bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Retrospective Case-Control Study to Identify Predictors of Unplanned Admission to Pediatric Intensive Care Within 24 Hours of Hospitalization*
Authors: Krmpotic Kristina , Lobos Anna-Theresa , Chan Jason , Toppozini Christina , McGahern Candice , Momoli Franco , Plint Amy C. 
Published: May 2019

Objectives:
To identify the clinical findings available at the time of hospitalization from the emergency department that are associated with deterioration within 24 hours.

Design:
A retrospective case-control study.

Setting:
A pediatric hospital in Ottawa, ON, Canada.

Patients:
Children less than 18 years old who were hospitalized via the emergency department between January 1, 2008, and December 31, 2012. Cases (n = 98) had an unplanned admission to the PICU or unexpected death on the hospital ward within 24 hours of hospitalization and controls (n = 196) did not.

Interventions:
None.

Main Results:
Ninety-eight children (53% boys; mean age 63.2 mo) required early unplanned admission to the PICU. Multivariable conditional logistic regression resulted in a model with five predictors reaching statistical significance: higher triage acuity score (odds ratio, 4.1; 95% CI, 1.7–10.2), tachypnea in the emergency department (odds ratio, 4.6; 95% CI, 1.8–11.8), tachycardia in the emergency department (odds ratio, 2.6; 95% CI, 1.1–6.5), PICU consultation in the emergency department (odds ratio, 8.0; 95% CI, 1.1–57.7), and admission to a ward not typical for age and/or diagnosis (odds ratio, 4.5; 95% CI, 1.7–11.6).

Conclusions:
We have identified risk factors that should be included as potential predictor variables in future large, prospective studies to derive and validate a weighted scoring system to identify hospitalized children at high risk of early clinical deterioration.
Etiologies and Clinical Outcomes of Patients With Secondary Hemophagocytic Lymphohistiocytosis at a Tertiary PICU
Authors: Dao Dyda , Xoay Tran D. , Galeano Belinda K. , Phuc Phan H. , Ouellette Yves 
Published: May 2019

Objectives:
To assess the etiologies and outcomes of patients with secondary hemophagocytic lymphohistiocytosis in the PICU.

Design:
Prospective observational cohort study.

Setting:
A single PICU at a pediatric tertiary hospital in Hanoi, Vietnam.

Patients:
Pediatric patients meeting the criteria for secondary hemophagocytic lymphohistiocytosis.

Interventions:
None.

Measurements and Main Results:
Between June 2017 and May 2018, 25 consecutive patients with a mean (sd) age of 23.3 months (21.6 mo) were included. Collected variables included etiologies of hemophagocytic lymphohistiocytosis and clinical and laboratory findings at admission. The Pediatric Index of Mortality 2 score at admission was calculated. Outcomes were death and multiple organ dysfunction. The severity of multiple organ dysfunction was assessed by the Pediatric Logistic Organ Dysfunction 2 score. The mean (sd) Pediatric Index of Mortality 2 predicted mortality rate was 5.6% (7.6%). Cytomegalovirus and Epstein-Barr virus coinfections (60%) were the most common suspected etiology of hemophagocytic lymphohistiocytosis. Other etiologies included Epstein-Barr virus sole infections (20%), cytomegalovirus sole infections (16%), and one unknown cause (4%). Multiple organ dysfunction (excluding hematologic failure) was found in 22 patients (88%) with death occurring in 14 patients (56%). The mean (sd) Pediatric Logistic Organ Dysfunction 2 predicted mortality rate among patients with multiple organ dysfunction was 11.9% (11.2%). Despite having lower Pediatric Index of Mortality 2 predicted mortality rates at admission, Epstein-Barr virus-cytomegalovirus coinfection cases with multiple organ dysfunction had slightly greater Pediatric Logistic Organ Dysfunction 2 predicted mortality rates than Epstein-Barr virus sole infection cases with multiple organ dysfunction: 12.2% (10.5%) versus 11.3% (11.0%). However, these rates were lower than cytomegalovirus sole infection cases with multiple organ dysfunction (14.4% [16.3%]). Area under the curve values for Pediatric Index of Mortality 2 and Pediatric Logistic Organ Dysfunction 2 were 0.74 (95% CI, 0.52–0.95) and 0.78 (95% CI, 0.52–1.00), respectively, suggesting that both scales were fair to good at predicting mortality.

