bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 pandemic and lockdown measures impact on mental health among the general population in Italy. An N=18147 web-based survey
Authors: Rossi Rodolfo , Socci Valentina , Talevi Dalila , Mensi Sonia , Niolu Cinzia , Pacitti Francesca , Di Marco Antinisca , Rossi Alessandro , Siracusano Alberto , Di Lorenzo Giorgio
Published: April 2020

Background

The psychological impact of the COronaVIrus Disease 2019 (COVID-19) outbreak and lockdown measures on the Italian population are unknown.

The current study assesses rates of mental health outcomes in the Italian general population three to four weeks into lockdown measures and explores the impact of COVID-19 related potential risk factors.

Methods

A web-based survey spread throughout the internet between March 27th and April 6th 2020. 18147 individuals completed the questionnaire, 79.6% women.

Selected outcomes were post-traumatic stress symptoms (PTSS), depression, anxiety, insomnia, perceived stress and adjustment disorder symptoms (ADS). Seemingly unrelated logistic regression analysis was performed to identify COVID-19 related risk factors.

Results

Respondents endorsing PTSS, depression, anxiety, insomnia, high perceived stress and adjustment disorder were 6604 (37%), 3084 (17.3%), 3700 (20.8%), 1301 (7.3%), 3895 (21.8%) and 4092 (22.9%), respectively. Being woman and younger age were associated with all of the selected outcomes. Quarantine was associated with PTSS, anxiety and ADS. Any recent COVID-related stressful life event was associated with all the selected outcomes. Discontinued working activity due to the COVID-19 was associated with all the selected outcomes, except for ADS; working more than usual was associated with PTSS, Perceived stress and ADS. Having a loved one deceased by COVID-19 was associated with PTSS, depression, perceived stress and insomnia.

Conclusion

We found high rates of negative mental health outcomes in the Italian general population three weeks into the COVID-19 lockdown measures and different COVID-19 related risk factors. These findings warrant further monitoring on the Italian population’s mental health.
Detection of Early HIV-1 Infection among Febrile Persons and Blood Donors in Oyo State, Nigeria
Authors: Olusola Babatunde A. , Olaleye David O. , Odaibo Georgina N.
Published: April 2020

About 37.9 million persons are infected with HIV globally resulting in 770,000 deaths. Over 50% of this infection and deaths occur in Sub-Saharan Africa with countries like Nigeria greatly affected. The country also has one of the highest rate of new infections globally. Diverse HIV-1 subtypes have been identified in the country. Febrile persons and blood donors pose a great transmission risk in the country especially during the early stages of infection. HIV-1 rapid kits are routinely used for diagnosis among the general population and high risk groups. However, there is limited information on the usefulness of HIV rapid kits for early detection especially in areas where diverse HIV-1 subtypes circulate. In this study, the prevalence of early HIV-1 infection as well as circulating HIV-1 subtypes among febrile persons and blood donors were determined. Furthermore, the sensitivity of a widely used HIV-1 rapid antibody kit was compared with those of Antigen/Antibody ELISA based methods. Participants were recruited from selected hospitals in Ibadan and Saki, Nigeria. The prevalence of early HIV infection among 1028 febrile persons (Ibadan: 2.22%; Saki: 1.36%) and blood donors (5.07%) studied were significantly different (P<0.03674). CRF02_AG was the predominant subtype detected with more diverse HIV-1 subtypes observed among febrile persons compared to blood donors. About 1.2% of the samples detected on Antibody based ELISA methods were undetectable on the HIV-1 rapid antibody kit. Genetic diversity of HIV-1 strains among infected individuals in Oyo State, Nigeria is still relatively high. This diversity is likely impacting on diagnosis.
Transmission routes of Covid-19 virus in the Diamond Princess Cruise ship
Authors: Xu Pengcheng , Qian Hua , Miao Te , Yen Hui-Ling , Tan Hongwei , Kang Min , Cowling Benjamin J. , Li Yuguo
Published: April 2020

Background

An outbreak of COVID-19 occurred on the Diamond Princess cruise ship in January and February 2020. We analysed information about cases to infer transmission dynamics and potential modes of transmission.

Methods

We collected the daily number of 197 symptomatic cases, and that of the 146 passenger cases in two categories, i.e. those who stayed and did not stay in the same stateroom. We retrieved the quarantine details and the ship’s 14-day itinerary. We searched the websites of national/local health authority along the cruise routes and local news using Google for locally confirmed cases associated with the ship. We obtained the design of air conditioning and sewage treatment of the ship from literature. We back-calculated the dates of infection from the epidemic curve and compared with the start of on-board quarantine.

Results

Major infections started on Jan 28 and completed by Feb 6 for passengers except those who stayed in the same stateroom with infected individual(s). No other confirmed cases were identified among the disembarked people in Hong Kong except an 80 years old passenger. No confirmed cases were reported in three other stopovers between Jan 27-31 associated with disembarked passengers or visitors from the ship, however two Okinawa taxi drivers became confirmed cases in association with driving the ship passengers. Infection among passengers after Feb 6 was limited to those who stayed in the same stateroom with an infected passenger. Infections in crew members peaked on Feb 7, suggesting significant transmission among crew members after quarantine on Feb 5.

