bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Modelling Analysis of Strategies for Relaxing COVID-19 Social Distancing
Authors: Milne George J , Xie Simon , Poklepovich Dana 
Published: May 2020

AbstractBackgroundThe ability of countries to contain and control COVID-19 virus transmission via social distancing is critical in the absence of a vaccine. Early activation of robust measures has been shown to control the daily infection rate, and consequential pressure on the health care system. As countries begin to control COVID-19 spread an understanding of how to ease social distancing measures to prevent a rebound in cases and deaths is required.MethodsUsing COVID-19 transmission data from the outbreak source in Hubei Province, China prior to activation of containment measures, we adapted an established individual-based simulation model of the city of Newcastle, Australia. Simulation of virus transmission in this model, with and without, social distancing measures activated permitted us to quantify social distancing effectiveness. Optimal strategies for relaxing social distancing were determined under two settings: with high numbers of daily cases, as in New York; and where early social distancing activation resulted in limited ongoing transmission, as in Perth, Australia.FindingsIn countries where strong social distancing measures were activated after the COVID-19 virus had spread widely, our study found these measures are required to be maintained for significant periods before being eased, to return to a situation where daily case numbers become low. In countries where early responses to the COVID-19 pandemic have been highly successful, as in Australia, we show that a staged relaxation of social distancing prevents a rebound in cases.InterpretationModelling studies and direct observation have shown that robust and timely social distancing have the most effect in containing the spread of the COVID-19 virus. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society and economic activity. This study demonstrates the necessity of holding robust social distancing in place until COVID-19 virus transmission has significantly decreased, and how they may then be safely eased.
Immunochromatographic test for the detection of SARS-CoV-2 in saliva
Authors: Kashiwagi Katsuhito , Ishii Yoshikazu , Aoki Kotaro , Yagi Shintaro , Maeda Tadashi , Miyazaki Taito , Yoshizawa Sadako , Aoyagi Katsumi , Tateda Kazuhiro 
Published: May 2020

AbstractWe evaluated the rapid immunochromatographic test for SARS-CoV-2 antigen detection using 16 saliva specimens collected from 6 COVID-19 hospitalized patients, and detected N-antigen in 4 of 7 RT-PCR positive specimens. The POCT antigen test using saliva is highly considered to be a game-changer for COVID-19 diagnosis.
Epidemiological study to detect active SARS-CoV-2 infections and seropositive persons in a selected cohort of employees in the Frankfurt am Main metropolitan area
Authors: Krähling Verena , Kern Martin , Halwe Sandro , Müller Helena , Rohde Cornelius , Savini Massimiliano , Schmidt Michael , Wilhelm Jochen , Becker Stephan , Ciesek Sandra , Gottschalk René 
Published: May 2020

AbstractSo far, 170,000 Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infections have been confirmed in Germany, of which more than 5,000 have been detected in the Frankfurt am Main metropolitan region. When examining 1,000 nasopharyngeal swabs and serum samples from healthy volunteers from this region, one RT-PCR-positive and five antibody-positive persons were identified. The five positive serum samples were confirmed to be specific. Four of the five positive sera cross-neutralized SARS-CoV.
Risk factors affecting COVID-19 case fatality rate: A quantitative analysis of top 50 affected countries
Authors: Goh Hui Poh , Mahari Wafiah Ilyani , Ahad Norhadyrah Izazie , Chaw Li Ling , Kifli Nurolaini , Goh Bey Hing , Yeoh Siang Fei , Ming Long Chiau 
Published: May 2020

AbstractBackgroundLatest clinical data on treatment on coronavirus disease 2019 (COVID-19) indicated that older patients and those with underlying history of smoking, hypertension or diabetes mellitus might have poorer prognosis of recovery from COVID-19. We aimed to examine the relationship of various prevailing population-based risk factors in comparison with mortality rate and case fatality rate (CFR) of COVID-19.MethodsDemography and epidemiology data which have been identified as verified or postulated risk factors for mortality of adult inpatients with COVID-19 were used. The number of confirmed cases and the number of deaths until April 16, 2020 for all affected countries were extracted from Johns Hopkins University COVID-19 websites. Datasets for indicators that are fitting with the factors of COVID-19 mortality were extracted from the World Bank database. Out of about 185 affected countries, only top 50 countries were selected to be analyzed in this study. The following seven variables were included in the analysis, based on data availability and completeness: 1) proportion of people aged 65 above, 2) proportion of male in the population, 3) diabetes prevalence, 4) smoking prevalence, 5) current health expenditure, 6) number of hospital beds and 7) number of nurses and midwives. Quantitative analysis was carried out to determine the correlation between CFR and the aforementioned risk factors.ResultsUnited States shows about 0.20% of confirmed cases in its country and it has about 4.85% of CFR. Luxembourg shows the highest percentage of confirmed cases of 0.55% but a low 2.05% of CFR, showing that a high percentage of confirmed cases does not necessarily lead to high CFR. There is a significant correlation between CFR, people aged 65 and above (p = 0.35) and diabetes prevalence (p = 0.01). However, in our study, there is no significant correlation between CFR of COVID-19, male gender (p = 0.26) and smoking prevalence (p = 0.60).ConclusionOlder people above 65 years old and diabetic patients are significant risk factors for COVID-19. Nevertheless, gender differences and smoking prevalence failed to prove a significant relationship with COVID-19 mortality rate and CFR.
Engineered membranes for residual cell trapping on microfluidic blood plasma separation systems. A comparison between porous and nanofibrous membranes
Authors: Lopresti Francesco , Keraite Ieva , Ongaro Alfredo E. , Howarth Nicola M. , La Carrubba Vincenzo , Kersaudy-Kerhoas Maïwenn 
Published: May 2020

AbstractBlood-based clinical diagnostics require challenging limit-of-detection for low abundance, circulating molecules in plasma. Micro-scale blood plasma separation (BPS) has achieved remarkable results in terms of plasma yield or purity, but rarely achieving both at the same time. Here, we proposed the first use of electrospun polylactic-acid (PLA) membranes as filters to remove residual cell population from continuous hydrodynamic-BPS devices. The membranes hydrophilicity was improved by adopting a wet chemistry approach via surface aminolysis as demonstrated through Fourier Transform Infrared Spectroscopy and Water Contact Angle analysis. The usability of PLA-membranes was assessed through degradation measurements at extreme pH values. Plasma purity and hemolysis were evaluated on plasma samples with residual red blood cell content (1, 3, 5% hematocrit) corresponding to output from existing hydrodynamic BPS systems. Commercially available membranes for BPS were used as benchmark. Results highlighted that the electrospun membranes are suitable for downstream residual cell removal from blood, permitting the collection of up to 2 mL of pure and low-hemolyzed plasma. Fluorometric DNA quantification revealed that electrospun membranes did not significantly affect the concentration of circulating DNA. PLA-based electrospun membranes can be combined with hydrodynamic BPS in order to achieve high volume plasma separation at over 99% plasma purity.
Body size and climate as predictors of plumage colouration and sexual dichromatism in parrots
Authors: Carballo Luisana , Delhey Kaspar , Valcu Mihai , Kempenaers Bart 
Published: May 2020

AbstractPsittaciformes (parrots, cockatoos and lorikeets) comprise one of the most colourful clades of birds. Their unique pigments and cavity nesting habits are two potential explanations for their colourful character. However, plumage colour varies substantially between parrot species and sometimes also between males and females of the same species. Here, we use comparative analyses to evaluate what factors correlate with colour elaboration, colour diversity and sexual dichromatism. Specifically, we test the association between different aspects of parrot colouration and (1) the intensity of sexual selection and social interactions, (2) variation along the slow-fast life-history continuum and (3) climatic variation. We show that larger species and species that live in warm environments display more elaborated colours, yet smaller species have higher levels of sexual dichromatism. Larger parrots tend to have darker and more blue and red colours. Parrots that live in humid environments are darker and redder, whilst species inhabiting warm regions have more blue plumage colours. In general, the variables we considered explain small to moderate amounts of variation in parrot colouration (up to 20%). Our data suggest that sexual selection may be acting more strongly on males in small, short-lived parrots leading to sexual dichromatism. More elaborate colouration in both males and females of the larger, long-lived species with slow tropical life-histories suggests that mutual mate choice and reduced selection for crypsis may be important in these species, as has been shown for passerines.
Effects of anesthesia and oral cleft types on academic achievement
Authors: Nadal Saskia Gladys 
Published: May 2020

