bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alignment-free filtering for cfNA fusion fragments
Authors: Yang Xiao , Saito Yasushi , Rao Arjun , Kim Hyunsung John , Singh Pranav , Scott Eric , Larson Matthew , Pan Wenying , Desai Mohini , Hubbell Earl 
Published: May 2019

Abstract

Motivation
Cell-free nucleic acid (cfNA) sequencing data require improvements to existing fusion detection methods along multiple axes: high depth of sequencing, low allele fractions, short fragment lengths and specialized barcodes, such as unique molecular identifiers.

Results
AF4 was developed to address these challenges. It uses a novel alignment-free kmer-based method to detect candidate fusion fragments with high sensitivity and orders of magnitude faster than existing tools. Candidate fragments are then filtered using a max-cover criterion that significantly reduces spurious matches while retaining authentic fusion fragments. This efficient first stage reduces the data sufficiently that commonly used criteria can process the remaining information, or sophisticated filtering policies that may not scale to the raw reads can be used. AF4 provides both targeted and de novo fusion detection modes. We demonstrate both modes in benchmark simulated and real RNA-seq data as well as clinical and cell-line cfNA data.

Availability and implementation
AF4 is open sourced, licensed under Apache License 2.0, and is available at: https://github.com/grailbio/bio/tree/master/fusion.
Establishment of novel monoclonal antibodies for identification of type A spermatogonia in teleosts†
Authors: Hayashi Makoto , Ichida Kensuke , Sadaie Sakiko , Miwa Misako , Fujihara Ryo , Nagasaka Yasuhiko , Yoshizaki Goro 
Published: May 2019

AbstractWe recently established a germ cell transplantation system in salmonids. Donor germ cells transplanted into the body cavity of recipient embryos migrate toward and are incorporated into the recipient gonad, where they undergo gametogenesis. Among the various types of testicular germ cells, only type A spermatogonia (A-SG) can be incorporated into the recipient gonads. Enriching for A-SG is therefore important for improving the efficiency of germ cell transplantation. To enrich for A-SG, an antibody against a cell surface marker is a convenient and powerful approach used in mammals; however, little is known about cell surface markers for A-SG in fish. To that end, we have produced novel monoclonal antibodies (mAbs) against cell-surface molecules of rainbow trout (Oncorhynchus mykiss) A-SG. We inoculated mice with living A-SG isolated from pvasa-GFP transgenic rainbow trout using GFP-dependent flow cytometry. By fusing lymph node cells of the inoculated mice with myeloma cells, we generated 576 hybridomas. To identify hybridomas that produce mAbs capable of labeling A-SG preferentially and effectively, we screened them using cell ELISA, fluorescence microscopy, and flow cytometry. We thereby identified two mAbs that can label A-SG. By using flow cytometry with these two antibodies, we could enrich for A-SG with transplantability to recipient gonads from amongst total testicular cells. Furthermore, one of these mAbs could also label zebrafish (Danio rerio) spermatogonia. Thus, we expect these monoclonal antibodies to be powerful tools for germ cell biology and biotechnology.
What has single-cell RNA-seq taught us about mammalian spermatogenesis?
Authors: Suzuki Shinnosuke , Diaz Victoria D , Hermann Brian P 
Published: May 2019

AbstractMammalian spermatogenesis is a complex developmental program that transforms mitotic testicular germ cells (spermatogonia) into mature male gametes (sperm) for production of offspring. For decades, it has been known that this several-weeks-long process involves a series of highly ordered and morphologically recognizable cellular changes as spermatogonia proliferate, spermatocytes undertake meiosis, and spermatids develop condensed nuclei, acrosomes, and flagella. Yet, much of the underlying molecular logic driving these processes has remained opaque because conventional characterization strategies often aggregated groups of cells to meet technical requirements or due to limited capability for cell selection. Recently, a cornucopia of single-cell transcriptome studies has begun to lift the veil on the full compendium of gene expression phenotypes and changes underlying spermatogenic development. These datasets have revealed the previously obscured molecular heterogeneity among and between varied spermatogenic cell types and are reinvigorating investigation of testicular biology. This review describes the extent of available single-cell RNA-seq profiles of spermatogenic and testicular somatic cells, how those data were produced and evaluated, their present value for advancing knowledge of spermatogenesis, and their potential future utility at both the benchtop and bedside.
Why only humans and social insects have a division of labour
Authors: Pagano Ugo 
Published: May 2019

