bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of Reported Tidal Volume During Neonatal Ventilation With Airway Leak: A Lung Model Study
Authors: Moon Kazue , Takeuchi Muneyuki , Tachibana Kazuya , Mizuguchi Soichi , Hirano Shinya 
Published: October 2018

Objectives:
To determine the accuracy of tidal volume reported by neonatal ventilators, with and without leak compensation, in invasive and noninvasive ventilation modes in the presence of airway leak; and, to determine what factors have a significant effect on the accuracy of tidal volume reported by ventilators with leak compensation in the presence of airway leak. We hypothesized that ventilators with a leak compensation function that includes estimation of tidal volume could accurately report tidal volume in the presence of airway leak, but that the accuracy of reported tidal volume may be affected by variables such as the identity of the ventilator, lung mechanics, leak size, positive end-expiratory pressure level, and body size.

Design:
In vitro assessment of ventilator volume delivery was conducted for seven acute care ventilators using a passive lung simulator.

Setting:
Laboratory-based measurements.

Interventions:
The error of reported tidal volume was calculated under three ventilation modes (noninvasive-pressure-control, invasive-pressure-control, and invasive-dual-control ventilation), three models of lung mechanics (normal and restrictive and obstructive lung disease), a range of airway leak values, two positive end-expiratory pressure values, and two body weights for each ventilator. Ventilators with and without leak compensation were studied.

Measurements and Main Results:
In the absence of airway leak, all ventilators reported tidal volume accurately. In the presence of airway leak, the error of reported tidal volume increased for all ventilators without a leak compensation algorithm while ventilators with leak compensation that included estimation of tidal volume accurately reported tidal volume. In the presence of airway leak, clinically significant effects on the error of reported tidal volume by ventilators with leak compensation were associated with the choice of ventilator in all modes and with lung mechanics in invasive ventilation modes.

Conclusions:
Reported tidal volume is affected by the presence of airway leak, but in many ventilators a leak compensation algorithm that includes estimation of tidal volume can correct for the discrepancy between actual and reported tidal volume. However, even in ventilators with leak compensation, choice of ventilator and lung mechanics in invasive ventilation modes have a significant effect on error of reported tidal volume.
Vascular Endothelial Growth Factor and Soluble Vascular Endothelial Growth Factor Receptor as Novel Biomarkers for Poor Outcomes in Children With Severe Sepsis and Septic Shock
Authors: Whitney Jane E. , Silverman Melanie , Norton Jackson S. , Bachur Richard G. , Melendez Elliot 
Published: October 2018

Objectives
Vascular endothelial growth factor (VEGF) and its receptor, soluble fms-like tyrosine kinase (sFLT), are biomarkers of endothelial activation. Vascular endothelial growth factor and sFLT have been associated with sepsis severity among adults, but pediatric data are lacking. The goal of this study was to assess VEGF and sFLT as predictors of outcome for children with sepsis.

Methods
Biomarkers measured for each patient at time of presentation to the emergency department were compared in children with septic shock versus children with sepsis without shock. For children with septic shock, the associations between biomarker levels and clinical outcome measures, including intensive care unit and hospital length of stay, vasoactive inotrope score, and measures of organ dysfunction, were assessed.

Results
Soluble fms-like tyrosine kinase and VEGF were elevated in children with septic shock (n = 73) compared with those with sepsis (n = 93). Elevated sFLT but not VEGF was associated with longer intensive care unit length of stay (P = 0.003), longer time requiring vasoactive agents (P < 0.001), higher maximum vasoactive inotrope score (P < 0.001), and higher maximum pediatric logistic organ dysfunction score (P < 0.001).

