Pub Date : 2021-11-15DOI: 10.33892/aph.2021.91.224-225
M. Gertsiuk, T. Gertsiuk
{"title":"Chemical-Analytical Control of Harmful Substances in the Quality Management System of Medicinal Plant Raw Materials","authors":"M. Gertsiuk, T. Gertsiuk","doi":"10.33892/aph.2021.91.224-225","DOIUrl":"https://doi.org/10.33892/aph.2021.91.224-225","url":null,"abstract":"","PeriodicalId":6941,"journal":{"name":"Acta pharmaceutica Hungarica","volume":"253 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77090113","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}
Pub Date : 2021-11-15DOI: 10.33892/aph.2021.91.140-141
D. Steinhilber, E. Proschak
Besides its function as key enzyme in the biosynthesis of leukotrienes (Figure 1), there is accumulating evidence that 5-lipoxygenase (5-LO) has additional, noncanonical functions. The enzyme is mainly expressed in leukocytes. After stimulation of neutrophils, the enzyme is activated by an increase in intracellular calcium concentration and by phosphorylation by 5-LO kinases. Leukotrienes are considered as proinflammatory mediators which are involved in host defense reactions and which contribute to allergic and inflammatory reactions (1). Zileuton (Figure 2) is the only approved 5-LO inhibitor, which binds to the iron ion in the active cite. Cys-LT1 receptor antagonists which block the action of LTC4 and its metabolites in the lung are approved for the treatment of asthma and allergic rhinitis. Expression of the enzyme is regulated in a cell cycle and cell differentiationdependent manner (2). It is a TGF-β and vitamin D response gene which seems to be controlled by transcription factors that regulate stemness, lineage-specific differentiation of myeloid and lymphocytic cells including p53, SMAD1, C/EBPα, GATA2, PU.1, RUNX1, RUNX3 and the WNT pathway (3). Aberrant 5-LO expression is observed in many cancer tissues and cells which suggested that the 5-LO pathway might be involved in cancer development (for review see (4)). A clear evidence for the role of 5-LO in cancer came from the observation that 5-LO knockout prevents the development of chronic myeloid leukemia in a murine BCR/ABL leukemia model (5). Interestingly, 5-LO knockout does not seem to lead to a defect in normal hematopoiesis. First mechanistic insights into the role of 5-LO came from the observation that 5-LO alters nuclear trafficking of p53 and leads to inhibition of apoptosis (6).
{"title":"5-Lipoxygenase: Its Noncanonical Function Unravels its Inhibitors as Powerful Antileukemic Drugs","authors":"D. Steinhilber, E. Proschak","doi":"10.33892/aph.2021.91.140-141","DOIUrl":"https://doi.org/10.33892/aph.2021.91.140-141","url":null,"abstract":"Besides its function as key enzyme in the biosynthesis of leukotrienes (Figure 1), there is accumulating evidence that 5-lipoxygenase (5-LO) has additional, noncanonical functions. The enzyme is mainly expressed in leukocytes. After stimulation of neutrophils, the enzyme is activated by an increase in intracellular calcium concentration and by phosphorylation by 5-LO kinases. Leukotrienes are considered as proinflammatory mediators which are involved in host defense reactions and which contribute to allergic and inflammatory reactions (1). Zileuton (Figure 2) is the only approved 5-LO inhibitor, which binds to the iron ion in the active cite. Cys-LT1 receptor antagonists which block the action of LTC4 and its metabolites in the lung are approved for the treatment of asthma and allergic rhinitis. Expression of the enzyme is regulated in a cell cycle and cell differentiationdependent manner (2). It is a TGF-β and vitamin D response gene which seems to be controlled by transcription factors that regulate stemness, lineage-specific differentiation of myeloid and lymphocytic cells including p53, SMAD1, C/EBPα, GATA2, PU.1, RUNX1, RUNX3 and the WNT pathway (3). Aberrant 5-LO expression is observed in many cancer tissues and cells which suggested that the 5-LO pathway might be involved in cancer development (for review see (4)). A clear evidence for the role of 5-LO in cancer came from the observation that 5-LO knockout prevents the development of chronic myeloid leukemia in a murine BCR/ABL leukemia model (5). Interestingly, 5-LO knockout does not seem to lead to a defect in normal hematopoiesis. First mechanistic insights into the role of 5-LO came from the observation that 5-LO alters nuclear trafficking of p53 and leads to inhibition of apoptosis (6).","PeriodicalId":6941,"journal":{"name":"Acta pharmaceutica Hungarica","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84457582","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}
Pub Date : 2021-11-15DOI: 10.33892/aph.2021.91.179-180
Bálint Basa, G. Jakab, E. Balogh, Bence Borbás, I. Antal
