bluuebunny/crossref_metadata_2025_split huggingface dataset:
Untangling factors associated with country-specific COVID-19 incidence, mortality and case fatality rates during the first quarter of 2020
Authors: Shagam Lev 
Published: April 2020

AbstractAt early stages of the COVID-19 pandemic which we are experiencing, the publicly reported incidence, mortality and case fatality rates (CFR) vary significantly between countries. Here we aim to untangle factors that are associated with the differences during the first quarter of the year 2020. Number of performed COVID-19 tests has a strong correlation with country-specific incidence (p < 2 × 10−16) and mortality rate (p = 5.1 × 10−8). Using multivariate linear regression we show that incidence and mortality rates correlate significantly with GDP per capita (p = 2.6 × 10−15 and 7.0 × 10−4, respectively), country-specific duration of the outbreak (2.6 × 10−4 and 0.0019), fraction of citizens over 65 years old (p = 0.0049 and 3.8 × 10−4) and level of press freedom (p = 0.021 and 0.019) which cumulatively explain 80% of variability of incidence and more than 60% of variability of mortality of the disease during the period analyzed. Country hemisphere demonstrated significant correlation only with mortality (p = 0.17 and 0.036) whereas population density (p = 0.94 and p = 0.75) and latitude (p = 0.61 and 0.059) did not reach significance in our model. Case fatality rate is shown to rise as the outbreak progresses (p=0.028). We rank countries by COVID-19 mortality corrected for incidence and the factors that were shown to affect it, and by CFR corrected for outbreak duration, yielding very similar results. Among the countries where the outbreak started after the 15th of February and with at least 1000 registered patients during the period analyzed, the lowest corrected CFR are seen in Israel, South Africa and Chile. The ranking results should be considered with caution as they do not consider all confounding factors or data reporting biases.
Merging the Traditional with the NewCME-accredited Twitter Journal Clubs
Authors: Desai Tejas 
Published: April 2020

Twitter journal clubs are increasingly popular amongst healthcare providers. Most journal clubs rely on voluntary physician participation. Offering continuing medical education credit may incentivize and improve these journal clubs.In this investigation a series of 5 consecutive publication-sponsored Twitter journal clubs were analyzed in calendar year 2016, in which the latter 3 journal clubs offered CME credit. Various quality metrics were measured and analyzed to identify sustainable improvements in those journal clubs that offered CME credit.Overall, Twitter journal clubs that offered CME credit performed better in certain quality metrics, to wit activity, originality, and evidence-based tweeting, but fared poorly in number of and type of participant interactions.Twitter journal clubs are in their infancy and physician participation remains steady. Offering CME credit improves certain quality metrics within these journal clubs. This investigation should encourage more publications to sponsor CME-accredited Twitter journal clubs.
Ethnic and socioeconomic differences in SARS-CoV-2 infection: prospective cohort study using UK Biobank
Authors: Niedzwiedz Claire L , O’Donnell Catherine A , Jani Bhautesh Dinesh , Demou Evangelia , Ho Frederick K , Celis-Morales Carlos , Nicholl Barbara I , Mair Frances , Welsh Paul , Sattar Naveed , Pell Jill P , Katikireddi S Vittal 
Published: April 2020

AbstractBackgroundUnderstanding of the role of ethnicity and socioeconomic position in the risk of developing SARS-CoV-2 infection is limited. We investigated this in the UK Biobank study.MethodsThe UK Biobank study recruited 40-70 year olds in 2006-2010 from the general population, collecting information about self-defined ethnicity and socioeconomic variables (including area-level socioeconomic deprivation and educational attainment). SARS-CoV-2 test results from Public Health England were linked to baseline UK Biobank data. Poisson regression with robust standard errors was used to assess risk ratios (RRs) between the exposures and dichotomous variables for: being tested, having a positive test and testing positive in hospital. We also investigated whether ethnicity and socioeconomic position were associated with having a positive test amongst those tested. We adjusted for covariates including age, sex, social variables (including healthcare work and household size), behavioural risk factors and baseline health.ResultsAmong 428,225 participants in England, 1,474 had been tested and 669 tested positive between 16 March and 13 April 2020. Black, south Asian and white Irish people were more likely to have confirmed infection (RR 4.01 (95%CI 2.92-5.12); RR 2.11 (95%CI 1.43-3.10); and RR 1.60 (95% CI 1.08-2.38) respectively) and were more likely to be hospital cases compared to the White British. While they were more likely to be tested, they were also more likely to test positive. Adjustment for baseline health and behavioural risk factors led to little change, with only modest attenuation when accounting for socioeconomic variables. Socioeconomic deprivation and having no qualifications were consistently associated with a higher risk of confirmed infection (RR 2.26 (95%CI 1.76-2.90); and RR 1.91 (95%CI 1.53-2.38) respectively).ConclusionsSome minority ethnic groups have a higher risk of confirmed SARS-CoV-2 infection in the UK Biobank study which was not accounted for by differences in socioeconomic conditions, measured baseline health or behavioural risk factors. An urgent response to addressing these elevated risks is required.
The Potential Impact of Interruptions to HIV Services: A Modelling Case Study for South Africa
Authors: Jewell Britta , Smith Jennifer , Hallett Timothy 
Published: April 2020

