bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infective endocarditis in children: an update
Authors: Dixon Garth , Christov Georgi 
Published: March 2017

Purpose of review
Infective endocarditis in children remains a clinical challenge. Here, we review the impact of the updated 2015 American Heart Association and European Society of Cardiology guidelines on management as well as the significance of the new predisposing factors, diagnostic and treatment options, and the impact of the 2007–2008 change in prophylaxis recommendations.

Recent findings
The new 2015 infective endocarditis guidelines introduced the endocarditis team, added the new imaging modalities of computer tomography and PET–computer tomography into the diagnostic criteria and endorsed the concept of safety of relatively early surgical treatment. The impact of the restriction of infective endocarditis prophylaxis since the 2007–2008 American Heart Association and National Institute for Health and Care Excellence recommendations is uncertain, with some studies showing no change and other more recent studies showing increased incidence. The difficulties in adjusting for varying confounding factors are discussed. The relative proportion of the device-related infective endocarditis is increasing. Special attention is paid to relatively high incidence of percutaneous pulmonary valve implantation-related infective endocarditis with low proportion of positive echo signs, disproportionate shift in causative agents, and unusual complication of acute obstruction. The significance of incomplete neoendothelialization on the risk of infective endocarditis on intracardiac devices is also discussed.

Summary
The impact of changes in the infective endocarditis prophylaxis recommendations in pediatric patients is still uncertain. The device-related infective endocarditis has increasing importance, with the incidence on transcatheter implanted bovine jugular vein pulmonary valves being relatively high. The use of novel imaging, laboratory diagnostic techniques, and relatively early surgery in particular circumstances is important for management of paediatric infective endocarditis.
Endothelial cells and lymphatics at the interface between the immune and central nervous systems: implications for multiple sclerosis
Authors: Meyer Céline , Martin-Blondel Guillaume , Liblau Roland S. 
Published: March 2017

Purpose of review
The central nervous system (CNS) has a unique relationship with the immune system. This review highlights the distinct roles of lymphatic vessels and endothelial cells in the interface between CNS and immune cells and invites to revisit the concept of CNS immune privilege.

Recent findings
T cells can follow several routes to penetrate the CNS parenchyma but may also benefit, together with antigen-loaded presenting cells, from the newly described lymphatic network to exit the CNS. CNS endothelial cells (EC) critically positioned at the interface between circulating immune cells and the CNS regulate the multistep cascade for immune cell trafficking into the CNS. They can also be considered as semiprofessional antigen-presenting cells through their ability to present antigens to T cells and to regulate their activation through co-stimulatory and inhibitory molecules.

Summary
The lymphatic network linking the CNS to draining lymph nodes may contribute to the inflammatory reaction occurring in multiple sclerosis (MS). The abundance and strategic positioning of endothelial cells at the blood–brain barrier level most likely endow them with an important role in controlling local adaptive immune responses, rendering them potential therapeutic targets in neuro-inflammatory such as MS.
Stimulus-Induced Rhythmic, Periodic, or Ictal Discharges in Coma—Incidence and Interrater Reliability of Continuous EEG After a Standard Stimulation Protocol: A Prospective Study
Authors: Alsherbini Khalid A. , Plancher Joao Mc-O'Neil , Ficker David M. , Foreman Brandon P. , Adeoye Opeolu M. , Ying Jun , Privitera Michael D. 
Published: March 2017

Purpose:
Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) are often seen during continuous electroencephalographic (cEEG) monitoring in coma. Given their uncertain clinical significance, our prospective study evaluated incidence of SIRPIDs in comatose patients in the neuroscience intensive care unit (NSICU) who underwent a standard stimulation protocol and defined interreader reliability for cEEG.

Methods:
Of 146 patients prospectively screened who underwent cEEG during a 6-month period, 53 patients were included and 93 patients were excluded. Our protocol used a sequence of auditory, mild tactile, and painful stimuli tested in a quiet room. Continuous electroencephalogram were then reviewed offline by blinded experts, with interrater agreement assessed by kappa statistic. By Pearson χ2 and Wilcoxon rank-sum tests, we then compared binary and numerical clinical features between those with and without SIRPIDs.

Results:
Of 53 patients who underwent our protocol, one patient with a corrupt cEEG file was excluded. Traumatic brain injury was the most common diagnosis. Moderate interrater agreement was observed for 66 total stimulations: 20 patients (38.5%) had possible or definite SIRPIDs by minimum one reviewer. For 19 stimulations reviewed by a third reviewer, consensus was reached in 10 cases making the incidence of SIRPIDs 19.3% in our cohort. There was a moderate interrate agreement with kappa of 0.5 (95% confidence interval: 0.1, 0.7). Median intensive care unit stay was 15 days in patients with SIRPIDs versus 6.5 days in those without (P = 0.021).

