bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Educational Interventions in Improving Measures of Living-donor Kidney Transplantation Activity: A Systematic Review and Meta-analysis
Authors: Sandal Shaifali , Dendukuri Nandini , Wang Shouao , Guadagno Elena , Ekmekjian Taline , Alam Ahsan 
Published: April 2019

Background.
To address patient-level barriers to living-donor kidney transplantation (LDKT), centers have implemented educational interventions. Recently, some have highlighted several gaps in knowledge and lack of evidence of efficacy of these interventions. No review has synthesized the available data.

Methods.
We conducted a systematic review and meta-analysis of studies conducted to increase measures of LDKT. Outcomes of interest were LDKT rates, donor evaluation, donor contact/inquiry, total transplantation rates, and change in knowledge scores and pursuit behaviors. A literature search was conducted across 7 databases from inception until 2017. Educational interventions were a decision/teaching aid alone or with personalized sessions. Comparator was another intervention or nonspecific education. Random effects meta-analysis was performed to pool risk ratios (RRs) across studies.

Results.
Of the 1813 references, 15 met the inclusion criteria; 9 were randomized control trials. When compared with nonspecific education, interventions increased LDKT rates (RR = 2.54; 95% confidence interval [CI], 1.49-4.35), donor evaluation (RR = 3.82; 95% CI, 1.91-7.64), and donor inquiry/contact (RR = 2.41; 95% CI, 1.53-3.80), but not total transplants (RR = 1.24; 95% CI, 0.96-1.61). Significant increased mean knowledge scores postintervention was noted, and most showed favorable trends in pursuit behaviors. Quality across the studies was mixed and sometimes difficult to assess. The biggest limitations were small sample size, selection bias, and short follow-ups.

Conclusions.
Educational interventions improve measures of LDKT activity; however, current literature is heterogeneous and at risk of selection bias. Prospective studies with diverse patient populations, longer follow-ups, and robust outcomes are needed to inform clinical practice.
HLA Class I–sensitized Renal Transplant Patients Have Antibody Binding to SLA Class I Epitopes
Authors: Martens Gregory R. , Ladowski Joseph M. , Estrada Jose , Wang Zheng-Yu , Reyes Luz M. , Easlick Juliet , Smith Clarkson , Butler James R. , Sidner Richard A. , Eckhoff Devin E. , Tector Matthew , Tector Joseph 
Published: April 2019

Background.
Highly sensitized patients are difficult to match with suitable renal allograft donors and may benefit from xenotransplant trials. We evaluate antibody binding from sensitized patients to pig cells and engineered single allele cells to identify anti-human leukocyte antigen (HLA) antibody cross-species reactivity with swine leukocyte antigen (SLA). These novel testing strategies assess HLA/SLA epitopes and antibody-binding patterns and introduce genetic engineering of SLA epitopes.

Methods.
Sensitized patient sera were grouped by calculated panel reactive antibody and luminex single antigen reactivity profile and were tested with cloned GGTA1/CMAH/B4GalNT2 glycan knockout porcine cells. Pig reactivity was assessed by direct flow cytometric crossmatch and studied following elution from pig cells. To study the antigenicity of individual class I HLA and SLA alleles in cells, irrelevant sera binding to lymphoblastoid cells were minimized by CRISPR/Cas9 elimination of endogenous class I and class II HLA, B-cell receptor, and Fc receptor genes. Native HLA, SLA, and mutants of these proteins after mutating 144K to Q were assessed for antibody binding.

Results.
Those with predominately anti-HLA-B&C antibodies, including Bw6 and Bw4 sensitization, frequently have low pig reactivity. Conversely, antibodies eluted from porcine cells are more commonly anti-HLA-A. Single HLA/SLA expressing engineered cells shows variable antigenicity and mutation of 144K to Q reduces antibody binding for some sensitized patients.