the interest toward additive manufacturing is growing considering the formulation of personalized medicines [1]. 3D printing is commonly an additive process, which results in various layer-bylayer built objects. A vast number of methods are available beyond 3D Printing but there are only few of them which can be employed for tailored pharmaceutical manufacturing (e.g. Photopolymerization, Selective Laser Sintering (SLS) and Fused Deposition Modelling (FDM)) [2]. During these methods the number of unit operations is minimalized, and the opportunity to fabricate every single printlet shaped according to the individuals’ profile with only minimal human intervention can be the cause of the increased research activity in this field [3]. The additional benefit of this type of manufacturing is the capability of producing customized ways of medication for pediatrics, geriatrics and patients suffering from organ dsyfunctions, avoiding the slightest chance of reaching toxic doses in their body. Several types of dosage forms were previously microfabricated including floating systems, pulsatile drug release tablets and zero-order release forms [4]. The first 3D printed orodispersible tablet was approved by the FDA in 2015.[5] The objective of our study was to design and print biodegradable drug delivery systems. Commercially available filament materials were screened as well as the print settings were optimized. In addition, the influence of design parameters including wall thickness, morphology, number and size of pores on the drug delivery in case of model drugs was investigated. Moreover, the applicability of matrix polymers and gelling agents in the process of 3D printing was studied. There were some formulations aiming the study of dose proportionality, in order to expand the opportunities of personalized medication. 2. Materials and methods
{"title":"The Application of 3D Printing in the Formulation of Personalized Drug Delivery Systems","authors":"Bálint Basa, G. Jakab, E. Balogh, Bence Borbás, I. Antal","doi":"10.33892/aph.2021.91.179-180","DOIUrl":"https://doi.org/10.33892/aph.2021.91.179-180","url":null,"abstract":"the interest toward additive manufacturing is growing considering the formulation of personalized medicines [1]. 3D printing is commonly an additive process, which results in various layer-bylayer built objects. A vast number of methods are available beyond 3D Printing but there are only few of them which can be employed for tailored pharmaceutical manufacturing (e.g. Photopolymerization, Selective Laser Sintering (SLS) and Fused Deposition Modelling (FDM)) [2]. During these methods the number of unit operations is minimalized, and the opportunity to fabricate every single printlet shaped according to the individuals’ profile with only minimal human intervention can be the cause of the increased research activity in this field [3]. The additional benefit of this type of manufacturing is the capability of producing customized ways of medication for pediatrics, geriatrics and patients suffering from organ dsyfunctions, avoiding the slightest chance of reaching toxic doses in their body. Several types of dosage forms were previously microfabricated including floating systems, pulsatile drug release tablets and zero-order release forms [4]. The first 3D printed orodispersible tablet was approved by the FDA in 2015.[5] The objective of our study was to design and print biodegradable drug delivery systems. Commercially available filament materials were screened as well as the print settings were optimized. In addition, the influence of design parameters including wall thickness, morphology, number and size of pores on the drug delivery in case of model drugs was investigated. Moreover, the applicability of matrix polymers and gelling agents in the process of 3D printing was studied. There were some formulations aiming the study of dose proportionality, in order to expand the opportunities of personalized medication. 2. Materials and methods","PeriodicalId":6941,"journal":{"name":"Acta pharmaceutica Hungarica","volume":"567 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83353972","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}
Pub Date : 2021-11-15DOI: 10.33892/aph.2021.91.152-153
J. Josephs, A. Bailey, S. Houel
Biotherapeutics exemplified by monoclonal antibodies (mAbs) are large complex molecules that are recombinantly expressed by cellular fermentation. While the primary sequence of the protein remains the same. Post translational modifications such as glycosylation are dependent on the cell lines chosen, the fermentation media, conditions, and length of fermentation. Clipping, deamidation, oxidation, etc. may occur during fermentation, purification, and storage. Biotransformations may take place in vivo after administration of the therapeutic agent. Traditionally these modifications are observed analytically by a bottom-up approach, whereby the protein is proteolytically digested with enzymes such as trypsin to generate short peptides that are much easier to separate chromatographically and characterize by mass spectrometry. This is approach is well established, reliable, and