Conclusions:
Our prospective study of SIRPIDs in the neuroscience intensive care unit found a 19% incidence by cEEG using a standard stimulation protocol, most often rhythmic delta activity, and showed a moderate interrater agreement.
Bridging Computational Neuroscience and Machine Learning on Non-Stationary Multi-Armed Bandits
Authors: Velentzas George , Tzafestas Costas , Khamassi Mehdi 
Published: March 2017

AbstractFast adaptation to changes in the environment requires both natural and artificial agents to be able to dynamically tune an exploration-exploitation trade-off during learning. This trade-off usually determines a fixed proportion of exploitative choices (i.e. choice of the action that subjectively appears as best at a given moment) relative to exploratory choices (i.e. testing other actions that now appear worst but may turn out promising later). The problem of finding an efficient exploration-exploitation trade-off has been well studied both in the Machine Learning and Computational Neuroscience fields. Rather than using a fixed proportion, non-stationary multi-armed bandit methods in the former have proven that principles such as exploring actions that have not been tested for a long time can lead to performance closer to optimal - bounded regret. In parallel, researches in the latter have investigated solutions such as progressively increasing exploitation in response to improvements of performance, transiently increasing exploration in response to drops in average performance, or attributing exploration bonuses specifically to actions associated with high uncertainty in order to gain information when performing these actions. In this work, we first try to bridge some of these different methods from the two research fields by rewriting their decision process with a common formalism. We then show numerical simulations of a hybrid algorithm combining bio-inspired meta-learning, kalman filter and exploration bonuses compared to several state-of-the-art alternatives on a set of non-stationary stochastic multi-armed bandit tasks. While we find that different methods are appropriate in different scenarios, the hybrid algorithm displays a good combination of advantages from different methods and outperforms these methods in the studied scenarios.
Comparison Of Multi-locus Sequence Typing software For next generation sequencing data
Authors: Page Andrew J. , Alikhan Nabil-Fareed , Carleton Heather A. , Seemann Torsten , Keane Jacqueline A. , Katz Lee S. 
Published: March 2017

ABSTRACTMulti-locus sequence typing (MLST) is a widely used method for categorising bacteria. Increasingly MLST is being performed using next generation sequencing data by reference labs and for clinical diagnostics. Many software applications have been developed to calculate sequence types from NGS data; however, there has been no comprehensive review to date on these methods. We have compared six of these applications against real and simulated data and present results on: 1. the accuracy of each method against traditional typing methods, 2. the performance on real outbreak datasets, 3. in the impact of contamination and varying depth of coverage, and 4. the computational resource requirements.DATA SUMMARYSimulated reads for datasets testing coverage and mixed samples have been deposited in Figshare; DOI:https://doi.org/10.6084/m9.figshare.4602301.vlOutbreak databases are available from Github; url -https://github.com/WGS-standards-and-analysis/datasetsDocker containers used to run each of the applications are available from Github; url –https://tinyurl.com/z7ks2ftAccession numbers for the data used in this paper are available in the Supplementary material.We confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. ☒IMPACT STATEMENTSequence typing is rapidly transitioning from traditional sequencing methods to using whole genome sequencing. A number ofin silicoprediction methods have been developed on anad hocbasis and aim to replicate Multi-locus sequence typing (MLST). This is the first study to comprehensively evaluate multiple MLST software applications on real validated datasets and on common simulated difficult cases. It will give researchers a clearer understanding of the accuracy, limitations and computational performance of the methods they use, and will assist future researchers to choose the most appropriate method for their experimental goals.
Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data
Authors: Racle Julien , de Jonge Kaat , Baumgaertner Petra , Speiser Daniel E. , Gfeller David 
Published: March 2017

AbstractImmune cells infiltrating tumors can have important impact on tumor progression and response to therapy. We present an efficient algorithm to simultaneously estimate the fraction of cancer and immune cell types from bulk tumor gene expression data. Our method integrates novel gene expression profiles from each major non-malignant cell type found in tumors, renormalization based on cell-type specific mRNA content, and the ability to consider uncharacterized and possibly highly variable cell types. Feasibility is demonstrated by validation with flow cytometry, immunohistochemistry and single-cell RNA-Seq analyses of human melanoma and colorectal tumor specimens. Altogether, our work not only improves accuracy but also broadens the scope of absolute cell fraction predictions from tumor gene expression data, and provides a unique novel experimental benchmark for immunogenomics analyses in cancer research.
Probabilistic recovery of cryptic haplotypes from metagenomic data
Authors: Nicholls Samuel M. , Aubrey Wayne , de Grave Kurt , Schietgat Leander , Creevey Christopher J. , Clare Amanda 
Published: March 2017

