julilili42/papers huggingface dataset:
Inflammatory and regenerative processes in bioresorbable synthetic pulmonary valves up to 2 years in sheep: Spatiotemporal insights augmented by Raman microspectroscopy
2021-04-08

Abstract In situ heart valve tissue engineering is an emerging approach in which resorbable, off-the-shelf available scaffolds are used to induce endogenous heart valve restoration. Such scaffolds are designed to recruit endogenous cells in vivo , which subsequently resorb polymer and produce and remodel new valvular tissue in situ . Recently, preclinical studies using electrospun supramolecular elastomeric valvular grafts have shown that this approach enables in situ regeneration of pulmonary valves with long-term functionality in vivo . However, the evolution and mechanisms of inflammation, polymer absorption and tissue regeneration are largely unknown, and adverse valve remodeling and intra- and inter-valvular variability have been reported. Therefore, the goal of the present study was to gain a mechanistic understanding of the in vivo regenerative processes by combining routine histology and immunohistochemistry, using a comprehensive sheep-specific antibody panel, with Raman microspectroscopy for the spatiotemporal analysis of in situ tissue-engineered pulmonary valves with follow-up to 24 months from a previous preclinical study in sheep. The analyses revealed a strong spatial heterogeneity in the influx of inflammatory cells, graft resorption, and foreign body giant cells. Collagen maturation occurred predominantly between 6 and 12 months after implantation, which was accompanied by a progressive switch to a more quiescent phenotype of infiltrating cells with properties of valvular interstitial cells. Variability among specimens in the extent of tissue remodeling was observed for follow-up times after 6 months. Taken together, these findings advance the understanding of key events and mechanisms in material-driven in situ heart valve tissue engineering.
<span data-preserver-spaces="true">Curating and Comparing 114 Strain-Specific Genome-Scale Metabolic Models of <em><span data-preserver-spaces="true">Staphylococcus aureus</em>
2021-04-08

Staphylococcus aureus is a high-priority pathogen causing severe infections with high morbidity and mortality worldwide. Many S. aureus strains are methicillin-resistant (MRSA) or even multi-drug resistant. It is one of the most successful and prominent modern pathogens. An effective fight against S. aureus infections requires novel targets for antimicrobial and antistaphylococcal therapies. Recent advances in whole-genome sequencing and high-throughput techniques facilitate the generation of genome-scale metabolic models (GEMs). Among the multiple applications of GEMs is drug-targeting in pathogens. Hence, comprehensive and predictive metabolic reconstructions of S. aureus could facilitate the identification of novel targets for antimicrobial therapies. This review aims at giving an overview of all available GEMs of multiple S. aureus strains. We downloaded all 114 available GEMs of S. aureus for further analysis. The scope of each model was evaluated, including the number of reactions, metabolites, and genes.Furthermore, all models were quality-controlled using Mᴇᴍᴏᴛᴇ, an open-source application with standardized metabolic tests. Growth capabilities and model similarities were examined. This review should lead as a guide for choosing the appropriate GEM for a given research question. With the information about the availability, the format, and the strengths and potentials of each model, one can either choose an existing model or combine several models to create models with even higher predictive values. This facilitates model-driven discoveries of novel antimicrobial targets to fight multi-drug resistant S. aureus strains.
Anti-SARS-CoV-2 Spike Protein and Anti-Platelet Factor 4 Antibody Responses Induced by COVID-19 Disease and ChAdOx1 nCov-19 vaccination
2021-04-09

<title>Abstract</title> <bold>Background</bold>: Some recipients of ChAdOx1 nCoV-19 COVID-19 Vaccine AstraZeneca develop antibody-mediated vaccine-induced thrombotic thrombocytopenia (VITT), associated with cerebral venous and other unusual thrombosis resembling autoimmune heparin-induced thrombocytopenia. A prothrombotic predisposition is also observed in Covid-19. We explored whether antibodies against the SARS-CoV-2 spike protein induced by Covid-19 cross-react with platelet factor 4 (PF4/CXLC4), the protein targeted in both VITT and autoimmune heparin-induced thrombocytopenia.<bold>Methods</bold>: Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared via prediction tools and 3D modelling software (IMED, SIM, MacMYPOL). Sera from 222 PCR-confirmed Covid-19 patients from five European centers were tested by PF4/heparin ELISA, heparin-dependent and PF4-dependent platelet activation assays. Immunogenic reactivity of purified anti-PF4 and anti-PF4/heparin antibodies from patients with VITT were tested against recombinant SARS-CoV-2 spike protein. <bold>Results</bold>: Three motifs within the spike protein sequence share a potential immunogenic epitope with PF4. Nineteen of 222 (8.6%) Covid-19 patient sera tested positive in the IgG-specific PF4/heparin ELISA, none of which showed platelet activation in the heparin-dependent activation assay, including 10 (4.5%) of the 222 Covid-19 patients who developed thromboembolic complications. Purified anti-PF4 and anti-PF4/heparin antibodies from two VITT patients did not show cross-reactivity to recombinant SARS-CoV-2 spike protein. <bold>Conclusions</bold>: The antibody responses to PF4 in SARS-CoV-2 infection and after vaccination with COVID-19 Vaccine AstraZeneca differ. Antibodies against SARS-CoV-2 spike protein do not cross-react with PF4 or PF4/heparin complexes through molecular mimicry. These findings make it very unlikely that the intended vaccine-induced immune response against SARS-CoV-2 spike protein would itself induce VITT.
Spontaneously scalarized black holes in dynamical Chern-Simons gravity: Dynamics and equilibrium solutions
2021-04-09

