bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of parameters affecting performance and reliability of machine learning-based antibiotic susceptibility testing from whole genome sequencing data
Authors: Hicks Allison L. , Wheeler Nicole , Sánchez-Busó Leonor , Rakeman Jennifer L. , Harris Simon R. , Grad Yonatan H. 
Published: April 2019

AbstractPrediction of antibiotic resistance phenotypes from whole genome sequencing data by machine learning methods has been proposed as a promising platform for the development of sequence-based diagnostics. However, there has been no systematic evaluation of factors that may influence performance of such models, how they might apply to and vary across clinical populations, and what the implications might be in the clinical setting. Here, we performed a meta-analysis of seven large Neisseria gonorrhoeae datasets, as well as Klebsiella pneumoniae and Acinetobacter baumannii datasets, with whole genome sequence data and antibiotic susceptibility phenotypes using set covering machine classification, random forest classification, and random forest regression models to predict resistance phenotypes from genotype. We demonstrate how model performance varies by drug, dataset, resistance metric, and species, reflecting the complexities of generating clinically relevant conclusions from machine learning-derived models. Our findings underscore the importance of incorporating relevant biological and epidemiological knowledge into model design and assessment and suggest that doing so can inform tailored modeling for individual drugs, pathogens, and clinical populations. We further suggest that continued comprehensive sampling and incorporation of up-to-date whole genome sequence data, resistance phenotypes, and treatment outcome data into model training will be crucial to the clinical utility and sustainability of machine learning-based molecular diagnostics.Author SummaryMachine learning-based prediction of antibiotic resistance from bacterial genome sequences represents a promising tool to rapidly determine the antibiotic susceptibility profile of clinical isolates and reduce the morbidity and mortality resulting from inappropriate and ineffective treatment. However, while there has been much focus on demonstrating the diagnostic potential of these modeling approaches, there has been little assessment of potential caveats and prerequisites associated with implementing predictive models of drug resistance in the clinical setting. Our results highlight significant biological and technical challenges facing the application of machine learning-based prediction of antibiotic resistance as a diagnostic tool. By outlining specific factors affecting model performance, our findings provide a framework for future work on modeling drug resistance and underscore the necessity of continued comprehensive sampling and reporting of treatment outcome data for building reliable and sustainable diagnostics.
Comparative transcriptomics analyses across species, organs and developmental stages reveal functionally constrained lncRNAs
Authors: Darbellay Fabrice , Necsulea Anamaria 
Published: April 2019

AbstractBackgroundTranscription of long non-coding RNAs (lncRNAs) is pervasive, but their functionality is disputed. As a class, lncRNAs show little selective constraint and negligible phenotypic effects upon perturbation. However, key biological roles were demonstrated for individual lncRNAs. Most validated lncRNAs were implicated in gene expression regulation, in pathways related to cellular pluripotency, differentiation and organ morphogenesis, suggesting that functional lncRNAs may be more abundant in embryonic development, rather than in adult organs.ResultsHere, we perform a multi-dimensional comparative transcriptomics analysis, across five developmental time-points (two embryonic stages, newborn, adult and aged individuals), four organs (brain, kidney, liver and testes) and three species (mouse, rat and chicken). Overwhelmingly, lncRNAs are preferentially expressed in adult and aged testes, consistent with the presence of permissive transcription during spermatogenesis. LncRNAs are often differentially expressed among developmental stages and are less abundant in embryos and newborns compared to adult individuals, in agreement with a requirement for tighter expression control and less tolerance for noisy transcription early in development. However, lncRNAs expressed during embryonic development show increased levels of evolutionary conservation, both in terms of primary sequence and of expression patterns, and in particular at their promoter regions. We find that species-specific lncRNA transcription is frequent for enhancer-associated loci and occurs in parallel with expression pattern changes for neighboring protein-coding genes.ConclusionsWe show that functionally constrained lncRNA loci are enriched in developing organ transcriptomes, and propose that many of these loci may function in an RNA-independent manner.
Machine learning prediction of emesis and gastrointestinal state in ferrets
Authors: Nanivadekar Ameya C. , Miller Derek M. , Fulton Stephanie , Wong Liane , Ogren John , Chitnis Girish , McLaughlin Bryan , Zhai Shuyan , Fisher Lee E. , Yates Bill J. , Horn Charles C. 
Published: April 2019

AbstractAlthough electrogastrography (EGG) could be a critical tool in the diagnosis and treatment of patients with gastrointestinal (GI) disease, it remains under-utilized. The lack of spatial and temporal resolution using current EGG methods presents a significant roadblock to more widespread usage. Human and preclinical studies have shown that GI myoelectric electrodes can record signals containing significantly more information than can be derived abdominal surface electrodes. The current study sought to assess the efficacy of multi-electrode arrays, surgically implanted on the serosal surface of the GI tract, from gastric fundus to duodenum, in recording myoelectric signals. It also examines the potential for machine learning algorithms to predict functional states, such as retching and emesis, from GI signal features. Studies were performed using ferrets, a gold standard model for emesis testing. Our results include simultaneous recordings from up to six GI recording sites in both anesthetized and chronically implanted free-moving ferrets. Testing conditions to produce different gastric states included gastric distension, intragastric infusion of emetine (a prototypical emetic agent), and feeding. Despite the observed variability in GI signals, machine learning algorithms, including k nearest neighbors and support vector machines, were able to detect the state of the stomach with high overall accuracy (>80%). The present study is the first demonstration of machine learning algorithms to detect the physiological state of the stomach and onset of retching and could provide insight into methodologies to treat GI diseases and control symptoms such as nausea and vomiting.
piNET: a versatile web platform for downstream analysis and visualization of proteomics data
Authors: Shamsaei Behrouz , Chojnacki Szymon , Pilarczyk Marcin , Najafabadi Mehdi , Chen Chuming , Ross Karen , Matlock Andrea , Muhlich Jeremy , Chutipongtanate Somchai , Vidovic Dusica , Sharma Vagisha , Vasiliauskas Juozas , Jaffe Jake , MacCoss Michael , Wu Cathy , Pillai Ajay , Ma’ayan Avi , Schurer Stephan , Medvedovic Mario , Meller Jarek 
Published: April 2019

ABSTRACTLarge proteomics data, including those generated by mass spectrometry, are being generated to characterize biological systems at the protein level. Computational methods and tools to identify and quantify peptides, proteins and post-translational modifications (PTMs) that are captured in modern mass spectrometers have matured over the years. On the other hand, tools for downstream analysis, interpretation and visualization of proteomics data sets, in particular those involving PTMs, require further improvement and integration to accelerate scientific discovery and maximize the impact of proteomics studies by connecting them better with biological knowledge across not only proteomics, but also other Omics domains. With the goal of addressing these challenges, the piNET server has been developed as a versatile web platform to facilitate mapping, annotation, analysis and visualization of peptide, PTM, and protein level quantitative data generated by either targeted, shotgun or other proteomics approaches. Building on our experience with large scale analysis of gene and protein expression profiles as part of the Library of Integrated Network Cellular Signatures (LINCS) project, piNET has been designed as a fast, versatile and easy to use web-based tool with three modules that provide mapping from peptides (with PTMs) to proteins, from PTM sites to modifying enzymes that target those sites, and finally from proteins (with PTMs) to pathways, and for further mechanistic insights to LINCS signatures of chemical and genetic perturbations. piNET is freely available at http://www.pinet-server.org.
Xyloglucan homeostasis and microtubule dynamics synergistically maintain meristem geometry and robustness of phyllotaxis in Arabidopsis
Authors: Zhao Feng , Chen Wenqian , Sechet Julien , Martin Marjolaine , Bovio Simone , Lionnet Claire , Long Yuchen , Battu Virginie , Mouille Grégory , Monéger Françoise , Traas Jan 
Published: April 2019

ABSTRACTThe shoot apical meristem (SAM) gives rise to all aerial organs of the plant. The cell walls are supposed to play a central role in this process, translating molecular regulation into dynamic changes of growth rates and directions, although their precise role in morphogenesis during organ formation remains not well understood. Here we investigate the role of xyloglucans (XyGs), which form a major, yet functionally poorly characterized, wall component in the SAM. Using immunolabeling, biochemical analysis, genetic approaches, micro-indentation, laser ablations and live imaging, we show that XyGs are important for meristem shape and phyllotaxis, although no difference in cell wall stiffness could be observed when XyGs are perturbed. Mutations in enzymes required for XyG synthesis also affect other cell wall components such as cellulose content and the pectin methylation status. Interestingly, we show that the control of cortical microtubules dynamics by the severing enzyme KATANIN becomes vital when XyGs are perturbed or absent. This suggests an active role of the cytoskeleton in compensating for altered wall composition.
Heterologous Expression of Pediocin PA-1 inEscherichia coli
Authors: Anh Thu Nguyen Pham , Hong Thuy Dao Thi , Nghia Nguyen Hieu , Phuong Thao Dang Thi 
Published: April 2019

AbstractPediocin PA-1 is an antimicrobial peptide which has a strongly activity against some Gram – positive pathogens such asListeria monocytogenes, Staphylococcus aureus, Enterococcus faecalis…With the broad inhibitory spectrum as well as pH and temperature stability, pediocin has a potential application in food preservation as well as pharmaceutical industry. For higher manufactory efficiency, pediocin has been expressed in both prokaryote and eukaryote heterologous expression system, mostly on Escherichia coli with different strategies. Here, we show a new strategy to produce pediocin fromEscherichia coliBL21(DE3) system as fusion form by using a vector containing NusA tag. Our results showed that NusA fused pediocin almost presented in soluble form with high efficiency (79.8 mg/l obtained by Ni-NTA purification). After remove the fusion tag, recombinant pediocin showed antimicrobial activity againstListeria monocytogenesATCC 13932 as 23.5×103Au/mg as well as againstEnterococcus faecalis, Lactobacillus plantarum, and Streptococcus thermophilus, especiallyVibrio parahaemolyticus– a Gram-negative bacteria which have not been reported in antimicrobial spectrum of pediocin on Bactibase. Recombinant pediocin is recorded to be stable to a wide range of pH (1-12 for 1 hour) and temperature (100°C for 15 min) as well as sensitive to protease treatment as the nature pediocin. These characteristics opened a prospect of using pediocin as bio-preservative compound in food industry.
Genomic prediction accuracies and abilities for growth and wood quality traits of Scots pine, using genotyping-by-sequencing (GBS) data
Authors: Calleja-Rodriguez Ainhoa , Pan Jin , Funda Tomas , Chen Zhi-Qiang , Baison John , Isik Fikret , Abrahamsson Sara , Wu Harry X. 
Published: April 2019

ABSTRACTHigher genetic gains can be achieved through genomic selection (GS) by shortening time of progeny testing in tree breeding programs. Genotyping-by-sequencing (GBS), combined with two imputation methods, allowed us to perform the current genomic prediction study in Scots pine (Pinus sylvestrisL.). 694 individuals representing 183 full-sib families were genotyped and phenotyped for growth and wood quality traits. 8719 SNPs were used to compare different genomic prediction models. In addition, the impact on the predictive ability (PA) and prediction accuracy to estimate genomic breeding values was evaluated by assigning different ratios of training and validation sets, as well as different subsets of SNP markers. Genomic Best Linear Unbiased Prediction (GBLUP) and Bayesian Ridge Regression (BRR) combined with expectation maximization (EM) imputation algorithm showed higher PAs and prediction accuracies than Bayesian LASSO (BL). A subset of approximately 4000 markers was sufficient to provide the same PAs and accuracies as the full set of 8719 markers. Furthermore, PAs were similar for both pedigree- and genomic-based estimations, whereas accuracies and heritabilities were slightly higher for pedigree-based estimations. However, prediction accuracies of genomic models were sufficient to achieve a higher selection efficiency per year, varying between 50-87% compared to the traditional pedigree-based selection.
Longitudinal white matter development in children is associated with puberty, attentional difficulties, and mental health
Authors: Genc Sila , Malpas Charles B , Gulenc Alisha , Sciberras Emma , Efron Daryl , Silk Timothy J , Seal Marc L 
Published: April 2019