AbstractHumans and social insects are located at extreme points of the set of possible evolutionary paths. However, they share a complex division of labour and comprise a large proportion of the earth’s biomass. These observations prompt two questions: If there are evident evolutionary advantages of cooperation and specialisation, why have only few species been able to increase their fitness in this way? Why have these characteristics emerged as such extremely different forms of life? In order to answer these two questions, we will focus on possible ‘transition societies’ in the evolutionary paths towards social species. We will argue that, in both the human and social insect cases, sexual selection had a crucial role in the development of the division of labour and entailed that the division of labour required either minimum or maximum unitary investments in the offspring. The species located in between these two extremes could not exploit the advantages of specialisation.
Toward a Sign Language-Friendly Questionnaire Design
Authors: Bosch-Baliarda Marta , Soler Vilageliu Olga , Orero Pilar 
Published: May 2019

AbstractThe United Nations Convention on the Rights of Persons with Disabilities requests “Nothing about us without us.” User-centered methodological research is the way to comply with this convention. Interaction with the deaf community must be in their language; hence sign language questionnaires are one of the tools to gather data. While in the past interacting with an online video questionnaire was out of the question, today it is a reality. This article focuses on the design of an interactive video questionnaire for sign language users. From a historical review of the existing literature on research methods and previous sign language questionnaire, the article examines the design features affected in the process of making accessible questionnaires with sign language videos: format and layout. The article finishes with the solution developed toward mainstreaming sign language questionnaires in order to contribute to a diverse and inclusive society for all citizens.
Disparities in esophageal cancer: less treatment, less surgical resection, and poorer survival in disadvantaged patients
Authors: Schlottmann Francisco , Gaber Charles , Strassle Paula D , Herbella Fernando A M , Molena Daniela , Patti Marco G 
Published: May 2019

SUMMARY
The incidence of esophageal cancer has increased steadily in the last decades in the United States. The aim of this paper was to characterize disparities in esophageal cancer treatment in different racial and socioeconomic population groups and compare long-term survival among different treatment modalities. A retrospective analysis of the National Cancer Database was performed including adult patients (≥18 years old) with a diagnosis of resectable (stages I–III) esophageal cancer between 2004 and 2015. Multivariable logistic regression models were used to determine the odds of being offered no treatment at all and surgical treatment across race, primary insurance, travel distance, income, and education levels. Multivariable Cox proportional hazards models were used to compare 5-year survival rates across different treatment modalities. A total of 60,621 esophageal cancer patients were included. Black patients, uninsured patients, and patients living in areas with lower levels of education were more likely to be offered no treatment. Similarly, black race, female patients, nonprivately insured patients, and those living in areas with lower median residential income and lower education levels were associated with lower rates of surgery. Patients receiving surgical treatment, compared to both no treatment and definitive chemoradiation, had significant better long-term survival in stage I, II, and III esophageal cancer. In conclusion, underserved patients with esophageal cancer appear to have limited access to surgical care, and are, in fact, more likely to not be offered any treatment at all. Considering the survival benefits associated with surgical resection, greater public health efforts to reduce disparities in esophageal cancer are needed.
Management of cardiogenic shock complicating myocardial infarction: an update 2019
Authors: Thiele Holger , Ohman E Magnus , de Waha-Thiele Suzanne , Zeymer Uwe , Desch Steffen 
Published: May 2019

Abstract
Cardiogenic shock (CS) remains the most common cause of death in patients admitted with acute myocardial infarction (AMI) and mortality remained nearly unchanged in the range of 40–50% during the last two decades. Early revascularization, vasopressors and inotropes, fluids, mechanical circulatory support, and general intensive care measures are widely used for CS management. However, there is only limited evidence for any of the above treatment strategies except for revascularization and the relative ineffectiveness of intra-aortic balloon pumping. This updated review will outline the management of CS complicating AMI with major focus on state-of-the art treatment.
De novo transcriptome assembly: A comprehensive cross-species comparison of short-read RNA-Seq assemblers
Authors: Hölzer Martin , Marz Manja 
Published: May 2019

Abstract

Background
In recent years, massively parallel complementary DNA sequencing (RNA sequencing [RNA-Seq]) has emerged as a fast, cost-effective, and robust technology to study entire transcriptomes in various manners. In particular, for non-model organisms and in the absence of an appropriate reference genome, RNA-Seq is used to reconstruct the transcriptome de novo. Although the de novo transcriptome assembly of non-model organisms has been on the rise recently and new tools are frequently developing, there is still a knowledge gap about which assembly software should be used to build a comprehensive de novo assembly.

