bluuebunny/crossref_metadata_2025_split huggingface dataset:
Speed, accuracy, sensitivity and quality control choices for detecting clinically relevant microbes in whole blood from patients
Authors: Thornton James , Watts George S. , Youens-Clark Ken , Cranmer Lee D. , Hurwitz Bonnie L. 
Published: February 2019

ABSTRACTInfections are a serious health concern worldwide, particularly in vulnerable populations such as the immunocompromised, elderly, and young. Advances in metagenomic sequencing availability, speed, and decreased cost offer the opportunity to supplement or replace culture-based identification of pathogens with DNA sequence-based diagnostics. Adopting metagenomic analysis for clinical use requires that all aspects of the pipeline are optimized and tested, including data analysis. We tested the accuracy, sensitivity, and resource requirements of Centrifuge within the context of clinically relevant bacteria. Binary mixtures of bacteria showed Centrifuge reliably identified organisms down to 0.1% relative abundance. A staggered mock bacterial community showed Centrifuge outperformed CLARK while requiring less computing resources. Shotgun metagenomes obtained from whole blood in three febrile neutropenia patients showed Centrifuge could identify both bacteria and viruses as part of a culture-free workflow. Finally, Centrifuge results changed minimally by eliminating time-consuming read quality control and host screening steps.AUTHOR SUMMARYImmunocompromised patients, such as those with febrile neutropenia (FN), are susceptible to infections, yet cultures fail to identify causative organisms ~80% of the time. High-throughput metagenomic sequencing offers a promising approach for identifying pathogens in clinical samples. Mining through metagenomes can be difficult given the volume of reads, overwhelming human contamination, and lack of well-defined bioinformatics methods. The goal of our study was to assess Centrifuge, a leading tool for the identification and quantitation of microbes, and provide a streamlined bioinformatics workflow real-word data from FN patient blood samples. To ensure the accuracy of the workflow we carefully examined each step using known bacterial mixtures that varied by genetic distance and abundance. We show that Centrifuge reliably identifies microbes present at just 1% relative abundance and requires substantially less computer time and resource than CLARK. Moreover, we found that Centrifuge results changed minimally by quality control and host-screening allowing for further reduction in compute time. Next, we leveraged Centrifuge to identify viruses and bacteria in blood draws for three FN patients, and confirmed suspected pathogens using genome coverage plots. We developed a web-based tool in iMicrobe and detailed protocols to promote re-use.
MakeHub: Fully automated generation of UCSC Genome Browser Assembly Hubs
Authors: Hoff Katharina J. 
Published: February 2019

AbstractNovel genomes are today often annotated by small consortia or individuals whose background is not from bioinformatics. This audience requires tools that are easy to use. This need had been addressed by several genome annotation tools and pipelines. Visualizing resulting annotation is a crucial step of quality control. The UCSC Genome Browser is a powerful and popular genome visualization tool. Assembly Hubs allow browsing genomes that are hosted locally via already available UCSC Genome Browser servers. The steps for creating custom Assembly Hubs are well documented and the required tools are publicly available. However, the number of steps for creating a novel Assembly Hub is large. In some cases the format of input files needs to be adapted which is a difficult task for scientists without programming background. Here, we describe the novel command line tool MakeHub that generates Assembly Hubs for the UCSC Genome Browser in a fully automated fashion. The pipeline also allows extending previously created Hubs by additional tracks.MakeHub is freely available for download from https://github.com/Gaius-Augustus/MakeHub.Contactkatharina.hoff@uni-greifswald.de
Branching Networks Can Have Opposing Influences on Genetic Variation in Riverine Metapopulations
Authors: Chiu Ming-Chih , Li Bin , Nukazawa Kei , Resh Vincent H. , Carvajal Thaddeus , Watanabe Kozo 
Published: February 2019

