bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Frequency Oscillations in the Scalp EEG of Intensive Care Unit Patients With Altered Level of Consciousness
Authors: Ferrari-Marinho Taissa , Perucca Piero , Amiri Mina , Dubeau Francois , Gotman Jean , Caboclo Luis Otavio 
Published: July 2019

Purpose:
In comatose patients, distinguishing between nonconvulsive status epilepticus and diffuse structural or metabolic encephalopathies is often challenging. Both conditions can generate periodic discharges on EEG with similar morphology and periodicity. We investigated the occurrence of high-frequency oscillations—potential biomarkers of epileptogenesis—on scalp EEG of comatose patients with periodic discharges in the EEG.

Methods:
Fifteen patients were included. Patients were divided into three groups, according to underlying etiology: Group 1, seizure related; group 2, structural; group 3, nonstructural. EEG recordings were compared with respect to the presence and rates of gamma (30–80 Hz) and ripples (80–250 Hz).

Results:
Patients were 23 to 106 years old (median, 68 years); 60% were female. 206 channels were eligible for analysis (median, 15 channels/patient). Overall, 43% of channels showed gamma, and 24% had ripples. Group 2 showed the highest proportion of channels with gamma (47%), followed by group 1 (38%) and group 3 (36%). Mean gamma rates were higher in group 2 (4.65 gamma/min/channel) than in group 1 (1.52) and group 3 (1.44) (P < 0.001). Group 2 showed the highest proportion of channels with ripples (29.2%), followed by group 1 (15%) and group 3 (24.2%). Mean ripple rates were higher in group 2 (5.09 ripple/min/channel) than in group 1 (0.96) and group 3 (0.83) (P < 0.001).

Conclusions:
Fast oscillations, including high-frequency oscillations, can be detected in scalp EEG of patients with altered consciousness. High rates of fast activity may suggest an underlying structural brain lesion. Future studies are needed to determine whether fast oscillations in the setting of acute/subacute brain lesions are a biomarker of subsequent development of human epilepsy.
Towards Improved Molecular Identification Tools in Fine Fescue (FestucaL., Poaceae) Turfgrasses: Nuclear Genome Size, Ploidy, and Chloroplast Genome Sequencing
Authors: Qiu Yinjie , Hirsch Cory D. , Yang Ya , Watkins Eric 
Published: July 2019

AbstractFine fescues (FestucaL., Poaceae) are turfgrass species that perform well in low-input environments. Based on morphological characteristics, the most commonly-utilized fine fescues are divided into five taxa: three are subspecies withinF. rubraL. and the remaining two are treated as species within theF. ovinaL. complex. Morphologically, these five taxa are very similar, both identification and classification of fine fescues remain challenging. In an effort to develop identification methods for fescues, we used flow cytometry to estimate genome size, ploidy level, and sequenced the chloroplast genome of all five taxa. Fine fescue chloroplast genome sizes ranged from 133,331 to 133,841 bp and contained 113 to 114 genes. Phylogenetic relationship reconstruction using whole chloroplast genome sequences agreed with previous work based on morphology. Comparative genomics suggested unique repeat signatures for each fine fescue taxon that could potentially be used for marker development for taxon identification.
HD-tDCS over mIPS causally modulates online reach correction
Authors: Goettker Alexander , Caie Brandon , Jeyachandra Jerrold , Xu Sisi , Gallivan Jason , Dmochowski Jacek , Fiehler Katja , Blohm Gunnar 
Published: July 2019

