bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying the risk of local Zika virus transmission in the continental US during the 2015-2016 ZIKV epidemic
Authors: Sun Kaiyuan , Zhang Qian , Pastore-Piontti Ana , Chinazzi Matteo , Mistry Dina , Dean Natalie E. , Rojas Diana P. , Merler Stefano , Poletti Piero , Rossi Luca , Halloran M. Elizabeth , Longini Ira M. , Vespignani Alessandro 
Published: April 2018

AbstractBackgroundLocal mosquito-borne Zika virus (ZIKV) transmission has been reported in two counties of the continental United State (US), prompting the issuance of travel, prevention, and testing guidance across the continental US. Large uncertainty, however, surrounds the quantification of the actual risk of ZIKV introduction and autochthonous transmission across different areas of the US.MethodWe present a framework for the projection of ZIKV autochthonous transmission in the continental US during the 2015-2016 epidemic, using a data-driven stochastic and spatial epidemic model accounting for seasonal, environmental and detailed population data. The model generates an ensemble of travel-related case counts and simulate their potential to trigger local transmission at individual level.ResultsWe estimate the risk of ZIKV introduction and local transmission at the county level and at the 0.025° x 0.025° cell level across the continental US. We provide a risk measure based on the probability of observing local transmission in a specific location during a ZIKV epidemic modeled after the one observed during the years 2015-2016. The high spatial and temporal resolutions of the model allow us to generate statistical estimates of the number of ZIKV introductions leading to local transmission in each location. We find that the risk is spatially heterogeneously distributed and concentrated in a few specific areas that account for less than 1% of the continental US population. Locations in Texas and Florida that have actually experienced local ZIKV transmission are among the places at highest risk according to our results. We also provide an analysis of the key determinants for local transmission, and identify the key introduction routes and their contributions to ZIKV spread in the continental US.ConclusionsThis framework provides quantitative risk estimates, fully captures the stochas-ticity of ZIKV introduction events, and is not biased by the under-ascertainment of cases due to asymptomatic infections. It provides general information on key risk determinants and data with potential uses in defining public health recommendations and guidance about ZIKV risk in the US.
Approaches to maximize sgRNA-barcode coupling in Perturb-seq screens
Authors: Adamson Britt , Norman Thomas M. , Jost Marco , Weissman Jonathan S. 
Published: April 2018

ABSTRACTPerturb-seq is a platform for single-cell gene expression profiling of pooled CRISPR screens. Like many functional genomics platforms, Perturb-seq relies on lentiviral transduction to introduce perturbation libraries to cells. On this platform, these are barcoded sgRNA libraries. A critical consideration for performing Perturb-seq experiments is uncoupling of barcodes from linked sgRNA expression cassettes, which can occur during lentiviral transduction of co-packaged libraries due to reverse transcriptase-mediated template switching. This problem is common to lentiviral libraries designed with linked variable regions. Here, we demonstrate that recombination between Perturb-seq vectors scrambles linked variable regions separated by 2 kb. This predicts information loss in Perturb-seq screens performed with co-packaged libraries. We also demonstrate ways to address this problem and discuss best practices for single-cell screens with transcriptional readouts.
Hippocampal knockdown of Piwil1 and Piwil2 enhances contextual fear memory in mice
Authors: Leighton Laura J. , Wei Wei , Ratnu Vikram Singh , Li Xiang , Zajaczkowski Esmi L. , Spadaro Paola A. , Khandelwal Nitin , Kumar Arvind , Bredy Timothy W. 
Published: April 2018

AbstractThe Piwi pathway is a conserved gene regulatory mechanism comprised of Piwi-like proteins and Piwi-interacting RNAs, which modulates gene expression via RNA interference and epigenetic mechanisms. The mammalian Piwi pathway has been defined by its role in transposon control during spermatogenesis, and despite an increasing number of studies demonstrating its expression in the nervous system, relatively little is known about its function in neurons or potential contribution to gene regulation in the brain. We have discovered that all three Piwi-like genes are expressed in several regions of the mouse brain, and that simultaneous knockdown of Piwil1 and Piwil2 in the adult mouse hippocampus enhances contextual fear memory without affecting generalised anxiety. Our results implicate the Piwi pathway in control of plasticity-related gene expression in the adult mammalian brain.
Analysis of an open source, closed-loop, realtime system for hippocampal sharp-wave ripple disruption
Authors: Dutta Shayok , Ackermann Etienne , Kemere Caleb 
Published: April 2018