ABSTRACTThe pubertal period involves dynamic white matter development. This period also corresponds with rapid gains in higher cognitive functions including attention, as well as increased risk of developing mental health difficulties. This longitudinal study comprised children aged 9-13 years (n=130). Diffusion magnetic resonance imaging (dMRI) data were acquired (b=2800 s/mm2, 60 directions) at two time-points. We derived measures of fibre density and morphology using the fixel-based analysis framework and performed a tract-based mixed-effects modelling analysis to understand patterns of white matter development with respect to age, pubertal stage, attentional difficulties, and internalising and externalising problems. We observed significant increases in apparent fibre density across a large number of white matter pathways, including major association and commissural pathways. We observed a linear relationship between fibre density and morphology with pubertal stage, in the right superior longitudinal fasciculus and in the right inferior longitudinal fasciculus. In terms of symptom severity, fibre density was positively associated with attentional dysfunction in the right uncinate fasciculus. Overall, white matter development across ages 9-13 years involved the expansion of major white matter fibre pathways, with key right-lateralised association pathways linked with pubertal development and attentional difficulties.
Developmentally regulatedtcf7l2splice variants mediate transcriptional repressor functions during eye formation
Authors: Young Rodrigo M. , Ewan Kenneth B. , Ferrer Veronica P. , Allende Miguel L. , Godovac-Zimmermann Jasminka , Dale Trevor C. , Wilson Stephen W. 
Published: April 2019

AbstractTcf7l2 mediates Wnt/β-Catenin signalling during development and is implicated in cancer and type-2 diabetes. The mechanisms by which Tcf7l2 and Wnt/β-Catenin signalling elicits such a diversity of biological outcomes are poorly understood. Here, we study alternatively splicedtcf7l2in zebrafish and show that only splice variants that include exon 5 and an analogous humantcf7l2variant can effectively provide compensatory repressor function to restore eye formation in embryos lackingtcf7l1a/tcf7l1bfunction. Knockdown of exon 5 specifictcf7l2variants intcf7l1amutants also compromises eye formation and these variants can effectively repress Wnt pathway activity in reporter assays using Wnt target gene promoters. We show that the repressive activities of exon5-coded variants are likely explained by their interaction with Tle co-repressors. Furthermore, phosphorylated residues in Tcf7l2 coded exon5 facilitate repressor activity. Our studies suggest that developmentally regulated splicing oftcf7l2can influence the transcriptional output of the Wnt pathway.
Shariaventure capital as financing alternative of Muslim entrepreneurs
Authors: Fathonih Ah. , Anggadwita Grisna , Ibraimi Sadudin 
Published: April 2019