Conclusions:
Viral infections, particularly Epstein-Barr virus-cytomegalovirus coinfections, were a common cause of secondary hemophagocytic lymphohistiocytosis. The implication of these coinfections on the clinical course of hemophagocytic lymphohistiocytosis needs to be delineated.
Risks of harm with cannabinoids, cannabis, and cannabis-based medicine for pain management relevant to patients receiving pain treatment: protocol for an overview of systematic reviews
Authors: Gilron Ian , Blyth Fiona M. , Degenhardt Louisa , Di Forti Marta , Eccleston Christopher , Haroutounian Simon , Moore Andrew , Rice Andrew S.C. , Wallace Mark 
Published: May 2019

Abstract

Introduction:
With the increasing availability of cannabis and cannabinoids and their potential utility for pain treatment, there is a growing need to evaluate the risk-benefit considerations of cannabinoids for the management of pain. As part of the IASP Cannabis and Cannabinoids Task Force, this protocol describes a planned overview of systematic reviews summarizing the risks of harm with cannabinoids that are relevant to patients receiving pain treatment.

Methods:
This overview will involve literature searches of several databases and a defined search strategy that will target systematic reviews or meta-analyses of cannabinoids where harms are the primary focus. Data extraction will include various features of the cannabinoid(s) and the harm(s) being studied as well as other methodological features of each included systematic review. Methodological quality of each included review will be assessed using AMSTAR-2 as well as compliance with the PRISMA harms checklist. Prospero registration pending.

Discussion:
The broad overview of reviews defined by this protocol is expected to synthesize available good quality evidence of harms that will help inform risk-benefit considerations about the use of cannabinoids for pain management.
Do Quality Improvement Initiatives Improve Outcomes for Patients in Antiretroviral Programs in Low- and Middle-Income Countries? A Systematic Review
Authors: Hargreaves Sally , Rustage Keiran , Nellums Laura B. , Bardfield Joshua E. , Agins Bruce , Barker Pierre , Massoud M. Rashad , Ford Nathan P. , Doherty Meg , Dougherty Gillian , Singh Satvinder 
Published: May 2019

Background:
There have been a range of quality improvement (QI) and quality assurance initiatives in low- and middle-income countries to improve antiretroviral therapy (ART) treatment outcomes for people living with HIV. To date, these initiatives have not been systematically assessed and little is known about how effective, cost-effective, or sustainable these strategies are in improving clinical outcomes.

Methods:
We conducted a systematic review adhering to PRISMA guidelines (PROSPERO ID: CRD42017071848), searching PubMed, MEDLINE, Embase, Web of Science, and the Cochrane database of controlled trials for articles reporting on the effectiveness of QI and quality assurance initiatives in HIV programs in low- and middle-income countries in relation to ART uptake, retention in care, adherence, viral load suppression, mortality, and other outcomes including cost-effectiveness and long-term sustainability.

Results:
One thousand eight hundred sixty articles were found, of which 29 were included. QI approaches were categorized as follows: (1) health system approaches using QI methods; (2) QI learning networks including collaboratives; (3) standard-based methods that use QI tools to improve performance gaps; and (4) campaigns using QI methods. The greatest improvements were seen in ART uptake [median increase of 14.0%; interquartile range (IQR) −9.0 to 29.3], adherence [median increase of 22.0% (IQR −7.0 to 25.0)], and viral load suppression [median increase 26.0% (IQR −8.0 to 26.0)].