AbstractBrain lesion and stimulation studies have suggested posterior parietal cortex and the medial intraparietal sulcus in particular as a crucial hub for online movement error corrections. However, causal evidence for this is still sparse. Indeed, lesion studies are potentially confounded by compensatory reorganization mechanisms while brain stimulation studies have produced heterogeneous results when employing transcranial magnetic stimulation. Here we designed a new complementary paradigm using fMRI-guided high-definition transcranial direct current stimulation (HD-tDCS) of the left medial intraparietal sulcus (mIPS) together with regression-based mediation analysis to re-examine the causal role of mIPS in online reach corrections to jumping targets. We obtained two independent measures of stimulation-induced changes in brain activity by modeling current flow in the brain and through EEG recordings before and after HD-tDCS stimulation. Third, to quantify behavioral effects of HD-tDCS we computed movement curvature as a measure of online correction. We demonstrate that both of our measurements of brain activity were consistent with a polarity-specific modulation of the online correction for targets jumping to the contralateral side of the stimulation. Importantly, using a mediation analysis of the relationship between stimulation current and movement curvature suggests that the induced current modifies brain activity, which then leads to the observed behavioral changes. This unique combination of methods and analysis thus provides complementary evidence for the crucial role of the posterior parietal cortex in online error correction, while at the same time setting a new methodological standard with respect to the causal influence of transcranial direct current stimulation.New & NoteworthyTranscranial direct current stimulation (tDCS) is an interesting and potentially useful tool for asking causal scientific questions and design clinical treatments. With our unique combination of highly accurate fMRI guided stimulation, current forward modeling, EEG recordings before and after the stimulation and behavioral changes we could unravel the causal structure of tDCS. Our approach naturally deals with the variability of tDCS results, increasing its potential usefulness as a tool for research and clinical applications.
Effects of size and elasticity on the relation between flow velocity and wall shear stress in side-wall aneurysms: A lattice Boltzmann-based computer simulation study
Authors: Wang Haifeng , Krüger Timm , Varnik Fathollah 
Published: July 2019

AbstractBlood flow in an artery is a fluid-structure interaction problem. It is widely accepted that aneurysm formation, enlargement and failure are associated with wall shear stress (WSS) which is exerted by flowing blood on the aneurysmal wall. To date, the combined effect of aneurysm size and wall elasticity on intra-aneurysm (IA) flow characteristics, particularly in the case of side-wall aneurysms, is poorly understood. Here we propose a model of three-dimensional viscous flow in a compliant artery containing an aneurysm by employing the immersed boundary-lattice Boltzmann-finite element method. This model allows to adequately account for the elastic deformation of both the blood vessel and aneurysm walls. Using this model, we perform a detailed investigation of the flow through aneurysm under different conditions with a focus on the parameters which may influence the wall shear stress. Most importantly, it is shown in this work that the use of flow velocity as a proxy for wall shear stress is well justified only in those sections of the vessel which are close to the ideal cylindrical geometry. Within the aneurysm domain, however, the correlation between wall shear stress and flow velocity is largely lost due to the complexity of the geometry and the resulting flow pattern. Moreover, the correlations weaken further with the phase shift between flow velocity and transmural pressure. These findings have important implications for medical applications since wall shear stress is believed to play a crucial role in aneurysm rupture.
On the early-life origins of vulnerability to opioid addiction
Authors: Levis Sophia C , Bentzley Brandon S , Molet Jenny , Bolton Jessica L , Perrone Christina R , Baram Tallie Z , Mahler Stephen V 
Published: July 2019

AbstractThe origins and neural bases of the current opioid addiction epidemic are unclear. Genetics plays a major role in addiction vulnerability, but cannot account for the recent exponential rise in opioid abuse, so environmental factors must contribute. Individuals with history of early-life adversity (ELA) are disproportionately prone to opioid addiction, yet whether ELA interacts with factors such as increased access to opioids to directly influence brain development and function and cause opioid addiction vulnerability is unknown. We simulated ELA in female rats and this led to a striking opioid addiction-like phenotype. This was characterized by resistance to extinction, increased relapse-like behavior, and, as in addicted humans, major increases in opioid economic demand. By contrast, seeking of a less salient natural reward was unaffected by ELA, whereas demand for highly palatable treats was augmented. These discoveries provide novel insights into the origins and nature of reward circuit malfunction that may set the stage for addiction.
The case for using Mapped Exonic Non-Duplicate (MEND) read counts in RNA-Seq experiments: examples from pediatric cancer datasets
Authors: Beale Holly C. , Roger Jacquelyn M. , Cattle Matthew A. , McKay Liam T. , Thomson Drew K. A. , Learned Katrina , Lyle A. Geoffrey , Kephart Ellen T. , Currie Rob , Lam Du Linh , Sanders Lauren , Pfeil Jacob , Vivian John , Bjork Isabel , Salama Sofie R. , Haussler David , Vaske Olena M. 
Published: July 2019