PurposeMuslim entrepreneurs face various obstacles when starting their business, especially in gaining access to financing. Some financing practices have someShariaviolations, so this paper tries to explore the opportunities and challenges of one financing alternative for Muslim entrepreneurship development in Indonesia that fully complies withShariaprinciples. This paper aims to further understand the concept of venture capital and how it relates to Islamic teachings, and the paper ends with the suggestion for future research direction.Design/methodology/approachThis study uses qualitative methods with descriptive and exploratory analysis. A case study approach using semi-structured in-depth interviews with several key informants were conducted to identify the opportunities and challenges for Muslim entrepreneurs in gaining access to Islamic financing. Various literary syntheses are also provided to better understand alternative financing for business development of Muslim entrepreneurs.FindingsMuslim entrepreneurship, depending on their goals and needs in obtaining financing, uses different models in the process of agreements with capital-funding institutions based onShariaprinciples.Shariaventure capital is one alternative financing that gives freedom for Muslim entrepreneurs to develop their business based on the Islamic system, without thinking about the requirements that must be met in obtaining access to the financing. However, it seems that this scheme still has relatively low interest, especially from Muslim entrepreneurs because they do not know the information and procedures ofShariaventure capital.Practical implicationsSome policy implications include increasing capital fromShariaventure capital institutions, the role of the government in providing adequate policy support and incentives and broader socialization and education about the existence and importance of developingShariaventure capital. Practical implications include useful information for Muslim entrepreneurs to address financing issues in their entrepreneurial activities and suggest insights for future research.Originality/valueThis study provides the link of financial access for Muslim entrepreneurs toShariaventure capital as a new financing business innovation. Thus, it contributes to the literature onShariaventure capital and Muslim entrepreneurship. The authors also propose some useful recommendations for further research in this field.
A qualitative research to explore practices that are utilised for managing talent development in the higher education environment
Authors: Mohammed Atheer Abdullah , Hafeez-Baig Abdul , Gururajan Raj 
Published: April 2019

PurposeThe purpose of this paper is to investigate generated themes associated with talent development in the Australian higher education sector. This is because there are pragmatic advantages for universities that are focused on developing talents. For example, talent is a primary source of competitive advantage for educational institutions.Design/methodology/approachThis study depends on the individual interview method as the main tool for data collection. The sample consisted of six participants who are talented. High-level individual interviews were transcribed and thematically analysed using NVivo 11.FindingsIndividual interviews have identified four key themes of talent development: performance management, coaching talent, leadership development and talent acquisition.Research limitationsThis study only targeted one country (Australia), and one sector (higher education). Hence, the generalisability of these results is limited to the Australian university sector in Queensland.Practical implicationsThis study collects rich and original qualitative data regarding talent development in the higher education domain. Therefore, for instance, the research findings validate what was already found but are significant because practical data rather than theoretical were gathered through a discussion with experts in talent management. This study has a high quality because of strengthening the effect of an in-depth case study.Originality/valueThe study offers a value added to talent management theory through investigating themes of talent development for the higher education sector. This would assist researchers in this field to provide a deeper understanding and develop a theoretical foundation for their further studies. This implication is unique to the advancement of talent management theory.
International orientation of professional football beyond Europe
Authors: Fleischmann A. Carolin , Fleischmann Martin 
Published: April 2019

PurposeThe purpose of this paper is to investigate how professional football clubs from the English Premier League, German Bundesliga and Spanish Primera División use digital media to expand their international reach in emerging football markets (EFM) outside of Europe. Based on the EPRG framework and Rugman’s home-region hypothesis, the aim is to broaden the perspective where “sports go global” for a further understanding of actors’ international orientation in the digital sphere.Design/methodology/approachThe study is based on data from desk research and a qualitative survey, comprising information on international digital media activities of 58 European clubs. Cluster analysis is used to identify different international orientations with regard to digital media activities.FindingsThe data provide evidence that clubs differ strongly in their orientations towards EFM. While some global players that provide digital media content in several EFM languages and attract a large share of Facebook followers from EFM exist, other clubs focus on their home region. League-specific differences become apparent.Originality/valueThis study determines the international online orientations of European football clubs by combining two previously separated research streams in football management studies: internationalisation and digital media activities. Most clubs with a strong EFM fan base choose polycentric, multi-language digital media strategies, followed by geocentric, standardised approaches. By offering a novel angle on internationalisation in professional football, this study contributes towards optimising clubs’ international online strategies for EFM, which are markets that promise high growth rates.