highly effective. However, the relationship of multiple modifications and heterogeneity are lost through this approach Intact mass measurement allows direct analysis of proteins which can provide greater insights into multiple modifications within a single protein molecule. This aspect of heterogeneity may be lost when analyzing via a bottom-up approach. The inherent difficulty of intact mass analysis of large therapeutic proteins is that they are harder to chromatograph under conditions that are compatible with mass spectrometry ion sources and the multiple charge states resulting from electrospray ionization increases the spectral complexity in addition to the underlying heterogeneity of the protein. Reverse phase chromatography provides good resolution and peak shape while the denaturing conditions afford a more efficient and therefore sensitive ionization. Size exclusion chromatography (SEC) has lower resolution and is a non-focusing separation technique. However, this can be conducted under native conditions (1) that while less sensitive/efficient than denaturing conditions results in a smaller number of charge states at higher m/z, simplifying the spectra (Figure 1). PL-26 Advances in LC/MS for the Characterization of Biotherapeutics
{"title":"Advances in LC/MS for the Characterization of Biotherapeutics","authors":"J. Josephs, A. Bailey, S. Houel","doi":"10.33892/aph.2021.91.152-153","DOIUrl":"https://doi.org/10.33892/aph.2021.91.152-153","url":null,"abstract":"Biotherapeutics exemplified by monoclonal antibodies (mAbs) are large complex molecules that are recombinantly expressed by cellular fermentation. While the primary sequence of the protein remains the same. Post translational modifications such as glycosylation are dependent on the cell lines chosen, the fermentation media, conditions, and length of fermentation. Clipping, deamidation, oxidation, etc. may occur during fermentation, purification, and storage. Biotransformations may take place in vivo after administration of the therapeutic agent. Traditionally these modifications are observed analytically by a bottom-up approach, whereby the protein is proteolytically digested with enzymes such as trypsin to generate short peptides that are much easier to separate chromatographically and characterize by mass spectrometry. This is approach is well established, reliable, and highly effective. However, the relationship of multiple modifications and heterogeneity are lost through this approach Intact mass measurement allows direct analysis of proteins which can provide greater insights into multiple modifications within a single protein molecule. This aspect of heterogeneity may be lost when analyzing via a bottom-up approach. The inherent difficulty of intact mass analysis of large therapeutic proteins is that they are harder to chromatograph under conditions that are compatible with mass spectrometry ion sources and the multiple charge states resulting from electrospray ionization increases the spectral complexity in addition to the underlying heterogeneity of the protein. Reverse phase chromatography provides good resolution and peak shape while the denaturing conditions afford a more efficient and therefore sensitive ionization. Size exclusion chromatography (SEC) has lower resolution and is a non-focusing separation technique. However, this can be conducted under native conditions (1) that while less sensitive/efficient than denaturing conditions results in a smaller number of charge states at higher m/z, simplifying the spectra (Figure 1). PL-26 Advances in LC/MS for the Characterization of Biotherapeutics","PeriodicalId":6941,"journal":{"name":"Acta pharmaceutica Hungarica","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83618044","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}
Pub Date : 2021-11-15DOI: 10.33892/aph.2021.91.146-147
Clive G. Wilson, G. Halbert, I. Khadra, C. Dunn
The in vitro testing of drug formulations is an essential safety/quality test in formulation assessment, process evaluation and batch release. In addition, it is desirable that the media be physiologically relevant, assist in the prediction of IVIVC and provide data that could be used in computer modelling. The number of relevant chemical variables has expanded with the adoption of biorelevant fluid compositions for fasted and fed states and the expansion of simulated gastric and intestinal fluids into simple colonic media. Dissolution in variants of these media is justified on the grounds of human variability and diet, but the number of permutations possible eventually becomes prohibitively large for the pharmaceutical industry. A compromise between a minimum set of compositions and the chance of missing what would be clinically significant effect has to be balanced. Over a number of iterative processes based on the design of experiments approach, we have attempted to progress towards a minimized matrix of compositions.