Results
Here, we present a large-scale comparative study in which 10 de novo assembly tools are applied to 9 RNA-Seq data sets spanning different kingdoms of life. Overall, we built &gt;200 single assemblies and evaluated their performance on a combination of 20 biological-based and reference-free metrics. Our study is accompanied by a comprehensive and extensible Electronic Supplement that summarizes all data sets, assembly execution instructions, and evaluation results. Trinity, SPAdes, and Trans-ABySS, followed by Bridger and SOAPdenovo-Trans, generally outperformed the other tools compared. Moreover, we observed species-specific differences in the performance of each assembler. No tool delivered the best results for all data sets.

Conclusions
We recommend a careful choice and normalization of evaluation metrics to select the best assembling results as a critical step in the reconstruction of a comprehensive de novo transcriptome assembly.
A highly predictive signature of cognition and brain atrophy for progression to Alzheimer's dementia
Authors: Tam Angela , Dansereau Christian , Iturria-Medina Yasser , Urchs Sebastian , Orban Pierre , Sharmarke Hanad , Breitner John , Bellec Pierre ,   Alzheimer's Disease Neuroimaging Initiative
Published: May 2019

Abstract

Background
Clinical trials in Alzheimer's disease need to enroll patients whose cognition will decline over time, if left untreated, in order to demonstrate the efficacy of an intervention. Machine learning models used to screen for patients at risk of progression to dementia should therefore favor specificity (detecting only progressors) over sensitivity (detecting all progressors), especially when the prevalence of progressors is low. Here, we explore whether such high-risk patients can be identified using cognitive assessments and structural neuroimaging by training machine learning tools in a high-specificity regime.

Results
A multimodal signature of Alzheimer's dementia was first extracted from the ADNI1 dataset. We then validated the predictive value of this signature on ADNI1 patients with mild cognitive impairment (N = 235). The signature was optimized to predict progression to dementia over 3 years with low sensitivity (55.1%) but high specificity (95.6%), resulting in only moderate accuracy (69.3%) but high positive predictive value (80.4%, adjusted for a “typical” 33% prevalence rate of true progressors). These results were replicated in ADNI2 (N = 235), with 87.8% adjusted positive predictive value (96.7% specificity, 47.3% sensitivity, 85.1% accuracy).

Conclusions
We found that cognitive measures alone could identify high-risk individuals, with structural measurements providing a slight improvement. The signature had comparable receiver operating characteristics to standard machine learning tools, yet a marked improvement in positive predictive value was achieved over the literature by selecting a high-specificity operating point. The multimodal signature can be readily applied for the enrichment of clinical trials.
How altering the modular architecture affects aspects of lectin activity: case study on human galectin-1
Authors: Kutzner Tanja J , Gabba Adele , FitzGerald Forrest G , Shilova Nadezhda V , García Caballero Gabriel , Ludwig Anna-Kristin , Manning Joachim C , Knospe Clemens , Kaltner Herbert , Sinowatz Fred , Murphy Paul V , Cudic Mare , Bovin Nicolai V , Gabius Hans-Joachim 
Published: May 2019