AbstractBackgroundThe accuracy of gene expression as measured by RNA sequencing (RNA-Seq) is dependent on the amount of sequencing performed. However, some types of reads are not informative for determining this accuracy. Unmapped and non-exonic reads do not contribute to gene expression quantification. Duplicate reads can be the product of high gene expression or technical errors.FindingsWe surveyed bulk RNA-Seq datasets from 2179 tumors in 48 cohorts to determine the fractions of uninformative reads. Total sequence depth was 0.2-668 million reads (median (med.) 61 million; interquartile range (IQR) 53 million). Unmapped reads constitute 1-77% of all reads (med. 3%; IQR 3%); duplicate reads constitute 3-100% of mapped reads (med. 27%; IQR 30%); and non-exonic reads constitute 4-97% of mapped, non-duplicate reads (med. 25%; IQR 21%). Informative reads--Mapped, Exonic, Non-duplicate (MEND) reads--constitute 0-79% of total reads (med. 50%; IQR 31%). Further, we find that MEND read counts have a 0.22 Pearson correlation to the number of genes expressed above 1 Transcript Per Million, while total reads have a correlation of −0.05.ConclusionsSince the fraction of uninformative reads vary, we propose using only definitively informative reads, MEND reads, for the purposes of asserting the accuracy of gene expression measured in a bulk RNA-Seq experiment. We provide a Docker image containing 1) the existing required tools (RSeQC, sambamba and samblaster) and 2) a custom script. We recommend that all results, sensitivity studies and depth recommendations use MEND units.
Viral gene drive in herpesviruses
Authors: Walter Marius , Verdin Eric 
Published: July 2019

AbstractHerpesviruses are ubiquitous pathogens in need of novel therapeutic solutions. Current engineered gene drive strategies rely on sexual reproduction, and are thought to be restricted to sexual organisms. Here, we report on the design of a novel gene drive system that allows the spread of an engineered trait in populations of DNA viruses and, in particular, herpesviruses. We describe the successful transmission of a gene drive sequence between distinct strains of human cytomegalovirus (human herpesvirus 5) and show that gene drive viruses can efficiently target and replace wildtype populations in cell culture experiments. Our results indicate that viral gene drives can be used to suppress a viral infection and may represent a novel therapeutic strategy against herpesviruses.
The Implications of Over-Estimating Gene Tree Discordance on a Rapid-Radiation Species Tree (Blattodea: Blaberidae)
Authors: Evangelista Dominic A. , Gilchrist Michael A. , Legendre Frédéric , O’Meara Brian 
Published: July 2019

AbstractPatterns of discordance between gene trees and the species trees they reside in are crucial to the debate over the superiority of coalescent or concatenation approaches to tree inference. However, errors in estimating gene tree topologies obfuscate the issue by making gene trees appear erroneously discordant with the species tree. We thus test the prevalence of discordance between gene trees and their species tree using an empirical dataset for a clade with a rapid radiation (Blaberidae). We find that one model of codon evolution (FMutSel0) prefers gene trees that are less discordant, while another (SelAC) shows no such preference. We compare the species trees resulting from the selected sets of gene trees on the basis of internal consistency, predictive ability, and congruence with independent data. The species tree resulting from gene trees those chosen by FMutSel0, a set with low discordance, is the most robust and biologically plausible. Thus, we conclude that the results from FMutSel0 are better supported: simple models (i.e., GTR and ECM) infer trees with erroneously high levels of gene tree discordance. Furthermore, the amount of discordance in the set of gene trees has a large effect on the downstream phylogeny. Thus, decreasing gene tree error by lessening erroneous discordance can result in higher quality species trees. These results allow us to support relationships among blaberid cockroaches that were previously in flux as they now demonstrate molecular and morphological congruence.
Mendelian Randomization analyses reveal a causal effect of thyroid function on stroke via atrial fibrillation
Authors: Marouli Eirini , Kus Aleksander , Del Greco M. Fabiola , Chaker Layal , Peeters Robin , Teumer Alexander , Deloukas Panos , Medici Marco 
Published: July 2019

