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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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hydroxychloroquine and azithromycin on viral load in the upper respiratory tract of severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) patients. The authors report that hydroxychloroquine (HCQ) had significant virus reducing effects, and that dual treatment of both HCQ and azithromycin further enhanced virus reduction. These data have triggered speculation whether these drugs should be considered as candidates for the treatment of severe COVID-19. However, questions have been raised regarding the study's data integrity, statistical analyses, and experimental design. We therefore reanalysed the original data to interrogate the main claims of the paper. Here we apply Bayesian statistics to assess the robustness of the original paper's claims by testing four variants of the data: 1) The assumes a positive effect, compared to a model of no effect. We find that the statistical evidence is highly sensitive to these data variants. Statistical evidence for the positive effect model ranged from strong for the original data (BF +0 ~11), to moderate when including patients who deteriorated (BF +0 ~4.35), to anecdotal when excluding untested patients (BF +0 ~2), and to anecdotal negative evidence if untested patients were assumed positive (BF +0 ~0.6). To assess whether HCQ is more effective when combined with AZ, we performed the same tests, and found only anecdotal evidence for the positive effect model for the original data (BF +0 ~2.8), and moderate evidence for all other variants of the data (BF +0 ~5.6). Our analyses only explore the effects of different assumptions about excluded and untested patients. These assumptions are not adequately reported, nor are they justified in the original paper, and we find that varying them causes substantive changes to the evidential support for the main claims of the original paper. This statistical uncertainty is exacerbated by the fact that the treatments were not randomised, and subject to several confounding variables including the patients consent to treatment, different care centres, and clinical decision-making. Furthermore, while the viral load measurements were noisy, showing multiple reversals between test outcomes, there is greater certainty around other clinical outcomes such as the 4 patients who seriously deteriorated. The fact that all of these belonged to the HCQ group should be assigned greater weight when evaluating the potential clinical efficacy of HCQ. Randomised controlled trials are currently underway, and will be critical in resolving this uncertainty as to whether HCQ and AZ are effective as a treatment for COVID-19. Warning: There have been reports of people self-administering chloroquine phosphate (intended for treatment of disease in aquarium fish) , which has led to at least one death and one serious illness. We state that under no circumstances should people self-administer hydroxychloroquine, chloroquine phosphate, azithromycin, or anything similar-sounding, or indeed any other drug, unless approved by a medical doctor. The FDA has issued a specific warning: https://www.fda.gov/animal-veterinary/product-safety-information/fda-letter-stakeholders-do-not-use-chloroquine-phosphate-intended-fis h-treatment-covid-19-humans . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not peer-reviewed) The copyright holder for this preprint .
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Reply to Gautret et al. 2020: A Bayesian reanalysis of the effects of hydroxychloroquine and azithromycin on viral carriage in patients with COVID-19


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This experiment was conducted to evaluate whether pretreatment with fenofibrate could mitigate acute lung injury (ALI) in a mice model of intestinal ischemia/reperfusion (I/R). Male C57BL/6 mice were randomly assigned into three groups (n = 6): sham, intestinal I/R + vehicle, and intestinal I/R + fenofibrate. Intestinal I/R was achieved by clamping the superior mesenteric artery. Fenofibrate (100 mg/kg) or equal volume of vehicle was injected intraperitoneally 60 minutes before the ischemia. At the end of experiment, measurement of pathohistological score, inflammatory mediators and other markers were performed. In addition, a 24-hour survival experiment was conducted in intestinal I/R mice treated with fenofibrate or vehicle. The chief results were as anticipated. Pathohistological evaluation indicated that fenofibrate ameliorated the local intestine damage and distant lung injury. Pretreatment with fenofibrate significantly decreased inflammatory factors in both the intestine and the lung. Consistently, renal creatine levels and hepatic ALT levels were significantly decreased in the fenofibrate group. Moreover, serum systemic inflammatory response indicators were significantly alleviated in the fenofibrate group. In addition, fenofibrate