Conclusions.
Anti-HLA antibodies cross-react with SLA class I in predictable patterns, which can be identified with histocompatibility strategies, and SLA class I is a possible target of genetic engineering.
Peptidylarginine Deiminase inhibition abolishes the production of large extracellular vesicles fromGiardia intestinalis, affecting host-pathogen interactions by hindering adhesion to host cells
Authors: Gavinho Bruno , Rossi Izadora Volpato , Evans-Osses Ingrid , Lange Sigrun , Ramirez Marcel Ivan 
Published: April 2019

AbstractGiardia intestinalisis an anaerobic protozoan that is an important etiologic agent of inflammation-driven diarrhea worldwide. Although self-limiting, a deep understanding of the factors involved in the pathogenicity that produces the disruption of the intestinal barrier remains unknown. There is evidence that under diverse conditions, the parasite is capable of shedding extracellular vesicles (EVs) which could modulate the physiopathology of giardiasis. Here we describe new insights ofG. intestinalisEV production, revealing its capacity to shed two different enriched EV populations (large and small extracellular vesicles) and identified a relevant adhesion function associated only with the larger population. Our work also aimed at assessing the influences of two recently identified inhibitors of EV release in mammalian cells, namely peptidylarginine deiminase (PAD) inhibitor and cannabidiol (CBD), on EV release fromGiardiaand their putative effects on host-pathogen interactions. PAD-inhibitor Cl-amidine and CBD were both able to effectively reduce EV shedding, the PAD-inhibitor specifically affecting the release of large extracellular vesicles and interfering within vitrohost-pathogen interactions. The strong efficacy of the PAD-inhibitor onGiardiaEV release indicates a phylogenetically conserved pathway of PAD-mediated EV release, most likely affecting theGiardiaarginine deiminase (GiADI) homolog of mammalian PADs. While there is still much to learn aboutG. intestinalisinteraction with its host, our results suggest that large and small EVs may be differently involved in protozoa communication, and that EV-inhibitor treatment may be a novel strategy for recurrent giardiasis treatment.
Robust Pavlovian-to-Instrumental and Pavlovian-to-Metacognitive Transfers in human reinforcement learning
Authors: Ting Chih-Chung , Palminteri Stefano , Engelmann Jan B. , Lebreton Maël 
Published: April 2019

AbstractIn simple instrumental-learning tasks, humans learn to seek gains and to avoid losses equally well. Yet, two effects of valence are observed. First, decisions in loss-contexts are slower, which is consistent with the Pavlovian-instrumental transfer (PIT) hypothesis. Second, loss contexts decrease individuals’ confidence in their choices – a bias akin to a Pavlovian-to-metacognitive transfer (PMT). Whether these two effects are two manifestations of a single mechanism or whether they can be partially dissociated is unknown. Here, across six experiments, we attempted to disrupt the PIT effects by manipulating the mapping between decisions and actions and imposing constraints on response times (RTs). Our goal was to assess the presence of the metacognitive bias in the absence of the RT bias. Were observed both PIT and PMT despite our disruption attempts, establishing that the effects of valence on motor and metacognitive responses are very robust and replicable. Nonetheless, within- and between-individual inferences reveal that the confidence bias resists the disruption of the RT bias. Therefore, although concomitant in most cases, PMT and PIT seem to be – partly – dissociable. These results highlight new important mechanistic constraints that should be incorporated in learning models to jointly explain choice, reaction times and confidence.
Distributed Code for Semantic Relations Predicts Neural Similarity
Authors: Chiang Jeffrey N. , Peng Yujia , Lu Hongjing , Holyoak Keith J. , Monti Martin M. 
Published: April 2019