In the present paper, we construct spontaneously scalarized rotating black\\nhole solutions in dynamical Chern-Simons (dCS) gravity by following the scalar\\nfield evolution in the decoupling limit. For the range of parameters where the\\nKerr black hole becomes unstable within dCS gravity the scalar field grows\\nexponentially until it reaches an equilibrium configuration that is independent\\nof the initial perturbation. Interestingly, the symmetry of the\\nscalar field is broken and a strong maximum around only one of the rotational\\naxes can be observed. The black hole scalar charge is calculated for two\\ncoupling functions suggesting that the main observations would remain\\nqualitatively correct even if one considers coupling functions/coupling\\nparameters producing large deviations from the Kerr solution beyond the\\ndecoupling limit approximation.\\n
Combination versus monotherapy as definitive treatment for Pseudomonas aeruginosa bacteraemia: a multicentre retrospective observational cohort study
2021-04-09

Abstract Background Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality. Methods This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009–15. We evaluated the association between β-lactam plus aminoglycoside or quinolone combination therapy versus β-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy. Results Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64–1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens. Conclusions In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials.
The Dual Role of the Glycolipid Envelope in Different Cell Types of the Multicellular Cyanobacterium Anabaena variabilis ATCC 29413
2021-04-09

Anabaena variabilis is a filamentous cyanobacterium that is capable to differentiate specialized cells, the heterocysts and akinetes, to survive under different stress conditions. Under nitrogen limited condition, heterocysts provide the filament with nitrogen by fixing N 2 . Akinetes are spore-like dormant cells that allow survival during adverse environmental conditions. Both cell types are characterized by the presence of a thick multilayered envelope, including a glycolipid layer. While in the heterocyst this glycolipid layer is required for the maintenance of a microoxic environment and nitrogen fixation, its function in akinetes is completely unknown. Therefore, we constructed a mutant deficient in glycolipid synthesis and investigated the performance of heterocysts and akinetes in that mutant strain. We chose to delete the gene Ava_2595 , which is homolog to the known hglB gene, encoding a putative polyketide synthase previously shown to be involved in heterocyst glycolipid synthesis in Anabaena sp. PCC 7120, a species which does not form akinetes. Under the respective conditions, the Ava_2595 null mutant strain formed aberrant heterocysts and akinete-like cells, in which the specific glycolipid layers were absent. This confirmed firstly that both cell types use a glycolipid of identical chemical composition in their special envelopes and, secondly, that HglB is essential for glycolipid synthesis in both types of differentiated cells. As a consequence, the mutant was not able to fix N 2 and to grow under diazotrophic conditions. Furthermore, the akinetes lacking the glycolipids showed a severely reduced tolerance to stress conditions, but could germinate normally under standard conditions. This demonstrates the importance of the glycolipid layer for the ability of akinetes as spore-like dormant cells to withstand freezing, desiccation, oxidative stress and attack by lytic enzymes. Our study established the dual role of the glycolipid layer in fulfilling different functions in the evolutionary-related specialized cells of cyanobacteria. It also indicates the existence of a common pathway involving HglB for the synthesis of glycolipids in heterocysts and akinetes.
Exploring semantic differences between the Indonesian prefixesPE-andPEN-using a vector space model
2021-04-09

Abstract Indonesian has two prefixes, PE- and PEN- , that are similar in form and meaning, but are probably not allomorphs. In this study, we applied a distributional vector space model to clarify whether these prefixes have discriminable semantics. Comparisons of pairs of words within and across morphologically defined sets of words revealed that cosine similarities of pairs consisting of a word with PE- and a word with PEN- were reduced compared to pairs of only PE- words, or of only PEN- words. Furthermore, nouns with PE- were more similar to their base words than was the case for words with PEN- . The specialized use of PE- for words denoting agents, and the specialized use of PEN- for denoting instruments, was also visible in the semantic vector space. These differences in the semantics of PE- and PEN- thus provide further quantitative support for the independent status of PE- as opposed to PEN- .
First Genome-Scale Metabolic Model of Dolosigranulum pigrum Confirms Multiple Auxotrophies
2021-04-09