Conclusions
Vascular endothelial growth factor and sFLT measured in the emergency department are elevated in children with septic shock, and elevated sFLT but not VEGF is associated with worse clinical outcomes.
Attitudes and Opinions of Adolescent Females Regarding 2 Methods of Bladder Filling for Transabdominal Ultrasound
Authors: Waterhouse Marie R. , Pham Phung K. , Chang Todd P. 
Published: October 2018

Objectives
Adolescent female patients who are not sexually active and who present to a pediatric emergency department with abdominal pain require a full bladder prior to transabdominal ultrasound. Procedures to fill the bladder are largely institution or provider dependent. We examined adolescent females' attitudes and opinions toward 2 common methods of bladder filling, intravenous fluid administration and transurethral Foley catheter placement, by means of a Q-sort study.

Methods
Two convenience samples of adolescent female patients in the pediatric emergency department at an academic children's hospital participated in the study. In part 1, subjects underwent a semistructured interview to elicit their opinions regarding 2 methods of bladder filling: intravenous fluid or transurethral catheter. The summation of subject statements was then narrowed down to a final Q set of 25 statements. In part 2, a second sample of subjects independently arranged this Q set according to their own agreement or disagreement with each statement. Principal components analysis was conducted to examine factors or collections of statements representing a shared viewpoint and to describe commonalities.

Results
Part 1 was completed with 9 subjects, and part 2 with 26 subjects. Factors revealed from the Q-sort data included acceptance of tests deemed medically necessary, desire for parental involvement, and a wish to minimize discomfort. Most adolescents aligned with 1 of these 3 factors.

Conclusions
Adolescent female patients varied in their attitudes and opinions regarding intravenous catheter hydration and Foley catheter placement for transabdominal ultrasound. Knowledge of adolescent viewpoints may help better inform practitioner-patient communication for this procedure.
Intranetwork and Internetwork Effects of Navigated Transcranial Magnetic Stimulation Using Low- and High-Frequency Pulse Application to the Dorsolateral Prefrontal Cortex: A Combined rTMS–fMRI Approach
Authors: Zhang Haosu , Sollmann Nico , Castrillón Gabriel , Kurcyus Katarzyna , Meyer Bernhard , Zimmer Claus , Krieg Sandro M. 
Published: October 2018

Purpose:
Although transcranial magnetic stimulation (TMS) is routinely applied in neuroscience and clinical settings, not much is known about its effects on brain networks. Therefore, this pilot study was set up using repetitive navigated transcranial magnetic stimulation (rTMS) combined with resting-state functional MRI (rs-fMRI) to explore frequency-dependent stimulation effects on an intranetwork and internetwork level.

Methods:
Six healthy subjects (median age: 23.5 years) underwent two rTMS sessions (1 and 10 Hz), 7 days apart, and prestimulation and poststimulation rs-fMRI. Repetitive navigated transcranial magnetic stimulation was delivered to the left dorsolateral prefrontal cortex, with the exact stimulation target being determined by independent component analysis. Alterations of functional connectivity strength were evaluated using seed-based correlation analyses within and between the salience network, central executive network, and posterior and anterior default mode network.

Results:
Low-frequency rTMS resulted in significant intranetwork alterations only for the anterior default mode network and primarily within the left hemisphere. In contrast, high-frequency rTMS led to changes within all four networks of interest. Moreover, the posterior and anterior default mode network largely showed opposite effects to rTMS, and the anterior default mode network was rather isolated from the other networks, which was especially true for low-frequency rTMS. Changes in functional connectivity strength because of low-frequency rTMS were even detectable 7 days after stimulation.

Conclusions:
This is one of the first studies using neuronavigated TMS with independent component analysis–based target selection to explore frequency-dependent stimulation effects in a combined rTMS–fMRI approach. Future studies including higher subject numbers may define the underlying mechanisms for the different responses to low- and high-frequency rTMS.
Transient arousal modulations contribute to resting-state functional connectivity changes associated with head motion parameters
Authors: Gu Yameng , Han Feng , Sainburg Lucas E. , Liu Xiao 
Published: October 2018