SummaryThe numbers of deaths caused by HIV could increase substantially if the COVID-19 epidemic leads to interruptions in the availability of HIV services. We compare publicly available scenarios for COVID-19 mortality with predicted additional HIV-related mortality based on assumptions about possible interruptions in HIV programs. An interruption in the supply of ART for 40% of those on ART for 3 months could cause a number of deaths on the same order of magnitude as the number that are anticipated to be saved from COVID-19 through social distancing measures. In contrast, if the disruption can be managed such that the supply and usage of ART is maintained, the increase in AIDS deaths would be limited to 1% over five years, although this could still be accompanied by substantial increases in new HIV infections if there are reductions in VMMC, oral PrEP use, and condom availability.
Short term Biological Variation of Differential Count in Healthy Subjects in a South Asian Population
Authors: Gupta Arvind Kumar , Arathi K. , Tayal Sakshi Garg , Mehan Anoushika , Sahay Rishabh , Kumar Utpal , Anthony Michael Leonard , Singh Neha , Chandra Harish , Chowdhury Nilotpal 
Published: April 2020

ABSTRACTIntroductionEstimates of Within-Subject and between subject biological variation in South Asia are sorely lacking. Therefore, we attempted to estimate the short-term estimates of the same for Differential Counts (DC).MethodsThe study was conducted on twenty eight healthy volunteers (15 males and 13 females). After morning collection of blood in K3-EDTA vials analysis was conducted in triplicate on the Sysmex XN-1000 analyzer for six consecutive days. The Within subject, between subject and analytical coefficient of variation of the DC was calculated from the results by nested repeated measures ANOVA after outlier exclusion. The Reference change values (RCV) were also calculated.ResultsThe within-subject variation for Eosinophil Count in our group from South Asia was greater than the published European and American studies. The between-subject variation in monocytes and basophils were also increased. Males and females showed similar biological variation for DC. The Within-subject variation of other parameters (Neutrophils, Lymphocytes, Monocytes and Basophils) were similar or showed only mild differences to the published studies.ConclusionThe markedly different within-subject variation for Eosinophil counts suggest that the RCV for DC in South Asians need to be different from the published data in order to have clinical relevance. The Within-subject variation values of the other parameters seem transportable from the published European and American studies, but small differences found mean that further regional estimates need to be found for robust evidence of the same.
A systematic review and meta-analysis of Anakinra, Sarilumab, Siltuximab and Tocilizumab for Covid-19
Authors: Khan Fasihul , Stewart Iain , Fabbri Laura , Moss Samuel , Robinson Karen A. , Smyth Alan , Jenkins Gisli 
Published: April 2020