Conclusions

We infer that the ship central air conditioning system did not play a role, i.e. the long-range airborne route was absent in the outbreak. Most transmission appears to have occurred through close contact and fomites.

Significance Statement

Transmission by the long-range airborne route for SARS-CoV-2 in the 2020 Diamond Princess Covid-19 outbreak has been debated with significant implication for intervention. We found that the transmission by close contact and fomite explains the outbreak, and the central air-conditioning system did not play a role, demonstrating the importance of social distancing, good hygiene and maintaining good building ventilation for intervention.
Efficacy of remdesivir versus placebo for the treatment of COVID-19: A protocol for systematic review and meta-analysis of randomized controlled trials
Authors: Gebrie Desye , Getnet Desalegn , Manyazewal Tsegahun
Published: April 2020

Background

In spite of the global containment on prevention efforts, the spread of coronavirus disease 2019 (COVID-19) is continuing to rise, with 1.1 million confirmed cases and 60,124 deaths recorded worldwide since 04 April 2020. The outbreak has a significant threat to international health and economy. At present, there is no approved vaccine or treatment for the disease, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomized controlled trials to compare the effectiveness of remdesivir and placebo in patients with COVID-19.

Method and analysis

We will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Google scholar databases without restriction in year of publication. We will include randomized controlled trials that assessed the effectiveness of remdesivir versus placebo for patients confirmed with COVID-19. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA 2015) guidelines for the design and reporting of the results. The primary endpoint will be time to clinical recovery. The secondary endpoints will be all cause mortality, discharged date, frequency of respiratory progression, and treatment-emergent adverse events. Two independent authors will perform study selection, data extraction, and methodology quality assessment. RevMan 5.3 software will be used for statistical analysis. Random/fixed effect model will be carried out to calculate mean differences for continuous outcomes and risk ratio for dichotomous outcomes between remdesivir and placebo.

Ethics and dissemination

This study does not require ethical approval, because no participant’s data will be involved in this systematic review and meta-analysis. The findings of this study will be published in reputable and peer-reviewed journal.

Registration

This review protocol is submitted in PROSPERO database for registration and we will include the registration number in the revised version of the manuscript.

Strengths and limitations of this study

➣

This systematic review and meta-analysis will be derived from only randomized controlled trials which will increase the quality of evidences.

➣

This systematic review and meta-analysis will be derived from only randomized controlled trials which will reduce between study heterogeneity.

➣

Subgroup and sensitivity analysis will be carried out to identify possible reasons that may cause significant heterogeneity between studies.

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The use of Cochrane risk of bias tool to assess risk of bias for each included studies to extract and synthesize evidence based conclusions.

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One of the limitation of this study might be the restriction of trials published in English language.
Using random testing in a feedback-control loop to manage a safe exit from the COVID-19 lockdown
Authors: Müller Markus , Derlet Peter M. , Mudry Christopher , Aeppli Gabriel
Published: April 2020

We argue that frequent sampling of the fraction of infected people (either by random testing or by analysis of sewage water), is central to managing the COVID-19 pandemic because it both measures in real time the key variable controlled by restrictive measures, and anticipates the load on the healthcare system due to progression of the disease. Knowledge of random testing outcomes will (i) significantly improve the predictability of the pandemic, (ii) allow informed and optimized decisions on how to modify restrictive measures, with much shorter delay times than the present ones, and (iii) enable the real-time assessment of the efficiency of new means to reduce transmission rates.

Here we suggest, irrespective of the size of a suitably homogeneous population, a conservative estimate of 15’000 for the number of randomly tested people per day which will suffice to obtain reliable data about the current fraction of infections and its evolution in time, thus enabling close to real-time assessment of the quantitative effect of restrictive measures. Still higher testing capacity permits detection of geographical differences in spreading rates. Furthermore and most importantly, with daily sampling in place, a reboot could be attempted while the fraction of infected people is still an order of magnitude higher than the level required for a relaxation of restrictions with testing focused on symptomatic individuals. This is demonstrated by considering a feedback and control model of mitigation where the feed-back is derived from noisy sampling data.
Near- and forecasting the SARS-COV-2 epidemic requires a global view and multiple methods
Authors: Austin Daren
Published: April 2020

Conventional epidemiological models require estimates of important parameters including incubation time and case fatality rate that may be unavailable in the early stage of an epidemic. For the ongoing SARS-COV-2 epidemic, with no previous population exposure, alternative prediction methods less reliant on assumptions may prove more effective in the near-term. We present three methods used to provide early estimates of likely SARS-COV-2 epidemic progression. During the first stage of the epidemic, growth rate charts revealed the UK, Italy and Spain as outliers, with differentially increasing growth of deaths over cases. A novel data-driven time-series model was then used to near-cast 7-day future cases and deaths with much greater precision. Finally, an epidemio-statistical model was used to bridge from near-casting to forecasting the future course of the global epidemic. By applying multiple approaches to global SARS-COV-2 data, coupled with mixed-effects methods, countries further ahead in the epidemic provide valuable information for those behind. Using current daily global data, we note convergence in near-term predictions for Italy signifying an appropriate call on the future course of the global epidemic. For the UK and elsewhere, prediction of peak and eventual time to resolution is now possible.
How do environmental, economic and health factors influence regional vulnerability to COVID-19?
Authors: Tahmasebi Pejman , Shokri-Kuehni Salome M.S. , Sahimi Muhammad , Shokri Nima
Published: April 2020

