Antiviral Therapy最新文献

{"title":"Comparative efficacy and safety of tenofovir amibufenamide vs tenofovir alafenamide in the initial 48-week treatment of high viral load chronic hepatitis B: A single-centre retrospective study.","authors":"Qing Zhang,Jianhua Xu,Dan Liu,Lilin Wang,Shan Ren,Sujun Zheng,Xinyue Chen,Li Qi,Junfeng Lu","doi":"10.1177/13596535241284226","DOIUrl":"https://doi.org/10.1177/13596535241284226","url":null,"abstract":"BACKGROUND/AIMTenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB).METHODSWe retrospectively collected clinical data from March 1 2022 to June 30 2022 for highly viremic CHB patients who received either TMF (n = 58) or TAF (n = 32) as their initial monotherapy at Beijing YouAn Hospital. To understand the efficacy and safety of TMF over 48 weeks, we compared the virological response rates and HBeAg/HBsAg serological clearance rates between TMF and TAF groups. Also, the changes in serum creatinine, eGFR and serum lipid levels were assessed.RESULTSBaseline median HBV DNA levels were 7.85 (6.89, 8.36) IgIU/ml for TMF and 7.44 (6.89, 8.03) IgIU/ml for TAF. Median ALT levels were 102.0 (56.0, 210.0) U/L for TMF and 195.0 (73.5, 371.0) U/L for TAF, with HBeAg positivity rates of 70.7% and 75.0%, respectively. At 48 weeks, virological response rates (HBV DNA <10 IU/ml) were 43.5% (20/46) for TMF and 42.9% (12/28) for TAF (p = 1.000). ALT normalization rates were 87.9% for TMF and 90.6% for TAF (p = .969), and HBeAg serological clearance rates were 21.1% and 18.2%, respectively (p = 1.000). No patients achieved HBsAg clearance. Compared with the baseline, LDL-C levels increased, while eGFR decreased, with no significant differences in serum creatinine, triglycerides and total cholesterol levels noted at week 48 for both TMF and TAF groups.CONCLUSIONTMF demonstrates comparable antiviral efficacy to TAF when used as initial therapy in highly viremic CHB patients, with similar impacts on renal function and lipid profiles.","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of risk factors and prediction model construction for varicella encephalitis in children: A retrospective cohort study.","authors":"Ce Wang, Li Tang, Dandan Guo","doi":"10.1177/13596535241291132","DOIUrl":"https://doi.org/10.1177/13596535241291132","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to analyze the risk factors for varicella encephalitis in children and establish a predictive model.</p><p><strong>Methods: </strong>This retrospective cohort study included a varicella encephalitis group (<i>n</i> = 75) and a varicella-non-encephalitis group (<i>n</i> = 135). Logistic regression analysis was employed to find risk factors for varicella encephalitis and create a predictive model.</p><p><strong>Results: </strong>Older age, vomiting, poor mental status, and prolonged rash duration were independent risk factors for varicella encephalitis (<i>p</i> < .05). The predictive model for varicella encephalitis combined above four factors. The ROC curve of the predictive model showed an area under the curve of 0.955 (95% CI 0.925-0.986) for varicella encephalitis in children with a sensitivity of 94.7%, and a specificity of 86.0%.</p><p><strong>Conclusion: </strong>Children with varicella who are older, experience vomiting, exhibit poor mental status, or have a prolonged rash duration should be closely monitored clinically. The predictive model combining these four factors demonstrates good predictive efficiency.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Andrographolide suppresses SARS-CoV-2 infection by downregulating ACE2 expression: A mechanistic study.","authors":"Qing Li, Hongmei Lu, Yongdui Ruan, Yuxuan Geng, Zuguo Zhao, Ying Liu, Long Feng, Wentao Guo","doi":"10.1177/13596535241259952","DOIUrl":"10.1177/13596535241259952","url":null,"abstract":"<p><p>Angiotensin-converting enzyme 2 (ACE2) is the receptor that enables SARS-CoV-2 to invade host cells. Previous studies have reported that reducing ACE2 expression may have an anti-SARS-CoV-2 effect. In this study, we constructed a pGL4.10-F2-ACE2 vector with double luciferase genes (firefly and Renilla luciferase) under the control of the ACE2 promoter and used it to screen compounds from Chinese traditional medicinal herbs (CTMHs) that can inhibit ACE2 transcription in human cells. We transfected HEK293T cells with pGL4.10-F2-ACE2 and treated them with CTMH compounds and then measured fluorescence to evaluate the indirect inhibition of ACE2 transcription. Out of 37 compounds tested, andrographolide demonstrated a dose-dependent inhibition of ACE2 transcription. We further confirmed by RT-qPCR and Western blot assays that andrographolide also reduced ACE2 expression in BEAS-2B cells in a dose-dependent manner. Moreover, pseudovirus infection assays in BEAS-2B cells demonstrated that andrographolide can inhibit SARS-CoV-2 infection in a dose-dependent manner. These results suggest that andrographolide has potential anti-SARS-CoV-2 activity and could be a candidate drug for COVID-19 prevention and treatment.