Antiviral Chemistry and Chemotherapy最新文献

{"title":"Anti-HIV-1 activity determined by β-galactosidase activity in the multinuclear activation of an indicator assay is comparable with that by a conventional focus counting method","authors":"F. Miyamoto, Kumi Kawaji, S. Oishi, N. Fujii, M. Kaku, E. Kodama","doi":"10.1177/2040206615614164","DOIUrl":"https://doi.org/10.1177/2040206615614164","url":null,"abstract":"Background Direct comparison of enzymatic and original blue cell-counting detections with the multinuclear activation of an indicator (MAGI) cells, so far, remains to be performed in parallel. Although inhibitors for reverse transcription solely inhibit the reverse transcription step, those for HIV-1 entry block syncytium formation of HIV-1-infected MAGI cells in addition to the entry (dual inhibition). It raises a concern that reduction of enzymatic activity is artificially influenced by syncytium-blocking activity of inhibitors for entry. Methods The MAGI cells with a syncytium inducible strain, HIV-1IIIB, were used for anti-HIV activity determination both with conventional counting with X-Gal staining and measurement of chlorophenol red β-d-galactopyranoside conversion with a plate reader. Results Infectivity of HIV-1 in the MAGI cells was highly correlated with both methods. In microscopic observation, small blue cells with single or a couple of nuclei were dominantly observed in the presence of inhibitors for entry, but not in the presence of those for reverse transcription. Actual anti-HIV-1 activities were comparable or moderately sensitive in the chlorophenol red β-d-galactopyranoside method. Conclusions Antiviral activities of inhibitors for entry obtained from both enzymatic and counting methods appear to be comparable, even in infection of a highly syncytia inducible HIV-1IIIB strain.","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"46 1","pages":"77 - 82"},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88613162","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":"Design, synthesis, and anti-HIV-1 activity of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives.","authors":"Norikazu Sakakibara,&nbsp;Masanori Baba,&nbsp;Mika Okamoto,&nbsp;Masaaki Toyama,&nbsp;Yosuke Demizu,&nbsp;Takashi Misawa,&nbsp;Masaaki Kurihara,&nbsp;Kohji Irie,&nbsp;Yoshihisa Kato,&nbsp;Tokumi Maruyama","doi":"10.1177/2040206614566584","DOIUrl":"https://doi.org/10.1177/2040206614566584","url":null,"abstract":"<p><strong>Background: </strong>A new series of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors.</p><p><strong>Methods: </strong>A series of new 6-azido and 6-amino derivatives of 1-substituted-3-(3,5-dimethylbenzyl)uracils were synthesized using our previously reported method, and three acyclic derivatives were synthesized from urea. The anti-HIV-1 activities of these compounds were determined based on the inhibition of virus-induced cytopathogenicity in MT-4 cells. The cytotoxicities of the compounds were evaluated using the viability of mock-infected cells.</p><p><strong>Results: </strong>Some of these compounds showed good-to-moderate activities against HIV-1 with half maximal effective concentration (EC50) values in the submicromolar or subnanomolar range. Compared with emivirine, compound 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil showed significant anti-HIV-1 activity with an EC50 value of 10 nM and a high selectivity index of 1923. Preliminary structure-activity relationship studies and molecular modeling analyses were carried out to explore the major interactions between HIV-1 reverse transcriptase and the potent inhibitor 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil; these results may be important for further development of this class of compounds as anti-HIV-1 agents.</p><p><strong>Conclusion: </strong>The excellent activity of 6-amino-3-(3,5-dimethylbenzyl)-1-(4-aminobenzyl)uracil (EC50: 0.010 ± 0.006 µM, SI: >1923) may serve as the basis for conducting further investigations on the behavior of this class of compounds against drug-resistant mutants.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"24 1","pages":"3-18"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206614566584","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34266262","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":"Efficacy of N-methanocarbathymidine against genital herpes simplex virus type 2 shedding and infection in guinea pigs.","authors":"David I Bernstein,&nbsp;Fernando J Bravo,&nbsp;Derek A Pullum,&nbsp;Hui Shen,&nbsp;Mei Wang,&nbsp;Aquilur Rahman,&nbsp;Robert I Glazer,&nbsp;Rhonda D Cardin","doi":"10.1177/2040206614566581","DOIUrl":"https://doi.org/10.1177/2040206614566581","url":null,"abstract":"<p><strong>Background: </strong>Current approved nucleoside therapies for genital herpes simplex virus (HSV) infections are effective but improved therapies are needed for treatment of both acute and recurrent diseases.