We have studied the correlations between twelve environmental, economic and health variables, by carrying out a statistical analysis of the fatality rate of COVID-19 in 14 countries. Our statistical analysis indicates that, among the 12 variables, the diabetes percentage of the total population and the extent of the population ages 65 and older in each country are correlated most strongly with the total number of deaths in them. Although the strength of the correlations between the variables and the total ND may change as the ongoing pandemic evolves, the study highlights the importance of integrating regional-specific variables in the modelling efforts aimed at projecting how the spread of the virus may influence different parts of the world.
Case- fatality rate in COVID- 19 patients: A meta- analysis of publicly accessible database
Authors: Maitra Souvik , Biswas Mansij , Bhattacharjee Sulagna
Published: April 2020

A novel coronavirus was reported in Wuhan, China in December 2019 to cause severe acute respiratory symptoms (COVID-19). In this meta-analysis, we estimated case fatality rate from COVID-19 infection by random effect meta-analysis model with country level data. Publicly accessible web database WorldOMeter (https://www.worldometers.info/coronavirus/) was accessed on 24th March 2020 GMT and reported total number of cases, total death, active cases and seriously ill/ critically ill patients were retrieved. Primary outcome of this meta-analysis was case fatality rate defined by total number of deaths divided by total number of diagnosed cases. Pooled case fatality rate (95% CI) was 1.78 (1.34-2.22) %. Between country heterogeneity was 0.018 (p<0.0001). Pooled estimate of composite poor outcome (95% CI) was 4.06 (3.24-4.88) % at that point of time after exclusion of countries reported small number of cases. Pooled mortality rate (95% CI) was 33.97 (27.44-40.49) % amongst closed cases (where patients have recovered or died) with. Meta regression analysis identified statistically significant association between health expenditure and case fatality rate (p=0.0017).
Cardiac imaging of aortic valve area from 26,142 UK Biobank participants reveal novel genetic associations and shared genetic comorbidity with multiple disease phenotypes
Authors: Córdova-Palomera Aldo , Tcheandjieu Catherine , Fries Jason , Varma Paroma , Chen Vincent S. , Fiterau Madalina , Xiao Ke , Tejeda Heliodoro , Keavney Bernard , Cordell Heather J. , Tanigawa Yosuke , Venkataraman Guhan , Rivas Manuel , Ré Christopher , Ashley Euan , Priest James R.
Published: April 2020

The aortic valve is an important determinant of cardiovascular physiology and anatomic location of common human diseases. From a sample of 26,142 European-ancestry participants, we estimated functional aortic valve area by planimetry from prospectively obtained cardiac MRI sequences of the aortic valve. A genome-wide association study of aortic valve area in these UK Biobank participants showed two significant associations indexed by rs71190365 (chr13:50764607,DLEU1, p=1.8×10−9) and rs35991305 (chr12:94191968,CRADD, p=3.4×10−8). From the GWAS findings we constructed a polygenic risk score for aortic valve area, which in a separate cohort of 311,728 individuals without imaging demonstrated that smaller aortic valve area is predictive of increased risk for aortic valve disease (Odds Ratio 0.88,p=2.3×10−6). After excluding subjects with a medical diagnosis of aortic valve stenosis (remaining n=310,546 individuals), phenome-wide association of >10,000 traits showed multiple links between the polygenic score for aortic valve disease and key health-related comorbidities involving the cardiovascular system and autoimmune disease. Genetic correlation analysis supports a shared genetic etiology with between aortic valve size and birthweight along with other cardiovascular conditions. These results illustrate the use of automated phenotyping of cardiac imaging data from the general population to investigate the genetic etiology of aortic valve disease, perform clinical prediction, and uncover new clinical and genetic correlates of cardiac anatomy.
COVID-19 Global Pandemic Planning: Decontamination and Reuse Processes for N95 Respirators
Authors: Perkins Douglas J , Villescas Steven , Wu Terry H. , Muller Timothy , Bradfute Steven , Hurwitz Ivy , Cheng Qiuying , Wilcox Hannah , Weiss Myissa , Bartlett Chris , Langsjoen Jens , Seidenberg Phil
Published: April 2020

