bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterisation of a phospholipid scramblase in the malaria parasite Plasmodium falciparum
Authors: Haase Silvia , Condron Melanie , Miller David , Cherkaoui Dounia , Jordan Sarah , Gulbis Jacqueline M , Baum Jake 
Published: June 2020

AbstractRecent studies highlight the emerging role of lipids as important messengers in malaria parasite biology. In an attempt to identify interacting proteins and regulators of these dynamic and versatile molecules, we hypothesised the involvement of phospholipid translocases and their substrates in the infection of the host erythrocyte by the malaria parasite Plasmodium spp. Here, using a data base mining approach, we have identified a putative phospholipid (PL) scramblase in P. falciparum (PfPLSCR) that is conserved across the genus and in closely related unicellular algae. By reconstituting recombinant PfPLSCR into liposomes, we demonstrate metal ion dependent PL translocase activity and substrate preference, confirming PfPLSCR as a bona fide scramblase. We confirm that PfPLSCR is expressed during asexual and sexual parasite development, localising to different membranous compartments of the parasite throughout the intra-erythrocytic life cycle. Two different gene knockout approaches, however, suggest that PfPLSCR is not essential for erythrocyte invasion and asexual parasite development, pointing towards a possible role in other stages of the parasite life cycle.
tacost: Testing and simulating the performance of acoustic tracking systems
Authors: Beleyur Thejasvi 
Published: June 2020

Abstracttacostis a Python package to allow the testing of acoustic tracking systems. While many microphone array systems have been characterised analytically and experimentally – these are time-intensive methods.tacostprovides a simulation based framework to rapidly assess the tracking behaviour of multiple array geometries, and the dissection of other relevant parameters. This paper explains briefly the design of the package and highlights two example use cases in which the tracking accuracy of different microphone geometries are characterised.
Life-long telomere attrition predicts health and lifespan in a large mammal
Authors: Seeker Luise A. , Underwood Sarah L. , Wilbourn Rachael V. , Fairlie Jennifer , Froy Hannah , Holland Rebecca , Ilska Joanna J. , Psifidi Androniki , Bagnall Ainsley , Whitelaw Bruce , Coffey Mike , Banos Georgios , Nussey Daniel H. 
Published: June 2020

AbstractTelomere length measured in blood cells is predictive of subsequent adult health and survival across a range of vertebrate species. However, we currently do not know whether such associations result from among-individual differences in telomere length determined genetically or by environmental factors early in life, or from differences in the rate of telomere attrition over the course of life. Here, we measured relative leukocyte telomere length (RLTL) multiple times across the entire lifespan of dairy cattle in a research population that is closely monitored for health and milk production and where individuals are only culled in response to health issues and less due to poor milk production than on purely commercial farms. Our results clearly show that the average amount of telomere attrition over an individual’s life, not their average or early life telomere length predicted when an individual was culled. Within-individual telomere length attrition could reflect environmental or physiological insults which may accumulate to predict individual health-span. We also show that animals with more telomere attrition in their first year of life were culled at a younger age, indicating that early life stressors may have a prolonged effect on adult life.
Stable integration of an optimized inducible promoter system enables spatiotemporal control of gene expression throughout avian development
Authors: Chu Daniel , Nguyen An , Smith Spenser S. , Vavrušová Zuzana , Schneider Richard A. 
Published: June 2020

AbstractPrecisely altering gene expression is critical for understanding molecular processes of embryogenesis. Although some tools exist for transgene misexpression in developing chick embryos, we have refined and advanced them by simplifying and optimizing constructs for spatiotemporal control. To maintain expression over the entire course of embryonic development we use an enhancedpiggyBactransposon system that efficiently integrates sequences into the host genome. We also incorporate a DNA targeting sequence to direct plasmid translocation into the nucleus and a D4Z4 insulator sequence to prevent epigenetic silencing. We designed these constructs to minimize their size and maximize cellular uptake, and to simplify usage by placing all of the integrating sequences on a single plasmid. Following electroporation of stage HH8.5 embryos, our tetracycline-inducible promoter construct produces robust transgene expression in the presence of doxycycline at any point during embryonic developmentin ovoor in culture. Moreover, expression levels can be modulated by titrating doxycycline concentrations and spatial control can be achieved using beads or gels. Thus, we have generated a novel, sensitive, tunable, and stable inducible-promoter system for high-resolution gene manipulationin vivo.
A link between inflammatory biomarkers and lung ultrasound observations in patients with SARS-CoV-2 infection
Authors: Wangüemert Pérez Aurelio Luis , Figueira Gonçalves Juan Marco , Hernández Pérez José María , Ramallo- Fariña Yolanda , del Castillo Rodríguez José Carlos 
Published: June 2020