</p><p><strong>Methods: </strong>The effects of N-methanocarbathymidine were evaluated and compared to acyclovir using guinea pig models of acute and recurrent infection. For acute disease following intravaginal inoculation of 10(6 )pfu HSV-2 (MS strain), animals were treated intraperitoneally beginning 24 h post-infection, and the effects on disease severity, vaginal virus replication, subsequent recurrences, and latent virus loads were evaluated. For evaluation of recurrent infection, animals were treated for 21 days beginning 14 days after infection and disease recurrence and recurrent shedding were evaluated.</p><p><strong>Results: </strong>Treatment of the acute disease with N-methanocarbathymidine significantly reduced the severity of acute disease and decreased acute vaginal virus shedding more effectively than acyclovir. Significantly, none of the animals developed visible disease in the high-dose N-methanocarbathymidine group and this was the only group in which the number of days with recurrent virus shedding was reduced. Treatment of recurrent disease was equivalent to acyclovir when acyclovir was continuously supplied in the drinking water.</p><p><strong>Conclusion: </strong>N-methanocarbathymidine was effective as therapy for acute and recurrent genital HSV-2 disease in the guinea pig models.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"24 1","pages":"19-27"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206614566581","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34266263","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":"Identification of a dibenzocyclooctadiene lignan as a HIV-1 non-nucleoside reverse transcriptase inhibitor.","authors":"Ying-Shan Han,&nbsp;Wei-Lie Xiao,&nbsp;Hongtao Xu,&nbsp;Victor G Kramer,&nbsp;Yudong Quan,&nbsp;Thibault Mesplède,&nbsp;Maureen Oliveira,&nbsp;Susan P Colby-Germinario,&nbsp;Han-Dong Sun,&nbsp;Mark A Wainberg","doi":"10.1177/2040206614566580","DOIUrl":"https://doi.org/10.1177/2040206614566580","url":null,"abstract":"<p><strong>Background: </strong>Due to resistance to all classes of anti-HIV drugs and drug toxicity, there is a need for the discovery and development of new anti-HIV drugs.</p><p><strong>Methods: </strong>HIV-1 inhibitors were identified and biologically characterized for mechanism of action.</p><p><strong>Results: </strong>We identified a dibenzocyclooctadiene lignan, termed HDS2 that possessed anti-HIV activity against a wide variety of viral strains with EC50 values in the 1-3 µM range. HDS2 was shown to act as an NNRTI by qPCR and in vitro enzyme assays.</p><p><strong>Conclusions: </strong>This compound provides a new scaffold for further optimization of activity through structure-guided design.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"24 1","pages":"28-38"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206614566580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34266264","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":"Influence of L-lysine amino acid on the HIV-1 RNA replication in vitro.","authors":"Evgeny Vlad Butorov","doi":"10.1177/2040206614566582","DOIUrl":"https://doi.org/10.1177/2040206614566582","url":null,"abstract":"<p><strong>Background: </strong>Virus replication strongly depends on host metabolic machinery and essential cellular factors, in particular, on amino acid profiles. Amino acids play an important role in the pathogenesis of all virus-related infections both as basic substrates for protein synthesis and as regulators in many metabolic pathways, including gene expression. The inhibitory effects of deficiency or excess of these essential elements on virus replication are widely appreciated. Although the same interrelationship between host cellular factors and HIV have been recognized for a long time, the effects of amino acids on HIV-1 RNA replication dynamic is not yet well documented. Our aim was to determine in this pilot study the direct effect of L-lysine amino acid on HIV-1 RNA replication in vitro in HIV-infected patients.</p><p><strong>Methods: </strong>A total of 100 HIV-1-infected males without highly active antiretroviral therapy (HAART) were monitored in our center. The patients were in stage A of the disease according to the 1993 Centers for Disease Control (CDC) classification system for HIV-infection. Patients with HIV were enrolled in one stage (A) of the disease with the average amount CD4 lymphocytes in the range of 200-300 cells/µL at the time of sample acquisition. For evaluation of the effects of essential L-lysine amino acid on HIV-1 RNA replication level, we used a model of amino acid-excess system in vitro following incubation of plasma samples for 24 h at 25 °C. Quantitative HIV-1 RNA assay was performed using (RT-PCR) reverse-transcriptase polymerase chain reaction (Rotor-Gene Q, QIAGEN, Germany).