Coronavirus disease 2019 (COVID-19) is an illness caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first identified as a cluster of respiratory illness in Wuhan City, Hubei Province, China in December 2019, and has rapidly spread across the globe to greater than 200 countries. Healthcare providers are at an increased risk for contracting the disease due to occupational exposure and require appropriate personal protective equipment (PPE), including N95 respirators. The rapid worldwide spread of high numbers of COVID-19 cases has facilitated the need for a substantial supply of PPE that is largely unavailable in many settings, thereby creating critical shortages. Creative solutions for the decontamination and safe reuse of PPE to protect our frontline healthcare personnel are essential. Here, we describe the development of a process that began in late February 2020 for selecting and implementing the use of hydrogen peroxide vapor (HPV) as viable method to reprocess N95 respirators. Since pre-existing HPV decontamination chambers were not available, we optimized the sterilization process in an operating room after experiencing initial challenges in other environments. Details are provided about the prioritization and implementation of processes for collection and storage, pre-processing, HPV decontamination, and post-processing of filtering facepiece respirators (FFRs). Important lessons learned from this experience include, developing an adequate reserve of PPE for effective reprocessing and distribution, and identifying a suitable location with optimal environmental controls (i.e., operating room). Collectively, information presented here provides a framework for other institutions considering decontamination procedures for N95 respirators.
Sphingolipid Biosynthesis Inhibition As A Host Strategy Against Diverse Pathogens
Authors: Kumar Sandeep , Li Jinmei , Park Jiwoong , Hart Sydney K. , Song Niki J. , Burrow Damon T. , Bean Nicholas L. , Jacobs Nicholas C. , Coler-Reilly Ariella , Pendergrass Anastasiia Onyshchenko , Pierre Tanya H. , Bradley India C. , Carette Jan E. , Varadarajan Malini , Brummelkamp Thijn R. , Dolle Roland , Peterson Tim R.
Published: April 2020

Chloroquine is an anti-malarial and immunosuppressant drug that has cationic amphipathic chemical properties. We performed genome-wide screens in human cells with chloroquine and several other widely used cationic amphipathic drugs (CADs) including the anti-depressants, sertraline (Zoloft) and fluoxetine (Prozac), the analgesic nortriptyline (Pamelor), the anti-arrhythmic amiodarone (Cordarone), and the anti-hypertensive verapamil (Calan) to characterize their molecular similarities and differences. Despite CADs having different disease indications but consistent with them sharing key chemical properties, we found CADs to have remarkably similar phenotypic profiles compared with non-CADs we and others have previously screened (1–5). The most significant genetic interaction for all CADs was the initiating step in sphingolipid biosynthesis catalyzed by serine palmitoyltransferase (SPT). A comparison of genome-wide screens performed with diverse pathogens from viruses, bacteria, plants, and parasites including Ebola (6), adeno-associated virus AAV2 (7), HIV (8), Rotavirus (9), Influenza A (10), Zika virus (11), Picornavirus (12), Exotoxin A (13), Cholera toxin (14), Type III secretion system and Shiga toxin (15, 16), Ricin toxin (17), and Toxoplasma gondii (18) showed SPT as a top common host factor and 80% overlap overall in top hits specifically with CADs. Potential sphingolipid-mediated mechanisms for the host response- and virulence-modulating effects of CADs involve autophagy and SERPINE1/PAI-1 (plasminogen activator inhibitor-1). Chloroquine has recently shown potential as an anti-viral agent for the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease (19, 20). Our study demonstrates that numerous readily available drugs molecularly function highly similar to chloroquine, which suggests they might be considered for further pre-clinical investigation in the context of SARS-CoV-2. More generally, our work suggests the diverse pathogen mitigating potential of drugs that inhibit host sphingolipid biosynthesis such as CADs.

Brief Summary

Our study demonstrates that numerous readily available drugs molecularly function highly similar to chloroquine, which suggests they might be considered for further pre-clinical investigation in the context of SARS-CoV-2.
Molecular Mechanism of Action of Repurposed Drugs and Traditional Chinese Medicine Used for the Treatment of Patients Infected With COVID-19: A Systematic Scoping Review
Authors: Lem Fui Fui , Opook Fernandes , Lee Dexter Jiunn Herng , Chee Fong Tyng , Lawson Fahcina P. , Chin Su Na
Published: April 2020

Background

The emergence of COVID-19 as a pandemic has resulted in the need for urgent development of vaccines and drugs and the conduction of clinical trials to fight the outbreak. Because of the time constraints associated with the development of vaccines and effective drugs, drug repurposing and other alternative treatment methods have been used to treat patients that have been infected by the SARS-CoV-2 virus and have acquired COVID-19.

Objective

The objective of this systematic scoping review is to provide an overview of the molecular mechanism of action of repurposed drugs or alternative treatment medicines used to attenuate COVID-19 disease.

Data Sources

The research articles or grey literature, including theses, government reports, and official news online, were identified from 4 databases and 1 search engine. The full content of a total of 160 articles that fulfilled our inclusion criteria was analyzed and information about 6 drugs (ritonavir, lopinavir, oseltamivir, remdesivir, favipiravir, and chloroquine) and 4 traditional Chinese medicines (Shuang Huang Lian Kou Fu Ye, TCM combination of Bu Huan Jin Zheng Qi San and Da Yuan Yin, Xue Bi Jing Injection and Qing Fei Pai Du Tang) were extracted.

Conclusions

All of the repurposed drugs that have been used for the treatment of COVID-19 depend on the ability of the drug to inhibit the proliferation of the SARS-CoV-2 virus by binding to enzyme active sites, viral chain termination, or triggering of the molecular pathway, whereas traditional Chinese medicine has a pivotal role in triggering the inflammation pathway, such as the neuraminidase blocker, to fight the SARS-CoV-2 virus. This review provides an insight to experimental validation of drugs and alternative medicine used for the treatment and control of COVID-19.
Protecting our health care workers while protecting our communities during the COVID-19 pandemic: a comparison of approaches and early outcomes in two Italian regions, 2020
Authors: Binkin Nancy , Michieletto Federica , Salmaso Stefania , Russo Francesca
Published: April 2020

Introduction

Italy, which has been hard-hit by the COVID-19 pandemic, has an overriding national strategy, but its 21 regions have adapted their response based on the organization of their curative and public health services. In this paper, we compare short-term outcomes for two northern Italian regions which had almost simultaneous initial outbreaks: Lombardy, which had a patient-centered approach that relied on primary care physicians and hospital care, and Veneto, which focused on community-based diagnosis and care.