AbstractAimFractal networks, represented by branching complexity in rivers, are ubiquitous in nature. In rivers, the number of either distal (e.g., in headwater streams) or confluent (e.g., in mainstems) locations can be increased along with their branching complexity. Distal- or confluent-spatial locations can result in fewer or greater corridor linkages that can alter genetic divergence at the metapopulation scale. These mechanisms underlying the resulting genetic structuring remain poorly understood at the metapopulation scale, particularly in terms of the roles of species-specific dispersal traits. The objective of this study is to mechanistically understand how branching complexity can simultaneously influence genetic divergence in opposite directions.LocationNortheastern JapanMethodsTo evaluate the integrated influences of network complexity and species dispersal on genetic divergence among populations at the catchment scale, we conducted simulation modelling on a mechanistic framework based on Bayesian inference by adapting empirical genetic data from four macroinvertebrate species. Simulations were then done using empirical and virtual species-characteristics on virtual river networks.ResultsOur novel simulation showed that both greater landscape connectivity (resulting from shorter watercourse distance) and greater isolation of distal locations occurred in the more-branched river networks. These two spatial features have negative and positive influences on genetic divergence, with their relative importance varying among different species and dispersal characteristics. Specifically, genetic divergence at the metapopulation scale increased for species having higher downstream-biased dispersal but decreased for species having higher upstream-biased dispersal. Distal populations (e.g., in headwaters) have higher genetic independence when downstream-biased asymmetry is higher.Main conclusionsWe found a strong association between species dispersal and evolutionary processes such as gene flow and genetic drift. This association mediates the pervasive influences of branching complexity on genetic-divergence in the metapopulation. It also highlights the importance of considering species dispersal-patterns when developing management strategies in the face of rapid environmental-change scenarios.
Egalitarian binding partners, Dynein Light Chain and Bicaudal-D, act sequentially to link mRNA to the Dynein motor
Authors: Goldman Chandler H. , Veeranan-Karmegam Rajalakshmi , Neiswender Hannah , Gonsalvez Graydon B. 
Published: February 2019

AbstractA widely conserved mechanism of polarity establishment is the localization of mRNA to specific cellular regions. While it is clear that many mRNAs are transported to their destinations along microtubule tracks, much less is known regarding the mechanism by which these mRNAs are linked to microtubule motors. The RNA binding protein Egalitarian (Egl) is necessary for localization of several mRNAs inDrosophilaoocytes and embryos. In addition to binding RNA, Egl also interacts with Dynein light chain (Dlc) and Bicaudal-D (BicD). The role of Dlc and BicD in mRNA localization has remained elusive. Like Egl, both proteins are required for oocyte specification. Null alleles in these genes result in an oogenesis block. In this report, we used an innovative approach to overcome the oogenesis block. Our findings reveal that the primary function of Dlc is to promote Egl dimerization. Loss of dimerization compromises the ability of Egl to bind RNA. Consequently, Egl is not bound to cargo, and is not able to efficiently associate with BicD and the Dynein motor. Our results therefore identify the key molecular steps required for assembling a localization competent mRNP.
A method for genome-wide genealogy estimation for thousands of samples
Authors: Speidel Leo , Forest Marie , Shi Sinan , Myers Simon R. 
Published: February 2019

AbstractKnowledge of genome-wide genealogies for thousands of individuals would simplify most evolutionary analyses for humans and other species, but has remained computationally infeasible. We developed a method, Relate, scaling to > 10,000 sequences while simultaneously estimating branch lengths, mutational ages, and variable historical population sizes, as well as allowing for data errors. Application to 1000 Genomes Project haplotypes produces joint genealogical histories for 26 human populations. Highly diverged lineages are present in all groups, but most frequent in Africa. Outside Africa, these mainly reflect ancient introgression from groups related to Neanderthals and Denisovans, while African signals instead reflect unknown events, unique to that continent. Our approach allows more powerful inferences of natural selection than previously possible. We identify multiple novel regions under strong positive selection, and multi-allelic traits including hair colour, BMI, and blood pressure, showing strong evidence of directional selection, varying among human groups.
Immune Responses to Human Induced Pluripotent Stem Cells and their Derived Myogenic Progenitors Are Mediated by Different Mechanisms in Humanized Mice
Authors: Benabdallah Basma , Désaulniers-Langevin Cynthia , Goyer Marie-Lyn , Colas Chloé , Maltais Chantale , Li Yuanyi , Guimond Jean V. , Tremblay Jacques P , Haddad Elie , Beauséjour Christian 
Published: February 2019

ABSTRACTIt is still unclear if immune responses will compromise the large scale utilization of cell therapies derived from human induced pluripotent stem cells (hiPSCs). To answer this question, we used humanized mouse models and evaluated the engraftment in skeletal muscle of myoblasts derived either directly from a muscle biopsy or differentiated from hiPSCs or fibroblasts. Our results showed that while allogeneic grafts were rejected, engraftment of autologous cells was tolerated, indicating reprogramming and differentiation procedures are not immunogenic. We also demonstrated that hiPSC-derived myogenic progenitors, in opposition to hiPSCs, are not targeted by natural killer (NK) cells both in vitro and in vivo. Yet, adoptive transfer of NK cells can prevent the formation of hiPSC-derived teratoma. Overall, our findings suggest that hiPSC-derived muscular therapies will be tolerated in presence of a competent human immune system and highlight the risk of forming a teratoma if using partially differentiated autologous human cells.HighlightshiPSC-derived myofibers are tolerated in autologous humanized mouse modelsInfiltration of autologous T cells is not predictive of successful skeletal muscle engraftmentAdoptive transfer of NK cells prevents the formation of hiPSCs derived teratomasNK cells are unable to reject established teratomas
Parthenolide Covalently Targets and Inhibits Focal Adhesion Kinase in Breast Cancer Cells
Authors: Berdan Charles A. , Ho Raymond , Lehtola Haley S. , To Milton , Hu Xirui , Huffman Tucker R. , Petri Yana , Altobelli Chad R. , Demeulenaere Sasha G. , Olzmann James A. , Maimone Thomas J. , Nomura Daniel K. 
Published: February 2019

AbstractParthenolide, a natural product from the feverfew plant and member of the large family of sesquiterpene lactones, exerts multiple biological and therapeutic activities including anti-inflammatory and anti-cancer effects. Herein, we further study parthenolide mechanism of action using activity-based protein profiling (ABPP)-based chemoproteomic platforms to map additional covalent targets engaged by parthenolide in human breast cancer cells. We find that parthenolide, as well as other related exocyclic methylene lactone-containing sesquiterpenes, covalently modify cysteine 427 (C427) of focal adhesion kinase 1 (FAK1) leading to impairment of FAK1-dependent signaling pathways and breast cancer cell proliferation, survival, and motility. These studies reveal a novel functional target exploited by members of a large family of anticancer natural products.
Characterization of single gene copy number variants in schizophrenia
Authors: Szatkiewicz Jin P. , Fromer Menachem , Nonneman Randal J. , Ancalade NaEshia , Johnson Jessica S. , Stahl Eli A. , Rees Elliott , Bergen Sarah , Hultman Christina , Kirov George , O’Donovan Michael , Owen Michael , Holmans Peter , Sklar Pamela , Sullivan Patrick F. , Purcell Shaun M. , Crowley James J. , Ruderfer Douglas M. 
Published: February 2019

AbstractGenetic studies of schizophrenia (SCZ) have now implicated numerous genomic loci that contribute to risk including several copy number variants (CNV) of large effect and hundreds of associated loci of small effect. However, in only a few cases has a specific gene been clearly identified. Rare CNV that affect only a single gene offer a potential avenue to discovering specific SCZ risk genes. Here, we use CNV generated from exome-sequencing of 4,913 SCZ cases and 6,188 controls in a homogenous Swedish cohort to assess the contribution of single-gene deletions and duplications to SCZ risk. As previously seen, we found an excess of rare deletions (p = 0.0004) and duplications (p = 0.0006) in SCZ cases compared to controls. When limiting to only single-gene CNV we identified nominally significant excess of deletions (p = 0.04) and duplications (p = 0.03). In an effort to increase the number of single-gene CNV, we reduced strict filtering criteria but required support from two independent CNV calling methods to create an expanded set that showed a significant burden of deletions in 11 out of 22 gene sets previously implicated in SCZ and in the combined set of genes across those sets (p = 0.008). Finally, for the significantly enriched set of voltage-gated calcium channels, we performed an extensive validation of all deletions generated from exome-sequencing as well as any deletion with evidence from previously analyzed genotyping arrays. In total, 4 exonic, single-gene deletions validated in cases and none in controls (p = 0.039), of which all were identified by exome-sequencing. Broadly, these results point to the potential contribution of single-gene CNV to SCZ and the added value of a deeper dive into CNV calls from exome-sequencing.
Detection and assembly of novel sequence insertions using Linked-Read technology
Authors: Meleshko Dmitry , Marks Patrick , Williams Stephen , Hajirasouliha Iman 
Published: February 2019

AbstractMotivationEmerging Linked-Read (aka read-cloud) technologies such as the 10x Genomics Chromium system have great potential for accurate detection and phasing of largescale human genome structural variations (SVs). By leveraging the long-range information encoded in Linked-Read sequencing, computational techniques are able to detect and characterize complex structural variations that are previously undetectable by short-read methods. However, there is no available Linked-Read method for detection and assembly of novel sequence insertions, DNA sequences present in a given sequenced sample but missing in the reference genome, without requiring whole genome de novo assembly. In this paper, we propose a novel integrated alignment-based and local-assembly-based algorithm, Novel-X, that effectively uses the barcode information encoded in Linked-Read sequencing datasets to improve detection of such events without the need of whole genome de novo assembly. We evaluated our method on two haploid human genomes, CHM1 and CHM13, sequenced on the 10x Genomics Chromium system. These genomes have been also characterized with high coverage PacBio long-reads recently. We also tested our method on NA12878, the wellknown HapMap CEPH diploid genome and the child genome in a Yoruba trio (NA19240) which was recently studied on multiple sequencing platforms. Detecting insertion events is very challenging using short reads and the only viable available solution is by long-read sequencing (e.g. PabBio or ONT). Our experiments, however, show that Novel-X finds many insertions that cannot be found by state of the art tools using short-read sequencing data but present in PacBio data. Since Linked-Read sequencing is significantly cheaper than long-read sequencing, our method using Linked-Reads enables routine large-scale screenings of sequenced genomes for novel sequence insertions.AvailabilitySoftware is freely available at https://github.com/1dayac/novel_insertionsContactimh2003@med.cornell.eduSupplementary informationSupplementary data are available at https://github.com/1dayac/novel_insertions_supplementary
Whole genomic sequencing as a tool for diagnosis of drug and multidrug-resistance tuberculosis in an endemic region in Mexico
Authors: Madrazo-Moya Carlos Francisco , Cancino-Muñoz Irving , Cuevas-Cordoba Betzaida , Gonzalez-Covarrubias Vanessa , Barbosa-Amezcua Martín , Soberón Xavier , Muñiz-Salazar Raquel , Martínez-Guarneros Armando , Backer Claudia , Zarrabal-Meza José , Sampieri-Ramirez Clara , Enciso-Moreno Antonio , Lauzardo Michael , Comas Iñaki , Zenteno-Cuevas Roberto 
Published: February 2019

