Lidia Łysenko, Patrycja Leśnik, Kamil Nelke, Hanna Gerber
{"title":"Immune disorders in sepsis and their treatment as a significant problem of modern intensive care.","authors":"Lidia Łysenko, Patrycja Leśnik, Kamil Nelke, Hanna Gerber","doi":"10.5604/01.3001.0010.3849","DOIUrl":"https://doi.org/10.5604/01.3001.0010.3849","url":null,"abstract":"<p><p>Despite the great advances in the treatment of sepsis over the past 20 years, sepsis remains the main cause of death in intensive care units. In the context of new possibilities of treating sepsis, a comprehensive response of the immune system to the infection, immunosuppression, in particular, has in recent years gained considerable interest. There is vast evidence pointing to the correlation between comorbid immunosuppression and an increased risk of recurrent infections and death. Immune disorders may impact the clinical course of sepsis. This applies in particular to patients with deteriorated clinical response to infections. They usually suffer from comorbidities and conditions accompanied by immunosuppression. Sepsis disrupts innate and adaptive immunity. The key to diagnose the immune disorders in sepsis and undertake targeted immunomodulatory therapy is to define the right biomarkers and laboratory methods, which permit prompt \"bedside\" diagnosis. Flow cytometry is a laboratory tool that meets these criteria. Two therapeutic methods are currently being suggested to restore the immune homeostasis of sepsis patients. Excessive inflammatory response may be controlled through extracorporeal blood purification techniques, in large part derived from renal replacement therapy. These are such techniques as high-volume haemofiltration, cascade haemofiltration, plasma exchange, coupled plasma filtration and adsorption, high-absorption membranes, high cut-off membranes. The main task of theses techniques is the selective elimination of middle molecular weight molecules, such as cytokines. Pharmacotherapy with the use of such immunostimulants as interleukin 7, granulocyte-macrophage colony-stimulating factor, interferon gamma, PD-1, PD-L1 and CTLA-4 antagonists, intravenous immunoglobulins may help fight immunosuppressive immune disorders.</p>","PeriodicalId":87132,"journal":{"name":"Postepy higieny i medycyny doswiadczalnej (Online)","volume":"71 1","pages":"703-712"},"PeriodicalIF":0.0,"publicationDate":"2017-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35501564","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 role of the BLCA-4 nuclear matrix protein in bladder cancer.","authors":"Beata Szymańska, Anna Długosz","doi":"10.5604/01.3001.0010.3847","DOIUrl":"https://doi.org/10.5604/01.3001.0010.3847","url":null,"abstract":"<p><p>Bladder cancer (BC) affects usually older people. According to information provided by the National Cancer Registry in 2012. BC was the 4th, in terms of illness, cancer in men and 11th in women. Early diagnosis of bladder cancer is important because detected later has worse prognosis.Diagnosis of bladder cancer is not simple and it is still very invasive. Usually the cystoscopy or endoscopic bladder biopsy with histopathological evaluation and cytology of urine sediment is used. This prompted researchers to look for alternative noninvasive methods of diagnosis of bladder cancer. Recently, it was described the group of six proteins (BLCA) specific for BC, with special attention to BLCA-4.BLCA-4 belongs to the nuclear matrix protein and has a high specificity for this type of cancer however the value of this marker in BC diagnosis is not yet established. Oxidative DNA damage play an important role in the pathogenesis of some human diseases, including cancer. Determination of 8-hydroxy-2'deoksyguanozyne (8-OHdG) is currently used in the evaluation of genotoxic damage.The aim of the work was to review information on BLCA-4, its function in the process of BC carcinogenesis and diagnostic value also in exposure to genotoxic compounds measured by 8-hydroxy-2'deoksyguanozyne (8-OHdG) level.