Methods

We used numerator and denominator data from public Italian government sources to calculate reported rates of COVID-19 testing/1000, COVID-19 cases/100,000 overall and for health care workers (HCWs) and non-HCWs, deaths per 100,000, and the percent of cases admitted to hospitals and ICUs for February 24-April 1, 2020.

Results

As of April 1, 2020, Lombardy experienced 44,733 cases and 7,539 deaths; for Veneto, the corresponding values were 9,625 and 499. The cumulative case rate was 445/100,000 for Lombardy and 196/100,000 for Veneto, a 2.3-fold difference. Mortality rates were 7.5 times higher in Lombardy than in Veneto (75/100,000 and 10/100,000, respectively). Cumulative rates of testing were nearly twice as high in Veneto and were 2.7 times higher in the first week of the epidemic. In Lombardy, 51.5% of patients were admitted, including, 5.2% to intensive care units; for Veneto, the corresponding figures were 25.1% and 4.3%, respectively. HCWs account for 14.3% of all cases in Lombardy compared with 4.4% in Veneto. In Lombardy, the rate among HCWs was 19.1 times higher than in the general population (6,924/100,000 versus 362/100,000), while in Veneto it was 3.9 times higher (676/100,000 versus 172/100,000).

Discussion

The community-based approach in Veneto appears to be associated with substantially reduced rates of cases, hospitalizations, deaths, and infection in HCWs compared with the patient-centered approach in Lombardy. Our findings suggest that the impact of COVID-19 can be reduced through strong and aggressive public health efforts to confirm and isolate initial cases and contacts in a timely way and to minimize unnecessary contact between HCWs and cases through home-based testing and pro-active home follow-up.
Immunological assays for SARS-CoV-2: an analysis of available commercial tests to measure antigen and antibodies
Authors: González John M. , Shelton William J. , Díaz-Vallejo Manuel , Rodriguez-Castellanos Victoria E. , Zuluaga Juan Diego H. , Chamorro Diego F. , Arroyo-Ariza Daniel
Published: April 2020

The rapid spread of SARS-CoV-2 coronavirus infection has led to the development of molecular and serologic tests in a short period of time. While tests such as RT-PCR have applications in the immediate diagnosis revealing the presence of the virus, serological tests can be used to determine previous exposure to the virus and complement acute diagnosis. Antibody production can occur as early as 5 days post-infection. Both IgM and IgG specific anti-SARS-COV-2 antibodies can be a useful tool to test faster and larger groups of individuals. The objective of this study was to carry out a review of the different serological tests offered to detect antigen or antibodies against SARS-CoV-2. This information should be useful for decision takers in different countries to choose a test according to their needs. Based on web pages that listed serological assays, we found 226 coming from 20 countries, the majority are indirect tests for specific antibodies detection (n 180) and use immunochromatography methods (n 110) with samples coming from blood-derived products (n 105). Measuring IgM/IgG at the same time (n 112) and a procedure time of <20 min (n 83) are the most common. The overall average sensitivity was 91.8% and specificity was 97%. Most of the tests are currently for in vitro diagnosis (IVD). This information gathered could change day by day due to the expedite process of production and emergency of authorization use.
Multi-Stage Group Testing Improves Efficiency of Large-Scale COVID-19 Screening
Authors: Eberhardt JN , Breuckmann NP , Eberhardt CS
Published: April 2020

Background

SARS-CoV-2 test kits are in critical shortage in many countries. This limits large-scale population testing and hinders the effort to identify and isolate infected individuals.

Objectives

Herein, we developed and evaluated multi-stage group testing schemes that test samples in groups of various pool sizes in multiple stages. Through this approach, groups of negative samples can be eliminated with a single test, avoiding the need for individual testing and achieving considerable savings of resources.

Study design

We designed and parameterized various multi-stage testing schemes and compared their efficiency at different prevalence rates using computer simulations.

Results

We found that three-stage testing schemes with pool sizes of maximum 16 samples can test up to three and seven times as many individuals with the same number of test kits for prevalence rates of around 5% and 1%, respectively. We propose an adaptive approach, where the optimal testing scheme is selected based on the expected prevalence rate.

Conclusion

These group testing schemes could lead to a major reduction in the number of testing kits required and help improve large-scale population testing in general and in the context of the current COVID-19 pandemic.
Neuropsychiatric adverse events of chloroquine: A real-world pharmacovigilance study using the FAERS database
Authors: Sato Kenichiro , Mano Tatsuo , Iwata Atsushi , Toda Tatsushi
Published: April 2020

Objectives

As of the early April 2020, the antimalarial drug, chloroquine, has been approved as an emergency treatment for the coronavirus disease 2019 (COVID-19) in the United States and in Europe. Although infrequent, neuropsychiatric symptoms have been reported in patients who received chloroquine for the treatment of malaria or autoimmune diseases. In this study, we investigated these adverse events (AEs) using a large self-reporting database.