ABSTRACTBackgroundThere is accumulating evidence for an overly activated immune response in severe Covid-19, with several studies exploring the therapeutic role of immunomodulation. Through systematic review and meta-analysis, we assess the effectiveness of specific interleukin inhibitors for the treatment of Covid-19.MethodsElectronic databases were searched on 7thJanuary 2021 to identify studies of immunomodulatory agents (anakinra, sarilumab, siltuximab and tocilizumab) for the treatment of Covid-19. The primary outcomes were severity on an ordinal scale measured at day 15 from intervention and days to hospital discharge. Key secondary endpoints included overall mortality.Results71 studies totalling 22,058 patients were included, six were randomised trials. Most explored outcomes in patients who received tocilizumab (59/71). In prospective studies, tocilizumab was associated with improved unadjusted survival (RR 0.83 95%CI 0.72;0.96 I2= 0.0%), but conclusive benefit was not demonstrated for other outcomes. In retrospective studies, tocilizumab was associated with less severe outcomes on an ordinal scale (Generalised odds ratio 1.34 95%CI 1.10;1.64, I2=98%) and adjusted mortality risk (HR 0.52 95%CI 0.41;0.66, I2=76.6%). The mean difference in duration of hospitalisation was 0.36 days (95%CI -0.07;0.80, I2=93.8%). There was substantial heterogeneity in retrospective studies, and estimates should be interpreted cautiously. Other immunomodulatory agents showed similar effects to tocilizumab, but insufficient data precluded meta-analysis by agent.ConclusionTocilizumab was associated with a lower relative risk of mortality in prospective studies, but effects were inconclusive for other outcomes. Current evidence for the efficacy of anakinra, siltuximab or sarilumab in Covid-19 is insufficient, with further studies urgently needed for conclusive findings.
A draft genome of grass pea (Lathyrus sativus), a resilient diploid legume
Authors: Emmrich Peter M. F. , Sarkar Abhimanyu , Njaci Isaac , Kaithakottil Gemy George , Ellis Noel , Moore Christopher , Edwards Anne , Heavens Darren , Waite Darren , Cheema Jitender , Trick Martin , Moore Jonathan , Webb Anne , Caiazzo Rosa , Thomas Jane , Higgins Janet , Swarbreck David , Kumar Shiv , Mundree Sagadevan , Loose Matt , Yant Levi , Martin Cathie , Wang Trevor L. 
Published: April 2020

AbstractWe have sequenced the genome of grass pea (Lathyrus sativus), a resilient diploid (2n=14) legume closely related to pea (Pisum sativum). We determined the genome size of the sequenced European accession (LS007) as 6.3 Gbp. We generated two assemblies of this genome, i) EIv1 using Illumina PCR-free paired-end sequencing and assembly followed by long-mate-pair scaffolding and ii) Rbp using Oxford Nanopore Technologies long-read sequencing and assembly followed by polishing with Illumina paired-end data. EIv1 has a total length of 8.12 Gbp (including 1.9 billion Ns) and scaffold N50 59,7 kbp. Annotation has identified 33,819 high confidence genes in the assembly. Rbp has a total length of 6.2 Gbp (with no Ns) and a contig N50 of 155.7 kbp. Gene space assessment using the eukaryote BUSCO database showed completeness scores of 82.8 % and 89.8%, respectively.
The flagellar motor ofVibrio alginolyticusundergoes major structural remodeling during rotational switching
Authors: Carroll Brittany L. , Nishikino Tatsuro , Guo Wangbiao , Zhu Shiwei , Kojima Seiji , Homma Michio , Liu Jun 
Published: April 2020

ABSTRACTThe bacterial flagellar motor is an intricate nanomachine that switches rotational directions between counterclockwise (CCW) and clockwise (CW) to direct the migration of the cell. The cytoplasmic ring (C-ring) of the motor, which is composed of FliG, FliM, and FliN, is known for controlling the rotational sense of the flagellum. However, the mechanism underlying rotational switching remains elusive. Here, we deployed cryo-electron tomography to visualize the C-ring in two rotational biased mutants (CCW-biasedfliG-G214S and CW-lockedfliG-G215A) inVibrio alginolyticus. Sub-tomogram averaging was utilized to resolve two distinct conformations of the C-ring. Comparison of the C-ring structures in two rotational senses provide direct evidence that the C-ring undergoes major structural remodeling during rotational switch. Specifically, FliG conformational changes elicit a large rearrangement of the C-ring that coincides with rotational switching, whereas FliM and FliN form a spiral-shaped base of the C-ring, likely stabilizing the C-ring during the conformational remodeling.
The Murphy number: how pitch moment of inertia dictates quadrupedal walking and running energetics
Authors: Polet Delyle T. 
Published: April 2020