AbstractTransient neural activity pervades hippocampal electrophysiological activity. During more quiescent states, brief ≈100 ms periods comprising large ≈150–250 Hz oscillations known as sharp-wave ripples (SWR) which co-occur with ensemble bursts of spiking activity, are regularly found in local field potentials recorded from area CA1. SWRs and their concomitant neural activity are thought to be important for memory consolidation, recall, and memory-guided decision making. Temporally-selective manipulations of hippocampal neural activity upon online hippocampal SWR detection have been used as causal evidence of the importance of SWR for mnemonic process as evinced by behavioral and/or physiological changes. However, though this approach is becoming more wide spread, the performance trade-offs involved in building a SWR detection and disruption system have not been explored, limiting the design and interpretation of SWR detection experiments. We present an open source, plug-and-play, online ripple detection system with a detailed performance characterization. Our system has been constructed to interface with an open source software platform, Trodes, and two hardware acquisition platforms, Open Ephys and SpikeGadgets. We show that our in vivo results — approximately 80% detection latencies falling in between ≈20–66 ms with ≈2 ms closed-loop latencies while maintaining <10 false detections per minute — are dependent upon both algorithmic trade-offs and acquisition hardware. We discuss strategies to improve detection accuracy and potential limitations of online ripple disruptions. By characterizing this system in detail, we present a template for analyzing other closed-loop neural detection and perturbation systems. Thus, we anticipate our modular, open source, realtime system will facilitate a wide range of carefully-designed causal closed-loop neuroscience experiments.
Prioritizing putative influential genes in early life cardiovascular disease susceptibility by applying tissue-specific Mendelian randomization
Authors: Taylor Kurt , Davey Smith George , Relton Caroline L , Gaunt Tom R , Richardson Tom G 
Published: April 2018

AbstractBackgroundThe extent to which changes in gene expression can influence cardiovascular disease risk across different tissue types has not yet been systematically explored. We have developed an analytical framework that integrates tissue-specific gene expression, Mendelian randomization and multiple-trait colocalization to develop functional mechanistic insight into the causal pathway from genetic variant to complex trait.MethodsWe undertook a transcriptome-wide association study in a population of young individuals to uncover genetic variants associated with both nearby gene expression and cardiovascular traits. Two-sample Mendelian randomization was then applied using large-scale datasets to investigate whether changes in gene expression within certain tissue types may influence cardiovascular trait variation. We subsequently performed Bayesian multiple-trait colocalization to further interrogate findings and also gain insight into whether DNA methylation, as well as gene expression, may play a role in disease susceptibility.ResultsEight genetic loci were associated with changes in gene expression and early life measures of cardiovascular function. Our Mendelian randomization analysis provided evidence of tissue-specific effects at multiple loci, of which the effects at theADCY3andFADS1loci for body mass index and cholesterol respectively were particularly insightful. Multiple trait colocalization uncovered evidence which suggested that changes in DNA methylation at the promoter region upstream ofFADS1/TMEM258may also play a role in cardiovascular trait variation along with gene expression. Furthermore, colocalization analyses were able to uncover evidence of tissue-specificity, most prominantly betweenSORT1expression in liver tissue and cholesterol levels.ConclusionsDisease susceptibility can be influenced by differential changes in tissue-specific gene expression and DNA methylation. Our analytical framework should prove valuable in elucidating mechanisms in disease, as well as helping prioritize putative causal genes at associated loci where multiple nearby genes may be co-regulated. Future studies which continue to uncover quantitative trait loci for molecular traits across various tissue and cell typse will further improve our capability to understand and prevent disease.
Avoiding misinterpretation of regression lines in allometry: is sexual dimorphism in digit ratio spurious?
Authors: Forstmeier Wolfgang 
Published: April 2018

AbstractThe statistical analysis of allometry (size-dependence of traits) is fraught with difficulty that is often underestimated. In light of some recent controversies about statistical methods and the resulting biological conclusions, I here discuss the interpretation of regression lines and show how to avoid spurious effects. General linear models based on ordinary least square (OLS) regression are often used to quantify sexual dimorphism in a trait of interest that is modelled as a function of sex while controlling for size as a covariate. However, an analysis of artificially generated data where males and females differ in size only, but are otherwise built according to the same principles, shows that the OLS method induces a spurious dimorphism where there is none. Hence, OLS-based general linear models should not be regarded as a fail-proof tool that automatically provides the correct answer to whatever question one has in mind. Here I show how to avoid misinterpretation and how to best proceed with answering the recent debate about sexual dimorphism in digit ratio, a trait that is thought to reflect sex-hormone levels during development. The limited data, currently available to me, suggests that the widely accepted sexual dimorphism in digit ratio might well be only a by-product of an allometric shift in shape, urgently calling for a re-examination in larger data sets on humans and other vertebrates.
CUDA RNAfold
Authors: Langdon W. B. , Lorenz Ronny 
Published: April 2018