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In-silico</i> approach to characterize the structure and function of a hypothetical protein of Monkeypox virus exploring Chordopox-A20R domain-containing protein activity.","authors":"Md Iqbal Hosen, Md Easin Mia, Md Nur Islam, Most Ummay Salma Khatun, Tanvir Hossain Emon, Md Anwar Hossain, Farzana Akter, Md Abdul Kader, Sadia Hossain Jeba, Asm Faisal, Md Abunasar Miah","doi":"10.1177/13596535241255199","DOIUrl":"10.1177/13596535241255199","url":null,"abstract":"<p><p><b>Background:</b> Monkeypox has emerged as a noteworthy worldwide issue due to its daily escalating case count. This illness presents diverse symptoms, including skin manifestations, which have the potential to spread through contact. The transmission of this infectious agent is intricate and readily transfers between individuals.<b>Methods:</b> The hypothetical protein MPXV-SI-2022V502225_00135 strain of monkeypox underwent structural and functional analysis using NCBI-CD Search, Pfam, and InterProScan. Quality assessment utilized PROCHECK, QMEAN, Verify3D, and ERRAT, followed by protein-ligand docking, visualization, and a 100-nanosecond simulation on Schrodinger Maestro.<b>Results:</b> Different physicochemical properties were estimated, indicating a stable molecular weight (49147.14) and theoretical pI (5.62) with functional annotation tools predicting the target protein to contain the domain of Chordopox_A20R domain. In secondary structure analysis, the helix coil was found to be predominant. The three-dimensional (3D) structure of the protein was obtained using a template protein (PDB ID: <i>6zyc.1</i>), which became more stable after YASARA energy minimization and was validated by quality assessment tools like PROCHECK, QMEAN, Verify3D, and ERRAT. Protein-ligand docking was conducted using PyRx 9.0 software to examine the binding and interactions between a ligand and a hypothetical protein, focusing on various amino acids. The model structure, active site, and binding site were visualized using the CASTp server, FTsite, and PyMOL. A 100 nanosecond simulation was performed with ligand CID_16124688 to evaluate the efficiency of this protein.<b>Conclusion:</b> The analysis revealed significant binding interactions and enhanced stability, aiding in drug or vaccine design for effective antiviral treatment and patient management.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of swallowability and acceptability of scored darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) tablets in HIV-1-infected children aged ≥6 to <12 years, using matching placebo tablets: A randomized study.","authors":"Sandy Van Hemelryck, Erika Van Landuyt, Veerle Hufkens, Simon Vanveggel","doi":"10.1177/13596535241248282","DOIUrl":"10.1177/13596535241248282","url":null,"abstract":"<p><strong>Background: </strong>Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) was developed as a once-daily, complete antiretroviral (ARV) regimen therapy to address the need for simplified protease inhibitor-based ARV regimens. This study assessed the swallowability and acceptability for long-term use of scored placebo tablets matching the D/C/F/TAF FDC tablets in children living with HIV-1.</p><p><strong>Methods: </strong>This study (NCT04006704) was a Phase 1, open-label, randomized, single-dose, 2-period, 2-sequence crossover study in children living with HIV-1, aged ≥6 to <12 years and weighing ≥25 to <40 kg, on a stable ARV regimen for ≥3 months. Participants were asked to swallow whole (size, 21 × 11 × 7 mm) and split matching placebo D/C/F/TAF tablets. Swallowability of the matching placebo D/C/F/TAF tablets (primary endpoint) was assessed by observers. Acceptability of taking matching placebo D/C/F/TAF tablets and current ARVs was evaluated by participants using a 3-point questionnaire. Participants rated the acceptability for long-term daily use of the placebo D/C/F/TAF tablets, and observers assessed how easily caregivers could split a scored tablet by hand, using 3-point questionnaires.