Materials and Methods

We conducted a disproportionality analysis for the detection of neuropsychiatric AE signals associated with the use of chloroquine (or hydroxychloroquine), reported to FAERS database between the fourth quarter of 2012 and the fourth quarter of 2019. Adjusted reporting odds ratio (ROR) for the development of each of the neuropsychiatric AEs following the use of chloroquine was calculated using a multilevel model.

Results

We included 2,389,474 AE cases, among which 520 cases developed neuropsychiatric AE following the use of chloroquine. Exposure to chloroquine was associated with a statistically significant high reporting of amnesia, delirium, hallucinations, depression, and loss of consciousness, (lower 95% confidence interval of the adjusted ROR > 1), although the degree of increase in their ROR was limited. There was no statistically significant high reporting of any other neuropsychiatric AE, including suicide, psychosis, confusion, and agitation.

Conclusion

Current pharmacovigilance study results did not suggest any potential link between the use of chloroquine and an increased risk of suicide, psychosis, confusion, and agitation, which would be informative during the emergency use of chloroquine for the treatment of COVID-19.
A spatially explicit and mechanistic model for exploring coral reef dynamics
Authors: Carturan Bruno S. , Maréchal Jean-Philippe , Bradshaw Corey J. A. , Pither Jason , Parrott Lael
Published: April 2020

The complexity of coral-reef ecosystems makes it challenging to predict their dynamics and resilience under future disturbance regimes. Models for coral-reef dynamics do not adequately accounts for the high functional diversity exhibited by corals. Models that are ecologically and mechanistically detailed are therefore required to simulate the ecological processes driving coral reef dynamics. Here we describe a novel model that includes processes at different spatial scales, and the contribution of species’ functional diversity to benthic-community dynamics. We calibrated and validated the model to reproduce observed dynamics using empirical data from Caribbean reefs. The model exhibits realistic community dynamics, and individual population dynamics are ecologically plausible. A global sensitivity analysis revealed that the number of larvae produced locally, and interaction-induced reductions in growth rate are the parameters with the largest influence on community dynamics. The model provides a platform for virtual experiments to explore diversity-functioning relationships in coral reefs.
Comprehensive transcriptome data of normal andAscosphaera apis-infected western honeybee larval guts
Authors: Du Yu , Wang Jie , Zhu Zhiwei , Jiang Haibin , Fan Xiaoxue , Fan Yuanchan , Zheng Yanzhen , Xiong Cuiling , Chen Dafu , Guo Rui
Published: April 2020

ABSTRAmT

Apis mellifera ligusticais a well-known subspecies of western honeybee,Apis mellifera. Ascosphaera apisis a common fungal pathogen of honeybee larvae, resulting in Chalkbrood disease. In this article, deep sequencing of un-treated 4-, 5-, and 6-day-old larval guts (AmCK1, AmCK2, AmCK3) andA. apis-treated 4-, 5- and 6-day-old larval guts (AmT1, AmT2, AmT3) ofApis mellifera ligusticawere conducted using Illumina HiSeq™ 4000 platform. In total, 85811046, 81962296, 85636572, 79267686, 82889882, and 100211796 raw reads were respectively yielded from above-mentioned six groups. The result of sequencing satuation analysis suggested that the sequencing depth in this work was enough to detect nearly all expressed genes. After quality control, 85739414, 81896402, 85573798, 79202304, 82828926, and 100128692 clean reads were obtained. Additionally, the GC content of each group was above 45.26%. Furthermore, 47035852, 65612676, 71803878, 62560904, 65018360, and 56278272 clean reads were mapped to theApis melliferagenome, including 41221479, 61172916, 66724233, 57531335, 60245732, and 52638986 unique mapped clean reads, and 2078427, 986825, 915375, 1082925, 1097130, and 716436 multiple mapped clean reads. In addition, exons were the most abundant regions mapped by clean reads, follow by intergenic regions and introns. The strand-specific cDNA library-based RNA sequencing data documented here will faciliate study on molecualr mechanisms underlying host immune response and host-pathogen interaction during chalkbrood disease, and benefit understanding of non-coding RNA-mediated cross-kingdom regulation betweenA. m. ligusticalarvae andA. apis.

Value of the Data

This data reported here could be used to explore circRNAs, lncRNAs, mRNAs and their competing endogenous RNA networks involved in response of western honeybee larvae toAscosphaera apisinfection.

The current data contributes to better understanding mechanisms regulating host-pathogen interaction during chalkbrood disease.

Our data can provide novel insights into understanding non-coding RNA-mediated cross-kingdom regulation betweenApis mellifera ligusticaandA. apis.
Anosmia and dysgeusia in patients with mild SARS-CoV-2 infection
Authors: Levinson Ruth , Elbaz Meital , Ben-Ami Ronen , Shasha David , levinson Tal , Choshen Guy , Petrov Ksenia , Gadoth Avi , Paran Yael
Published: April 2020

In this cohort of 42 patients with mild COVID19 we found a unique clinical feature of acute anosmia and dysgeusia in more than third of patients. Median onset of these features was 3.3 days after onset of illness (range 0-7) with rapid recovery in most patients.