ABSTRACTLung ultrasound (LUS) has shown to correlate well with the findings obtained by chest computed tomography (CT) in acute-phase COVID-19. Although there is a significant correlation between blood biomarkers and CT radiological findings, a potential correlation between biochemical parameters and LUS images is still unknown. Our purpose was to evaluate a potential association between lung lesions visualised by LUS and blood biomarkers as well as the ability to predict mortality from two different lung ultrasound scoring systems (LUSS). We performed a retrospective observational study on 45 patients aged >70 years with SARS-CoV-2 infection who required hospitalisation. LUS was carried out at admission and on day 7, when the clinical course was favourable or earlier in case of worsening. Disease severity was scored by means of LUSS in 8 (LUSS8) and in 12 (LUSS12) quadrants. LUS and blood draw for inflammatory marker analysis were performed at the same time. The correlation between biochemical parameters and either LUSS score was significant for ferritin levels. It was 0.486 (p=0.001) for LUSS8 and 0.458 (p=0.002) for LUSS12. Using a threshold score of 15 with LUSS12 predicted mortality in 86.7% of cases (ORcrude 31, CI 95% 4.79–200.51). Applying a threshold of 10 with LUSS8 predicted mortality in 88.9% (ORcrude 69.75, CI 95% 6.90–705.20). There is a correlation between ferritin levels and LUSS. The prognostic capacity of LUSS12 does not surpass that of LUSS8.“Take-home message”There is a correlation between lung ultrasound scoring results and serum ferritin levels in patients with SARS-CoV-2 infection.
Brain Impairment revealed by Multi-Modality MRI in Parkinson’s Disease
Authors: Ran Zhang , Ping Gong , Haitao Ge 
Published: June 2020

AbstractObjectiveTo study the abnormal brain regions of patients with Parkinson’s disease (PD) using multimodality MRI to provide complementary information for early detection for PD.Methods27 patients with early PD and 25 normal ageing volunteers were included in the study. Multimodality MRI data were acquired and processed to extract neuroimaging features to test the structural and functional changes using a two-sample t-test.ResultsThe changes of brain regions were disagreed for different modality MRI data between PD and normal ageing individuals. Nevertheless,the postcentral gyrus, precentral gyrus, lingual gyrus and paracentral lobule were significantly different for all three modalities.ConclusionMultimodality MRI data can reflect the structural and functional changes of PD, and reveal the hidden information which is of great significance to assist early detection for PD.
First results from the UK COVID-19 Serology in Oncology Staff Study (CSOS)
Authors: Favara DM , Cooke A , Doffinger R , Houghton S , Budriunaite I , Bossingham S , McAdam K , Corrie P , Ainsworth N 
Published: June 2020

AbstractBackgroundThe global SARS-CoV-2 (COVID-19) pandemic has caused substantial worldwide mortality. At present, there is no data regarding oncologist-specific SARS-CoV-2 infection/immunity rates in the United Kingdom (UK) which might impact planning for the management of potentially immunosuppressed cancer patients. Here, we present the first results from the COVID-19 Serology in Oncology Staff (CSOS) study with the aim of informing non-surgical oncology management guidelines.MethodsPatient-facing staff working in an oncology department during the COVID-19 pandemic at a large district general hospital in the East of England were invited to participate. Samples were collected during the first week of June 2020: blood for SARS-COV-2 antibody testing using a rapid lateral flow point of care (POC) assay and a laboratory Luminex based assay, as well as a nasopharyngeal swab for SARS-CoV-2 PCR testing. Participant characteristics were also collected.ResultsSeventy participants were recruited: nurses (45/70; 64.3%), doctors (15/70; 21.2%), and other patient-facing staff (10/70; 14.3%). The majority were female (61/70; 87.1%) with a mean age of 42 years (median 41; range 23-64 years). A minority were smokers (9/70; 10%) or had chronic underlying health conditions (16/70; 22.9%), the commonest being asthma. All participants were nasopharyngeal-swab PCR negative, although 4/70 (5.7%) had previously tested positive by NHS testing undertaken during the preceding months. 15/70 (21.4%) had positive SARS-CoV-2 antibodies using the Luminex test. Nurses had the highest incidence of positive antibodies (13/45; 28.9%), with a lower incidence in doctors (2/15; 13.3%) although this difference was not statistically significant (Fischer’s exact test p=0.3). No receptionists had positive antibody tests. All four participants with a previously reported positive PCR test were antibody-positive. 9/15 (60%) of antibody-positive participants reported previous symptoms suggestive of SARS-CoV-2 infection: a 3.6-fold higher odds than antibody-negative participants, of whom 16/55 reported symptoms (p=0.03). The mean duration of symptoms was 11 days (median 11; range 1-35 days) and the mean time from resolution of reported previous symptoms to antibody testing was 48.4 days (median 46; range 1-123 days).ConclusionThis study establishes the SARS-CoV-2 exposure and carriage rate amongst patient-facing staff working in the oncology department of a large UK general hospital during the pandemic. These results may help inform UK national oncology patient management prior to the development of a viable vaccine or treatment.
Effect of Dexamethasone in Hospitalized Patients with COVID-19 – Preliminary Report
Authors: Horby Peter , Lim Wei Shen , Emberson Jonathan , Mafham Marion , Bell Jennifer , Linsell Louise , Staplin Natalie , Brightling Christopher , Ustianowski Andrew , Elmahi Einas , Prudon Benjamin , Green Christopher , Felton Timothy , Chadwick David , Rege Kanchan , Fegan Christopher , Chappell Lucy C , Faust Saul N , Jaki Thomas , Jeffery Katie , Montgomery Alan , Rowan Kathryn , Juszczak Edmund , Baillie J Kenneth , Haynes Richard , Landray Martin J ,   RECOVERY Collaborative Group
Published: June 2020

ABSTRACTBackgroundCoronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death.MethodsThe Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality.Results2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14).ConclusionsIn patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.Trial registrationsThe RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).FundingMedical Research Council and National Institute for Health Research (Grant ref: MC_PC_19056).
Vitamin D insufficiency and deficiency and mortality from respiratory diseases in a cohort of older adults: potential for limiting the death toll during and beyond the COVID-19 pandemic
Authors: Brenner Hermann , Holleczek Bernd , Schöttker Ben 
Published: June 2020

AbstractBackgroundThe COVID-19 pandemic goes along with increased mortality from acute respiratory disease, and measures to limit the spread of the infection go along with increased risk of vitamin D deficiency, especially among high risk groups. It has been suggested that vitamin D3 supplementation might help to reduce respiratory disease mortality.MethodsWe assessed the prevalence of vitamin D insufficiency and deficiency, defined by 25(OH)D blood levels of 30-50 and <30 nmol/L, respectively, and their association with mortality from respiratory diseases during 15 years of follow-up in a cohort of 9,548 adults aged 50-75 years from Saarland, Germany.ResultsVitamin D insufficiency and deficiency were common (44% and 15%, respectively). Compared to sufficient vitamin D status, respiratory disease mortality was 2.1 (95%-CI 1.3-3.2)- and 3.0 (95%-CI 1.8-5.2)-fold increased, respectively. Although significant increases were seen in both women and men, they were much stronger among women, with 8.5 (95% CI 2.4-30.1) and 2.3 (95% CI 1.1-4.4)-fold increase of respiratory disease mortality in case of vitamin D deficiency among women and men, respectively (p-value for interaction =0.041). Overall, 41% (95% CI 20%-58%) of respiratory disease mortality was statistically attributable to vitamin D insufficiency or deficiency.ConclusionVitamin D insufficiency and deficiency are common and account for a large proportion of respiratory disease mortality in older adults, supporting suggestions that vitamin D3 supplementation might make a major contribution to limit the burden of the COVID-19 pandemic, particularly among women.
A juxtaposition of safety outcomes between various doses of sodium-glucose co-transporter inhibitors, in insulin-treated type-1 diabetes mellitus patients: a protocol for systematic review and meta-analysis of double-blinded randomized controlled trials
Authors: Saha Sumanta 
Published: June 2020

ABSTRACTAimsSeveral clinical trials have tested the safety profile of sodium-glucose co-transport inhibitors’ (SGLTis) in adult type 1 diabetes mellitus (T1DM) patients. However, no systematic review has compared its variation between large and low dose SGLTis. Henceforth, a review protocol is proposed here to review it. Besides, it will compare the side effects of each of these interventions with the placebo.MethodsDifferent electronic databases will be searched for randomized double-blinded placebo-controlled trials (published in the English language) studying the above objective, irrespective of their publication date. After selecting the eligible trials, their data on the study design, population characteristics, compared interventions, and outcomes of interest will be extracted. Then, utilizing the Cochrane tool, each trial’s risk of selection bias, detection bias, performance bias, attrition bias, reporting bias, and other bias will be judged. Next, depending on clinical heterogeneity among the trials, a random-effect or fixed-effect model meta-analysis will be used to compare the respective outcomes. Via the Chi2 and I2 statistics, the statistical inconsistency among the trials will be estimated. When this is substantial, subgroup analysis will follow. Publication bias will be evaluated by funnel plots and Egger’s test. A sensitivity analysis will be done to check different assumptions. If a quantitative juxtaposition is not possible, a narrative reporting will ensue. Conclusions: The proposed review will compare the safety profile between the mega and low dose SGLTis in insulin-treated T1DM patients. Besides, each of these two types of doses will be compared with placebo for the same.REGISTRATIONPROSPERO (Registration no. CRD42019146578)
The timing and effectiveness of implementing mild interventions of COVID-19 in large industrial regions via a synthetic control method
Authors: Tian Ting , Luo Wenxiang , Tan Jianbin , Jiang Yukang , Chen Minqiong , Pan Wenliang , Yang Songpan , Zhao Jiashu , Wang Xueqin , Zhang Heping 
Published: June 2020