AbstractWe add CUDA GPU C program code to RNAfold to enable both it to be run on nVidia gaming graphics hardware and so that many thousands of RNA secondary structures can be computed in parallel. RNAfold predicts the folding pattern for RNA molecules by using O(n3) dynamic programming matrices to minimise the free energy of treating them as a sequence of bases. We benchmark RNAfold on RNA STRAND and artificial sequences of upto 30 000 bases on two GPUs and a GPGPU Tesla. The speed up is variable but up to 14 times.
Agmatine accumulation byPseudomonas aeruginosaclinical isolates confers antibiotic tolerance and dampens host inflammation
Authors: McCurtain Jennifer L. , Gilbertsen Adam J. , Evert Clayton , Williams Bryan J. , Hunter Ryan C. 
Published: April 2018

ABSTRACTIn the cystic fibrosis (CF) airways,Pseudomonas aeruginosaundergoes diverse physiological changes in response to inflammation, antibiotic pressure, oxidative stress and a dynamic bioavailable nutrient pool. These include loss-of-function mutations that result in reduced virulence, altered metabolism and other phenotypes that are thought to confer a selective advantage for long-term persistence. Recently, clinical isolates ofP. aeruginosathat hyperproduce agmatine (decarboxylated arginine) were cultured from individuals with CF. Sputum concentrations of this metabolite were also shown to correlate with disease severity. This raised the question of whether agmatine accumulation might also confer a selective advantage forP. aeruginosa in vivoduring chronic colonization of the lung. Here, we screened a library ofP. aeruginosaCF clinical isolates and found that ~5% of subjects harbored isolates with an agmatine hyperproducing phenotype. Agmatine accumulation was a direct result of mutations inaguA, encoding the arginine deiminase that catalyzes the conversion of agmatine into various polyamines. We also found that agmatine hyperproducing isolates (aguA-) had increased tolerance to the cationic antibiotics gentamicin, tobramycin and colistin relative to their chromosomally complemented strains (aguA+). Finally, we revealed that agmatine diminishes IL-8 production by airway epithelial cells in response to bacterial infection, with a consequent decrease in neutrophil recruitment to the murine airways in an acute pneumonia model. These data highlight a potential new role for bacterial-derived agmatine that may have important consequences for the long-term persistence ofP. aeruginosain the CF airways.
Who is this gene and what does it do? A toolkit for munging transcriptomics data in python
Authors: Fisher Charles K. , Smith Aaron M. , Walsh Jonathan R. 
Published: April 2018

AbstractTranscriptional regulation is extremely complicated. Unfortunately, so is working with transcriptional data. Genes can be referred to using a multitude of different identifiers and are assigned to an ever increasing number of categories. Gene expression data may be available in a variety of units (e.g, counts, RPKMs, TPMs). Batch effects dominate signal, but metadata may not be available. Most of the tools are written in R. Here, we introduce a library, genemunge, that makes it easier to work with transcriptional data in python. This includes translating between various types of gene names, accessing Gene Ontology (GO) information, obtaining expression levels of genes in healthy tissue, correcting for batch effects, and using prior knowledge to select sets of genes for further analysis. Code for genemunge is freely available on Github.
Ranking genome-wide correlation measurements improves microarray and RNA-seq based global and targeted co-expression networks
Authors: Liesecke Franziska , Daudu Dimitri , Dugé de Bernonville Rodolphe , Besseau Sébastien , Clastre Marc , Courdavault Vincent , de Craene Johan-Owen , Crèche Joel , Giglioli-Guivarc’h Nathalie , Glévarec Gaëlle , Pichon Olivier , Dugé de Bernonville Thomas 
Published: April 2018

ABSTRACTCo-expression networks are essential tools to infer biological associations between gene products and predict gene annotation. Global networks can be analyzed at the transcriptome wide scale or after querying them with a set of guide genes to capture the transcriptional landscape of a given pathway in a process named Pathway Level Correlation (PLC). A critical step in network construction remains the definition of gene co-expression. In the present work, we compared how Pearson Correlation Coefficient (PCC), Spearman Correlation Coefficient (SCC), their respective ranked values (Highest Reciprocal Rank (HRR)), Mutual Information (MI) and Partial Correlations (PC) performed on global networks and PLCs. This evaluation was conducted on the model plant Arabidopsis thaliana using microarray and differently pre-processed RNA-seq datasets. We particularly evaluated how dataset x distance measurement combinations performed in 5 PLCs corresponding to 4 well described plant metabolic pathways (phenylpropanoid, carbohydrate, fatty acid and terpene metabolisms) and the cytokinin signaling pathway. Our present work highlights how PCC ranked with HRR is better suited for global network construction and PLC with microarray and RNA-seq data than other distance methods, especially to cluster genes in partitions similar to biological subpathways.
Comparing the financial reporting quality of Chinese and US public firms
Authors: Brown Kareen , Elayan Fayez A. , Li Jingyu , Liu Zhefeng 
Published: April 2018