</p>","PeriodicalId":87132,"journal":{"name":"Postepy higieny i medycyny doswiadczalnej (Online)","volume":"71 1","pages":"681-689"},"PeriodicalIF":0.0,"publicationDate":"2017-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35501563","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 miRNAs as non-invasive biomarkers for non-small cell lung cancer diagnosis, prognosis and prediction of treatment response.","authors":"Weronika Zofia Świtlik, Janusz Szemraj","doi":"10.5604/01.3001.0010.3845","DOIUrl":"https://doi.org/10.5604/01.3001.0010.3845","url":null,"abstract":"<p><p>The discovery of a new class of molecules, the 22-24 nucleotides long RNA, has initiated a new chapter in genetic information regulation studies. These molecules have a significant impact on the functioning of cells by means of negative regulation of expression of targeted mRNA. Special attention is given to exogenous, circulating miRNAs, whose levels of expression in different body fluids varies and can be deregulated by pathological, as well as physiological conditions. Extensive studies on the diagnostic potential of miRNAs are currently conducted. Attempts are made to determine specific profiles of miRNAs that will correlate with disease entity. The preliminary data gives hope that in the near future miRNAs will be applied as a diagnostic and prognostic biomarkers in many diseases. One of their most significant applications can be in the diagnosis of lung cancer - the most deadly form of cancer, due to its too late diagnosis. Abundant in miRNA molecules, blood and sputum constitute excellent diagnostic material for patients with lung cancer, especially those with non-small-cell lung cancer NSCLC. Easy procedures for obtaining this diagnostic material from patients and relatively easy analysis of miRNA expression, make these molecules promising in their use in diagnosis, predicting of therapy effects and prognosis for patients with NSCLC. This work presents information related to miRNA and their specific attributes. Moreover level of deregulated circulating miRNAs occurring in body fluids of patients with NSCLC is also discussed.</p>","PeriodicalId":87132,"journal":{"name":"Postepy higieny i medycyny doswiadczalnej (Online)","volume":"71 0","pages":"649-662"},"PeriodicalIF":0.0,"publicationDate":"2017-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35304938","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}
Mateusz Ogórek, Łukasz Gąsior, Olga Pierzchała, Regina Daszkiewicz, Małgorzata Lenartowicz
{"title":"Role of copper in the process of spermatogenesis.","authors":"Mateusz Ogórek, Łukasz Gąsior, Olga Pierzchała, Regina Daszkiewicz, Małgorzata Lenartowicz","doi":"10.5604/01.3001.0010.3846","DOIUrl":"https://doi.org/10.5604/01.3001.0010.3846","url":null,"abstract":"<p><p>Copper (Cu) is an essential trace element required for the normal development of living organisms. Due to its redox potential, copper is a cofactor in many enzymes responsible for important processes in cells. Copper deficiency has a significant influence on the reduction or the total eradication of copper-dependent enzymes in the body, thereby inhibiting cell life processes. On the other hand, copper is a very reactive element and in its free state, it can trigger the production of large amounts of free radicals, which will consequently lead to the damage of proteins and DNA. Because of those reasons, living organisms have developed precise mechanisms regulating the concentration of copper in cells. Copper also plays a very important role in male fertility. It is an essential element for the production of male gametes. The significant role of copper is also described in the processes of cell division - mitotic and meiotic. Copper-dependent enzymes such as ceruloplasmin, superoxide dismutase SOD1 and SOD3, group of metallothionein and cytochrome c oxidase are present at all stages of gametogenesis as well as in the somatic cells of the testis and in the somatic cells of epididymis. Substantial amounts of copper can also be found in liquids associated with sperm in the epididymis and prostate. Copper also affects the integral androgen distribution in terms of fertility on the line hypothalamic-pituitary-testis. Both copper increase and deficiency leads to a significant reduction in male fertility, which spans the entire spectrum of abnormalities at the sperm level, male gonad, production of hormones and distribution of micronutrients such as zinc and iron. Nowadays, the effects of copper on gametes production have become more important and are connected with the increasing levels of pollution with heavy metals in environment.