Dolosigranulum pigrum is a quite recently discovered Gram-positive coccus. It has gained increasing attention due to its negative correlation with Staphylococcus aureus, which is one of the most successful modern pathogens causing severe infections with tremendous morbidity and mortality due to its multiple resistances. As the possible mechanisms behind its inhibition of S. aureus remain unclear, a genome-scale metabolic model (GEM) is of enormous interest and high importance to better study its role in this fight. This article presents the first GEM of D. pigrum, which was curated using automated reconstruction tools and extensive manual curation steps to yield a high-quality GEM. It was evaluated and validated using all currently available experimental data of D. pigrum. With this model, already predicted auxotrophies and biosynthetic pathways could be verified. The model was used to define a minimal medium for further laboratory experiments and to predict various carbon sources’ growth capacities. This model will pave the way to better understand D. pigrum’s role in the fight against S. aureus.
Bayesian inverse problem of rotating neutron stars
2021-04-09

In this work we provide a framework that connects the co-rotating and counter\\nrotating -mode frequencies of rotating neutron stars with their stellar\\nstructure. The accurate computation of these modes for realistic equations of\\nstate has been presented recently and they are here used as input for a\\nBayesian analysis of the inverse problem. This allows to quantitatively\\nreconstruct basic neutron star parameters, such as the mass, radius, rotation\\nrate or universal scaling parameters. We find that future observations of both\\n -mode frequencies, in combination with a Bayesian analysis, would provide a\\npromising direction to solve the inverse stellar problem. We provide two\\ncomplementary approaches, one that is equation of state dependent and one that\\nonly uses universal scaling relations. We discuss advantages and disadvantages\\nof each approach, such as possible bias and robustness. The focus is on\\nastrophysically motivated scenarios in which informed prior information on the\\nneutron star mass or rotation rate can be provided and study how they impact\\nthe results.\\n
Bulk phase behaviour vs interface adsorption: Effects of anions and isotopes on β-lactoglobulin (BLG) interactions
2021-04-09

β-lactoglobulin does not show significant anion-induced or isotope-induced effects - neither in bulk nor at the solid-liquid interface, which deviates strongly from the behaviour of bovine serum albumin. We also provide a comprehensive discussion and comparison of protein-specific bulk and interface behaviour between bovine serum albumin and β-lactoglobulin dependent on anion, cation, solvent, and substrate properties. These findings pave the way for understanding the transition from adsorption to crystallisation.
Hypoxia and Microvascular Alterations Are Early Predictors of IDH-Mutated Anaplastic Glioma Recurrence
2021-04-09

Anaplastic gliomas (AG) represents aggressive brain tumors that often affect young adults. Although isocitrate-dehydrogenase (IDH) gene mutation has been identified as a more favorable prognostic factor, most IDH-mutated AG patients are confronted with tumor recurrence. Hence, increased knowledge about pathophysiological precursors of AG recurrence is urgently needed in order to develop precise diagnostic monitoring and tailored therapeutic approaches. In this study, 142 physiological magnetic resonance imaging (phyMRI) follow-up examinations in 60 AG patients after standard therapy were evaluated and magnetic resonance imaging (MRI) biomarker maps for microvascular architecture and perfusion, neovascularization activity, oxygen metabolism, and hypoxia calculated. From these 60 patients, 34 patients developed recurrence of the AG, and 26 patients showed no signs for AG recurrence during the study period. The time courses of MRI biomarker changes were analyzed regarding early pathophysiological alterations over a one-year period before radiological AG recurrence or a one-year period of stable disease for patients without recurrence, respectively. We detected intensifying local tissue hypoxia 250 days prior to radiological recurrence which initiated upregulation of neovascularization activity 50 to 70 days later. These changes were associated with a switch from an avascular infiltrative to a vascularized proliferative phenotype of the tumor cells another 30 days later. The dynamic changes of blood perfusion, microvessel density, neovascularization activity, and oxygen metabolism showed a close physiological interplay in the one-year period prior to radiological recurrence of IDH-mutated AG. These findings may path the wave for implementing both new MR-based imaging modalities for routine follow-up monitoring of AG patients after standard therapy and furthermore may support the development of novel, tailored therapy options in recurrent AG.
Giving the Value of a Variable
2021-04-09