PurposeThe purpose of this paper is to investigate whether US regulatory actions around reverse mergers (RM) have exerted any spillover effects on the Chinese firms listed in China and whether Chinese firms have exhibited lower financial reporting quality than their US counterparts.Design/methodology/approachTo test the possible spillover effect, this paper calculates three-day cumulative average abnormal returns (CAAR) and the aggregate CAAR for a series of US regulatory actions in 2010 and 2011. The study then compares the accrual quality, conditional conservatism, and information content of accruals of Chinese firms and US firms.FindingsThe paper documents a spillover effect of US actions around RM on Chinese stocks listed in China. Overall results do not support the perception that Chinese firms have lower financial reporting quality than their US counterparts.Research limitations/implicationsWhile this study provides evidence consistent with investors perceiving poor financial reporting quality among Chinese firms, that perception is not justified by empirical evidence.Practical implicationsInvestors need not be overly concerned about the financial reporting quality among the Chinese firms when they make asset allocation decisions.Social implicationsA reality check is important given that perceptions may be outdated, biased, misleading, and costly.Originality/valueThis study puts the financial reporting quality of Chinese firms into perspective helping global investors assess information risk for optimal resource allocation.
Job sharing as a tool for flexible work systems
Authors: Thakur Mahima , Bansal Anjali , Maini Rashmi 
Published: April 2018

PurposeWomen experience insurmountable work life balance challenges, which are the reasons a large percentage of women leak out of the workforce pipeline. Flexible work systems empower women to contribute in meaningful ways to their personal and professional lives. Job sharing is one such strategy of flexible work system, which is proposed as an empowering management practice. This paper aims to create a model of empowerment for housewives. Non-working housewives are the most neglected lot of society in terms of getting their dues.Design/methodology/approachFor the purpose of this study, qualitative study was conducted and data were analyzed using thematic content analysis. Focus group discussions with 266 housewives were conducted to find out their reasons of not joining the full-time workforce, and their willingness to contribute, if they have any. In-depth interviews of nine HR managers were also conducted to assess the openness of the corporate side toward job sharing as a work design. The paper has significance for the corporate as well as for the social and government agencies.FindingsQualitative data collected from 266 housewives presented three core themes – the bottlenecks to employment, the available opportunities of employment and growth and their preferred status of employment. The qualitative data further revealed that though they can easily do with some more money at their disposal, they cannot join in the full-time workforce as they have family responsibilities. They were willing to put in half a day’s work. Thus, the investigators recommended job sharing for them, which would engage this talented human resource and give them back their due for selflessly giving in their most productive years to their families. The interviews of nine HR managers from three multinational companies revealed the skillsets of these housewives as the major concern for putting them back on work.Originality/valueThe paper has significance for the corporate, women as the contingent workforce and social and government agencies.
Improvement of laboratory turnaround time using lean methodology
Authors: Gupta Shradha , Kapil Sahil , Sharma Monica 
Published: April 2018

Purpose
The purpose of this paper is to discuss the implementation of lean methodology to reduce the turnaround time (TAT) of a clinical laboratory in a super speciality hospital. Delays in report delivery lead to delayed diagnosis increased waiting time and decreased customer satisfaction. The reduction in TAT will lead to increased patient satisfaction, quality of care, employee satisfaction and ultimately the hospital’s revenue.

Design/methodology/approach
The generic causes resulting in increasing TAT of clinical laboratories were identified using lean tools and techniques such as value stream mapping (VSM), Gemba, Pareto Analysis and Root Cause Analysis. VSM was used as a tool to analyze the current state of the process and further VSM was used to design the future state with suggestions for process improvements.

Findings
This study identified 12 major non-value added factors for the hematology laboratory and 5 major non-value added factors for the biochemistry lab which were acting as bottlenecks resulting in limiting throughput. A four-month research study by the authors together with hospital quality department and laboratory staff members led to reduction of the average TAT from 180 to 95minutes in the hematology lab and from 268 to 208 minutes in the biochemistry lab.

Practical implications
Very few improvement initiatives in Indian healthcare are based on industrial engineering tools and techniques, which might be due to a lack of interaction between healthcare and engineering. The study provides a positive outcome in terms of improving the efficiency of services in hospitals and identifies a scope for lean in the Indian healthcare sector.

Social implications
Applying lean in the Indian healthcare sector gives its own potential solution to the problem caused, due to a wide gap between lean accessibility and lean implementation. Lean helped in changing the mindset of an organization toward providing the highest quality of services with faster delivery at an optimal cost.

Originality/value
This paper is an effort to reduce the gap between healthcare and industrial engineering and enhancing the use of lean practices in Indian healthcare. The study is motivated toward implementing lean methodology successfully in services.