusion: </strong>While the present study does not provide evidence supporting the potential role of HLA-DRB1 in the etiology of fibromyalgia, it does not exclude the possibility that there is a polygenic component to a putative genetic causative role.</p>","PeriodicalId":29815,"journal":{"name":"Recent Advances in Inflammation & Allergy Drug Discovery","volume":"16 1","pages":"16-18"},"PeriodicalIF":0.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10817001","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}