AbstractThe ability to generate and process semantic relations is central to many aspects of human cognition. Theorists have long debated whether such relations are coded as atomistic links in a semantic network, or as distributed patterns over some core set of abstract relations. The form and content of the conceptual and neural representations of semantic relations remains to be empirically established. The present study combined computational modeling and neuroimaging to investigate the representation and comparison of abstract semantic relations in the brain. By using sequential presentation of verbal analogies, we decoupled the neural activity associated with encoding the representation of the first-order semantic relation between words in a pair from that associated with the second-order comparison of two relations. We tested alternative computational models of relational similarity in order to distinguish between rival accounts of how semantic relations are coded and compared in the brain. Analyses of neural similarity patterns supported the hypothesis that semantic relations are coded, in the parietal cortex, as distributed representations over a pool of abstract relations specified in a theory-based taxonomy. These representations, in turn, provide the immediate inputs to the process of analogical comparison, which draws on a broad frontoparietal network. This study sheds light not only on the form of relation representations but also on their specific content.SignificanceRelations provide basic building blocks for language and thought. For the past half century, cognitive scientists exploring human semantic memory have sought to identify the code for relations. In a neuroimaging paradigm, we tested alternative computational models of relation processing that predict patterns of neural similarity during distinct phases of analogical reasoning. The findings allowed us to draw inferences not only about the form of relation representations, but also about their specific content. The core of these distributed representations is based on a relatively small number of abstract relation types specified in a theory-based taxonomy. This study helps to resolve a longstanding debate concerning the nature of the conceptual and neural code for semantic relations in the mind and brain.
Validation of new bioinformatic tools to identify expanded repeats: a non-reference intronic pentamer expansion inRFC1causes CANVAS
Authors: Rafehi Haloom , Szmulewicz David J , Bennett Mark F , Sobreira Nara LM , Pope Kate , Smith Katherine R , Gillies Greta , Diakumis Peter , Dolzhenko Egor , Eberle Michael A , Barcina María García , Breen David P , Chancellor Andrew M , Cremer Phillip D , Delatycki Martin B. , Fogel Brent L , Hackett Anna , Halmagyi G. Michael , Kapetanovic Solange , Lang Anthony , Mossman Stuart , Mu Weiyi , Patrikios Peter , Perlman Susan L , Rosemargy Ian , Storey Elsdon , Watson Shaun RD , Wilson Michael A , Zee David , Valle David , Amor David J , Bahlo Melanie , Lockhart Paul J 
Published: April 2019

ABSTRACTGenomic technologies such as Next Generation Sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion [(AAGGG)exp] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG)11short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS families and identified a core ancestral haplotype, estimated to have arisen in Europe over twenty-five thousand years ago. WGS of the fourRFC1negative CANVAS families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders.
Resting Eyes Closed Beta-Phase High Gamma-Amplitude Coupling Deficits in Children with Attention Deficit Hyperactivity Disorder
Authors: Ibanez-Soria David , Kroupi Eleni , Rojas Andrés , Castellano Marta , Picardo Jacobo , García-Banda Gloria , Saez Belen , Servera Mateu , Ruffini Giulio , Soria-Frisch Aureli 
Published: April 2019

AbstractObjectiveAttention-deficit hyperactivity disorder (ADHD) is the neurobehavioral disorder with the largest prevalence rate in childhood. ADHD is generally assessed based on physical examination of the child and interviews, and therefore prone to subjectivity. This fact may lead to a high risk of mis- and over-diagnosis, a problem that can be addressed through the use of objective markers.MethodsHere we propose to use phase-amplitude coupling as a digital biomarker in ADHD. We investigated the hypothesis that coupling between the phase of slow brain rhythms and the amplitude of fast rhythms is altered in the ADHD population. We tested this hypothesis measuring phase-amplitude coupling (PAC) in the 4 to 200Hz range in electroencephalographic (EEG) signals recorded in the central-frontal area in children during eyes closed resting state.ResultsUsing automatic clustering, we observed statistically significant beta-gamma PAC deficits in the ADHD population in the frontal-left hemisphere.ConclusionsThese findings suggests alterations in the beta-gamma coupling in the ADHD population. We discuss the hypothesis that these alterations may be indicators of working memory and attention deficits.SignificanceThe study of the coupling between the different brain rhythms can potentially contribute to the understanding and clinical diagnosis of ADHD.
The speciation and hybridization history of the genusSalmonella
Authors: Criscuolo Alexis , Issenhuth-Jeanjean Sylvie , Didelot Xavier , Thorell Kaisa , Hale James , Parkhill Julian , Thomson Nicholas R. , Weill François-Xavier , Falush Daniel , Brisse Sylvain 
Published: April 2019

