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In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
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Main point: Hydroxychloroquine was found to be more potent than chloroquine at inhibiting SARS-CoV-2 in vitro. Hydroxychloroquine sulfate 400 mg given twice daily for 1 day, followed by 200 mg twice daily for 4 more days is recommended to treat SARS-CoV-2 infection. Abstract Background. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first broke out in Wuhan (China) and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection. Methods. The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells. Physiologically-based pharmacokinetic models (PBPK) were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen whilst considering the drug's safety profile. Results. Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than chloroquine (EC50=5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance. Hydroxychloroquine was found to be more potent than chloroquine to 4 / 25 inhibit SARS-CoV-2 in vitro.
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In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)


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Despite the clinical relevance, dengue virus (DENV) research has been hampered by the absence of robust reverse genetic systems to manipulate the viral serotypes for propagation and generation of mutant viruses. In this article, we describe application of an infectious clone system for DENV serotype 1 (DENV1). Similar to previous clones in both flaviviruses and coronaviruses, the approach constructs a panel of contiguous cDNAs that span the DENV genome and can be systematically and directionally assembled to produce viable, full-length viruses. Comparison of the virus derived from the infectious clone with the original viral isolate reveals identical sequence, comparable endpoint titers, and similar focus staining. Both focus-forming assays and percent infection by flow cytometry revealed overlapping replication levels in two different cell types. Moreover, serotype-specific monoclonal antibodies (MAbs) bound similarly to infectious clone and the natural isolate. Using the clone, we were able to insert a DENV4 type-specific epitope recognized by primate MAb 5H2 into envelope (E) protein domain I (EDI) of DENV1 and recover a viable chimeric recombinant virus. The recombinant DENV1 virus was recognized and neutralized by the DENV4 type-specific 5H2 MAb. The introduction of the 5H2 epitope ablated two epitopes on DENV1 EDI recognized by human MAbs (1F4 and 14C10) that strongly neutralize DENV1. Together, the work demonstrates the utility of the infectious clone and provides a resource to rapidly manipulate the DENV1 serotype for generation of recombinant and mutant viruses.
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Epitope Addition and Ablation via Manipulation of a Dengue Virus Serotype 1 Infectious Clone


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Background: As the gatekeepers of rural residents' health, teams of village doctors play a vital role in improving rural residents' health. However, the high turnover of village doctors, both individually and collectively, threaten the stability of village medical teams. This research evaluated the influence of job satisfaction, resilience, and work engagement on the village doctors' turnover intention, and explored the mediating role of work engagement and resilience between job satisfaction and the turnover intention of village doctors in China. Methods: A quantitative study using a self-administered questionnaire containing mostly structured items was conducted among village doctors with a sample size of 2693 from 1345 rural clinics in Shandong province, China, during May and June 2019. All variables including demographic characteristics, job satisfaction, resilience, work engagement and turnover intention were based on available literature, and measured on a 5-or 6-point Likert scale. Such statistical methods as one-way ANOVA, bivariate correlation, exploratory factor analysis (EFA), and Structural Equation Modelling (SEM) were used. Results: Up to 46.9% of the subjects had a higher turnover intention and more than 26.3% of them had a medium turnover intention. The job satisfaction of village doctors could not only have a direct negative effect on turnover intention (β = − 0.37, p < 0.001), but also have an indirect effect through work engagement (β = − 0.04,=< 0.001). Meanwhile, work engagement also had a direct negative impact on turnover intention (β = − 0.13, p < 0.001), and resilience had an indirect negative impact on turnover intention through work engagement (β = − 0.09, p < 0.001). The above results of this study strongly confirmed that job satisfaction, resilience, and work engagement were early, powerful predicators of village doctors' turnover intention. (Continued on next page) Conclusion: According to the results, the following should be taken seriously to improve job satisfaction: reasonable and fair income, effective promotion mechanism, fair social old-age security, reasonable workload, and strong psychological coping mechanisms for work stress. The turnover intention of village doctors could be reduced through improving job satisfaction, resilience and work engagement.
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The influence of job satisfaction, resilience and work engagement on turnover intention among village doctors in China: a cross-sectional study