{"title":"The Gut in a Beaker: More Challenges for In Vitro Testing","authors":"Clive G. Wilson, G. Halbert, I. Khadra, C. Dunn","doi":"10.33892/aph.2021.91.146-147","DOIUrl":"https://doi.org/10.33892/aph.2021.91.146-147","url":null,"abstract":"The in vitro testing of drug formulations is an essential safety/quality test in formulation assessment, process evaluation and batch release. In addition, it is desirable that the media be physiologically relevant, assist in the prediction of IVIVC and provide data that could be used in computer modelling. The number of relevant chemical variables has expanded with the adoption of biorelevant fluid compositions for fasted and fed states and the expansion of simulated gastric and intestinal fluids into simple colonic media. Dissolution in variants of these media is justified on the grounds of human variability and diet, but the number of permutations possible eventually becomes prohibitively large for the pharmaceutical industry. A compromise between a minimum set of compositions and the chance of missing what would be clinically significant effect has to be balanced. Over a number of iterative processes based on the design of experiments approach, we have attempted to progress towards a minimized matrix of compositions.","PeriodicalId":6941,"journal":{"name":"Acta pharmaceutica Hungarica","volume":"83 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82392991","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}
Pub Date : 2021-11-15DOI: 10.33892/aph.2021.91.264-265
Miléna Lengyel, K. Süvegh, V. Antal, R. Zelkó, I. Antal, Nikolett Kállai-Szabó
{"title":"Hydrocolloid Gel-Formers and Polyvalent Cations in the Formation of Microparticles","authors":"Miléna Lengyel, K. Süvegh, V. Antal, R. Zelkó, I. Antal, Nikolett Kállai-Szabó","doi":"10.33892/aph.2021.91.264-265","DOIUrl":"https://doi.org/10.33892/aph.2021.91.264-265","url":null,"abstract":"","PeriodicalId":6941,"journal":{"name":"Acta pharmaceutica Hungarica","volume":"101 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83155452","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}
Pub Date : 2021-11-15DOI: 10.33892/aph.2021.91.130
Dange Veerapaneni
applications. In TDDS, nanoparticles could significant-ly improve the penetration of macromolecular drugs across the stratum corneum, with the po-tential to reduce immunogenicity and improve the bioavailability. The most common nanoparticles used TDDS are self-assembled liposomes, solid-li-pid nanoparticles, polymeric micelles, and inorganic nanoparticles. Compared with organic nanoparticles, inorganic nanoparticles offer higher physiochemical stability, easier surface functional-ization, and possess a tunable particle size and varied morphology. Thus, developing novel transdermal nanodevices based on inorganic nanoparticles is one of the fastest growing fields in nano-medicine.