AbstractBacteria and archaea make up most of natural diversity but the mechanisms that underlie the origin and maintenance of prokaryotic species are poorly understood. We investigated the speciation history of the genusSalmonella, an ecologically diverse bacterial lineage, within whichS. entericasubsp.entericais responsible for important human food-borne infections. We performed a survey of diversity across a large reference collection using multilocus sequence typing, followed by genome sequencing of distinct lineages. We identified eleven distinct phylogroups, three of which were previously undescribed. Strains assigned toS. entericasubsp.salamaeare polyphyletic, with two distinct lineages that we designate Salamae A and Salamae B. Strains of subspecieshoutenaeare subdivided into two groups, Houtenae A and B and are both related to Selander’s group VII. A phylogroup we designate VIII was previously unknown. A simple binary fission model of speciation cannot explain observed patterns of sequence diversity. In the recent past, there have been large scale hybridization events involving an unsampled ancestral lineage and three distantly related lineages of the genus that have given rise to Houtenae A, Houtenae B and VII. We found no evidence for ongoing hybridization in the other eight lineages but detected more subtle signals of ancient recombination events. We are unable to fully resolve the speciation history of the genus, which might have involved additional speciation-by-hybridization or multi-way speciation events. Our results imply that traditional models of speciation by binary fission and divergence may not apply inSalmonella.Data summaryIllumina sequence data were submitted to the European Nucleotide Archive under project number PRJEB2099 and are available from INSDC (NCBI/ENA/DDBJ) under accession numbers ERS011101 to ERS011146. The MLST sequence and profile data generated in this study have been publicly available on theSalmonellaMLST web site between 2010 and the migration of theSalmonellaMLST website to EnteroBase (https://enterobase.warwick.ac.uk/), and subsequently from there.
PIRATE: A fast and scalable pangenomics toolbox for clustering diverged orthologues in bacteria
Authors: Bayliss Sion C. , Thorpe Harry A. , Coyle Nicola M. , Sheppard Samuel K. , Feil Edward J. 
Published: April 2019

AbstractCataloguing the distribution of genes within natural bacterial populations is essential for understanding evolutionary processes and the genetic basis of adaptation. Here we present a pangenomics toolbox, PIRATE (Pangenome Iterative Refinement And Threshold Evaluation), which identifies and classifies orthologous gene families in bacterial pangenomes over a wide range of sequence similarity thresholds. PIRATE builds upon recent scalable software developments to allow for the rapid interrogation of thousands of isolates. PIRATE clusters genes (or other annotated features) over a wide range of amino-acid or nucleotide identity thresholds and uses the clustering information to rapidly classify paralogous gene families into either putative fission/fusion events or gene duplications. Furthermore, PIRATE orders the pangenome using a directed graph, provides a measure of allelic variation and estimates sequence divergence for each gene family. We demonstrate that PIRATE scales linearly with both number of samples and computation resources, allowing for analysis of large genomic datasets, and compares favorably to other popular tools. PIRATE provides a robust framework for analysing bacterial pangenomes, from largely clonal to panmictic species.AvailabilityPIRATE is implemented in Perl and is freely available under an GNU GPL 3 open source license fromhttps://github.com/SionBayliss/PIRATE.Supplementary InformationSupplementary data is available online.
Differential coupling of adult-born granule cells to parvalbumin and somatostatin interneurons
Authors: Groisman Ayelén I. , Yang Sung M. , Schinder Alejandro F. 
Published: April 2019