</p><p><strong>Results: </strong>The mean HIV-1 RNA levels were significantly higher in the enriched peripheral blood mononuclear cells plasma samples HIV-infected subjects after 24 h incubation at 25 °C temperature than in the plasma samples the same patients studied on the date of blood tests (p < 0.0001). The number of HIV-1 RNA copies increased in 1.5 times. We observed that in plasma of the same HIV-infected patients after adding L-lysine and following incubation in vitro, viral load increased significantly in comparison with standard samples (p < 0.0001). The increased viral load was found in 100/92 (92%) of HIV-infected subjects. The average number of HIV-1 RNA copies in samples had increased by 4.0 times. However, we found no difference in HIV-1 RNA levels after replacement of L-lysine for L-arginine in comparison samples in the same HIV-infected patients. It is obvious that the addition of L-arginine does not increase viral replication in vitro as L-lysine amino acid supplement does. Additionally, no increase in viral load was determined after adding L-lysine and non toxic doses of its inhibitor (L-lysine alpha-oxidase) in plasma samples.</p><p><strong>Conclusions: </strong>The results show that L-lysine amino acid excess is characterized by significant increased of HIV-1 RNA copies in enriched peripheral blood mononuclear","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"24 1","pages":"39-46"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2040206614566582","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34266265","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":"AVCC 1990-2015--A journal to combine antiviral biology and antiviral chemistry enters the third era.","authors":"Hugh J Field","doi":"10.1177/2040206615574801","DOIUrl":"10.1177/2040206615574801","url":null,"abstract":"","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"24 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890501/pdf/10.1177_2040206615574801.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34266261","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":"Recent findings on the mechanisms involved in tenofovir resistance.","authors":"Pinar Iyidogan,&nbsp;Karen S Anderson","doi":"10.3851/IMP2628","DOIUrl":"https://doi.org/10.3851/IMP2628","url":null,"abstract":"<p><p>Since its approval for clinical use in 2001, tenofovir (TFV) has become one of the most frequently prescribed nucleotide analogues used in combination with other antiretroviral agents against HIV-1 infection. Although reverse transcriptase inhibitors (RTIs) including TFV have been shown to be highly potent with reasonable safety profiles in the clinic, drug resistance hinders the effectiveness of current therapies and even causes treatment failure. Therefore, understanding the resistance mechanisms of RT and exploring the potential antiviral synergy between the different RTIs in combination therapies against the resistance mechanisms would greatly improve the long-term efficacy of existing and future regimens. We have studied the pyrophosphorolytic removal of TFV, a major resistance mechanism that RT utilizes, from two different viral sequences and observed interesting outcomes associated with the sequence context. Furthermore, addition of efavirenz, a non-nucleoside RTI, inhibits this removal process confirming the synergistic antiviral effects. This article highlights our recently published work on the viral sequence context contributing to the study of anti-HIV drug resistance in conjunction with the benefits of combining various RTIs that may have been neglected previously. </p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"23 6","pages":"217-22"},"PeriodicalIF":0.0,"publicationDate":"2014-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3851/IMP2628","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31488844","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":"Myristoylated derivatives of 2',3'-didehydro-2',3'-dideoxythymidine (stavudine) bi-functional prodrugs with potent anti-HIV-1 activity and low cytotoxicity.","authors":"Ramendra K Singh,&nbsp;Agnieszka Miazga,&nbsp;Aleksandra Dąbrowska,&nbsp;Andrzej Lipniacki,&nbsp;Andrzej Piasek,&nbsp;Tadeusz Kulikowski,&nbsp;David Shugar","doi":"10.3851/IMP2679","DOIUrl":"https://doi.org/10.3851/IMP2679","url":null,"abstract":"<p><strong>Background: </strong>To improve in vitro antiviral activity and selectivity of stavudine (d4T), a range of its bi-functional prodrugs, 5'-O-myristoylated derivatives, have been synthesized.</p><p><strong>Methods: </strong>Stavudine 5'-O-myristoylated esters were synthesized using modified Parang's procedure. The cytotoxicity and anti-HIV activity was evaluated in the established MT-4 cell line. The level of p24 protein in culture medium was assayed, and EC50 and EC90 values were determined.