administration significantly improved the survival rate. Collectively, our data indicated that pretreatment with fenofibrate prior to ischemia attenuated intestinal I/R injury and ALI. Acute lung injury (ALI) is a critically severe, life-threatening condition in ICU, characterized by high mortality of approximately 40% 1 . ALI, along with its more severe form, acute respiratory distress syndrome, often results from a massive insult to the lung, whether be the direct alveolar infiltration or the indirect effects of systemic inflammatory response syndrome or multiple organ dysfunction syndromes 2 . An effective treatment of this life-threatening disorder calls for a better understanding of the molecular pathophysiology of ALI. The intestine is recognized to be one of the largest immune barrier systems and to be the source of bacteria and endotoxins in the body 3 . Previous reports indicate that the intestinal organ plays a crucial role in the development of ALI 4 . Mesenteric artery ischemia, a commonly seen critical state during small bowel transplantation or trauma, may lead to intestinal ischemia/reperfusion (I/R) injury. During the process of intestinal I/R injury, local bacteria overgrow and translocate, gastrointestinal mobility decreases, and mucosal permeability increases, all of which subsequently lead to the local intestine damage or distant lung injuries through the activation of systemic inflammatory response syndrome or multiple organ dysfunction syndromes 5,6 . Intestinal I/R is, therefore, a useful model for the investigation of pathophysiological mechanism of indirect ALI. Fenofibrate is known as an agonist of the peroxisome proliferator-activated receptor -α (PPARα ), the nuclear receptor superfamily member 7 . As a nuclear receptor activator, fenofibrate up-regulates or down-regulates genes that are involved in many pathophysiological processes, such as oxidative stress, inflammation, and leukocyte endothelium interactions 8, 9 . Recent studies have demonstrated an anti-oxidant, anti-inflammatory, and anti-ischemic role of fenofibrate to attenuate I/R injury in kidney 10,11 , liver 12 , brain 13,14 and heart 15 . But to date there are no literatures reporting the protective effects of fenofibrate in I/R injury in the organ of intestine. Moreover, the functional significance of fenofibrate in the intestinal I/R-induced ALI remains unclear. Therefore, this experiment is aimed to investigate whether fenofibrate administration would ameliorate the lung injury and inflammation in the model of intestinal I/R injury. Animals. The male C57BL/6 mice (8-10-wk-old; 20 ± 2 g) were purchased from Charles River (Beijing, China). Mice were kept in a temperature (21 ± 2 °C) and humidity (60 ± 5%) controlled room on a 12-hour light/dark cycle. They were fed a standard mice chow and water ad liblitum. All experiments were performed in accordance with the Declaration of Helsinki and were approved by the Institutional Animal Ethical Committee of the Peking Union Medical College Hospital.
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Protective effects of fenofibrate against acute lung injury induced by intestinal ischemia/reperfusion in mice OPEN


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Coronaviruses are a large group of enveloped, single-stranded positive-sense RNA viruses that infect a wide range of avian and mammalian species, including humans. The emergence of deadly human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) have bolstered research in these viral and often zoonotic pathogens. While coronavirus cell and tissue tropism, host range, and pathogenesis are initially controlled by interactions between the spike envelope glycoprotein and host cell receptor, it is becoming increasingly apparent that proteolytic activation of spike by host cell proteases also plays a critical role. Coronavirus spike proteins are the main determinant of entry as they possess both receptor binding and fusion functions. Whereas binding to the host cell receptor is an essential first step in establishing infection, the proteolytic activation step is often critical for the fusion function of spike, as it allows for controlled release of the fusion peptide into target cellular membranes. Coronaviruses have evolved multiple strategies for proteolytic activation of spike, and a large number of host proteases have been shown to proteolytically process the spike protein. These include, but are not limited to, endosomal cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, and trypsin. This review focuses on the diversity of strategies coronaviruses have evolved to proteolytically activate their fusion protein during spike protein biosynthesis and the critical entry step of their life cycle, and highlights important findings on how proteolytic activation of coronavirus spike influences tissue and cell tropism, host range and pathogenicity.
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Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis