bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulating the evolutionary trajectories of metabolic pathways for insect symbionts in the genus Sodalis
Authors: Hall Rebecca J. , Thorpe Stephen , Thomas Gavin H. , Wood A. Jamie
Published: June 2020

Insect–bacterial symbioses are ubiquitous, but there is still much to uncover about how these relationships establish, persist and evolve. The tsetse endosymbiont

Sodalis glossinidius

displays intriguing metabolic adaptations to its microenvironment, but the process by which this relationship evolved remains to be elucidated. The recent chance discovery of the free-living species of the genus

Sodalis

,

Sodalis praecaptivus

, provides a serendipitous starting point from which to investigate the evolution of this symbiosis. Here, we present a flux balance model for

S. praecaptivus

and empirically verify its predictions. Metabolic modelling is used in combination with a multi-objective evolutionary algorithm to explore the trajectories that

S. glossinidius

may have undertaken from this starting point after becoming internalized. The order in which key genes are lost is shown to influence the evolved populations, providing possible targets for future in vitro genetic manipulation. This method provides a detailed perspective on possible evolutionary trajectories for

S. glossinidius

in this fundamental process of evolutionary and ecological change.
TheC. elegansproteasome subunit RPN-12 is required for hermaphrodite germline sex determination and oocyte quality
Authors: Fernando Lourds M. , Elliot Jeandele , Allen Anna K.
Published: June 2020

Background

The proteasome is a multi-subunit complex and a major proteolytic machinery in cells. Most subunits are essential for proteasome function, and depletion of individual subunits normally results in lethality. RPN-12/Rpn12/PSMD8 is a lid subunit of the 19S regulatory particle (RP) of the 26S proteasome. Studies inCaenorhabditis elegansdemonstrated that RNAi depletion of RPN-12 does not result in lethality. RPN-12 has not been well studied in higher eukaryotes. In this study we investigate the biological significance of RPN-12 inC. elegans.

Results

We found that the null mutantrpn-12(av93)did not cause major impairment of the proteolytic activity of the proteasome. Mostrpn-12(av93)hermaphrodites lack sperm leading to feminization of the germ line that can be partially rescued by mating to males. The lack of sperm phenotype can be suppressed by downregulation of TRA-1, a player in the hermaphrodite germline sex determination pathway. Also,rpn-12(av93)animals show significant nuclear accumulation of the meiotic kinase WEE-1.3, a protein predominantly localized to the perinuclear region. Interestingly, chemical inhibition of the proteasome did not cause nuclear accumulation of WEE-1.3.

Conclusions

RPN-12 plays a previously unknown role in oogenesis and the germline sex determination pathway inC. eleganshermaphrodites.
Understanding the Incidence of Covid-19 among the police force in Maharashtra through a mixed approach
Authors: Kokane Pravin , Maurya Priya , Muhammad T
Published: June 2020

Background

The study tries to understand the incidence of COVID-19 among police officials along with the challenges they face and their preparedness during the pandemic response in Maharashtra.

Method

The study analyzed the daily trends of confirmed, active, recovered, and deceased cases for Maharashtra and police professional. Ten telephonic in-depth interviews and a descriptive survey were conducted to obtain experiences of police regarding their combat against Covid-19.

Results

PPR (0.01 to 1.12), CRR (0 to 39.22) and CFR (0 to 1.07) have consistently increased and CRR found lower among police than the general population. The qualitative data by analyzing several indicators suggests that there is a higher individual efficacy over collective efficacy among the police force. Further, the long-time fight against Covid-19 had drained police force mentally and physically and this put them in higher risk.

Conclusion

Immediate priority interventions like provision of protective gears need to be provided by the government to control the risk of infection among police. Holistic support and recovery system from all stakeholders of society needed for the well-being of the police force so that they can soldier on to avert such a crisis in future.
Assessment of Early Mitigation Measures Against COVID-19 in Puerto Rico: March 15-May 15, 2020
Authors: Valencia Miguel , Becerra José E. , Reyes Juan C. , Castro Kenneth G.
Published: June 2020

Background

On March 15, 2020 Puerto Rico implemented non-pharmaceutical interventions (NPIs), including a mandatory curfew, as part of a state of emergency declaration to mitigate the community transmission of the SARS-CoV-2 virus. The strict enforcement of this curfew was extended through May 25, with a gradual relaxation beginning on May 1. This report summarizes an assessment of these early mitigation measures on the progression of COVID-19 in the island.

Methods and Findings

From March 15 to May 15, 2020, 41,748 results of molecular (RT-PCR) tests were reported to the Puerto Rico Department of Health. Of these, 1,866 (4.5%) were positive, corresponding to 1,219 individuals with COVID-19 included in the study. We derived the epidemic growth rates (r) and the corresponding reproductive numbers (R) from the epidemic curve of these 1,219 individuals with laboratory-confirmed diagnosis of COVID-19 using their date of test collection as a proxy for symptoms onset. We then compared the observed cases with the R-based epidemic model projections had the mitigation measures not been implemented. Computations were conducted in the R packages forecast, incidence and projections.

The number of daily RT-PCR-confirmed cases peaked on March 30 (84 cases), showing a weekly cyclical trend, with lower counts on weekends and a decreasing secular trend since March 30. The initial exponential growth rate (r) was 17.0% (95% CI: 8.4%, 25.6%), corresponding to a doubling of cases every 4.1 days, and to a reproduction number (Ro) of 1.89 (95% CI: 1.41, 2.39). After March 30, the r value reverted to an exponential decay rate (negative) of −3.6% (95% CI: −5.7%, −1.4%), corresponding to a halving of cases every 19.4 days and to an Ro of 0.90 (95% CI: 0.84, 0.97). Had the initial growth rate been maintained, a total of 18,699 (96%CI: 4,113, 87,438) COVID-19 cases would have occurred by April 30 compared with 1,119 observed.

Conclusions

Our findings are consistent with very effective implementation of early non-pharmaceutical interventions (NPIs) as mitigation measures in Puerto Rico. These results serve as a baseline to assess the impact of the transition from mitigation to containment stages in Puerto Rico.
One year of modeling and forecasting COVID-19 transmission to support policymakers in Connecticut
Authors: Morozova Olga , Li Zehang Richard , Crawford Forrest W.
Published: June 2020

To support public health policymakers in Connecticut, we developed a county-structured compartmental SEIR-type model of SARS-CoV-2 transmission and COVID-19 disease progression. Our goals were to provide projections of infections, hospitalizations, and deaths, as well as estimates of important features of disease transmission, public behavior, healthcare response, and clinical progression of disease. In this paper, we describe a transmission model developed to meet the changing requirements of public health policymakers and officials in Connecticut from March 2020 to February 2021. We outline the model design, implementation and calibration, and describe how projections and estimates were used to support decision-making in Connecticut throughout the first year of the pandemic. We calibrated this model to data on deaths and hospitalizations, developed a novel measure of close interpersonal contact frequency to capture changes in transmission risk over time and used multiple local data sources to infer dynamics of time-varying model inputs. Estimated time-varying epidemiologic features of the COVID-19 epidemic in Connecticut include the effective reproduction number, cumulative incidence of infection, infection hospitalization and fatality ratios, and the case detection ratio. We describe methodology for producing projections of epidemic evolution under uncertain future scenarios, as well as analytical tools for estimating epidemic features that are difficult to measure directly, such as cumulative incidence and the effects of non-pharmaceutical interventions. The approach takes advantage of our unique access to Connecticut public health surveillance and hospital data and our direct connection to state officials and policymakers. We conclude with a discussion of the limitations inherent in predicting uncertain epidemic trajectories and lessons learned from one year of providing COVID-19 projections in Connecticut.
An International Review of Tobacco Use and the COVID-19 Pandemic: Examining Hospitalization, Asymptomatic Cases, and Severity
Authors: Balabanski Lachezar L.
Published: June 2020

Background and objectives

Since the World Health Organization (WHO) declared a public health emergency of imminent concern in March 2020, the novel coronavirus (SARS-CoV-2) and its related disease (COVID-19) has become a topic of much needed research. This study primarily focused on what effect smoking had on hospitalization; however, asymptomaticity, and severity were discussed.

Data

Data was collected through searches on databases including PubMed and Google Scholar. Eligibility criteria included being RT-PCR verified and including smoking data.

Discussion

This study found that smokers were significantly underrepresented in COVID-19 hospitalization on a purely epidemiological level in some areas, including China and Manhattan, but not others: Seattle, Greater New York City Area, and Italy. Furthermore, smokers were equally represented in asymptomatic populations, but smokers will likely experience a more severe manifestation of the disease if they are symptomatic. Further inquiry into possible mechanisms by which the observed epidemiological effect is necessary, as it has implications for recommendations on loosening restrictions on social distancing measures.

Conclusions and Recommendations

This study recommends that smokers consider themselves to be at higher risk for COVID-19, as they may experience a more severe manifestation of the disease. Health care providers and policy makers should consider smokers at higher risk as well, as there is evidence to claim that smokers may contract a more severe form of COVID-19.
Systematic review of instruments for assessing culinary skills in adults: What is the quality of their psychometric properties?
Authors: Teixeira Aline Rissatto , Bicalho Daniela , Slater Betzabeth , Tacio de Mendonça Lima
Published: June 2020

Background

Culinary skills are important objects of study in the field of Public Health. Studies that propose to develop instruments for assessing such construct show lack of methodological uniformity to report validity and reliability of their instruments.

Objective

To identify studies that have developed instruments to measure culinary skills in adult population, and critically assess their psychometric properties.

Design

We conducted a systematic review according to the PRISMA statement. We searched literature PubMed/Medline, Scopus, LILACS, and Web of Science databases until January 2021, and consulted Google Scholar for relevant grey literature. Two reviewers independently selected the studies, conducted data extraction, and assessed the psychometric quality of the instruments. A third reviewer resolved any doubts or disagreements in all steps of the systematic review.

Results

The search identified 1148 potentially relevant studies, out of which 9 met the inclusion criteria. In addition, we included 3 studies by searching the related articles and the reference lists of these studies, totaling 12 included studies in this review. Ten studies reported the development of tools measuring culinary skills in adults and 2 studies performed cross-cultural adaptations of original instruments. We considered adequate quality of internal consistency reliability in four studies. One study received adequate rating for test-retest reliability. No studies presented adequate rating for content validity and four studies showed satisfactory results for at least one type of construct validity. One study reported criterion validity and the quality of this psychometric property was inadequate.

Conclusions

We identified many studies that surveyed culinary skills. Although the isolated measures appraised in this review show good promise in terms of quality of psychometric properties, no studies presented adequate measures for each aspect of reliability and validity. A more consistent and consensual definition of culinary skills is recommended. The flaws observed in these studies show that there is a need for ongoing research in the area of the psychometric properties of instruments assessing culinary skills.
Modeling the Spring 2020 New York City COVID-19 Epidemic: New Criteria and Methods for Prediction
Authors: Barlow D. A. , Baird J. K.
Published: June 2020

We report here on results obtained using the SIR epidemic model to study the spring 2020 COVID-19 epidemic in New York City (NYC). An approximate solution is derived for this non-linear system which is then used to derive an expression for the time to maximum infection. Additionally, expressions are obtained for estimating the transmission and recovery parameters using data collected in the first ten days of the epidemic. Values for these parameters are then generated using data reported for the spring 2020 NYC COVID-19 epidemic which are then used to estimate the time to maximum infection and the maximum number of infected. Complete details are given so that the method can be used in the event of future epidemics. An additional result of this study is that we are able to suggest a unique mitigation strategy.
Controlled-release urea combined with potassium chloride improved the soil fertility and growth of Italian ryegrass
Authors: Geng Jibiao , Yang Xiuyi , Huo Xianqi , Chen Jianqiu , Lei Shutong , Li Hui , Lang Ying , Liu Qianjin
Published: June 2020

A field experiment with a split-plot design was conducted to study the effect of nitrogen fertilizer type combined with different potassium fertilizer rates on the soil fertility and growth of Italian ryegrass. The main plots were assigned to controlled-release urea (CRU) and common urea, while low, moderate and high potassium chloride (KCl) rates (150, 300 and 450 kg ha−1, respectively) were assigned to the subplots. The results showed compared with the common urea, the CRU significantly increased the SPAD value, plant height, leaf area, and photosynthetic index. Moreover, the dry and fresh yields of the CRU increased by 10.9-25.3% and 11.8-17.7%, respectively. At the same time, compared with the KCl150 and KCl450 treatments, the KCl300 treatment resulted in better plant growth. Overall, the CRU×KCl300 maximized the soil inorganic nitrogen and different soil potassium forms. The root length, volume, surface area, average diameter, tips and branches were also improved, and there was a significant N×K interaction effect on the tips. Our analysis corroborated the CRU combined with 300 kg ha−1KCl fertilization enhances crop growth by improving leaf photosynthesis, soil fertility, and yield and should be recommended as the best fertilizer ratio for Italian ryegrass production.
What triggers online help-seeking retransmission during the COVID-19 period? Empirical evidence from Chinese social media
Authors: Luo Chen , Li Yuru , Chen Anfan , Tang Yulong
Published: June 2020

The past nine months witnessed COVID-19’s fast-spreading at the global level. Limited by medical resources shortage and uneven facilities distribution, online help-seeking becomes an essential approach to cope with public health emergencies for many ordinaries. This study explores the driving forces behind the retransmission of online help-seeking posts. We built an analytical framework that emphasized content characteristics, including information completeness, proximity, support seeking type, disease severity, and emotion of help-seeking messages. A quantitative content analysis was conducted with a probability sample consisting of 727 posts. The results illustrate the importance of individual information completeness, high proximity, instrumental support seeking. This study also demonstrates slight inconformity with the severity principle but stresses the power of anger in help-seeking messages dissemination. As one of the first online help-seeking diffusion analyses in the COVID-19 period, our research provides a reference for constructing compelling and effective help-seeking posts during a particular period. It also reveals further possibilities for harnessing social media’s power to promote reciprocal and cooperative actions as a response to this deepening global concern.
Cohen’s kappa statistics as a convenient means to identify accurate SARS-CoV-2 rapid antibody tests
Authors: Iseki Harukazu
Published: June 2020

There are many available rapid antibody tests, but the performance of such tests remains unclear. Moreover, it is difficult to compare among the various devices regarding their sensitivity & specificity.

In order to compare the performance of such devices, we used Cohen’ kappa statistics to assess the level of agreement between RT-PCR and rapid antibody tests. In doing this study, we considered the term of validity after symptom-onset to compare two tests. It takes more than a week to produce antibodies in the body, and RT-PCR thus gives negative result in the convalescent period. On ELISA data from the literature kappa statistics was calculated as 1.0 beyond 10 days after symptom-onset. By taking these factors into consideration, we evaluated agreement with samples collected beyond 10 days of symptom-onset during the active period.

We calculated the data from 9 devices, and the kappa statistics for English data were calculated as 0.64 on average. The same finding was 0.75 for Chinese data. These results corresponded with the values from sensitivity & specificity of their reports. Both reports had no details about the collection procedures. Kappa statistics might become even more accurate, if samples could be restricted to ones collected beyond 10 days. Regarding the data from our hospital’, the kappa statistics was 0.97 when restricted to samples collected beyond 10 days, which thus showed excellent agreement.

By using kappa statistics, the performances of rapid antibody tests can be shown as one figure, so that their comparison becomes easy to carry out.

Highlights

▪

Using kappa statistics, agreement between PCR and ELISA was perfect from the data beyond 10 days of symptom-onset.

▪

The results of kappa statistics corresponded with the values from sensitivity & specificity of the English and the Chinese literatures.

▪

Kappa statistics was calculated as 0.97 from the data beyond 10 days of symptom-onset, and sensitivity & specificity were 95.2% and 100% in our hospital.

▪

Kappa statistics is a convenient means to identify accurate rapid antibody tests.
Evaluating the Mental Health Impacts of the COVID-19 Pandemic in Urban South Africa: Perceived Risk of COVID-19 Infection and Childhood Trauma Predict Adult Depressive Symptoms
Authors: Kim Andrew Wooyoung , Nyengerai Tawanda , Mendenhall Emily
Published: June 2020

South Africa’s national lockdown introduced serious threats to public mental health in a society where one in three individuals develop a psychiatric disorder during their life. We aimed to evaluate the mental health impacts of the COVID-19 pandemic using a mixed methods design. This longitudinal study drew from a preexisting sample of 957 adults living in Soweto, a major township near Johannesburg. Psychological assessments were administered across two waves: between August 2019-March 2020 and during the first six weeks of the lockdown (late March-early May 2020). Interviews on COVID-19 experiences were administered in the second wave. Multiple regression models examined relationships between perceived COVID-19 risk and depression. Full data on perceived COVID-19 risk, depression, and covariates were available in 221 adults. 14.5% of adults were at risk for depression. Higher perceived COVID-19 risk predicted greater depressive symptoms (p < 0.001) particularly among adults with histories of childhood trauma, though this effect was marginally significant (p = 0.062). Adults were two times more likely to experience significant depressive symptoms for every one unit increase in perceived COVID-19 risk (p = 0.016; 95% CI [1.14, 3.49]). Qualitative data identified potent experiences of anxiety, financial insecurity, fear of infection, and rumination. Higher perceived risk of COVID-19 infection is associated with greater depressive symptoms among adults with histories of childhood trauma during the first six weeks of quarantine. High rates of severe mental illness and low availability of mental healthcare amidst COVID-19 emphasize the need for immediate and accessible psychological resources in South Africa.
A systematic review protocol of the antiviral activity of chloroquine and hydroxychloroquine against COVID-19
Authors: Mensah Kofi Boamah , Mensah Adwoa Bemah Boamah , Bangalee Varsha , Oosthuizen Frasia
Published: June 2020

Introduction

The recent outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), or COVID-19 with no approved medicines has led to global health threat. Currently, repositioning of old medicines seems the most responsible strategy for potential cure and prevention COVID-19. Hydroxychloroquine and chloroquine have shown promising efficacy against COVID-19 related pneumonia in clinical studies. However, the mode of drug action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection is not clear. This review aims to gather evidence on antiviral activity and possible mechanism of drug action of chloroquine and hydroxychloroquine on SARS-CoV-2, including in-vitro, animal studies, and studies in humans.

Method

A structured search of five bibliographic databases namely; Medline, Web of Science, PubMed, Cochrane CENTRAL, and Google Scholar will be undertaken to retrieve studies that describe the antiviral activity and possible mechanism of drug action of chloroquine and hydroxychloroquine on SARS-CoV-2. No restrictions will be placed on publication date, but studies will be limited to only publications in English. Duplication of studies will be removed using EndNote reference manager. Three authors will screen the citations independently based on inclusion criteria. Data extraction and assessment of risk of bias will be done independently. Meta-analysis of selected studies will be done wherever suitable.

Ethics and dissemination

Primary data collection will not be involved in this study, hence no need for formal ethical clearance. Findings from the study will be disseminated through a peer-reviewed publication and conference meeting.

Trial registration number

https://doi.org/10.17605/OSF.IO/7DJMU

Strengths and limitations of this study

This study is the first systematic review to gather current evidence on the antiviral effect and mode of action of chloroquine and hydroxychloroquine on SARS-CoV-2 infection. We expect that data that will be synthesis will provide enough information to inform COVID-19 care pathways and help clinicians caring for COVID-19 patients.