AbstractThe cryptic diversity of microbial communities represent an untapped biotechnological resource for biomining, biorefining and synthetic biology. Revealing this information requires the recovery of the exact sequence of DNA bases (or “haplotype”) that constitutes the genes and genomes of every individual present. This is a computationally difficult problem complicated by the requirement for environmental sequencing approaches (metagenomics) due to the resistance of the constituent organisms to culturingin vitro.Haplotypes are identified by their unique combination of DNA variants. However, standard approaches for working with metagenomic data require simplifications that violate assumptions in the process of identifying such variation. Furthermore, current haplotyping methods lack objective mechanisms for choosing between alternative haplotype reconstructions from microbial communities.To address this, we have developed a novel probabilistic approach for reconstructing haplotypes from complex microbial communities and propose the “metahaplome” as a definition for the set of haplotypes for any particular genomic region of interest within a metagenomic dataset. Implemented in the twin software tools Hansel and Gretel, the algorithm performs incremental probabilistic haplotype recovery using Naive Bayes — an efficient and effective technique.Our approach is capable of reconstructing the haplotypes with the highest likelihoods from metagenomic datasets withouta prioriknowledge or making assumptions of the distribution or number of variants. Additionally, the algorithm is robust to sequencing and alignment error without altering or discarding observed variation and uses all available evidence from aligned reads. We validate our approach using synthetic metahaplomes constructed from sets of real genes, and demonstrate its capability using metagenomic data from a complex HIV-1 strain mix. The results show that the likelihood framework can allow recovery from microbial communities of cryptic functional isoforms of genes with 100% accuracy.
Variation of the meiotic recombination landscape and properties over a broad evolutionary distance in yeasts
Authors: Brion Christian , Legrand Sylvain , Peter Jackson , Caradec Claudia , Pflieger David , Hou Jing , Friedrich Anne , Llorente Bertrand , Schacherer Joseph 
Published: March 2017

AbstractMeiotic recombination is a major factor of genome evolution, deeply characterized in only a few model species, notably the yeastSaccharomyces cerevisiae.Consequently, little is known about variations of its properties across species. In this respect, we explored the recombination landscape ofLachancea kluyveri,a protoploid yeast species that diverged from theSaccharomycesgenus more than 100 million years ago and we found striking differences withS. cerevisiae.These variations include a lower recombination rate, a higher frequency of chromosomes segregating without any crossover and the absence of recombination on the chromosome arm containing the sex locus. In addition, although well conserved within theSaccharomycesclade, theS. cerevisiaerecombination hotspots are not conserved over a broader evolutionary distance. Finally and strikingly, we found evidence of frequent reversion of meiotic commitment to mitotic growth allowing allele shuffling without meiosis completion. Identification of this major but underestimated evolutionary phenomenon illustrates the relevance of exploring non-model species.Author summaryMeiotic recombination promotes accurate chromosome segregation and genetic diversity. To date, the mechanisms and rules lying behind recombination were dissected using model organisms such as the budding yeastSaccharomyces cerevisiae. To assess the conservation and variation of this process over a broad evolutionary distance, we explored the meiotic recombination landscape inLachancea kluyveri,a budding yeast species that diverged fromS. cerevisiaemore than 100 million years ago. The meiotic recombination map we generated revealed that the meiotic recombination landscape and properties significantly vary across distantly related yeast species, supporting that recombination hotspots conservation across yeast species is likely associated to the conservation of synteny. Finally, the frequent meiotic reversions we observed led us to re-evaluate their evolutionary importance.
mRNA and long non-coding RNA expression profiles in rats reveal inflammatory features in sepsis-associated encephalopathy
Authors: Sun WenChong , Pei Ling , Liang Zuodi 
Published: March 2017

AbstractBackgroundSepsis-associated encephalopathy (SAE) is related to cognitive sequelae in patients in the intensive care unit (ICU) and can have serious impacts on quality of life after recovery. Although various pathogenic pathways are involved in SAE development, little is known concerning the global role of long non-coding RNAs (lncRNAs) in SAE.MethodsHerein, we employed transcriptome sequencing approaches to characterize the effects of lipopolysaccharide (LPS) on lncRNA expression patterns in brain tissue isolated from Sprague-Dawley (SD) rats with and without SAE. We performed high-throughput transcriptome sequencing after LPS was intraperitoneally injected and predicted targets and functions using bioinformatics tools. Subsequently, we explored the results in detail according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.ResultsLncRNAs were differentially expressed in brain tissue after LPS treatment. After 6 h of LPS exposure, expression of 400 lncRNAs were significantly changed, including an increase in 316 lncRNAs and a decrease in 84 lncRNAs. In addition, 155 mRNAs were differentially expressed, with 84 up-regulated and 71 down-regulated. At 24 h post-treatment, expression of 117 lncRNAs and 57 mRNAs was consistently elevated, while expression of 79 lncRNAs and 21 mRNAs was decreased (change > 1.5-fold; p < 0.05). We demonstrated for the first time that differentially expressed lncRNAs were predicted to be enriched in a post-chaperonin tubulin folding pathway (GO : 007023), which is closely related to the key step in the tubulin folding process.Interestingly, the predicted pathway (KEGG 04360: axon guidance) was significantly changed under the same conditions. These results reveal that LPS might influence the construction and polarization of microtubules, which exert predominant roles in synaptogenesis and related biofunctions in the rodent central nervous system (CNS).ConclusionsAn inventory of LPS-modulated expression profiles from the rodent CNS is an important step toward understanding the function of mRNAs, including lncRNAs, and suggests that microtubule malformation and dysfunction may be involved in SAE pathogenesis.
Increased pericarp cell length underlies a major QTL for grain weight in hexaploid wheat
Authors: Brinton Jemima , Simmonds James , Minter Francesca , Leverington-Waite Michelle , Snape John , Uauy Cristobal 
Published: March 2017