ObjectiveResearch looking simultaneously at the effects of anesthesia and oral cleft types on academic achievement is scarce. Available results are contradictory: some studies suggest that anesthesia exposure is responsible for underachievement, and others that responsibility falls instead on the type of orofacial cleft. This study investigates the potential compound effects of exposure to anesthesia and orofacial cleft types on the risk of academic underachievement.DesignCentre Labio Palatin Albert Coninck, Cliniques universitaires Saint-Luc, Brussels, Belgium, nationwide register-based study.SettingBirth cohort 1995-2007.PatientsTwenty-nine children with isolated orofacial clefts exposed to anesthesia.InterventionsAverage duration of exposure to anesthesia before the Certificat d Etudes de Base (CEB) exam was 382 minutes.Main Outcome Measure(s)Scores obtained by patients at the CEB exam were compared with the scores of the 6th grade Belgian general population who passed the same exam controlling for gender, school year, year they passed the exam, medical illnesses, duration of exposure to anesthesia in minutes and socioeconomic confounders.ResultsDoubling the time of anesthesia exposure produces a 17 percentage point increase in the probability that patients will underachieve. Cleft lip reduces while cleft right-left increases the duration of anesthesia exposure relative to cleft lip palate. Results do not change when anesthesia exposure only up to 4 years and socioeconomic factors are considered.ConclusionsBoth exposure to anesthesia and different types of orofacial cleft may result in underachievement at the CEB exam.
Novel missense mutation E585K in retinitis pigmentosa leads to compromisedRPGRsplicing diversity
Authors: Liu Yan-Shan , Wan Ji-Feng , Ren Chun-Yan , Xu Zhou-Heng , Pan Xu-Bin , Pan Jia-Qi , Gao Ruo-Nan , Liu Shao-Qiang , Zhang Jia-Li , Yao Qian-Hao , Wang Ji-Hong , Li En-Min , Rao Jun-Hua , Hou Ping , Chen Jian-Huan 
Published: May 2020

AbstractMutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, are the major cause of X-linked retinitis pigmentosa (RP). Herein we used whole-exome sequencing to screen possible novelRPGRmutations in RP patients, and identified a novel missense mutation E585K in a patient with early onset but slow disease progression, and a frameshift deletion E998Gfs*78 in a patient with RP sine pigmento and high myopia. Intriguingly, bioinformatic analysis indicated that E585K probably affectedRPGRRNA splicing instead of the protein sequence directly. Mini-gene assays in 293T cells revealed that splicing events of the E585K mutant were found to be also exist in wildtype, but with a shifted pattern. In the E585K mini-gene usage of an upstream alternative 5′ splice site (5′ ss) of exon 14 was enhanced, and other splicing events were suppressed, including the canonical 5′ ss of exon 14, skipping of exon 14/15 and retention of intron 14. As a result,RPGRsplicing products of the E585K mini-gene were predominated by transcripts containing a 4-bp deletion, with a small fraction of in-frame transcripts containing a retended intron 14, which might explain the slow disease progression in the patient carrying the mutation. RNA-Seq analysis further confirmed existence of these splicing events in endogenousRPGRRNA in human retina, pointing to compromised splicing diversity in the E585K mutant. Our findings thus added to the understanding of genotype-phenotype correlation in RP, and suggested that compromisedRPGRsplicing diversity might play a role in molecular mechanism of the disease.
Interpreting the pathogenicity of Joubert Syndrome missense variants inCaenorhabditis elegans
Authors: Lange Karen I. , Tsiropoulou Sofia , Kucharska Katarzyna , Blacque Oliver E. 
Published: May 2020