AbstractDiscoveries on involvement of glycan–protein recognition in many (patho)physiological processes are directing attention to exploring the significance of a fundamental structural aspect of sugar receptors beyond glycan specificity, i.e., occurrence of distinct types of modular architecture. In order to trace clues for defining design–functionality relationships in human lectins, a lectin's structural unit has been used as source material for engineering custom-made variants of the wild-type protein. Their availability facilitates comparative analysis toward the stated aim. With adhesion/growth-regulatory human galectin-1 as example, the strategy of evaluating how changes of its design (here, from the homodimer of non-covalently associated domains to (i) linker-connected di- and tetramers and (ii) a galectin-3-like protein) affect activity is illustrated by using three assay systems of increasing degree of glycan complexity. Whereas calorimetry with two cognate disaccharides and array testing with 647 (glyco)compounds disclosed no major changes, galectin histochemical staining profiles of tissue sections that present natural glycome complexity revealed differences between wild-type and linker-connected homo-oligomers as well as between the galectin-3-like variant and wild-type galectin-3 for cell-type positivity, level of intensity at the same site and susceptibility for inhibition by a bivalent glycocompound. These results underscore the strength of the documented approach. Moreover, they give direction to proceed to (i) extending its application to other members of this lectin family, especially galectin-3 and (ii) then analyzing impact of architectural alterations on cell surface lattice formation and ensuing biosignaling systematically, considering the variants’ potential for translational medicine.
Presence of NDM in non-E. coli Enterobacteriaceae in the poultry production environment
Authors: Zhang Rongmin , Li Jiyun , Wang Yang , Shen Jianzhong , Shen Zhangqi , Wang Shaolin 
Published: May 2019

Abstract

Objectives
Characterization of non-Escherichia coli NDM-carrying Enterobacteriaceae in the poultry production environment.

Methods
A total of 36 NDM-positive Enterobacteriaceae (22 Klebsiella pneumoniae, 13 Enterobacter cloacae and 1 Salmonella enterica) were isolated from a chicken farm and WGS was conducted using Illumina Hiseq2500. The genomic characterization of the isolates acquired through WGS analysis included the genomic context-flanking blaNDM genes, MLST, the antibiotic resistance genes (ARGs) and replicon types of plasmids. WGS information for another 73 K. pneumoniae isolates from different sources was retrieved from GenBank and then combined with isolates in this study for comparative genomic and phylogenetic analysis.

Results
Three types of genetic environment carrying blaNDM were identified in 36 non-E. coli Enterobacteriaceae isolates. Sequence comparison analysis indicated these genetic environments were completely identical to our previous findings. WGS further revealed three major types of plasmids (IncFIB, IncX3 and IncFII) from these isolates and the phylogenetic analysis suggested several K. pneumoniae isolates with ST11, ST37 and ST147 from the commercial chicken farm that were closely related to isolates of human origin.

Conclusions
The blaNDM-harbouring genetic contexts were identified not only in E. coli, but also in K. pneumoniae, E. cloacae and S. enterica, which may indicate that blaNDM has been widely disseminated to non-E. coli Enterobacteriaceae species in animal farms. The close relationship of K. pneumoniae isolates from different origins suggests they could serve as a key vehicle for the transfer of ARGs between humans and food animal production environments.
Heterogeneous resistance to colistin in Enterobacter cloacae complex due to a new small transmembrane protein
Authors: Huang Liang , Feng Yu , Zong Zhiyong 
Published: May 2019

Abstract

Background
Enterobacter strains can display heterogeneous resistance (heteroresistance) to colistin but the mechanisms remain largely unknown. We investigated potential mechanisms of colistin heteroresistance in an Enterobacter clinical strain, WCHECl-1060, and found a new mechanism.

Methods
Strain WCHECl-1060 was subjected to WGS to identify known colistin resistance mechanisms. Tn5 insertional mutagenesis, gene knockout and complementation and shotgun cloning were employed to investigate unknown colistin heteroresistance mechanisms. RNA sequencing was performed to link the newly identified mechanism with known ones.

Results
We showed that the phoP gene [encoding part of the PhoP-PhoQ two-component system (TCS)], the dedA(Ecl) gene (encoding an inner membrane protein of the DedA family) and the tolC gene (encoding part of the AcrAB-TolC efflux pump) are required for colistin heteroresistance. We identified a new gene, ecr, encoding a 72 amino acid transmembrane protein, which was able to mediate colistin heteroresistance. We then performed RNA sequencing and transcriptome analysis and found that in the presence of ecr the expression of phoP and the arnBCADTEF operon, which synthesizes and transfers l-Ara4N to lipid A, was increased significantly.