AbstractBackgroundSeveral observational studies suggest that variations in thyroid function, even within the normal range, are a risk factor for cardiovascular diseases, but it remains to be determined if these associations are causal or not. This study investigates whether the relationship between variation in normal range thyroid function, as well as hypothyroidism and hyperthyroidism, and the risk of stroke and Coronary Artery Disease (CAD) are causal and via which pathways these relations are mediated.Methods and FindingsWe performed Mendelian Randomization (MR) analyses for stroke and CAD using genetic instruments associated with TSH and FT4 levels respectively within either the normal range, hypothyroidism or hyperthyroidism. In detected associations, the potential mediatory role of known stroke and CAD risk factors was also examined. A one standard deviation increase in TSH was associated with a 5% decrease in the risk of stroke (OR=0.95, 95% CI= 0.91 to 0.99). Multivariable MR analyses indicated that this effect is mediated through atrial fibrillation (AF). Hashimoto’s Disease (HD) was associated with a 7% increased risk of CAD (OR=1.07, 95% CI= 1.01 to 1.13). The effect of Hashimoto’s Disease (HD) on CAD risk appears to be mediated via body mass index (BMI).ConclusionsThese results provide important new insights into the causal relationships and mediating pathways between thyroid function, stroke and CAD. Specifically, we identify normal range TSH levels and HD as potential modifiable risk factors for stroke and CAD, respectively.
Age and ketogenic diet have dissociable effects on synapse-related gene expression between hippocampal subregions
Authors: Hernandez Abbi R. , Hernandez Caesar M. , Truckenbrod Leah M. , Campos Keila T. , McQuail Joseph A. , Bizon Jennifer L. , Burke Sara N. 
Published: July 2019

AbstractAs the number of individuals living beyond the age of 65 is rapidly increasing, so is the need to develop strategies to combat the age-related cognitive decline that may threaten independent living. Although the link between altered neuronal signaling and age-related cognitive impairments is not completely understood, it is evident that declining cognitive abilities are at least partially due to synaptic dysfunction. Aging is accompanied by well-documented changes in both excitatory and inhibitory synaptic signaling across species. Age-related synaptic alterations are not uniform across the brain, however, with different regions showing unique patterns of vulnerability in advanced age. In the hippocampus, increased activity within the CA3 subregion has been observed across species, and this can be reversed with anti-epileptic medication (Bakker et al., 2012). In contrast to CA3, the dentate gyrus shows reduced activity with age and declining metabolic activity. Ketogenic diets have been shown to decrease seizure incidence and severity in epilepsy, improve metabolic function in diabetes type II, and improve cognitive function in aged rats. This link between neuronal activity and metabolism suggests that metabolic interventions may be able to ameliorate synaptic signaling deficits accompanying advanced age. We therefore investigated the ability of a dietary regimen capable of inducing nutritional ketosis and improving cognition to alter synapse-related gene expression across the dentate gyrus, CA3 and CA1 subregions of the hippocampus. Following 12 weeks of a ketogenic or calorie-matched standard diet, RTq-PCR was used to quantify expression levels of excitatory and inhibitory synaptic signaling genes within CA1, CA3 and dentate gyrus. While there were no age or diet-related changes in CA1 gene expression, expression levels were significantly altered within CA3 by age and within the dentate gyrus by diet for several genes involved in presynaptic glutamate regulation and postsynaptic excitation and plasticity. These data demonstrate subregion-specific alterations in synaptic signaling with age and the potential for a ketogenic diet to alter these processes in dissociable ways across different brain structures that are uniquely vulnerable in older animals.
Carotid intima-media thickness in UK Biobank: Identification of novel genome-wide loci, sex-specific effects and genetic correlations with obesity and glucometabolic traits
Authors: Strawbridge Rona J. , Ward Joey , Bailey Mark E.S. , Cullen Breda , Ferguson Amy , Graham Nicholas , Johnston Keira J.A. , Lyall Laura M. , Pearsall Robert , Pell Jill , Shaw Richard J , Tank Rachana , Lyall Donald M. , Smith Daniel J. 
Published: July 2019