AbstractCorrelations of resting-state functional magnetic resonance imaging (rsfMRI) signals are being widely used for assessing functional brain connectivity in health and disease. However, an association was recently observed between rsfMRI connectivity modulations and the head motion parameters and regarded as a causal relationship, which has raised serious concerns about the validity of many rsfMRI findings. Here, we studied the origin of this rsfMRI-motion association and its relationship to arousal modulations. By using a template-matching method to locate arousal-related fMRI changes, we showed that the effects of high motion time points on rsfMRI connectivity are largely due to their significant overlap with arousal-affected time points. The finding suggests that the association between rsfMRI connectivity and the head motion parameters arises from their co-modulations at transient arousal modulations, and this information is critical not only for proper interpretation of motion-associated rsfMRI connectivity changes but also for controlling the potential confounding effects of arousal modulation on rsfMRI metrics.
OSCA: a tool for omic-data-based complex trait analysis
Authors: Zhang Futao , Chen Wenhan , Zhu Zhihong , Zhang Qian , Nabais Marta F. , Qi Ting , Deary Ian J. , Wray Naomi R. , Visscher Peter M. , McRae Allan F. , Yang Jian 
Published: October 2018

AbstractThe rapid increase of omic data in the past decades has greatly facilitated the investigation of associations between omic profiles such as DNA methylation (DNAm) and complex traits in large cohorts. Here, we proposed a mixed-linear-model-based method (called MOMENT) that tests for association between a DNAm probe and trait with all other distal probes fitted in multiple random-effect components to account for the effects of unobserved confounders as well as the correlations between distal probes induced by the confounders. We demonstrated by simulations that MOMENT showed a lower false positive rate and more robustness than existing methods. MOMENT has been implemented in a versatile software package (called OSCA) together with a number of other implementations for omic-data-based analysis including the estimation of variance in a trait captured by all measures of multiple omic profiles, omic-data-based quantitative trait locus (xQTL) analysis, and meta-analysis of xQTL data.
Diversification and collapse of a telomere elongation mechanism
Authors: Saint-Leandre Bastien , Nguyen Son C. , Levine Mia T. 
Published: October 2018

AbstractIn virtually all eukaryotes, telomerase counteracts chromosome erosion by adding repetitive sequence to terminal ends.Drosophila melanogasterinstead relies on specialized retrotransposons that insert preferentially at telomeres. This exchange of goods between host and mobile element—wherein the mobile element provides an essential genome service and the host provides a hospitable niche for mobile element propagation—has been called a ‘genomic symbiosis’. However, these telomere-specialized, ‘jockey’ family elements may actually evolve to selfishly over-replicate in the genomes that they ostensibly serve. Under this intra-genomic conflict model, we expect rapid diversification of telomere-specialized retrotransposon lineages and possibly, the breakdown of this tenuous relationship. Here we report data consistent with both predictions. Searching the raw reads of the 15-million-year-old ‘melanogaster species group’, we generatedde novojockey retrotransposon consensus sequences and used phylogenetic tree-building to delineate four distinct telomere-associated lineages. Recurrent gains, losses, and replacements account for this striking retrotransposon lineage diversity. Moreover, an ancestrally telomere-specialized element has ‘escaped,’ residing now throughout the genome ofD. rhopaloa.InD. biarmipes,telomere-specialized elements have disappeared completely.De novoassembly of long-reads and cytogenetics confirmed this species-specific collapse of retrotransposon-dependent telomere elongation. Instead, telomere-restricted satellite DNA and DNA transposon fragments occupy its terminal ends. We infer thatD. biarmipesrelies instead on a recombination-based mechanism conserved from yeast to flies to humans. Combined with previous reports of adaptive evolution at host proteins that regulate telomere length, telomere-associated retrotransposon diversification and disappearance offer compelling evidence that intra-genomic conflict shapes Drosophila telomere evolution.
The Landscape of Parkin Variants Reveals Pathogenic Mechanisms and Therapeutic Targets in Parkinson’s Disease
Authors: Yi Wei , MacDougall Emma J. , Tang Matthew Y. , Krahn Andrea I. , Gan-Or Ziv , Trempe Jean-François , Fon Edward A. 
Published: October 2018