Conclusions
The small protein encoded by ecr represents a new colistin heteroresistance mechanism and is likely to mediate colistin heteroresistance via the PhoP-PhoQ TCS to act on the arnBCADTEF operon.
Association of Serum Cholesterol Ester Transfer Protein Levels with Taq IB Polymorphism in Acute Coronary Syndrome
Authors: Amer Noha N , Shaaban Gamal M 
Published: May 2019

Abstract
Information on the relationship between circulating cholesteryl ester transfer protein (CETP) levels and coronary heart disease (CHD) incidence (and also, therefore, acute coronary syndrome [ACS]) is conflicting. Many studies have been published concerning this relationship, most of which have incompatible results. In our study, we aimed to determine serum CETP levels in subject individuals with ACS and healthy control individuals, and the association of those levels with Taq IB polymorphism. The current study was conducted with 62 hospitalized patients who had been diagnosed with ACS and 26 controls. All subjects were selected from a previous study of which we are among the coauthors. Serum CETP levels were determined by quantitative enzyme-linked immunosorbent assay (ELISA). The mean serum CETP levels in all patients were significantly higher than those in controls. CETP TaqIB polymorphism affected serum CETP levels, with higher serum CETP for the GA genotype in both groups than in other genotypes. Although the AA genotype showed higher CETP levels than the GG genotype in patients with ACS, the GG showed higher CETP than the AA in healthy controls. Our results support an association between high serum CETP and ACS incidence. Our study helped address some of the controversies regarding the relationship of serum CETP mass to atherosclerosis, in addition to the association of ACS occurrence with circulating CETP levels.
‘Come and See the Blood in the Streets’: Luciano Berio, ‘Coro’, and the Affective Staging of the One-Crowd
Authors: Davis James 
Published: May 2019

Abstract
Luciano Berio’s most substantial work from the 1970s was Coro (1976)—an hour-long piece for chorus and orchestra. This work has attracted a small literature that attempts to understand it in terms of the philosophical framework of the French theorists Gilles Deleuze and Félix Guattari. These Deleuzo-Guattari speculations have remained rather abstract; specifically, they have not attempted to relate the work to the concrete political context of 1970s Italy. This essay attempts to enrich our understanding of Berio by relating the choral work to this political context. In so doing, it will contribute towards a more thorough understanding of the political significance and functioning of the works of one of Italy’s leading composers, and suggest a striking political alignment between his musical production and the radical extra-parliamentary political activity of the 1970s.
Detection of circumstellar helium in Type Iax progenitor systems
Authors: Jacobson-Galán Wynn V , Foley Ryan J , Schwab Josiah , Dimitriadis Georgios , Dong Shawfeng , Jha Saurabh W , Kasen Daniel , Kilpatrick Charles D , Thomas Rollin 
Published: May 2019

ABSTRACT
We present direct spectroscopic modelling of 44 Type Iax supernovae (SNe Iax) using spectral synthesis code SYNAPPS. We confirm detections of helium emission in the early-time spectra of two SNe Iax: SNe 2004cs and 2007J. These He i features are better fit by a pure-emission Gaussian than by a P-Cygni profile, indicating that the helium emission originates from the circumstellar environment rather than the SN ejecta. Based on the modelling of the remaining 42 SNe Iax, we find no obvious helium features in other SN Iax spectra. However, ${\approx } 76{{\ \rm per\ cent}}$ of our sample lack sufficiently deep luminosity limits to detect helium emission with a luminosity of that seen in SNe 2004cs and 2007J. Using the objects with constraining luminosity limits, we calculate that 33 per cent of SNe Iax have detectable helium in their spectra. We examine 11 SNe Iax with late-time spectra and find no hydrogen or helium emission from swept-up material. For late-time spectra, we calculate typical upper limits of stripped hydrogen and helium to be 2 × 10−3 M⊙ and 10−2 M⊙, respectively. While detections of helium in SNe Iax support a white dwarf–He star binary progenitor system (i.e. a single-degenerate [SD] channel), non-detections may be explained by variations in the explosion and ejecta material. The lack of helium in the majority of our sample demonstrates the complexity of SN Iax progenitor systems and the need for further modelling. With strong independent evidence indicating that SNe Iax arise from an SD channel, we caution the common interpretation that the lack of helium or hydrogen emission at late-time in SN Ia spectra rules out SD progenitor scenarios for this class.