</p><p><strong>Results: </strong>Among the 24 participants who enrolled and completed the study, 95.8% (23/24) were able to swallow the whole and split matching placebo D/C/F/TAF tablets after 1 or 2 attempts. Most participants (>70%) rated the acceptability of tablets for long-term daily use as acceptable or good to take. Breaking the tablets was considered easy or OK by 79.2% (19/24) of caregivers.</p><p><strong>Conclusion: </strong>Scored D/C/F/TAF FDC tablets are swallowable - with whole favoured over split - and considered at least acceptable for long-term daily intake in children living with HIV-1 aged ≥6 to <12 years.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04006704.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Failure of bamlanivimab with selection of E484K mutation in an allogeneic stem cell transplant recipient with nosocomial SARS-CoV-2 infection.","authors":"Inès Boussen, Maud Salmona, Flore Sicre De Fontbrune, Aliénor Xhaard, Nathalie De Castro, Constance Delaugerre, Marie-Laure Chaix, Jean-Michel Molina","doi":"10.1177/13596535221097495","DOIUrl":"10.1177/13596535221097495","url":null,"abstract":"<p><p>We report the case of an allogeneic stem cell transplant recipient with nosocomial acquisition of SARS-CoV-2 infection who received antispike neutralizing monoclonal antibody bamlanivimab 2 days after diagnosis of SARS-CoV-2 infection but progressed to severe COVID-19 pneumonia and died with the selection of E484K/Q resistance mutations to bamlanivimab.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139728864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse drug reactions attributed to generic substitution of antiretroviral medications among HIV treatment and pre-exposure prophylaxis clients in British Columbia, Canada.","authors":"Katherine J Lepik, Olivia L Hunt, Nic Bacani, Lu Wang, Marianne Harris, Junine Toy, Taylor McLinden, Paul Sereda, Linda J Akagi, Erin Ready, Julio Sg Montaner, Rolando Barrios","doi":"10.1177/13596535241233128","DOIUrl":"10.1177/13596535241233128","url":null,"abstract":"<p><strong>Background: </strong>In British Columbia, antiretrovirals (ARVs) for HIV treatment (HIV-Tx) and pre-exposure prophylaxis (PrEP) are free-of-charge through publicly-funded Drug Treatment Programs (DTPs). When available, less costly generics are substituted for brand-name ARVs. We describe the incidence and type of product substitution issue (PSI) adverse drug reactions (ADRs) attributed to generic ARVs.</p><p><strong>Methods: </strong>Cohorts included DTP clients ≥19 years who received generic ARVs for HIV-Tx (abacavir-lamivudine, emtricitabine-tenofovir DF, efavirenz-emtricitabine-tenofovir DF, atazanavir or darunavir between 01 Jun 2017 and 30 Jun 2022) or PrEP (emtricitabine-tenofovir DF, 01 Apr 2018 to 30 Jun 2022). Demographic, ARV and ADR data were extracted from DTP databases and summarized by descriptive statistics. PSI incidence was calculated for each product during the year following brand-to-generic and generic-to-generic transitions (first-year-post-rollout), and compared between generic versions using generalized estimating equations. For context, incidence of any ARV product-related ADR was calculated in the same 1-year periods.</p><p><strong>Results: </strong>During first-year-post-rollout periods, 5339 HIV-Tx (83% male, median age 52 years) and 8095 PrEP (99% male, median 33 years) clients received generic ARVs, and reported 78 and 23 generic PSIs, respectively. PSI incidence was <1% for most generic ARVs, with mild-moderate symptoms including gastrointestinal upset, headache, dizziness, fatigue/malaise and skin rash. In HIV-Tx clients, the efavirenz-containing product had higher PSI incidence than other ARVs (2.2%, <i>p</i> = .004), due to more neuropsychiatric adverse reactions. Any ADR incidence was stable across measurement periods, and generic PSIs represented less than one third of all product-related ADRs.</p><p><strong>Conclusions: </strong>Generic substitution of antiretrovirals for HIV-Tx and PrEP was well tolerated, with ≤2% incidence of mild-moderate PSI ADRs.