</p><p><strong>Results: </strong>Excellent anti-HIV activity was obtained for stavudine derivatives 2',3'-didehydro-2',3'-dideoxy-5'-O-(11-thioethylundecanoyl) thymidine, 2',3'-didehydro-2',3'-dideoxy-5'-O-(12-thioethyldodecanoyl) thymidine and 5'-O-(12-azidododecanoyl)-2',3'-didehydro-2',3'-dideoxythymidine with C10 and C11 alkyl chains bearing thioethyl- and azido- substituents. These prodrugs were more potent than the parent stavudine, as is clear from their EC50 values: 2',3'-didehydro-2',3'-dideoxy-5'-O-(11-thioethylundecanoyl) thymidine (R=CO(CH2)10SC2H5, EC50 0.06 μM), 2',3'-didehydro-2',3'-dideoxy-5'-O-(12-thioethyldodecanoyl) thymidine (R=CO(CH2)11SC2H5, EC50 0.09 μM) and 5'-O-(12-azidododecanoyl)-2',3'-didehydro-2',3'-dideoxythymidine (R=CO(CH2)11N3, EC50 0.06 μM), while 50% cytotoxic concentration was >16.65 μM, >7.5 μM and >18.53 μM, respectively.</p><p><strong>Conclusions: </strong>Overall data demonstrate that compounds 2',3'-didehydro-2',3'-dideoxy-5'-O-(11-thioethylundecanoyl) thymidine, 2',3'-didehydro-2',3'-dideoxy-5'-O-(12-thioethyldodecanoyl) thymidine and 5'-O-(12-azidododecanoyl)-2',3'-didehydro-2',3'-dideoxythymidine are very potent and selective anti-HIV agents and could be useful in treatment of HIV infections of the central nervous system.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"23 6","pages":"231-5"},"PeriodicalIF":0.0,"publicationDate":"2014-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3851/IMP2679","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31690619","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":"Inhibition of novel reassortant avian influenza H7N9 virus infection in vitro with three antiviral drugs, oseltamivir, peramivir and favipiravir.","authors":"Rui-Yuan Cao,&nbsp;Jun-Hai Xiao,&nbsp;Bin Cao,&nbsp;Song Li,&nbsp;Yohichi Kumaki,&nbsp;Wu Zhong","doi":"10.3851/IMP2672","DOIUrl":"https://doi.org/10.3851/IMP2672","url":null,"abstract":"<p><strong>Background: </strong>A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from three patients and was identified as H7N9 in China. Antiviral agents are required to treat patients with avian influenza H7N9 virus infection.</p><p><strong>Methods: </strong>In this study, we assessed the antiviral potential of oseltamivir, peramivir, favipiravir (T-705), amantadine and rimantadine against novel reassortant avian-origin influenza H7N9 virus in vitro.</p><p><strong>Results: </strong>All three avian influenza H7N9 virus strains were sensitive to oseltamivir, peramivir and favipiravir (T-705), but resistant to amantadine and rimantadine.</p><p><strong>Conclusions: </strong>Our data show a pattern of antiviral sensitivity for this novel H7N9 strain of influenza that suggests the compounds oseltamivir, peramivir and favipiravir should be useful for therapy.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"23 6","pages":"237-40"},"PeriodicalIF":0.0,"publicationDate":"2014-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3851/IMP2672","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31660054","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":"Characterization of permeability, stability and anti-HIV-1 activity of decitabine and gemcitabine divalerate prodrugs.","authors":"Christine L Clouser,&nbsp;Laurent Bonnac,&nbsp;Louis M Mansky,&nbsp;Steven E Patterson","doi":"10.3851/IMP2682","DOIUrl":"https://doi.org/10.3851/IMP2682","url":null,"abstract":"<p><strong>Background: </strong>Over 25 drugs have been approved for the treatment of HIV-1 replication. All but one of these drugs is delivered as an oral medication. Previous studies have demonstrated that two drugs, decitabine and gemcitabine, have potent anti-HIV-1 activities and can work together in synergy to reduce HIV-1 infectivity via lethal mutagenesis. For their current indications, decitabine and gemcitabine are delivered intravenously.</p><p><strong>Methods: </strong>As an initial step towards the clinical translation of these drugs for the treatment of HIV-1 infection, we synthesized decitabine and gemcitabine prodrugs in order to increase drug permeability, which has generally been shown to correlate with increased bioavailability in vivo. In the present study we investigated the permeability, stability and anti-HIV-1 activity of decitabine and gemcitabine prodrugs and selected the divalerate esters of each as candidates for further investigation.</p><p><strong>Results: </strong>Our results provide the first demonstration of divalerate prodrugs of decitabine and gemcitabine that are readily permeable, stable and possess anti-HIV-1 activity.</p><p><strong>Conclusions: </strong>These observations predict improved oral availability of decitabine and gemcitabine, and warrant further study of their ability to reduce HIV-1 infectivity in vivo.</p>","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"23 6","pages":"223-30"},"PeriodicalIF":0.0,"publicationDate":"2014-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3851/IMP2682","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31698791","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}