Abstract What does it mean to ‘give’ the value of a variable in an algebraic context, and how does giving the value of a variable differ from merely describing it? I argue that to answer this question, we need to examine the role that giving the value of a variable plays in problem-solving practice. I argue that four different features are required for a statement to count as giving the value of a variable in the context of solving an elementary algebra problem: the variable must be in the scope opened by the problem statement; the values given must be in the range of the variable, which is determined by the problem; the statement giving the values must represent a complete solution; and it must be in a canonical form . This account helps us better understand elementary algebra itself, as well as the use of algebraic tools to analyze phenomena in natural language.
Reply on RC1
2021-04-09

Detrital tracer thermochronology exploits the relationship between bedrock thermochronometric age-elevation profiles and a distribution of detrital grain-ages collected from river, glacial, or other sediment to study spatial changes in the distribution of catchment erosion. If ages increase linearly with elevation, spatially uniform erosion is expected to yield a detrital age distribution that mirrors the catchment's hypsometric curve. Alternatively, a mismatch between detrital and hypsometric distributions may indicate non-uniform erosion within a catchment. For studies seeking to identify the pattern of erosion, measured grain-age populations rarely exceed 100 grains due largely to the time and costs related to individual measurements. With sample sizes of this order, discerning between two detrital age distributions produced by different catchment erosion scenarios can be difficult at a high statistical confidence level. However, there is no established method to quantify the sample-size-dependent uncertainty inherent to detrital tracer thermochronology, and practitioners are often left wondering how many grains is enough?. Here, we investigate how sample size affects the uncertainty of detrital age distributions and how such uncertainty affects the ability to uniquely infer the erosional pattern of the upstream area. We do this using the Kolmogorov-Smirnov statistic as metric of dissimilarity among distributions, based on which the statistical confidence of detecting an erosional pattern is determined through Monte Carlo sampling. The techniques are implemented in a new tool (ESD_thermotrace) to consistently report confidence levels as a function of sample size and application-specific variables. The proposed tool is made available as a new open-source Python-based script along with test data. Testing between different hypothesized erosion scenarios with this tool provides thermochronologists with the minimum sample size (i.e. number of bedrock and detrital grain-ages) required to answer their specific scientific question, at their desired level of statistical confidence. Furthermore, in cases of unavoidably small sample size (e.g., due to poor grain quality or low sample volume), we provide a means to calculate the confidence level of interpretations made from the data.
First detection of porcine respirovirus 1 in Germany and the Netherlands
2021-04-10

Porcine respirovirus 1, also referred to as porcine parainfluenza virus 1 (PPIV-1), was first detected in deceased pigs from Hong Kong in 2013. It has since then been found in the USA, Chile and most recently in Hungary. Information on the pathogenicity and global spread is sparse. However, it has been speculated to play a role in the porcine respiratory disease complex. To investigate the porcine virome, we screened 53 pig samples from 26 farms within the Dutch-German border region using shotgun metagenomics sequencing (SMg). After detecting PPIV-1 in five farms through SMg, a real-time reverse transcriptase PCR (RT-qPCR) assay was designed, which not only confirmed the presence of the virus in 1 of the 5 farms but found an additional 6 positive farms. Phylogenetic analysis found the closest match to be the first detected PPIV-1 strain in Hong Kong. The Dutch-German region represents a significant area of pig farming within Europe and could provide important information on the characterization and circulation of porcine viruses, such as PPIV-1. With its recent detection in Hungary, these findings suggest widespread circulation of PPIV-1 in Central Europe, highlighting the need for further research on persistence, pathogenicity and transmission in Europe.
Not all Elementary School Teachers are Scared of Math
2021-04-10

Teachers are strong role models for their pupils, especially at the very beginning of education, and as such, pupils tend to share their teacher’s attitudes. This also holds true for math: If teachers feel anxious about math, the consequences on the mathematical education of their pupils is detrimental. Previous studies have shown that (future) elementary school teachers have higher levels of math anxiety than most people studying other subjects. Here, we set out to conceptually replicate these findings (e.g., meta-analysis by Hembree, 1990) by comparing math anxiety levels of pre-service and in-service German and Belgian elementary school teachers to a reference group of German university students from various fields of study. Moreover, we questioned this finding by asking which elementary school teachers experience math anxiety, considering gender, specialization, and experience, and investigated how math anxiety relates to teaching attitudes towards math. We replicated the previous finding by showing that female elementary school teachers have a higher level of math anxiety as compared to other female students. Importantly, female elementary school teachers without math specialization indeed had higher levels of math anxiety than female students from other fields. In contrast, female elementary school teachers with math specialization did not show an increased level of math anxiety as compared to the reference sample. Considering that not only these but all teachers, regardless of specialization, teach math in elementary school in the investigated educational systems, the math anxiety of elementary school teachers is a potential problem for their pupils’ math attitudes and learning.