Conclusions:
QI interventions can be effective in improving clinical outcomes; however, there was significant variability, making it challenging to identify which aspects of interventions lead to clinical improvements. Standardizing reporting and assessment of QI initiatives is needed, supported by national quality policies and directorates, and robust research.
7 Tesla MRI of the ex vivo human brain at 100 micron resolution
Authors: Edlow Brian L. , Mareyam Azma , Horn Andreas , Polimeni Jonathan R. , Witzel Thomas , Tisdall M. Dylan , Augustinack Jean , Stockmann Jason P. , Diamond Bram R. , Stevens Allison , Tirrell Lee S. , Folkerth Rebecca D. , Wald Lawrence L. , Fischl Bruce , van der Kouwe Andre 
Published: May 2019

AbstractWe present an ultra-high resolution MRI dataset of an ex vivo human brain specimen. The brain specimen was donated by a 58-year-old woman who had no history of neurological disease and died of non-neurological causes. After fixation in 10% formalin, the specimen was imaged on a 7 Tesla MRI scanner at 100 μm isotropic resolution using a custom-built 31-channel receive array coil. Single-echo multi-flip Fast Low-Angle SHot (FLASH) data were acquired over 100 hours of scan time (25 hours per flip angle), allowing derivation of a T1 parameter map and synthesized FLASH volumes. This dataset provides an unprecedented view of the three-dimensional neuroanatomy of the human brain. To optimize the utility of this resource, we warped the dataset into standard stereotactic space. We now distribute the dataset in both native space and stereotactic space to the academic community via multiple platforms. We envision that this dataset will have a broad range of investigational, educational, and clinical applications that will advance understanding of human brain anatomy in health and disease.
Using multiple reference genomes to identify and resolve annotation inconsistencies
Authors: Monnahan Patrick J. , Michno Jean-Michel , O’Connor Christine H. , Brohammer Alex B. , Springer Nathan M. , McGaugh Suzanne E. , Hirsch Candice N. 
Published: May 2019

AbstractBackgroundAdvances in sequencing technologies have led to the release of reference genomes and annotations for multiple individuals within more well-studied systems. While each of these new genome assemblies shares significant portions of synteny between each other, the annotated structure of gene models within these regions can differ. Of particular concern are split-gene misannotations, in which a single gene is incorrectly annotated as two distinct genes or two genes are incorrectly annotated as a single gene. These misannotations can have major impacts on functional prediction, estimates of expression, and many downstream analyses.ResultsWe developed a high-throughput method based on pairwise comparisons of annotations that detect potential split-gene misannotations and quantifies support for whether the genes should be merged into a single gene model. We demonstrate the utility of our method using gene annotations of three reference genomes from maize (B73, PH207, and W22), a difficult system from an annotation perspective due to the size and complexity of the genome. On average, we find several hundred of these potential split-gene misannotations in each pairwise comparison, corresponding to 3-5% of gene models across annotations. To determine which state (i.e. one gene or multiple genes) is biologically supported, we utilize RNAseq data from 10 tissues throughout development along with a novel metric and simulation framework. The methods we have developed require minimal human interaction and can be applied to future assemblies to aid in annotation efforts.ConclusionsSplit-gene misannotations occur at appreciable frequency in maize annotations. We have developed a method to easily identify and correct these misannotations. Importantly, this method is generic in that it can utilize any type of short-read expression data. Failure to account for split-gene misannotations has serious consequences for biological inference, particularly for expression-based analyses.
Repetitive DNA content in the maize genome is uncoupled from population stratification at SNP loci
Authors: Renny-Byfield Simon , Baumgarten Andy 
Published: May 2019

AbstractMotivationRepetitive DNA is a major component of plant genomes and is thought to be a driver of evolutionary novelty. Describing variation in repeat content among individuals and between populations is key to elucidating the evolutionary significance of repetitive DNA. However, the cost of producing references genomes has limited large-scale intraspecific comparisons to a handful of model organisms where multiple reference genomes are available.ResultsWe examine repeat content variation in the genomes of 94 elite inbred maize lines using graph-based repeat clustering, a reference-free and rapid assay of repeat content. We examine population structure using genome-wide repeat profiles and demonstrate the stiff-stalk and non-stiff-stalk heterotic populations are homogenous with regard to global repeat content. In contrast and similar to previously reported results, the same individuals show clear differentiation, and aggregate into two populations, when examining population structure using genome-wide SNPs. Additionally, we develop a novel kmer based technique to examine the chromosomal distribution of repeat clusters in silico and show a cluster dependent statistically significant association with gene density.ConclusionOur results indicate that repeat content variation in the heterotic populations of maize has not diverged and is uncoupled from population stratification at SNP loci. We also show that repeat families exhibit divergent patterns with regard to chromosomal distribution, some repeat clusters accumulate in regions of high gene density, whereas others aggregate in regions of low gene density.Author’s contributionsSRB and AB conceived the study, SRB performed the bioinformatic analysis, SRB wrote the paper with input from AB. email contacts: Simon Renny-Byfield: simon.renny-byfield@corteva.com, Andy Baumgarten: andy.baumgarten@corteva.com
Depth-resolved ultra-high field fMRI reveals feedback contributions to surface motion perception
Authors: Marquardt Ingo , De Weerd Peter , Schneider Marian , Gulban Omer Faruk , Ivanov Dimo , Uludağ Kâmil 
Published: May 2019