Furthermore, this systematic review will expand our knowledge on the benefits and risks of chloroquine and hydroxychloroquine in management of COVID-19 patients and identify areas of controversies, and quality assessment.

We anticipate that there will be few studies reporting on the mechanism of drug action and antiviral effects of chloroquine and hydroxychloroquine on SARS-CoV-2 infection.
Prevalence of IgG antibodies to SARS-CoV-2 in Wuhan – implications for the ability to produce long-lasting protective antibodies against SARS-CoV-2
Authors: Liu Tao , Wu Sanyun , Tao Huangheng , Zeng Guang , Zhou Fuling , Guo Fangjian , Wang Xinghuan
Published: June 2020

Background

It is to be determined whether people infected with SARS-CoV-2 will develop long-term immunity against SARS-CoV-2 and retain long-lasting protective antibodies after the infection is resolved. This study was to explore to explore the outcomes of IgG antibodies to SARS-CoV-2 in four groups of individuals in Wuhan, China.

Methods

We included the following four groups of individuals who received both COVID-19 IgM/IgG tests and RT-PCR tests for SARS-CoV-2 from February 29, 2020 to April 29, 2020: 1470 hospitalized patients with COVID-19 from Leishenshan Hospital, Zhongnan Hospital of Wuhan University, and Wuhan No. 7 Hospital, 3832 healthcare providers without COVID-19 diagnosis, 19555 general workers, and 1616 other patients to be admitted to the hospital (N=26473). COVID-19 patients who received IgM/IgG tests <21 days after symptom onset were excluded.

Results

IgG prevalence was 89.8% (95% CI 88.2-91.3%) in COVID-19 patients, 4.0% (95% CI 3.4-4.7%) in healthcare providers, 4.6 (95% CI 4.3-4.9 %) in general workers, and 1.0% in other patients (p all <0.001 for comparisons with COVID-19 patients). IgG prevalence increased significantly by age among healthcare workers and general workers. Prevalence of IgM antibodies to SARS-CoV-2 was 31.4% in COVID-19 patients, 1.5% in healthcare providers, 1.3% in general workers, and 0.2% in other patients.

Conclusions

Very few healthcare providers had IgG antibodies to SARS-CoV-2, though a significant proportion of them had been infected with the virus. After SARS-CoV-2 infection, people are unlikely to produce long-lasting protective antibodies against this virus.

Primary Funding Sources

Part of the study was supported by National Key Research and Development Program of China (2020YFC0845500). The content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsors.

Role of the Funder/Sponsor

The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication.

Data and code availability statement

Data and analyses codes are available from the corresponding authors on request. All request for raw and analyzed data and materials will be reviewed by the corresponding authors to verify whether the request is subject to any intellectual property or confidentiality obligations. Access will be granted after a signed data access agreement is attained.
Double COVID-19 Confirmed Case Fatality Rate in Countries with High Elderly Female Vitamin D Deficiency Prevalence
Authors: Bäcker Alex , Mageswaran Myron
Published: June 2020

A number of clues point to a possible role of vitamin D in fighting COVID-19: a reduction in case growth speed with solar zenith angle, higher fatality rate in black people, lower fatality rate in populations that spend more time outdoors. Yet a direct demonstration that vitamin D deficiency is associated with COVID-19 fatalities has remained elusive. We show here in a comparison of 32 countries that countries with high prevalence of vitamin D deficiency among elderly females show a confirmed case fatality rate twice as high as those with low prevalence. We then show that this effect cannot be explained by differences in life expectancy between countries. A mechanistic role for vitamin D in the severity of COVID-19 is proposed.

One Sentence Summary

Vitamin D deficiency among elderly females is associated with countrywide COVID-19 confirmed case fatality rates up to twice as high as those of countries with low vitamin D deficiency prevalence.
Associations of joint swelling, joint stiffness, and joint pain with physical activity in first-degree relatives of patients with rheumatoid arthritis
Authors: Hughes-Austin Jan M. , Ix Joachim H. , Ward Samuel R. , Weisman Michael H. , O’Dell James R. , Mikuls Ted R. , Buckner Jane H. , Gregersen Peter K. , Keating Richard M. , Demoruelle M. Kristen , Deane Kevin D. , Holers V. Michael , Norris Jill M.
Published: June 2020

Background

Physical activity (PA) in pre-clinical rheumatoid arthritis (RA) is associated with lower RA risk and disease severity. Yet, PA in RA patients is less than in counterparts without RA, which can be attributed partly to symptoms of inflammatory arthritis. Therefore, we investigated whether joint swelling, stiffness, or pain were associated with PA in first-degree relatives (FDRs) of RA patients, a population at higher risk for future RA.

