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.

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 .
Reply to Gautret et al. 2020: A Bayesian reanalysis of the effects of hydroxychloroquine and azithromycin on viral carriage in patients with COVID-19

The Sec7 domain ADP-ribosylation factor (Arf) guanine nucleotide exchange factors (GEFs) are found in all eukaryotes, and are involved in membrane remodeling processes throughout the cell. This review is focused on members of the GBF/Gea and BIG/Sec7 subfamilies of Arf GEFs, all of which use the class I Arf proteins (Arf1-3) as substrates, and play a fundamental role in traYcking in the endoplasmic reticulum (ER)-Golgi and endosomal membrane systems. Members of the GBF/Gea and BIG/Sec7 subfamilies are large proteins on the order of 200 kDa, and they possess multiple homology domains. Phylogenetic analyses indicate that both of these subfamilies of Arf GEFs have members in at least Wve out of the six eukaryotic supergroups, and hence were likely present very early in eukaryotic evolution. The homology domains of the large Arf1 GEFs play important functional roles, and are involved in interactions with numerous protein partners. The large Arf1 GEFs have been implicated in several human diseases. They are crucial host factors for the replication of several viral pathogens, including poliovirus, coxsackievirus, mouse hepatitis coronavirus, and hepatitis C virus. Mutations in the BIG2 Arf1 GEF have been linked to autosomal recessive periventricular heterotopia, a disorder of neuronal migration that leads to severe malformation of the cerebral cortex. Understanding the roles of the Arf1 GEFs in membrane dynamics is crucial to a full understanding of traYcking in the secretory and endosomal pathways, which in turn will provide essential insights into human diseases that arise from misregulation of these pathways.
Large Arf1 guanine nucleotide exchange factors: evolution, domain structure, and roles in membrane traYcking and human disease

Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments. Between 2002 and 2003, severe acute respiratory syndrome (SARS) caused by coronavirus (SARS-CoV) affected over 30 countries on five continents. Soon after, HCoV-NL63 was identified in a seven-month-old infant with bronchiolitis and conjunctivitis in 2004 1 , and followed by HCoV-HKU1 in 2005 2 . Later, the Middle East Respiratory Syndrome coronavirus (MERS-CoV) rapidly spread worldwide with fatality rates up to 30% 3 . Several reports have recently demonstrated the existence of a SARS-like coronavirus, which indicates that coronavirus-associated respiratory tract infections continue to have a significant epidemic potential 4-6 . Therefore, there remains an urgent requirement for standardization of treatments in order to develop more effective interventional strategies for coronavirus-associated diseases. Clinical treatments implemented following the sudden outbreak of SARS-CoV included empirical and experimental types, although their effectiveness and side effects remain controversial. Antiviral drugs, including ribavirin, lopinavir, and ritonavir, were prescribed soon after SARS-CoV was identified as the causative agent 7, 8 . Type I interferon was also used owing to its inhibitory effect on SARS-CoV replication 9 . Furthermore, the use of convalescent plasma or immunoglobulin was reported for the treatment of SARS 10 . More frequently, corticosteroids, including methylprednisolone alone or in combination with antiviral drugs, were administered to SARS patients to prevent immunopathological lung damage 11 , although the timing and dosage regimens for steroid administration were controversial 12, 13 . The administration of high-dose pulses of methylprednisolone has been associated with psychic derangements, acute myopathy, and osteonecrosis [14] [15] [16] . Considering the fact that these disorders usually progress to a chronic state, we propose that the SARS survivors may suffer from metabolic disturbances, Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 SCIeNTIfIC REPORTS | 7: 9110 |

Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection OPEN