AbstractMost quadrupedal mammals transition from a four-beat walk to a two-beat run (e.g. trot), but some transition to a four-beat run (e.g. amble). Recent analysis shows that a two-beat run minimizes work only for animals with a small pitch moment of inertia (MOI), though empirical MOI were not reported. It also remains unclear whether MOI affects gait energetics at slow speeds. Here I show that a particular normalization of the pitch moment of inertia (the Murphy number) has opposite effects on walking and running energetics. During walking, simultaneous fore and hindlimb contacts dampen pitching energy, favouring a four-beat gait that can distribute expensive transfer of support. However, the required pitching of a four-beat walk becomes more expensive as Murphy number increases. Using trajectory optimization of a simple model, I show that both the walking and slow running strategies used by dogs, horses, giraffes and elephants can be explained by work optimization under their specific Murphy numbers. Rotational dynamics have been largely ignored as a determining factor in quadrupedal locomotion, but appear to be a central factor in gait selection.
Flow-cell based technology for massively parallel characterization of base-modified DNA aptamers
Authors: Wu Diana , Feagin Trevor , Mage Peter , Rangel Alexandra , Wan Leighton , Kong Dehui , Li Anping , Coller John , Eisenstein Michael , Soh H. Tom 
Published: April 2020

AbstractAptamers incorporating chemically modified bases can achieve superior affinity and specificity compared to natural aptamers, but their characterization remains a labor-intensive, low-throughput task. Here we describe the ‘non-natural aptamer array’ (N2A2) system, in which a minimally modified Illumina MiSeq instrument is used for the high-throughput generation and characterization of large libraries (∼106) of base-modified DNA aptamer candidates on the basis of both target affinity and specificity. We first demonstrate the capability to screen multiple different base modifications to identify the optimal chemistry for high-affinity target binding. We next use N2A2 to generate aptamers that can maintain excellent specificity even in complex samples, with equally strong target affinity in both buffer and diluted human serum. Given that N2A2 requires only minor mechanical modifications to the MiSeq, we believe N2A2 offers a broadly accessible tool for generating high-quality affinity reagents for diverse applications.
Genome-wide association analysis reveals new insights into the genetic architecture of defensive, agro-morphological and quality-related traits in cassava
Authors: Rabbi Ismail Yusuf , Kayondo Siraj Ismail , Bauchet Guillaume , Yusuf Muyideen , Aghogho Cynthia Idhigu , Ogunpaimo Kayode , Uwugiaren Ruth , Smith Ikpan Andrew , Peteti Prasad , Agbona Afolabi , Parkes Elizabeth , Lydia Ezenwaka , Wolfe Marnin , Jannink Jean-Luc , Egesi Chiedozie , Kulakow Peter 
Published: April 2020

AbstractCassava (Manihot esculenta) is one of the most important starchy root crops in the tropics due to its adaptation to marginal environments. Genetic progress in this clonally propagated crop can be accelerated through the discovery of markers and candidate genes that could be used in cassava breeding programs. We carried out a genome-wide association study (GWAS) using a panel of 5,310 clones developed at the International Institute of Tropical Agriculture - Nigeria. The population was genotyped at more than 100,000 SNP markers via genotyping-by-sequencing (GBS). Genomic regions underlying genetic variation for 14 traits classified broadly into four categories: biotic stress (cassava mosaic disease and cassava green mite severity); quality (dry matter content and carotenoid content) and plant agronomy (harvest index and plant type). We also included several agro-morphological traits related to leaves, stems and roots with high heritability. In total, 41 significant associations were uncovered. While some of the identified loci matched with those previously reported, we present additional association signals for the traits. We provide a catalogue of favourable alleles at the most significant SNP for each trait-locus combination and candidate genes occurring within the GWAS hits. These resources provide a foundation for the development of markers that could be used in cassava breeding programs and candidate genes for functional validation.
Alpha-synuclein supports interferon stimulated gene expression in neurons
Authors: Massey Aaron R. , Monogue Brendan , Chen Yixi , Lesteberg Kelsey , Johnson Michaela E. , Bergkvist Liza , Steiner Jennifer A. , Ma Jiyan , Mahalingam Ravi , Kleinschmidt-Demasters B.K. , Escobar Galvis Martha L , Brundin Patrik , Kunath Tilo , Beckham J. David 
Published: April 2020