Methods

We evaluated associations of joint stiffness, joint swelling, and joint pain with PA time in 268 FDRs with ≥2 visits over an average 1.2 years. Clinicians confirmed joint swelling. Participants self-reported joint stiffness and/or pain. PA during a typical 24-hour day was quantified via questionnaire, weighted to reflect metabolic expenditure, where 24 hours was the minimum PA time. Linear mixed models evaluated associations between symptoms and change in PA over time, adjusting for age, sex, race, body mass index, smoking, and RA-related autoantibodies.

Results

Average weighted PA time was 37±7 hours. In cross-sectional analysis, PA time was 1.3±0.9 hours higher in FDRs reporting joint pain (p=0.15); and 0.8±1.6 and 0.4±1 hours lower in FDRs with joint swelling (p=0.60) and stiffness (p=0.69), respectively. Longitudinally, adjusting for baseline PA time, baseline symptoms were not significantly associated with changes in PA time. However, on average over time, joint stiffness and pain were associated with lower PA time (pinteraction=0.0002, pinteraction=0.002), and joint swelling was associated with higher PA time (pinteraction<0.0001)

Conclusion

Baseline symptoms did not predict future PA time, but on average over time, joint symptoms influenced PA time.
Global and local mobility as a barometer for COVID-19 dynamics
Authors: Linka Kevin , Goriely Alain , Kuhl Ellen
Published: June 2020

The spreading of infectious diseases including COVID-19 depends on human interactions. In an environment where behavioral patterns and physical contacts are constantly evolving according to new governmental regulations, measuring these interactions is a major challenge. Mobility has emerged as an indicator for human activity and, implicitly, for human interactions. Here we study the coupling between mobility and COVID-19 dynamics and show that variations in global air traffic and local driving mobility can be used to stratify different disease phases. For ten European countries, our study shows maximal correlation between driving mobility and disease dynamics with a time lag of 14.6 ± 5.6 days. Our findings suggests that local mobility can serve as a quantitative metric to forecast future reproduction numbers and identify the stages of the pandemic when mobility and reproduction become decorrelated.
A novel biparatopic antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy
Authors: Miao Xiaoniu , Luo Yi , Huang Xi , Lee Suki M. Y. , Yuan Zhijun , Tang Yongzhou , Chen Liandi , Wang Chao , Jiang Wenchao , Gao Wei , Song Xuedong , Yan Yao , Pang Tuling , Zou Yuefeng , Fu Weihui , Wan Liping , Gilbert-Jaramillo Javier , Knight Michael , Tan Tiong Kit , Rijal Pramila , Townsend Alain , Sun Joanne , Liu Xiaolin , James William , Tsun Andy , Xu Yingda
Published: June 2020

In the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provides a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain (NTD) of the viral S glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain (RBD) of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic virus infection in a standard assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.
Engineering of extracellular vesicles for display of protein biotherapeutics
Authors: Gupta Dhanu , Wiklander Oscar P.B , Görgens André , Conceição Mariana , Corso Giulia , Liang Xiuming , Seow Yiqi , Balsu Sriram , Felldin Ulrika , Bostancioglu Beklem , Fiona Lee Yi Xin , Hean Justin , Mäger Imre , Roberts Thomas C. , Gustafsson Manuela , Mohammad Dara K , Sork Helena , Bäcklund Alexandra , Edvard Smith C.I. , Wood Matthew J.A. , Vandenbroucke Roosmarijn , Nordin Joel Z. , Andaloussi Samir EL
Published: June 2020

Extracellular vesicles (EVs) have recently emerged as a highly promising cell-free bio-therapeutics. While a range of engineering strategies have been developed to functionalize the EV surface, current approaches fail to address the limitations associated with endogenous surface display, pertaining to the heterogeneous display of commonly used EV-loading moieties among different EV subpopulations. Here we present a novel engineering platform to display multiple protein therapeutics simultaneously on the EV surface. As proof-of-concept, we screened multiple endogenous display strategies for decorating the EV surface with cytokine binding domains derived from tumor necrosis factor receptor 1 (TNFR1) and interleukin 6 signal transducer (IL6ST), which can act as decoys for the pro-inflammatory cytokines TNFα and IL6, respectively. Combining synthetic biology and systematic screening of loading moieties, resulted in a three-component system which increased the display and decoy activity of TNFR1 and IL6ST, respectively. Further, this system allowed for combinatorial functionalization of two different receptors on the same EV surface. These cytokine decoy EVs significantly ameliorated disease phenotypes in three different inflammatory mouse models for systemic inflammation, neuroinflammation, and intestinal inflammation. Importantly, significantly improvedin vitroandin vivoefficacy of these engineered EVs was observed when compared directly to clinically approved biologics targeting the IL6 and TNFα pathways.
Characterization of the SARS-CoV-2 S Protein: Biophysical, Biochemical, Structural, and Antigenic Analysis
Authors: Herrera Natalia G. , Morano Nicholas C. , Celikgil Alev , Georgiev George I. , Malonis Ryan J. , Lee James H. , Tong Karen , Vergnolle Olivia , Massimi Aldo B. , Yen Laura Y. , Noble Alex J. , Kopylov Mykhailo , Bonanno Jeffrey B. , Garrett-Thomson Sarah C. , Hayes David B. , Bortz Robert H. , Wirchnianski Ariel S. , Florez Catalina , Laudermilch Ethan , Haslwanter Denise , Fels J. Maximilian , Dieterle M. Eugenia , Jangra Rohit K. , Barnhill Jason , Mengotto Amanda , Kimmel Duncan , Daily Johanna P. , Pirofski Liise-anne , Chandran Kartik , Brenowitz Michael , Garforth Scott J. , Eng Edward T. , Lai Jonathan R. , Almo Steven C.
Published: June 2020