ABSTRACTCiliopathies are inherited disorders caused by cilia defects. Variants in ciliopathy genes are frequently pleiotropic and represent excellent case studies for interrogating genotype-phenotype correlation. We have employedCaenorhabditis elegansand gene editing to characterise two pathogenic biallelic missense variants (P74S, G155S) in B9D2/mksr-2associated with Joubert Syndrome (JBTS). B9D2 functions within the MKS module at the transition zone (TZ) ciliary subcompartment, and regulates the cilium’s molecular composition and signaling function. Quantitative assays of cilium/TZ structure and function, together with knock-in reporters, confirm both variant alleles are pathogenic. G155S causes a more severe overall phenotype and disrupts endogenous MKSR-2 organisation at the TZ. Recapitulation of the patient biallelic genotype shows that heterozygous worms phenocopy worms homozygous for P74S. This study also reveals a close functional association between the B9 complex and TMEM216/MKS-2. These data establishC. elegansas a paradigm for interpreting JBTS mutations, and provide insight into MKS module organisation.
Reciprocal regulation of vacuolar calcium transport and V-ATPase activity, and the effects of Phosphatidylinositol 3,5-bisphosphate
Authors: Miner Gregory E. , Rivera-Kohr David A. , Zhang Chi , Sullivan Katherine D. , Guo Annie , Fratti Rutilio A. 
Published: May 2020

ABSTRACTYeast vacuoles are acidified by the V-ATPase, a protein complex comprised of the membrane embedded VOcomplex and the soluble cytoplasmic V1complex. The assembly of the V1-VOholoenzyme is required for the transfer of H+into the vacuole lumen for acidification. The assembly of the V1-VOholoenzyme is stabilized by the lipid phosphatidylinositol 3,5-bisphospate (PI(3,5)P2) made by the PI3P 5-kinase Fab1/PIKfyve. The absence of PI(3,5)P2leads to the dissociation of the V1complex from the membrane. Separately, PI(3,5)P2has been shown to modulate Ca2+transport across the vacuole membrane during fission and fusion. Here we examined whether the regulation of H+and Ca2+by PI(3,5)P2are interdependent. We show that modulating extraluminal Ca2+concentrations inhibit V-ATPase activity. As extraluminal CaCl2levels are raised, the activity of H+pumping is reduced. Conversely, chelating free Ca2+with EGTA stimulated vacuole acidification. Not only did Ca2+levels affect H+translocation, we also show that blocking V-ATPase activity inhibited Ca2+transport into the vacuole lumen. Together, these data illustrate that Ca2+transport and V-ATPase regulation are interconnected through the modulation of vacuolar lipid profiles.Summary StatementHere we show that Ca2+and H+transport across the vacuole membrane is reciprocally regulated and that it is linked to the production of Phosphatidylinositol 3,5-bisphoshpate.
Recurrent mutations in topoisomerase 2a cause a novel mutator phenotype in human cancers
Authors: Boot Arnoud , Rozen Steven G. 
Published: May 2020

AbstractTopoisomerases are essential for genome stability. Here, we link the p.K743N mutation in topoisomerase TOP2A to a previously undescribed mutator phenotype in human cancers. This phenotype primarily generates a distinctive pattern of duplications of 2 to 4 base pairs and deletions of 6 to 8 base pairs, which we call ID_TOP2A. All tumors carrying the TOP2A p.K743N mutation showed ID_TOP2A, which was absent in all of 12,269 other tumors. We also report evidence of structural variation associated with TOP2A p.K743N. All tumors with ID_TOP2A mutagenesis had several indels in known cancer genes, including frameshift mutations inPTENandTP53and an in-frame activating mutation inBRAF. Thus, ID_TOP2A mutagenesis almost certainly contributed to tumorigenesis in these tumors. This is the first report of topoisomerase-associated mutagenesis in human cancers, and sheds further light on TOP2A’s role in genome maintenance. We also postulate that tumors showing ID_TOP2A mutagenesis might be especially sensitive to topoisomerase inhibitors.
Mortality of the COVID-19 outbreak in Sweden in relation to previous severe disease outbreaks
Authors: Ledberg Anders 
Published: May 2020