SummaryCrop yields must increase to address food insecurity. Grain weight, determined by grain length and width, is an important yield component, but our understanding of the underlying genes and mechanisms is limited.We used genetic mapping and near isogenic lines (NILs) to identify, validate and fine map a major quantitative trait loci (QTL) on wheat chromosome 5A associated with grain weight. Detailed phenotypic characterisation of developing and mature grains from the NILs was performed.We identified a stable and robust QTL associated with a 6.9 % increase in grain weight. The positive interval leads to 4.0 % longer grains, with differences first visible twelve days post fertilization. This grain length effect was fine-mapped to a 4.3 cM interval. The locus also has a pleiotropic effect on grain width (1.5 %) during late grain development that determines the relative magnitude of the grain weight increase. Positive NILs have increased maternal pericarp cell length, an effect which is independent of absolute grain length.These results provide direct genetic evidence that pericarp cell length affects final grain size and weight in polyploid wheat. We propose that combining genes which control distinct biological mechanisms, such as cell expansion and proliferation, will enhance crop yields.
Intracellular Sodium Regulates Opioid Signalling in Peripheral Neurons
Authors: Kanellopoulos Alexandros H. , Zhao Jing , Emery Edward C. , Wood John N 
Published: March 2017

AbstractOpioid receptors signal more effectively in sensory neurons from pain-free mice lacking the voltagegated sodium channel Nav1.7. Type-A GPCRs are known to be regulated through a specific sodium binding site, the occupancy of which diminishes agonist binding. We have used an electrophysiological assay of Protein Kinase A activity to examine the role of intracellular sodium on opioid signalling. Phosphorylation of sodium channel Nav1.8 by activation of Protein Kinase A with db-cAMP is unaffected by altered intracellular sodium. By contrast, there is a dose-dependent inhibition of fentanyl action on Nav1.8 currents when intracellular sodium is increased from 0 mM to 20 mM. Fentanyl shows a 50% loss of activity and 80-fold increase in EC50with 20 mM intracellular sodium. These data demonstrate that altered intracellular sodium levels modulate opioid receptor signalling.
Examining the characteristics, philosophies, operating practices and growth strategies of village entrepreneurs
Authors: Smith Robert 
Published: March 2017

PurposeThe literature of entrepreneurship has an urban focus and despite the emergence of the rural entrepreneurship literature, we know little about the characteristics, philosophies, operating practices and growth strategies of ordinary village entrepreneurs’ in a UK context. As a concept, the “village entrepreneur” is contentious as theoretically there should be little difference between urban and rural entrepreneurs. Nevertheless, there is! The concept is important because many villages are in decline and are marginal places in terms of entrepreneurial opportunity. The paper aims to discuss these issues.Design/methodology/approachA review of the fragmented literature is conducted to synthesise and develop greater understanding. Drawing on a “life-story” approach the empirical strand comprises of an analysis of five ethnographic interviews with village entrepreneurs.FindingsThe respondents did not consider themselves entrepreneurs whom they characterised as flash, rogues and even crooked. Their embedded village entrepreneur persona was constructed around tales-of-character, hard work and perseverance. They prided themselves in making “slow-money” which they retain over their lifetime. Embeddedness, self-efficacy, character and morality were key themes encountered.Research limitations/implicationsFrom a research perspective the findings are based on a limited sample and the study was not specifically designed to capture data on characteristics, philosophies and operating practices. Further research on a larger scale is necessary to validate the findings.Practical implicationsFrom a practical perspective policy makers require to consider the notions of embeddedness, self-efficacy, character and morality when considering implementing growth strategies in rural areas.Originality/valueThis study contributes to the growing literature of rural entrepreneurship by expanding the typology of rural entrepreneurs and by detailing philosophies, operating practices, and growth strategies suitable and appropriate for small village and rural businesses.