AbstractBackgroundWhole genome sequencing (WGS) has been proposed as a tool for diagnosing drug resistance in tuberculosis. However, reports of its effectiveness in endemic countries with important numbers of drug resistance are scarce. The goal of this study was to evaluate the effectiveness of this procedure in isolates from a tuberculosis endemic region in Mexico.MethodsWGS analysis was performed in 81 tuberculosis positive clinical isolates with a known phenotypic profile of resistance against first-line drugs (isoniazid, rifampin, ethambutol, pyrazinamide and streptomycin). Mutations related to drug resistance were identified for each isolate; drug resistant genotypes were predicted and compared with the phenotypic profile. Genotypes and transmission clusters based on genetic distances were also characterized.FindingsPrediction by WGS analysis of resistance against isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin showed sensitivity values of 84%, 96%, 71%, 75% and 29%, while specificity values were 100%, 94%, 90%, 90% and 98%, respectively. Prediction of multidrug resistance showed a sensitivity of 89% and specificity of 97%. Moreover, WGS analysis revealed polymorphisms related to second-line drug resistance, enabling classification of eight and two clinical isolates as pre- and extreme drug-resistant cases, respectively.Four lineages were identified in the population (L1, L2, L3 and L4). The most frequent of these was L4, which included 90% (77) of the isolates. Six transmission clusters were identified; the most frequent was TC6, which included 13 isolates with a L4.1.1 and a predominantly multidrug-resistant condition.ConclusionThe results illustrate the utility of WGS for establishing the potential for prediction of resistance against first and second line drugs in isolates of tuberculosis from the region. They also demonstrate the feasibility of this procedure for use as a tool to support the epidemiological surveillance of drug- and multidrug-resistant tuberculosis.
Biochemical properties and in vitro biological activities of extracts from seven folk medicinal plants growing wild in southern Tunisia
Authors: Tlili Hajer , Hanen Najjaa , Arfa Abdelkerim Ben , Neffati Mohamed , Boubakri Abdelbasset , Buonocore Daniela , Dossena Maurizia , Verri Manuela , Doria Enrico 
Published: February 2019

ABSTRACTRecently, much attention has been paid to the extracts obtained from plant species in order to analyse their biological activities. Due to the climate diversity in Tunisia, the traditional pharmacopoeia consists of a wide arsenal of medicinal plant species since long used in folk medicine, in foods as spices, and in aromatherapy. Although many of these species are nearly facing extinction, only a small proportion of them have been scientifically studied. Therefore, this study explores the biochemical properties of seven spontaneous plants, which were harvested in the arid Tunisian desert: Marrubium vulgare L., Rhus tripartita (Ucria) D.C., Thymelaea hirsute (L.) Endl., Plantago ovata Forsk., Herniaria fontanesii J. Gay., Ziziphus lotus and Hyoscyamus albus. Extracts from these plants were found to contain different types of secondary metabolites (polyphenols, flavonoids, condensed tannins, crude saponins, carotenoids and alkaloids) that are involved in important biological activities. The biological activity of the extracts obtained from each Tunisian plant was assessed: first of all, leukaemia and colon cancer cell lines (K-562 and CaCo-2 respectively) were treated with different concentrations of extracts, and then the anti-proliferative activity was observed. The results showed, in particular, how the plant extract from Rhus tripartita significantly inhibits cell proliferation, especially on the K-562 tumour cell line. Subsequently, the anti-inflammatory activity was also assessed, and the results showed that Herniaria fontanesii and Marrubium vulgare possess the highest activity in the group of analysed plants. Finally, the greatest acetylcholinesterase inhibitory effect was exhibited by the extract obtained from Rhus tripartita.In conclusion, all the Tunisian plants we analysed were shown to contain a remarkable amount of different bio-active compounds, thus confirming their involvement in several biological activities. Rhus tripartita and Ziziphus lotus were shown to be particularly effective in anti-proliferative activity, while Herniaria fontanesii were shown to have the best anti-inflammatory activity.
Identifying the best practices in green operations strategy of hospitals
Authors: Migdadi Yazan Khalid Abed-Allah , Omari Abeer Ahmad 
Published: February 2019

Purpose
The purpose of this paper is to identify the best practices in the green operations strategy of hospitals.

Design/methodology/approach
A total of 25 cases from all over the world were investigated. The source of data was the annual sustainability reports that were retrieved from Global Reporting Initiative (GRI) database. The present research adopted the benchmarking method and the quantitative content analysis of sustainability reports. Then, the indicative models of best practices were developed by using two analysis approaches; within cluster analysis and across clusters analysis.

Findings
This study found four major taxonomies of green operation strategy in hospitals. The significant strategic groups were resources/waste management; electrical power management; non-hazardous waste management; and emissions/resources management. Indicative models for the relationship between actions and key green performance indicators were developed in the two stages of the analysis.

Originality/value
The best practices of green operations strategies in hospitals have not so far been investigated. Countries around the world should obey the new regulations for their environmental footprint; if they do, it will exert pressure on all sectors and organizations at all levels to take immediate steps to measure and improve their environmental performance.