The outbreak of novel coronavirus disease (COVID-19) has spread around the world since it was detected in December 2019. The Chinese government executed a series of interventions to curb the pandemic. The “battle” against COVID-19 in Shenzhen, China is valuable because populated industrial cities are the epic centres of COVID-19 in many regions. We made use of synthetic control methods to create a reference population matching specific characteristics of Shenzhen. With both the synthetic and observed data, we introduced an epidemic compartmental model to compare the spread of COVID-19 between Shenzhen and its counterpart regions in the United States that didn’t implement interventions for policy evaluation. Once the effects of policy interventions adopted in Shenzhen were estimated, the delay effects of those interventions were referred to provide the further control degree of interventions. Thus, the hypothetical epidemic situations in Shenzhen were inferred by using time-varying reproduction numbers in the proposed SIHR (Susceptible, Infectious, Hospitalized, Removed) model and considering if the interventions were delayed by 0 day to 5 days. The expected cumulative confirmed cases would be 1546, which is 5.75 times of the observed cumulative confirmed cases of 269 in Shenzhen on February 3, 2020, based on the data from the counterpart counties (mainly from Broward, New York, Santa Clara, Pinellas, and Westchester) in the United States. If the interventions were delayed by 5 days from the day when the interventions started, the expected cumulative confirmed cases of COVID-19 in Shenzhen on February 3, 2020 would be 676 with 95% credible interval (303,1959). Early implementation of mild interventions can subdue the epidemic of COVID-19. The later the interventions were implemented, the more severe the epidemic was in the hard-hit areas. Mild interventions are less damaging to the society but can be effective when implemented early.AMS 2000 subject classifications: Primary 00K00, 00K01; secondary 00K02.
The impact of asymptomatic COVID-19 infections on future pandemic waves
Authors: Fox Spencer J , Pasco Remy , Tec Mauricio , Du Zhanwei , Lachmann Michael , Scott James , Meyers Lauren Ancel 
Published: June 2020

Letter textThe prevalence of asymptomatic COVID-19 infections is largely unknown and may determine the course of future pandemic waves and the effectiveness of interventions. Using an epidemiological model fit to COVID-19 hospitalization counts from New York City, New York and Austin, Texas, we found that theundocumentedattack rate in the first pandemic wave depends on the proportion of asymptomatic infections but not on the infectiousness of such individuals. Based on a recent report that 22.7% of New Yorkers are seropositive for SARS-CoV-2, we estimate that 56% (95% CI: 53-59%) of COVID-19 infections are asymptomatic. Given uncertainty in the case hospitalization rate, however, the asymptomatic proportion could be as low as 20% or as high as 80%. We find that at most 1.26% of the Austin population was infected by April 27, 2020 and conclude that immunity from undetected infections is unlikely to slow future pandemic spread in most US cities in the summer of 2020.
The impact of COVID-19 non-pharmaceutical interventions on the future dynamics of endemic infections
Authors: Baker Rachel E. , Park Sang Woo , Yang Wenchang , Vecchi Gabriel A. , Metcalf C. Jessica E. , Grenfell Bryan T. 
Published: June 2020

AbstractNon-pharmaceutical interventions (NPIs) have been employed to reduce the transmission of SARS-CoV-2, yet these measures are already having similar effects on other directly-transmitted, endemic diseases. Disruptions to the seasonal transmission patterns of these diseases may have consequences for the timing and severity of future outbreaks. Here we consider the implications of SARS-CoV-2 NPIs for two endemic infections circulating in the United States of America (USA): respiratory syncytial virus (RSV) and seasonal influenza. Using laboratory surveillance data from 2020, we estimate that RSV transmission declined by at least 20% in the USA at the start of the NPI period. We simulate future trajectories of both RSV and influenza, using an epidemic model. As susceptibility increases over the NPI period, we find that substantial outbreaks of RSV may occur in future years, with peak outbreaks likely occurring in the winter of 2021-2022. Results for influenza broadly echo this picture, but are more uncertain; future outbreaks are likely dependent on the transmissibility and evolutionary dynamics of circulating strains.