AbstractInfluenza viruses have caused disease outbreaks in human societies for a long time. Influenza often has rapid onset and relatively short duration, both in the individual and in the population. The case fatality rate varies for different strains of the virus, as do the effects on total mortality. Outbreaks related to coronavirus infections have recently become a global concern but much less is known about the dynamics of these outbreaks and their effects on mortality.In this work, disease outbreaks in Sweden, in the time period of 1860-2020, are characterized and compared to the currently ongoing COVID-19 outbreak. The focus is on outbreaks with a sharp increase in all-cause mortality. Outbreak onset is defined as the time point when deaths counts starts to increase consistently for a period of 10 days. The duration of the outbreak is defined as the time period in which mortality rates are elevated. Excess mortality is estimated by standard methods.In total there were 15 outbreaks detected in the time period, the first 14 were likely caused by influenza virus infections, the last by SARS-CoV-2. The mortality dynamics of the SARS-CoV-2 outbreak is shown to be similar to outbreaks due to influenza virus, and in terms of the number of excess deaths, it is the worst outbreak in Sweden since the ’Spanish flu’ of 1918-1919.
Conditions for a second wave of COVID-19 due to interactions between disease dynamics and social processes
Authors: Pedro Sansao A. , Ndjomatchoua Frank T. , Jentsch Peter , Tchuenche Jean M. , Anand Madhur , Bauch Chris T. 
Published: May 2020

AbstractIn May 2020, many jurisdictions around the world began lifting physical distancing restrictions against the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), giving rise to concerns about a possible second wave of coronavirus disease 2019 (COVID-19). These restrictions were imposed as a collective population response to the presence of COVID-19 in communities. However, lifting restrictions is also a population response to their socio-economic impacts, and is expected to increase COVID-19 cases, in turn. This suggests that the COVID-19 pandemic exemplifies a coupled behaviour-disease system. Here we develop a minimal mathematical model of the interaction between social support for school and workplace closure and the transmission dynamics of SARS-CoV-2. We find that a second wave of COVID-19 occurs across a broad range of plausible model input parameters, on account of instabilities generated by behaviour-disease interactions. We conclude that second waves of COVID-19–should they materialize–can be interpreted as the outcomes of nonlinear interactions between disease dynamics and population behaviour.
The OncoSim-Breast cancer microsimulation model
Authors: Yong J.H.E. , Nadeau C. , Flanagan W. , Coldman A. , Asakawa K. , Garner R. , Fitzgerald N. , Yaffe M. , Miller A.B. 
Published: May 2020

ABSTRACTBackgroundThe increasing demand for health care resources requires measures to evaluate the impact of cancer control approaches. A cancer simulation model can help integrate new knowledge to inform clinical and policy decisions. OncoSim-Breast is a breast cancer simulation model. This paper aims to describe the key assumptions in the OncoSim-Breast model and how well it reproduces more recent breast cancer trends and the observed effects in a randomized screening trial.MethodsThe OncoSim-Breast model simulates the onset, growth and spread of invasive and ductal carcinoma in situ tumours. The model combines Canadian cancer incidence, mortality, screening program and cost data to project population-level outcomes. Users can change the model input to answer specific policy questions. Here we report three validation exercises. First, we compared the model’s projected breast cancer incidence and stage distributions with the observed data in the Canadian Cancer Registry. Second, we compared OncoSim’s projected breast cancer mortality with the Vital Statistics. Third, we replicated the UK Age trial to compare the model’s projections with the trial’s observed screening effects.ResultsOncoSim-Breast’s projected incidence, mortality and stage distribution of breast cancer were close to the observed data in the Canadian Cancer Registry and the Vital Statistics. OncoSim-Breast also reproduced the breast cancer screening effects observed in the UK Age trial.InterpretationOncoSim-Breast’s ability to reproduce the observed population-level breast cancer trends and the screening effects in a randomized trial increases the confidence of using its results to inform policy decisions related to early detection of breast cancer.