AbstractThe protein alpha-synuclein (asyn) is predominantly expressed in neurons and is associated with neurodegenerative diseases like Parkinson’s disease (PD); yet, a functional role for asyn in neurons is not clearly established. We have previously shown that asyn expression is up-regulated following viral infection in neurons and is critical for host immune responses to RNA virus infections. Here, we investigate the mechanisms underlying asyn-dependent immune responses to RNA virus infection in the brain. Using asyn knock-out (KO) mice and human neuronal models, we show that asyn is required for expression of the full repertoire of interferon-stimulated genes (ISGs) in neurons following acute RNA virus infection. Furthermore, treatment of asyn KO human neurons with poly I:C or type I interferon also fail to induce expression of the full complement of ISGs suggesting that asyn plays an important role in modulating neuronal innate immune responses. In brain tissue, asyn-dependent ISG expression is independent of microglia activation and supports activation of infiltrating lymphocytes following viral challenge. We also show that virus infections lead to accumulation of phosphorylated S129 asyn in human and non-human primate neuronal tissues. In a model of pS129 asyn pathology, we found that infection with West Nile virus increases microglia activation but does not significantly alter pS129 asyn pathology in the mouse model. Taken together, our results establish asyn as a novel, neuron-specific modulator of innate immunity by a mechanism that promotes interferon-stimulated gene expression and links responses to virus infection with formation of phosphorylated S129-asyn in neuronal tissue.
Computational investigation for modelling the protein-protein interaction of TasA(28-261)– TapA(33-253): a decisive process in biofilm formation byBacillus subtilis
Authors: Verma Nidhi , Srivastava Shubham , Malik Ruchi , Yadav Jay Kant , Goyal Pankaj , Pandey Janmejay 
Published: April 2020

AbstractBiofilms have significant role in microbial persistence, antibiotic resistance and chronic infections; consequently, there is a pressing need for development of novel “anti-biofilm strategies”. One of the fundamental mechanisms involved in biofilm formation is protein-protein interactions of ‘amyloid like proteins’ (ALPs) in extracellular matrix. Such interactions could be potential targets for development of novel anti-biofilm strategies; therefore, assessing the structural features of these interactions could be of great scientific value. Characterization of biomolecular interaction with conventional structure biology tools including X-Ray diffraction and Nuclear Magnetic Resonance is technically challenging, expensive and time-consuming. In contrast, modelling such interactions is time-efficient, economical and might provide deeper understanding of structural basis of interactions. Therefore, during the present study, protein-protein interaction of TasA(28-261)–TapA(33-253)(which is a decisive process for biofilm formation byBacillus subtilis) was modeled usingin silicoapproaches viz., molecular modelling, protein-protein docking and molecular dynamics simulations. Results identified amino-acid residues present within intrinsically disordered regions of both proteins to be critical for interaction. These results were further supported with PCA and FEL analyses. Results presented here represent novel finding and we hypothesize that aa identified during the present study could be targeted for inhibition of biofilm formation byB. subtilis.
Experimental evolution of virulence and associated traits in aDrosophila melanogaster–Wolbachiasymbiosis
Authors: Monnin David , Kremer Natacha , Michaud Caroline , Villa Manon , Henri Hélène , Desouhant Emmanuel , Vavre Fabrice 
Published: April 2020

AbstractEvolutionary theory predicts that vertically transmitted symbionts are selected for low virulence, as their fitness is directly correlated to that of their host. In contrast with this prediction, theWolbachiastrainwMelPop drastically reduces itsDrosophila melanogasterhost lifespan at high rearing temperatures. It is generally assumed that this feature is maintained because theD. melanogaster–wMelPop symbiosis is usually not exposed to environmental conditions in which the symbiont is virulent. To test this hypothesis, we submittedwMelPop-infectedD. melanogasterlines to 17 generations of experimental evolution at a high temperature, while enforcing late reproduction by artificial selection. The fly survival was measured at different time points, as well as two traits that have been proposed to be causally responsible forwMelPop virulence: its relative density and the mean number of copies of octomom, an 8-genes region of theWolbachiagenome. We hypothesised that these conditions (high temperature and late reproduction) would select for a reducedwMelPop virulence, a reducedwMelPop density, and a reduced octomom copy number. Our results indicate that density, octomom copy number and virulence are correlated to each other. However, contrary to our expectations, we could not detect any reduction in virulence during the course of evolution. We discuss the significance of our results with respect to the evolutionary causes ofwMelPop virulence.