</p>","PeriodicalId":87132,"journal":{"name":"Postepy higieny i medycyny doswiadczalnej (Online)","volume":"71 0","pages":"663-683"},"PeriodicalIF":0.0,"publicationDate":"2017-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35304939","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 α7-nACh nicotinic receptor and its role in memory and selected diseases of the central nervous system.","authors":"Urszula Baranowska, Róża Julia Wiśniewska","doi":"10.5604/01.3001.0010.3844","DOIUrl":"https://doi.org/10.5604/01.3001.0010.3844","url":null,"abstract":"<p><p>α7-nACh is one of the major nicotinic cholinergic receptor subtypes found in the brain. It is broadly expressed in the hippocampal and cortical neurons, the regions which play a key role in memory formation. Although α7-nACh receptors may serve as postsynaptic receptors mediating classical neurotransmission, they usually function as presynaptic modulators responsible for the release of other neurotransmitters, such as glutamate, γ-aminobutyric acid, dopamine, and norepinephrine. They can, therefore, affect a wide array of neurobiological functions. In recent years, research has found that a large number of agonists and positive allosteric modulators of α7-nAChR induce beneficial effects on learning and memory. Consistently, mice deficient in chrna7 (the gene encoding α7-nAChR protein), are characterized by memory deficits. In addition, decreased expression and function of α7-nAChR is associated agoniwith many neurological diseases including schizophrenia, bipolar disorder, learning disability, attention deficit hyperactivity disorder, Alzheimer disease, autism, and epilepsy. In the recent years many animal experiments and clinical trials using α7-nAChR ligands were conducted. The results of these studies strongly indicate that agonists and positive allosteric modulators of α7-nAChR are promising therapeutic agents for diseases associated with cognitive deficits.</p>","PeriodicalId":87132,"journal":{"name":"Postepy higieny i medycyny doswiadczalnej (Online)","volume":"71 0","pages":"633-648"},"PeriodicalIF":0.0,"publicationDate":"2017-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35304937","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}
Izabela Koss-Mikołajczyk, Monika Baranowska, Jacek Namieśnik, Agnieszka Bartoszek
{"title":"Determination of antioxidantactivity of phytochemicals in cellular models by fluorescence/luminescence methods.","authors":"Izabela Koss-Mikołajczyk, Monika Baranowska, Jacek Namieśnik, Agnieszka Bartoszek","doi":"10.5604/01.3001.0010.3841","DOIUrl":"https://doi.org/10.5604/01.3001.0010.3841","url":null,"abstract":"<p><p>As soon as the role of Reactive Oxygen Species (ROS) in so-called civilization diseases, which include non-infectious chronic diseases such as cancer, diabetes or high blood pressure has been discovered, and the possibility of employing antioxidants as a remedy for these diseases have been proposed, scientists developed a broad spectrum of methods to determine antioxidant activity of pure chemicals and plant extracts, as well as dietary supplements. Most of these methods are based on simple redox reactions between antioxidant and ROS (for example ABTS, DPPH, or FRAP tests). However, chemical methods of assessing antioxidant activity are rarely biologically relevant. They do not mirror the real effect of antioxidants in living organisms, because they are used in non-physiological conditions of temperature and pH; neither they take metabolism nor intracellular transport under consideration. The perfect model for assessment of antioxidant activity in living organisms would be human or animal model, but such determinations are very complicated and often ambiguous. The current best alternative to chemical and human tests are assays employing cell culture models being less expensive than human tests, yet still reflecting biological systems more convincingly than chemical assays. Cellular antioxidant assays are performed under physiological pH and temperature, but most importantly, they take metabolism and intracellular transport under consideration. In this review, we present cellular tests used to determine antioxidant activity that are based on luminescence and fluorescence methods.</p>","PeriodicalId":87132,"journal":{"name":"Postepy higieny i medycyny doswiadczalnej (Online)","volume":"71 0","pages":"602-617"},"PeriodicalIF":0.0,"publicationDate":"2017-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35395628","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}
Szymon Wojciech Kmiecik, Mateusz Adam Krzyścik, Beata Filip-Psurska, Joanna Wietrzyk, Janusz Boratyński, Tomasz Marek Goszczyński