Article Summary Line

Anosmia and dysgeusia appeared early in third of our patients with mild SARS-CoV-2 infection and were short-lived in most patients.
Western Ghats Myrtaceae are not Gondwana elements but likely dispersed from south-east Asia
Authors: Ray Rajasri , Chattopadhyay Balaji , Garg Kritika M , Ramachandra TV , Ray Avik
Published: April 2020

Gondwana break-up is one of the key sculptors of the global biogeographic pattern including Indian subcontinent. Myrtaceae, a Gondwana family, demonstrates a high diversity across Indian Western Ghats. A rich paleo-records in Deccan Intertrappean bed in India strive to reconcile two contending hypothesis of origin and diversification of Myrtaceae in India, namely Gondwana elements floated on peninsular India or lineages invading from south-east Asia. In this study, we have reconstructed the biogeographic history of Myrtaceae of Western Ghats of India combining fossil-calibrated phylogeny, ancestral area reconstruction, and comparing various dispersal models.

Phylogenetic reconstructions divided lineages into multiple clades at the tribal level that mostly is in agreement with previous descriptions. Dated tree indicated a presumable Gondwanan origin of Myrtaceae (95.7 Ma). The Western Ghats taxa are relatively younger and seem to have arrived either through long-distance oceanic dispersal in middle Eocene (Rhodomyrtus tomentosa), and Miocene (Eugenia) or through major overland dispersals throughout Miocene (Syzygium). However, late Cretaceous fossilsin India lends support to the existence of proto-Myrtaceae on floating peninsular India. Taken together, we conclude that Myrtaceae lineages on the biotic ferry were perhaps extirpated by Deccan volcanism leaving a little or no trace of living Gondwanan link, while the Western Ghats was likely enriched by dispersed elements either from south-east Asia or from South America.
Environment-dependent behavioral traits and experiential factors shape addiction vulnerability
Authors: Fouyssac Maxime , Puaud Mickaël , Ducret Eric , Marti-Prats Lucia , Vanhille Nathalie , Ansquer Solène , Zhang Xinxuan , Belin-Rauscent Aude , Giuliano Chiara , Houeto Jean-Luc , Everitt Barry. J , Belin David
Published: April 2020

The transition from controlled drug use to drug addiction depends on an interaction between a vulnerable individual, their environment and a drug. Here we tested the hypothesis that conditions under which individuals live influence behavioral vulnerability traits and experiential factors operating in the drug taking environment to determine the vulnerability to addiction. The role of behavioural vulnerability traits in mediating the influence of housing conditions on the tendency to acquire cocaine self-administration was characterised in 48 rats housed in either an enriched (EE) or a standard (SE) environment. Then, the influence of these housing conditions on the individual vulnerability to develop addiction-like behaviour for cocaine or alcohol was measured in 72 EE or SE rats after several months of cocaine self-administration or intermittent alcohol drinking, respectively. The determining role of negative experiential factors in the drug taking context was further investigated in 48 SE rats that acquired alcohol drinking as a self-medication strategy. The environment influenced the acquisition of drug intake through its effect on behavioral markers of resilience to addiction. In contrast, the initiation of drug taking as a coping strategy or in a negative state occasioned by the contrast between enriched housing conditions and a relatively impoverished drug taking setting, facilitated the development of compulsive cocaine and alcohol intake. These data demonstrate that addiction vulnerability depends on environmentally determined experiential factors, suggesting that initiating drug use through negative reinforcement-based self-medication facilitates the development of addiction in vulnerable individuals.

Significance Statement

The factors that underlie an individual’s vulnerability to switch from controlled, recreational drug use to addiction are not well understood. We showed that in individuals housed in enriched conditions, the experience of drugs in the relative social and sensory impoverishment of the drug taking context, and the associated change in behavioural traits of resilience to addiction, exacerbate the vulnerability to develop compulsive drug intake. We further demonstrated that the acquisition of alcohol drinking as a mechanism to cope with distress increases the vulnerability to develop compulsive alcohol intake. Together these results demonstrate that experiential factors in the drug taking context shape the vulnerability to addiction.
Lateralized role of prefrontal cortex in guiding orienting behavior
Authors: Mohebi Ali , Oweiss Karim G.
Published: April 2020

Orienting movements are essential to sensory-guided reward-seeking behaviors. Prefrontal cortex (PFC) is believed to exert top-down control over a range of goal-directed behaviors and is hypothesized to bias sensory-guided movements. However, the nature of PFC involvement in controlling sensory-guided orienting behaviors has remained largely unknown. Here, we trained rats on a delayed two-alternative forced-choice task requiring them to hold an orienting decision in working memory before execution is cued. Medial PFC (mPFC) Inactivation using either Muscimol or optogenetics impaired choice behavior. However, optogenetic impairment depended on the specific trial epoch during which inactivation took place. In particular, we found a lateralized role for mPFC during the presentation of instruction cues but this role became bilateral when inactivation occurred later in the delay period. Electrophysiological recording of multiple single-unit activity further provided evidence that this lateralized selectivity is cell-type specific. Our results suggest a previously unknown role of mPFC in mediating sensory-guided representation of orienting behavior and a potentially distinct cell-type specific role in shaping such representation across time.
Cyclopamine sensitizes Glioblastoma cells to Temozolomide treatment through Sonic Hedgehog pathway
Authors: Carballo Gabriela Basile , Matias Diana , Honorato Jessica , Pessoa Luciana Santos , Arrais Neto Ananias Matos , de Sampaio e Spohr Tania Cristina Leite
Published: April 2020