AbstractMutations in Parkin (PARK2), which encodes an E3 ubiquitin ligase implicated in mitophagy, are the most common cause of early onset Parkinson’s Disease (PD). Hundreds of naturally occurring Parkin variants have been reported, both in PD patient and population databases. However, the effects of the majority of these variants on the function of Parkin and in PD pathogenesis remains unknown. Here we develop a framework for classification of the pathogenicity of Parkin variants based on the integration of clinical and functional evidence – including measures of mitophagy and protein stability, and predictive structural modeling – and assess 51 naturally occurring Parkin variants accordingly. Surprisingly, only a minority of Parkin variants, even among those previously associated with PD, disrupted Parkin function. Moreover, a few of these naturally occurring Parkin variants actually enhanced mitophagy. Interestingly, impaired mitophagy in several of the most common pathogenic Parkin variants could be rescued both by naturally-occurring (p.V224A) and structure-guided designer (p.W403A; p.F146A) hyperactive Parkin variants. Together, the findings provide a coherent framework to classify Parkin variants based on pathogenicity and suggest that several pathogenic Parkin variants represent promising targets to stratify patients for genotype-specific drug design.
Variation in pigmentation gene expression is associated with distinct aposematic color morphs in the poison frog, Dendrobates auratus
Authors: Stuckert Adam M. M. , Moore Emily , Coyle Kaitlin P. , Davison Ian , MacManes Matthew D. , Roberts Reade , Summers Kyle 
Published: October 2018

AbstractColor and pattern phenotypes have clear implications for survival and reproduction in many species. However, the mechanisms that produce this coloration are still poorly characterized, especially at the genomic level. Here we have taken a transcriptomics-based approach to elucidate the underlying genetic mechanisms affecting color and pattern in a highly polytypic poison frog. We sequenced RNA from the skin from four different color morphs during the final stage of metamorphosis and assembled a de novo transcriptome. We then investigated differential gene expression, with an emphasis on examining candidate color genes from other taxa. Overall, we found differential expression of a suite of genes that control melanogenesis, melanocyte differentiation, and melanocyte proliferation (e.g., tyrpl, lefl, leol, and mitf) as well as several differentially expressed genes involved in purine synthesis and iridophore development (e.g., arfgapl, arfgap2, airc, and gairt). Our results provide evidence that several gene networks known to affect color and pattern in vertebrates play a role in color and pattern variation in this species of poison frog.
Cold-Induced Thermogenesis Increases Acetylation on the Brown Fat Proteome and Metabolome
Authors: Entwisle Samuel W. , Sanchez-Gurmaches Joan , Lawrence Robert T. , Pedersen David J. , Jung Su Myung , Martin-Perez Miguel , Guilherme Adilson , Czech Michael P. , Guertin David A. , Villen Judit 
Published: October 2018

ABSTRACTStimulating brown adipose tissue (BAT) energy expenditure could be a therapy for obesity and related metabolic diseases. Achieving this requires a systems-level understanding of the biochemical underpinnings of thermogenesis. To identify novel metabolic features of active BAT, we measured protein abundance, protein acetylation, and metabolite levels in BAT isolated from mice living in their thermoneutral zone or in colder environments. We find that the enzymes which synthesize lipids from cytosolic acetyl-coA are among the most robustly increased proteins after cold acclimation, consistent with recent studies highlighting the importance of anabolicde novolipogenesis in BAT. In addition, many mitochondrial proteins are hyperacetylated by cold acclimation, including several sites on UCP1, which may have functional relevance. Metabolomics analysis further reveals cold-dependent increases to acetylated carnitine and several amino acids. This BAT multi-omics resource highlights widespread proteomic and metabolic changes linked to acetyl-CoA synthesis and utilization that may be useful in unraveling the remarkable metabolic properties of active BAT.
Evaluation of North American Asian Citrus Psyllid (Hemiptera: Liviidae) Population Genetics using cytochrome P450 melt curve analysis
Authors: Macias-Velasco Juan F. , Brunson Ryan T. , Hunter Wayne B. , Bextine Blake R. 
Published: October 2018