{"title":"Methotrexate and epirubicin conjugates as potential antitumor drugs.","authors":"Szymon Wojciech Kmiecik, Mateusz Adam Krzyścik, Beata Filip-Psurska, Joanna Wietrzyk, Janusz Boratyński, Tomasz Marek Goszczyński","doi":"10.5604/01.3001.0010.3842","DOIUrl":"https://doi.org/10.5604/01.3001.0010.3842","url":null,"abstract":"<p><strong>Introduction: </strong>The use of hybrid molecules has become one of the most significant approaches in new cytotoxic drug design. This study describes synthesis and characterization of conjugates consisting of two well-known and characterized chemotherapeutic agents: methotrexate (MTX) and epirubicin (EPR). The synthesized conjugates combine two significant anticancer strategies: combinatory therapy and targeted therapy. These two drugs were chosen because they have different mechanisms of action, which can increase the anticancer effect of the obtained conjugates. MTX, which is a folic acid analog, has high cytotoxic properties and can serve as a targeting moiety that can reach folate receptors (FRs) overexpresing tumor cells. Combination of nonselective drugs such as EPR with MTX can increase the selectivity of the obtained conjugates, while maintaining the high cytotoxic properties.</p><p><strong>Materials and methods: </strong>Conjugates were purified by RP-HPLC and the structure was investigated by MS and MS/MS methods. The effect of the conjugates on proliferation of LoVo, LoVo/Dx, MCF-7 and MV-4-11 human cancer cell lines was determined by SRB or MTT assay.</p><p><strong>Results: </strong>The conjugation reaction results in the formation of monosubstituted (α, γ) and disubstituted MTX derivatives. In vitro proliferation data demonstrate that the conjugates synthesized in our study show lower cytotoxic properties than both chemotherapeutics used alone.</p><p><strong>Discussion: </strong>Epirubicin cytotoxicity was not observed in obtained conjugates. Effective drugs release after internalization needs further investigation.</p>","PeriodicalId":87132,"journal":{"name":"Postepy higieny i medycyny doswiadczalnej (Online)","volume":"71 0","pages":"618-623"},"PeriodicalIF":0.0,"publicationDate":"2017-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35395630","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}
Tomasz Kamiński, Małgorzata Michałowska, Dariusz Pawlak
{"title":"Aryl hydrocarbon receptor (AhR) and its endogenous agonist - indoxyl sulfate in chronic kidney disease.","authors":"Tomasz Kamiński, Małgorzata Michałowska, Dariusz Pawlak","doi":"10.5604/01.3001.0010.3843","DOIUrl":"https://doi.org/10.5604/01.3001.0010.3843","url":null,"abstract":"<p><p>The indoxyl sulfate (IS, indoxyl sulphate) is the end product of dietary tryptophan degradation by indole pathway and significantly higher serum and tissue concentrations of this compound is observed in patients with impaired renal function. Despite the high albumin binding affinity, the remaining free fraction of IS has a number of biological effects related to the generation of oxidative stress andactivation of signaling pathways related to NF-кB, p53 protein, STAT3, TGF-β and Smad2/3. IS induces the inflammatory process, exerts nephrotoxic activity and is also a factor impairing the cardiovascular system.Its high concentrations are associated with the occurrence of cardiovascular incidents, whose frequency is significantly higher in patients with chronic kidney disease. Evaluation of the mechanisms that underlie the high reactivity of indoxyl sulfate and its biological effects showed that this compound is an agonist of the aryl hydrocarbon receptor (AhR). This receptor plays an important role in maintaining homeostasis Moreover, AhR exerts high transcriptional activity, so ligands of obciążethis receptor may exert different biological effects. The following paper describes the role of indoxyl sulfate as AhR ligand in the context of the excessive accumulation, which appears as one of the symptoms associated with chronic kidney disease.