Aim

Glioblastoma is an extremely aggressive glioma, resistant to radio and chemotherapy usually performed with temozolomide. One of the main reasons for glioblastoma resistance to conventional therapies is due to the presence of cancer stem-like cells. These cells could recapitulate some signaling pathways important for embryonic development, such as Sonic hedgehog. Here, we investigated if the inhibitor of the Sonic hedgehog pathway, cyclopamine, could potentiate the temozolomide effect in cancer stem-like cells and glioblastoma cell linesin vitro.

Main methods

The viability of glioblastoma cells exposed to cyclopamine and temozolomide treatment was evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay while the induction of apoptosis was assessed by western blot. The stemness properties of glioma cells were verified by clonogenic and differentiation assay and the expression of stem cell markers were measured by fluorescence microscopy and western blot.

Key findings

The glioblastoma viability was reduced by cyclopamine treatment. Cyclopamine potentiated temozolomide treatment in glioblastoma cell lines by inducing apoptosis through activation of caspase-3 cleaved. Conversely, the combined treatment of cyclopamine and temozolomide potentiated the stemness properties of glioblastoma cells by inducing the expression of SOX-2 and OCT-4.

Significance

Cyclopamine plays an effect on glioblastoma cell lines but also sensibilize them to temozolomide treatment. Thus, first-line treatment with Sonic hedgehog inhibitor followed by temozolomide could be used as a new therapeutic strategy for glioblastoma patients.
A single dose of ChAdOx1 MERS provides broad protective immunity against a variety of MERS-CoV strains
Authors: van Doremalen Neeltje , Haddock Elaine , Feldmann Friederike , Meade-White Kimberly , Bushmaker Trenton , Fischer Robert J. , Okumura Atsushi , Hanley Patrick W. , Saturday Greg , Edwards Nick J. , Clark Madeleine H.A. , Lambe Teresa , Gilbert Sarah C. , Munster Vincent J.
Published: April 2020

Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans via the dromedary camel reservoir and can transmit between humans, most commonly via nosocomial transmission. Currently, no licensed vaccine is available. Previously we showed that vaccination of transgenic mice with ChAdOx1 MERS, encoding the MERS S protein, prevented disease upon lethal challenge. In the current study we show that rhesus macaques seroconverted rapidly after a single intramuscular vaccination with ChAdOx1 MERS. Upon MERS-CoV challenge vaccinated animals were protected against respiratory injury and pneumonia and had a reduction in viral load in lung tissue of several logs. Furthermore, we did not detect MERS-CoV replication in type I and II pneumocytes of ChAdOx1 MERS vaccinated animals. A prime-boost regimen of ChAdOx1 MERS boosted antibody titers, and viral replication was completely absent from the respiratory tract tissue of these rhesus macaques. Finally, we investigated the ability of ChAdOx1 MERS to protect against six different MERS-CoV strains, isolated between 2012 to 2018, from dromedary camels and humans in the Middle East and Africa. Antibodies elicited by ChAdOx1 MERS in rhesus macaques were able to neutralize all MERS-CoV strains. Vaccination of transgenic hDPP4 mice with ChAdOx1 MERS completely protected the animals against disease and lethality for all different MERS-CoV strains. The data support further clinical development of ChAdOx1 MERS supported by CEPI.

One Sentence Summary

Prime-only vaccination with ChAdOx1 MERS provides protective immunity against HCoV-EMC/2012 replication in rhesus macaques, and a wide variety of MERS-CoV strains in mice.
FingerprintContacts: Predicting Alternative Conformations of Proteins from Coevolution
Authors: Feng Jiangyan , Shukla Diwakar
Published: April 2020

Proteins are dynamic molecules which perform diverse molecular functions by adopting different three-dimensional structures. Recent progress in residue-residue contacts prediction opens up new avenues for thede novoprotein structure prediction from sequence information. However, it is still difficult to predict more than one conformation from residue-residue contacts alone. This is due to the inability to deconvolve the complex signals of residue-residue contacts, i.e. spatial contacts relevant for protein folding, conformational diversity, and ligand binding. Here, we introduce a machine learning based method, called FingerprintContacts, for extending the capabilities of residue-residue contacts. This algorithm leverages the features of residue-residue contacts, that is, (1) a single conformation outperforms the others in the structural prediction using all the top ranking residue-residue contacts as structural constraints, and (2) conformation specific contacts rank lower and constitute a small fraction of residue-residue contacts. We demonstrate the capabilities of FingerprintContacts on eight ligand binding proteins with varying conformational motions. Furthermore, FingerprintContacts identifies small clusters of residue-residue contacts which are preferentially located in the dynamically fluctuating regions. With the rapid growth in protein sequence information, we expect FingerprintContacts to be a powerful first step in structural understanding of protein functional mechanisms.