AbstractThe Asian Citrus Psyllid (ACP) (Diaphorina citri) is a Hemipteran which feeds on Citrus and is the principal vector of the pathogenCandidatusLiberibacter asiaticus (Las); the primary causal agent of Huanglongbing (HLB) or citrus greening disease. Currently HLB is the single greatest threat to the American citrus industry. Previous work has shown that that Cytochrome P450 (CYP4) genes are associated with insecticidal resistance to neonicotinoid insecticides. Infection by Las has also been shown to affect the expression of CYP4 genes. In this study the genetic relationships of ACP populations was evaluated using melting curve analysis of CYP4 genes. Principal component analysis shows the presence of two potential haplotypes. The groups identified by principal component analysis are significantly different from each other (P < 0.05) for all CYP4 genes tested. All populations are most likely within 2-3 mutations of each other. The existence of these mutations sheds light on the potential evolution of ACP in North America. Indicating either coevolution with Las or difference in imidacloprid basal selective pressure in the United States and Mexico.
Sparse Recovery Methods for Cell Detection and Layer Estimation
Authors: LaGrow Theodore J. , Moore Michael G. , Prasad Judy A. , Webber Alexis , Davenport Mark A. , Dyer Eva L. 
Published: October 2018

ABSTRACTRobust methods for characterizing the cellular architecture (cytoarchitecture) of the brain are needed to differentiate brain areas, identify neurological diseases, and model architectural differences across species. Current methods for mapping the cytoarchitecture and, in particular, identifying laminar (layer) divisions in tissue samples require the expertise of trained neuroanatomists to manually annotate the various regions-of-interest and cells within an image. However, as neuroanatomical datasets grow in volume, manual annotations become inefficient, impractical, and risk the potential of biasing results. In this paper, we propose an automated framework for cellular detection and density estimation that enables the detection of laminar divisions within retinal and neocortical histology datasets. Our approach for layer detection uses total variation minimization to find a small number of change points in the density that signify the beginning and end of each layer. We apply these methods to micron-scale histology images from a variety of cortical areas of the mouse brain and retina, as well as synthetic datasets. Our results demonstrate the feasibility of using automation to reveal the cytoarchitecture of neurological samples in high-resolution images.
The RNA-binding ATPase, Armitage, Couples piRNA Amplification in Nuage to Phased piRNA Production on Mitochondria
Authors: Ge Daniel Tianfang , Wang Wei , Tipping Cindy , Gainetdinov Ildar , Weng Zhiping , Zamore Phillip D. 
Published: October 2018

SUMMARYPlWI-interacting RNAs (piRNAs) silence transposons inDrosophilaovaries, ensuring female fertility. Two coupled pathways generate germline piRNAs: the ping-pong cycle, in which the PIWI proteins Aubergine and Ago3 increase the abundance of pre-existing piRNAs, and the phased piRNA pathway, which generates strings of tail-to-head piRNAs, one after another. Proteins acting in the ping-pong cycle localize to nuage, whereas phased piRNA production requires Zucchini, an endonuclease on the mitochondrial surface. Here, we report that Armitage (Armi), an RNA-binding ATPase localized to both nuage and mitochondria, links the ping-pong cycle to the phased piRNA pathway. Mutations that block phased piRNA production deplete Armi from nuage. Armi ATPase mutants cannot support phased piRNA production and inappropriately bind mRNA instead of piRNA precursors. We propose that Armi shuttles between nuage and mitochondria, feeding precursor piRNAs generated by Ago3 cleavage into the Zucchini-dependent production of Aubergine- and Piwi-bound piRNAs on the mitochondrial surface.