</p>","PeriodicalId":87132,"journal":{"name":"Postepy higieny i medycyny doswiadczalnej (Online)","volume":"71 0","pages":"624-632"},"PeriodicalIF":0.0,"publicationDate":"2017-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35304936","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":"Novel strategies for treatment of pulmonary arterial hypertension.","authors":"Magdalena Jasińska-Stroschein, Daria Orszulak-Michalak","doi":"10.5604/01.3001.0010.3838","DOIUrl":"https://doi.org/10.5604/01.3001.0010.3838","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a rare disorder associated with abnormally elevated pulmonary pressures that, if untreated, leads to right heart failure and premature death. Special population include patents with pulmonary arterial hypertension (PAH). A greater understanding of the epidemiology, pathogenesis, and pathophysiology of PAH has led to significant advances over the past few years. Modern drug therapy provides a significant improvement in patient symptomatic status and a slower rate of clinical deterioration. Despite this, PAH remains a chronic disease without a cure. There is a need for the development of novel therapies and therapeutic strategies, as treatment options are neither universally available nor always effective, possibly due to the large number of mediator and signaling pathways with downstream effectors which are implicated in the pathobiology of PH, and which are not fully reversed during PAH therapy. In the following pages, we review novel strategies for treatment of PAH. For this purpose we summarized the role of specific drug therapies that involve: endothelin receptor antagonists (ERA), phosphodiesterase type 5 inhibitors (PDE-5i) and prostacyclin and prostanoids (PGI2). We focused on novel molecular mechanisms in PAH of recently approved: Guanylate cyclase stimulator and non-prostanoid IP receptor agonist. We discussed novel approach to combined therapy, as well as a new generation of investigational drugs and promising PAH-associated signaling pathways, such as, PDGF, RhoA/ROCK RAAS, HT-5 and others.</p>","PeriodicalId":87132,"journal":{"name":"Postepy higieny i medycyny doswiadczalnej (Online)","volume":"71 0","pages":"577-588"},"PeriodicalIF":0.0,"publicationDate":"2017-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35395623","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}
Anna Michalska-Falkowska, Paweł Tomasz Sacha, Henryk Grześ, Tomasz Hauschild, Piotr Wieczorek, Dominika Ojdana, Elżbieta Anna Tryniszewska
{"title":"Emergence of Pseudomonas aeruginosa with class 1 integron carrying blaVIM-2 and blaVIM-4 in the University Clinical Hospital of Bialystok (northeastern Poland).","authors":"Anna Michalska-Falkowska, Paweł Tomasz Sacha, Henryk Grześ, Tomasz Hauschild, Piotr Wieczorek, Dominika Ojdana, Elżbieta Anna Tryniszewska","doi":"10.5604/01.3001.0010.3839","DOIUrl":"https://doi.org/10.5604/01.3001.0010.3839","url":null,"abstract":"<p><p>The effectiveness of carbapenems, considered as last-resort antimicrobials in severe infections, becomes compromised by bacterial resistance. The production of metallo-β-lactamases (MBLs) is the most significant threat to carbapenems activity among Pseudomonas aeruginosa. The aim of this study was to assess the presence and type of MBLs genes in carbapenem-resistant P. aeruginosa clinical strains, to identify the location of MBLs genes and to determine genetic relatedness between MBL-producers using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The first identified MBL-positive (with blaVIM genes) P. aeruginosa strains were isolated from patients hospitalized in the University Clinical Hospital of Bialystok in the period from September 2012 to December 2013. Variants of MBLs genes and variable integron regions were characterized by PCR and sequencing. PFGE was performed after digesting of bacterial genomes by XbaI enzyme. By MLST seven housekeeping genes were analyzed for the determination of sequence type (ST). Three strains carried the blaVIM-2 gene and one harbored the blaVIM-4 gene. The blaVIM genes resided within class 1 integrons. PCR mapping of integrons revealed the presence of four different cassette arrays. Genetic relatedness analysis by PFGE classified VIM-positive strains into four unrelated pulsotypes (A-D). MLST demonstrated the presence of four (ST 111, ST27, and ST17) different sequence type including one previously undescribed new type of ST 2342. Antimicrobial susceptibility testing showed that VIM-positive strains were resistant to carbapenems, cephalosporins, aminoglycosides, and quinolones, intermediate to aztreonam, and susceptible only to colistin. Integrons mapping, PFGE, and MLST results may point to different origin of these strains and independent introduction into hospitalized patients.</p>","PeriodicalId":87132,"journal":{"name":"Postepy higieny i medycyny doswiadczalnej (Online)","volume":"71 0","pages":"589-594"},"PeriodicalIF":0.0,"publicationDate":"2017-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35395624","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}