AbstractHuman visual surface perception has neural correlates in early visual cortex, but the extent to which feedback contributes to this activity is not well known. Feedback projections preferentially enter superficial and deep anatomical layers, while avoiding the middle layer, which provides a hypothesis for the cortical depth distribution of fMRI activity related to feedback in early visual cortex. Here, we presented human participants uniform surfaces on a dark, textured background. The grey surface in the left hemifield was either perceived as static or moving based on a manipulation in the right hemifield. Physically, the surface was identical in the left visual hemifield, so any difference in percept likely was related to feedback. Using ultra-high field fMRI, we report the first evidence for a depth distribution of activation in line with feedback during the (illusory) perception of surface motion. Our results fit with a signal re-entering in superficial depths of V1, followed by a feedforward sweep of the re-entered information through V2 and V3, as suggested by activity centred in the middle-depth levels of the latter areas. This positive modulation of the BOLD signal due to illusory surface motion was on top of a strong negative BOLD response in the cortical representation of the surface stimuli, which depended on the presence of texture in the background. Hence, the magnitude and sign of the BOLD response to the surface strongly depended on background properties, and was additionally modulated by the presence or absence of illusory motion perception in a manner compatible with feedback. In summary, the present study demonstrates the potential of depth resolved fMRI in tackling biomechanical questions on perception that so far were only within reach of invasive animal experimentation.
Trans-omic analysis reveals allosteric and gene regulation-axes for altered glucose-responsive liver metabolism associated with obesity
Authors: Kokaji Toshiya , Hatano Atsushi , Ito Yuki , Yugi Katsuyuki , Eto Miki , Ohno Satoshi , Fujii Masashi , Hironaka Ken-ichi , Egami Riku , Inoue Hiroshi , Uda Shinsuke , Kubota Hiroyuki , Suzuki Yutaka , Ikeda Kazutaka , Arita Makoto , Matsumoto Masaki , Nakayama Keiichi I. , Hirayama Akiyoshi , Soga Tomoyoshi , Kuroda Shinya 
Published: May 2019

AbstractImpaired glucose tolerance associated with obesity causes postprandial hyperglycemia and can lead to type 2 diabetes. To study the differences in liver metabolism in the healthy and obese states, we constructed and analyzed trans-omic glucose-responsive metabolic networks with layers for metabolites, expression data for metabolic enzyme genes, transcription factors, and insulin signaling proteins from the livers of healthy and obese mice. We integrated multi-omic time-course data from wild-type (WT) and leptin-deficient obese (ob/ob) mice after orally administered glucose. In WT mice, metabolic reactions were rapidly regulated (within 10 minutes of oral glucose administration) primarily by glucose-responsive metabolites, especially ATP and NADP+, which functioned as allosteric regulators and substrates of metabolic enzymes, and by Akt-dependent glucose-responsive genes encoding metabolic enzymes. Inob/obmice, most rapid regulation by glucose-responsive metabolites was absent; instead, glucose administration produced slow changes in the expression of metabolic enzyme-encoding genes to alter metabolic reactions in a time scale of hours. Few common regulatory events occurred in both the healthy and obese mice. Thus, our trans-omic network analysis revealed regulation of liver metabolism in response to glucose is mediated through different mechanisms in the healthy and obese states: Rapid changes in allosteric regulators and substrates and in gene expression dominate the healthy state, and slow transcriptional regulation dominates the obese state.One Sentence SummaryRapid changes in regulatory metabolites and gene expression dominate the healthy state, and slow transcriptional regulation dominates the obese state.
Characterization of the untranslated region of lymphocytic choriomeningitis virus S segment
Authors: Taniguchi Satoshi , Yoshikawa Tomoki , Shimojima Masayuki , Fukushi Shuetsu , Kurosu Takeshi , Tani Hideki , Fukuma Aiko , Kato Fumihiro , Nakayama Eri , Maeki Takahiro , Tajima Shigeru , Lim Chang-Kweng , Ebihara Hideki , Kyuwa Shigeru , Morikawa Shigeru , Saijo Masayuki 
Published: May 2019