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139904878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA.","authors":"Nicolas Margot, Nina Pennetzdorfer, Vidula Naik, Martin Rhee, Christian Callebaut","doi":"10.1177/13596535231220754","DOIUrl":"10.1177/13596535231220754","url":null,"abstract":"<p><strong>Background: </strong>Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function for the treatment of heavily treatment-experienced people with HIV (PWH) harbouring multidrug resistance in combination with an optimized background regimen (OBR). Here, we describe in vitro analysis of the interplay between entry inhibitors (EI; enfuvirtide, fostemsavir, ibalizumab, and maraviroc) susceptibility and LEN susceptibility in samples from 72 participants in the phase 2/3 CAPELLA study, as well as the emergence of resistance in CAPELLA through 52 weeks.</p><p><strong>Methods: </strong>The phenotypic susceptibility to EIs of screening samples from participants was analysed using entry assays, and susceptibility to LEN was generated. Genotypic and phenotypic resistance to LEN was evaluated for subjects with virological failure through Week 52.</p><p><strong>Results: </strong>Overall, viruses with resistance to EIs showed no cross-resistance to LEN, with a mean fold change from wild type close to 1.0. Of the 22 participants analysed for resistance through Week 52, 9 participants (13%) had emergence of capsid resistance mutation(s) while the remaining 13 participants (18%) had no change in the capsid sequence.</p><p><strong>Conclusion: </strong>The <i>gag</i> sequence from EI-resistant isolates did not affect LEN susceptibility. The lack of cross-resistance to LEN across ARV-resistant isolates supports the use of LEN in PWH regardless of their treatment history. During the second half-year period of the CAPELLA Study, development of LEN resistance was rare and was overall associated with functional LEN monotherapy due to either nonadherence or resistance-driven non-susceptibility to OBR.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138794829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dolutegravir and rilpivirine as successful initial antiretroviral therapy in a treatment-naive patient with HIV-1: A case report.","authors":"S Jawad Zafar, Bruce L Gilliam, Sarah A Schmalzle","doi":"10.1177/13596535231218875","DOIUrl":"10.1177/13596535231218875","url":null,"abstract":"","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RVX-208, an inducer of Apolipoprotein A-I, inhibits the particle production of hepatitis B virus through activation of cGAS-STING pathway.","authors":"Dan Shu, Lin Cheng, Kefei Yuan, Dan Liu, He Wei","doi":"10.1177/13596535231219639","DOIUrl":"10.1177/13596535231219639","url":null,"abstract":"<p><strong>Background: </strong>Previously, we have demonstrated that Apolipoprotein A-I (ApoA-I) could inhibit the secretion of Hepatitis B virus (HBV), suggesting that stimulation of ApoA-I may block particle production. In the present study, we evaluated the anti-HBV effect of RVX-208, a small-molecule stimulator of ApoA-I gene expression.</p><p><strong>Methods: </strong>RVX-208 was used to treat HepG2.2.15 cell, a HepG2 derived cell line stably producing HBV virus. Real-time PCR was performed to examine the HBV DNA levels. Magnetic particles, which were coated with anti-HBS or anti-HBE antibody, were used to examine the HBsAg and HBeAg levels in the supernatant of cultured HepG2.2.15 cells in combination with the enzyme conjugates that were prepared with horseradish peroxidase labelled anti-HBS or anti-HBE antibody in a double antibody sandwich manner. RNA-seq, immunoblots and real-time PCR were used to analyze the functional mechanism of RVX-208.</p><p><strong>Results: </strong>RVX-208 could elevate the ApoA-I protein levels in HepG2.2.15 cells. In the meantime, RVX-208 significantly repressed HBV DNA, HBsAg and HBeAg levels in the supernatants of HepG2.2.15 cells. RNA-seq data revealed that RVX-208 treatment not only affected the cholesterol metabolism, which is closely related to ApoA-I, but also regulated signalling pathways that are associated with antiviral immune response. Moreover, mechanistic studies demonstrated that RVX-208 could activate cGAS-STING pathway and upregulate the transcription of a series of interferons, pro-inflammatory cytokines and chemokines with antiviral potential that are at the downstream of cGAS-STING pathway.</p><p><strong>Conclusion: </strong>Our study demonstrated that RVX-208, an inducer of ApoA-I, could suppress HBV particle production through activation of cGAS-STING pathway.</p>","PeriodicalId":8364,"journal":{"name":"Antiviral Therapy","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}