Coronavirus disease 2019 (COVID-19) is a global health crisis caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and there is a critical need to produce large quantities of high-quality SARS-CoV-2 Spike (S) protein for use in both clinical and basic science settings. To address this need, we have evaluated the expression and purification of two previously reported S protein constructs in Expi293F™and ExpiCHO-S™cells, two different cell lines selected for increased expression of secreted glycoproteins. We show that ExpiCHO-S™cells produce enhanced yields of both SARS-CoV-2 S proteins. Biochemical, biophysical, and structural (cryo-EM) characterization of the SARS-CoV-2 S proteins produced in both cell lines demonstrate that the reported purification strategy yields high quality S protein (non-aggregated, uniform material with appropriate biochemical and biophysical properties). Importantly, we show that multiple preparations of these two recombinant S proteins from either cell line exhibit identical behavior in two different serology assays. We also evaluate the specificity of S protein-mediated host cell binding by examining interactions with proposed binding partners in the human secretome. In addition, the antigenicity of these proteins is demonstrated by standard ELISAs, and in a flexible protein microarray format. Collectively, we establish an array of metrics for ensuring the production of high-quality S protein to support clinical, biological, biochemical, structural and mechanistic studies to combat the global pandemic caused by SARS-CoV-2.
Interplay of curvature and rigidity in shape-based models of confluent tissue
Authors: Sussman Daniel M.
Published: June 2020

Rigidity transitions in simple models of confluent cells have been a powerful organizing principle in understanding the dynamics and mechanics of dense biological tissue. In this work we explore the interplay between geometry and rigidity in two-dimensional vertex models confined to the surface of a sphere. By considering shapes of cells defined by perimeters whose magnitude depends on geodesic distances and areas determined by spherical polygons, the critical shape index in such models is affected by the size of the cell relative to the radius of the sphere on which it is embedded. This implies that cells can collectively rigidify by growing the size of the sphere, i.e. by tuning the curvature of their domain. Finite-temperature studies indicate that cell motility is affected well away from the zero-temperature transition point.
The adaptive function of sexual reproduction: resampling the genotype pool
Authors: Hickey Donal A. , Golding G. Brian
Published: June 2020

Recombination allows a finite population to resample the genotype pool, i.e., the universe of all possible genotypic combinations. This is important in populations that contain abundant genetic variation because, in such populations, the number of potential genotypes is much larger than the number of individuals in the population. Here, we show how recombination, in combination with natural selection, enables an evolving sexual population to replace existing genotypes with new, higher-fitness genotypic combinations. In contrast to this, an asexual population is limited to selection among existing genotypes. Since it has been shown that most eukaryotic species are genetically polymorphic, our model can explain the ubiquity of sex among such species. The model also indicates that classic population genetics theory is applicable to ecological studies of natural selection acting on standing genetic variation.
Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney
Authors: Muto Yoshiharu , Wilson Parker C. , Wu Haojia , Waikar Sushrut S. , Humphreys Benjamin D.
Published: June 2020

The integration of single cell transcriptome and chromatin accessibility datasets enables a deeper understanding of cell heterogeneity. We performed single nucleus ATAC (snATAC-seq) and RNA (snRNA-seq) sequencing to generate paired, cell-type-specific chromatin accessibility and transcriptional profiles of the adult human kidney. We demonstrate that snATAC-seq is comparable to snRNA-seq in the assignment of cell identity and can further refine our understanding of functional heterogeneity in the nephron. The majority of differentially accessible chromatin regions are localized to promoters and a significant proportion are closely-associated with differentially expressed genes. Cell-type-specific enrichment of transcription factor binding motifs implicates the activation of NFκB that promotesVCAM1expression and drives transition between a subpopulation of proximal tubule epithelial cells. These datasets can be visualized at this resource:http://humphreyslab.com/SingleCell/. Our multi-omics approach improves the ability to detect unique cell states within the kidney and redefines cellular heterogeneity in the proximal tubule and thick ascending limb.
An efficient root transformation system for recalcitrantVicia sativa
Authors: Nguyen Vy , Searle Iain R.
Published: June 2020