ABSTRACTLymphocytic choriomeningitis virus (LCMV) is a prototypic arenavirus. The viral genome consists of two RNA segments, L and S. The 5’- and 3’-termini of both L and S segments are highly conserved among arenaviruses. These regions consist of 19 complementary base pairs and are essential for viral genome replication and transcription. In addition to these 19 nucleotides in the 5’- and 3’-termini, there are untranslated regions (UTRs) composed of 58 and 41 nucleotide residues in the 5’ and 3’ UTRs, respectively, in the LCMV S segment. Their functional roles, however, have yet to be elucidated. In this study, a reverse genetics and a minigenome system for the LCMV strain WE were established and used to analyze the function of these regions. The results obtained from these analyses, plus RNA secondary structure prediction, revealed that not only these 19 nucleotides but also the 20th–40th and 20th–38th nucleotides located downstream of the 19 nucleotides in the 5’- and 3’-termini, respectively, are heavily involved in viral genome replication and transcription. Furthermore, the introduction of mutations in these regions depressed viral propagationin vitroand enhanced attenuationin vivo. Conversely, recombinant LCMVs (rLCMVs), which had various deletions in the other UTRs, propagated as well as wild-type LCMVin vitrobut were attenuatedin vivo. Most mice previously infected with rLCMVs with mutated UTRs, when further infected with a lethal dose of wild-type LCMV, survived. These results suggest that rLCMVs with mutated UTRs could be candidates for an LCMV vaccine.IMPORTANCEThe function of untranslated regions (UTRs) of the arenavirus genome has not well been studied except for the 19 nucleotides of the 5’- and 3’-termini. In this study the function of the UTRs of the LCMV S segment was analyzed. It was found that not only the 19 nucleotides of the 5’- and 3’-termini but also the 20th–40th and 20th–38th nucleotides located downstream of the 19 nucleotides in the 5’- and 3’-termini, respectively, were involved in viral genome replication and transcription. Furthermore, other UTRs in the S segment were involved in virulencein vivo. The introduction of mutations to these regions makes it possible to establish attenuated LCMV and potentially develop LCMV vaccine candidates.
Time of day is associated with paradoxical reductions in global signal fluctuation and functional connectivity
Authors: Orban Csaba , Kong Ru , Li Jingwei , Chee Michael W.L. , Yeo B. T. Thomas 
Published: May 2019

1.AbstractThe brain exhibits substantial diurnal variation in physiology and function but neuroscience studies rarely report or consider the effects of time of day. Here, we examined variation in resting-state fMRI in around 900 subjects scanned between 8am to 10pm on two different days. Multiple studies across animals and humans have demonstrated that the brain’s global signal amplitude (henceforth referred to as “fluctuation”) increases with decreased arousal. Thus, in accord with known circadian variation in arousal, we hypothesised that global signal fluctuation would be lowest in the morning, increase in the mid-afternoon and dip in the early evening. Instead, we observed a cumulative decrease (22% between 9am to 9pm) in global signal fluctuation as the day progressed. To put the magnitude of this decrease in context, we note that task-evoked fMRI responses are typically in the order of 1% to 3%. Respiratory variation also decreased with time of day, although control analyses suggested that this did not account for the reduction in GS fluctuation. Finally, time of day was associated with marked decreases in resting state functional connectivity across the whole brain. The magnitude of decrease was significantly stronger than associations between functional connectivity and behaviour (e.g., fluid intelligence). These findings reveal unexpected effects of time of day on the resting human brain, which challenge the prevailing notion that the brain’s global signal reflects mostly arousal and physiological artefacts. We conclude by discussing potential mechanisms for the observed diurnal variation in resting brain activity and the importance of accounting for time of day in future studies.