{"title":"Advances in Transdermal Drug Delivery System","authors":"Dange Veerapaneni","doi":"10.33892/aph.2021.91.130","DOIUrl":"https://doi.org/10.33892/aph.2021.91.130","url":null,"abstract":"applications. In TDDS, nanoparticles could significant-ly improve the penetration of macromolecular drugs across the stratum corneum, with the po-tential to reduce immunogenicity and improve the bioavailability. The most common nanoparticles used TDDS are self-assembled liposomes, solid-li-pid nanoparticles, polymeric micelles, and inorganic nanoparticles. Compared with organic nanoparticles, inorganic nanoparticles offer higher physiochemical stability, easier surface functional-ization, and possess a tunable particle size and varied morphology. Thus, developing novel transdermal nanodevices based on inorganic nanoparticles is one of the fastest growing fields in nano-medicine.","PeriodicalId":6941,"journal":{"name":"Acta pharmaceutica Hungarica","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88636101","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}
Pub Date : 2021-11-15DOI: 10.33892/aph.2021.91.253-254
M. Király, K. Sántha, B. Kállai-Szabó, Nikolett Kállai-Szabó, I. Antal, K. Ludányi
{"title":"β-Galactosidase Containing Innovative Drug Delivery System","authors":"M. Király, K. Sántha, B. Kállai-Szabó, Nikolett Kállai-Szabó, I. Antal, K. Ludányi","doi":"10.33892/aph.2021.91.253-254","DOIUrl":"https://doi.org/10.33892/aph.2021.91.253-254","url":null,"abstract":"","PeriodicalId":6941,"journal":{"name":"Acta pharmaceutica Hungarica","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87590521","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}
Pub Date : 2021-11-15DOI: 10.33892/aph.2021.91.202-203
D. Oral, Gökalp Çetin, Aylin Balcı, P. Erkekoğlu, R. Şimşek
Hypertension is the biggest risk factor for atherosclerosis, which is a chronic vascular inflammatory disease. Normal endothelial cellular functions are disturbed in atherosclerosis. 1,4-dihydropiridines (1,4-DHPs) are an important class of bioactive molecules. Studies on 1,4DHP ring system have come by a new dimension after nifedipine and later amlodipine were introduced. Since then, several modifications were experimented on 1,4-DHP ring and investigation of other pharmacological activities along with their cardiovascular effects has gained speed. Hexahydrokinolines, the analogues of 1,4-DHP, are now intensively investigated for their calcium channel blocking activities. In the recent years, their inhibitory effects on transforming growth factor beta (TGF-β), their anti-atherogenic and anti-inflammatory effects were also discovered. The aim of this study was to evaluate the effects of 1,4-DHP derivatives on TGF-β in silico. In addition, the cytotoxic and oxidative stress-producing effects of 1,4-DHP derivatives (with a general formula of alkyl 4-(2-fluoro-4-(trifluoromethyl) phenyl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) were determined in mouse 3T3 fibroblast cells.
{"title":"Synthesis and Characterization of New Hexahydroquinoline Derivatives, In Silico Determination of Their Inhibitory Effects on Transforming Growth Factor Beta (TGF-β) and Their Effects on Oxidative Stress In Vitro","authors":"D. Oral, Gökalp Çetin, Aylin Balcı, P. Erkekoğlu, R. Şimşek","doi":"10.33892/aph.2021.91.202-203","DOIUrl":"https://doi.org/10.33892/aph.2021.91.202-203","url":null,"abstract":"Hypertension is the biggest risk factor for atherosclerosis, which is a chronic vascular inflammatory disease. Normal endothelial cellular functions are disturbed in atherosclerosis. 1,4-dihydropiridines (1,4-DHPs) are an important class of bioactive molecules. Studies on 1,4DHP ring system have come by a new dimension after nifedipine and later amlodipine were introduced. Since then, several modifications were experimented on 1,4-DHP ring and investigation of other pharmacological activities along with their cardiovascular effects has gained speed. Hexahydrokinolines, the analogues of 1,4-DHP, are now intensively investigated for their calcium channel blocking activities. In the recent years, their inhibitory effects on transforming growth factor beta (TGF-β), their anti-atherogenic and anti-inflammatory effects were also discovered. The aim of this study was to evaluate the effects of 1,4-DHP derivatives on TGF-β in silico. In addition, the cytotoxic and oxidative stress-producing effects of 1,4-DHP derivatives (with a general formula of alkyl 4-(2-fluoro-4-(trifluoromethyl) phenyl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) were determined in mouse 3T3 fibroblast cells.","PeriodicalId":6941,"journal":{"name":"Acta pharmaceutica Hungarica","volume":"367 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91465657","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}
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