Common vetch (Vicia sativa) is a multi-purpose legume widely used in pasture and crop rotation systems. Vetch seeds have desirable nutritional characteristics and are often used to feed ruminant animals. Although transcriptomes are available for vetch, problems with genetic transformation and plant regeneration hinder functional gene studies in this legume species. Therefore, the aim of this study was to develop an efficient and rapid hairy root transformation system for common vetch to facilitate functional gene analysis. We infected the hypocotyls of five-day oldin vitroorin vivo,soil grown, seedlings withAgrobacterium rhizogenesand produced transformed hairy roots 28 days later at 24% and 43% efficiency, respectively. Seventy-nine percent of the hairy roots from thein vitroplants showed stable expression of a co-transformed marker β-glucuronidase (GUS). In summary, transgenic hairy roots were obtained within 28 days, and are sufficient to facilitate functional gene analysis in common vetch.
Autumn larval cold tolerance does not predict the northern range limit of a widespread butterfly species
Authors: Tremblay Philippe , MacMillan Heath A. , Kharouba Heather M.
Published: June 2020

Climate change is driving range shifts, and a lack of cold tolerance is hypothesized to constrain insect range expansion at poleward latitudes. However, few, if any, studies have tested this hypothesis during autumn when organisms are subjected to sporadic low temperature exposure but may not have become cold tolerant yet. In this study, we integrated organismal thermal tolerance measures into species distribution models for larvae of the Giant Swallowtail butterfly,Papilio cresphontes, living at the northern edge of its actively expanding range. Cold hardiness of field-collected larvae was determined using three common metrics of cold-induced physiological thresholds: the supercooling point (SCP), critical thermal minimum (CTmin), and survival following cold exposure.P. cresphonteslarvae in autumn have a CTminof 2.14°C, and were determined to be tolerant of chilling. These larvae have a SCP of −6.6°C and can survive prolonged exposure to −2°C. They generally die, however, at temperatures below their SCP (−8°C), suggesting they are chill tolerant or modestly freeze avoidant. Using this information, we examined the importance of low temperatures at a broad scale, by comparing species distribution models ofP. cresphontesbased only on environmental data derived from other sources to models that also included the cold tolerance parameters generated experimentally. Our modelling revealed that growing degree-days and precipitation best predicted the distribution ofP. cresphontes, while the cold tolerance variables did not explain much variation in habitat suitability. As such, the modelling results were consistent with our experimental results: low temperatures in autumn are unlikely to limit the distribution ofP. cresphontes. Further investigation into the ecological relevance of the physiological thresholds determined here will help determine how climate limits the distribution ofP. cresphontes. Understanding the factors that limit species distributions is key to predicting how climate change will drive species range shifts.
LDBlockShow: a fast and convenient tool for visualizing linkage disequilibrium and haplotype blocks based on variant call format files
Authors: Dong Shan-Shan , He Wei-Ming , Ji Jing-Jing , Zhang Chi , Guo Yan , Yang Tie-Lin
Published: June 2020

The triangular correlation heatmap aiming to visualize the linkage disequilibrium (LD) pattern and haplotype block structure of SNPs is ubiquitous component of population-based genetic studies. However, current tools suffered from the problem of time and memory consuming, and direct calculation from variant call format (VCF) files is not supported. Here we developed LDBlockShow, an open source software, for visualizing LD and haplotype blocks from VCF files. It is time and memory saving. In a test dataset with 100 SNPs from 60,000 subjects, it was at least 429.03 times faster and used only 0.04% – 20.00% of physical memory as compared to other tools. In addition, it could generate figures that simultaneously display additional statistical context (e.g., associationPvalues) and genomic region annotations. It can also compress the SVG files with large number of SNPs and support subgroup analysis. This fast and convenient tool would facilitate the visualization of LD and haplotype blocks for geneticists.
Risk of death by age and gender from CoVID-19 in Peru, March-May, 2020
Authors: Munayco Cesar , Chowell Gerardo , Tariq Amna , Undurraga Eduardo A. , Mizumoto Kenji
Published: June 2020

Peru implemented strict social distancing measures during the early phase of the epidemic and is now experiencing one of the largest CoVID-19 epidemics in Latin America. Estimates of disease severity are an essential indicator to inform policy decisions about the intensity and duration of interventions needed to mitigate the outbreak. Here we derive delay-adjusted case fatality rates (aCFR) of CoVID-19 in a middle-income country in South America.

We used government-reported time series of CoVID-19 cases and deaths stratified by age group and gender.

Our estimates as of May 25, 2020, of the aCFR for men and women are 10.8% (95%CrI: 10.5–11.1%) and 6.5% (95%CrI: 6.2–6.8%), respectively, and an overall aCFR of 9.1% (95%CrI: 8.9–9.3%). Our results show that senior individuals are the most severely affected by CoVID-19, particularly men, with aCFR of almost 60% for those aged 80-years. We found that men have a significantly higher cumulative morbidity ratio than women across most age groups (proportion test, p-value< 0.001), with the exception of those aged 0–9 years.

The COVID-19 epidemic is imposing a large mortality burden in Peru. Senior individuals, especially those who are older than 70 years of age, are being disproportionately affected by the COVID-19 pandemic.