ABSTRACTThe dentate gyrus of the hippocampus is dominated by a strong GABAergic tone that maintains sparse levels of activity. Adult neurogenesis disrupts this balance through the continuous addition of new granule cells (GCs) that display high excitability while develop and connect within the preexisting host circuit. The dynamics of the connectivity map for developing GCs in the local inhibitory networks remains unknown. We used optogenetics to study afferent and efferent synaptogenesis between new GCs and GABAergic interneurons expressing parvalbumin (PV-INs) and somatostatin (SST-INs). Inputs from PV-INs targeted the soma and remained immature until they grew abruptly in >4-week-old GCs. This transition was accelerated by exposure to enriched environment. Inputs from SST-INs were dendritic and developed slowly until reaching maturity by 8 weeks. Synaptic outputs from GCs onto PV-INs matured faster than those onto SST-INs, but also required several weeks. In the mature dentate network, PV-INs exerted an efficient control of GC spiking and were involved in both feedforward and feedback loops, a mechanism that would favor lateral inhibition and sparse coding. Our results reveal a long-lasting transition where adult-born neurons remain poorly coupled to inhibition, which might enable a parallel streaming channel from the entorhinal cortex to CA3 pyramidal cells.
Nanog regulates Pou3f1 expression and represses anterior fate at the exit from pluripotency
Authors: Barral Antonio , Rollan Isabel , Sanchez-Iranzo Hector , Jawaid Wajid , Badia-Careaga Claudio , Menchero Sergio , Gomez Manuel J. , Torroja Carlos , Sanchez-Cabo Fatima , Göttgens Berthold , Manzanares Miguel , de Aja Julio Sainz 
Published: April 2019

ABSTRACTPluripotency is regulated by a network of transcription factors that maintains early embryonic cells in an undifferentiated state while allowing them to proliferate. NANOG is a critical factor for maintaining pluripotency and its role in primordial germ cell differentiation has been well described. However, Nanog is expressed during gastrulation across all the posterior epiblast, and only later in development its expression is restricted to primordial germ cells. In this work, we unveiled a previously unknown mechanism by which Nanog specifically represses the anterior epiblast lineage. Analysis of transcriptional data from both embryonic stem cells and gastrulating mouse embryos revealed Pou3f1 expression to be negatively correlated with that of Nanog during the early stages of differentiation. We have functionally demonstrated Pou3f1 to be a direct target of NANOG by using a dual transgene system for the controlled expression of Nanog. Use of Nanog null ES cells further demonstrated a role for Nanog in repressing anterior neural genes. Deletion of a NANOG binding site (BS) located nine kilobases downstream of the transcription start site of Pou3f1 revealed this BS to have a specific role in the regionalization of the expression of this gene in the embryo. Our results indicate an active role of Nanog inhibiting the neural fate by repressing Pou3f1 at the onset of gastrulation.
The full-length transcriptome ofC. elegansusing direct RNA sequencing
Authors: Roach Nathan P. , Sadowski Norah , Alessi Amelia F. , Timp Winston , Taylor James , Kim John K. 
Published: April 2019

AbstractCurrent transcriptome annotations have largely relied on short read lengths intrinsic to most widely used high-throughput cDNA sequencing technologies. For example, in the annotation of theCaenorhabditis eleganstranscriptome, more than half of the transcript isoforms lack full-length support and instead rely on inference from short reads that do not span the full length of the isoform. We applied nanopore-based direct RNA sequencing to characterize the developmental polyadenylated transcriptome ofC. elegans. Taking advantage of long reads spanning the full length of mRNA transcripts, we provide support for 20,902 splice isoforms across 14,115 genes, without the need for computational reconstruction of gene models. Of the isoforms identified, 2,188 are novel splice isoforms not present in the Wormbase WS265 annotation. Furthermore, we identified 16,325 3’ untranslated region (3’UTR) isoforms, 2,304 of which are novel and do not fall within 10 bp of existing 3’UTR datasets and annotations. Combining 3’UTRs and splice isoforms we identified 25,944 full-length isoforms. We also determined that poly(A) tail lengths of transcripts vary across development, as do the strengths of previously reported correlations between poly(A) tail length and expression level, and poly(A) tail length and 3’UTR length. Finally, we have formatted this data as a publically accessible track hub, enabling researchers to explore this dataset easily in a genome browser.