AbstractObjectivesAtherosclerosis is the underlying cause of most cardiovascular disease, but mechanisms underlying atherosclerosis are incompletely understood. Ultra-sound measurement of the carotid artery intima-media thickness (cIMT) can be used to measure vascular remodelling, which is indicative of atherosclerosis. Genome-wide association studies have identified a number of genetic loci associated with cIMT, but heterogeneity of measurements collected by many small cohorts have been a major limitation in these efforts. Here we conducted genome-wide association analyses in UK Biobank (N=22,179), the largest single study with consistent cIMT measurements.Approach and resultsWe used BOLT-LMM to run linear regression of cIMT in UK Biobank, adjusted for age, sex, genotyping platform and population structure. In white British participants, we identified 4 novel loci associated with cIMT and replicated most previously reported loci. In the first sex-specific analyses of cIMT, we identified a female-specific locus on Chromosome 5, associated with cIMT in women only and highlightVCANas a good candidate gene at this locus. Genetic correlations with body-mass index and glucometabolic traits were also observed.ConclusionThese findings replicate previously reported associations, highlight novel biology and provide new directions for investigating the sex differences observed in cardiovascular disease presentation and progression.
ERK activation in CAR T cells is amplified by CD28-mediated increase in CD3ζ phosphorylation
Authors: Rohrs Jennifer A. , Siegler Elizabeth L. , Wang Pin , Finley Stacey D. 
Published: July 2019

ABSTRACTChimeric antigen receptors (CARs) are engineered receptors that mediate T cell activation. CARs are comprised of activating and costimulatory intracellular signaling domains derived from endogenous T cells that initiate signaling required for T cell activation, including ERK activation through the MAPK pathway. Understanding the mechanisms by which co-stimulatory domains influence signaling can help guide the design of next-generation CARs. Therefore, we constructed an experimentally-validated computational model of anti-CD19 CARs in T cells bearing the CD3ζ domain alone or in combination with CD28. We used ensemble modeling to explore different mechanisms of CD28 co-stimulation on the ERK response time. Model simulations show that CD28 primarily influences ERK activation by enhancing the phosphorylation kinetics of CD3ζ, predictions that are validated by experimental measurements. Overall, we present a mechanistic mathematical modeling framework that can be used to gain insights into the mechanism of CAR T cell activation and produce new testable hypotheses.
Characterizing the Emergence of Liver and Gallbladder from the Embryonic Endoderm through Single-Cell RNA-Seq
Authors: Mu Tianhao , Xu Liqin , Zhong Yu , Liu Xinyu , Zhao Zhikun , Huang Chaoben , Lan Xiaofeng , Lufei Chengchen , Zhou Yi , Su Yixun , Xu Luang , Jiang Miaomiao , Zhou Hongpo , Lin Xinxin , Wu Liang , Peng Siqi , Liu Shiping , Brix Susanne , Dean Michael , Dunn Norris R. , Zaret Kenneth S. , Fu Xin-Yuan , Hou Yong 
Published: July 2019

AbstractThe liver and gallbladder are among the most important internal organs derived from the endoderm. Several inductive signals regulate liver development, yet the pure nascent hepatic and gallbladder cells are unable to be isolated due to limited cell markers and cell numbers. The transcriptome networks of the hepatic lineage in the endoderm, and how the gallbladder differentiates from the adjacent endoderm population, are not fully understood. Using a transgenic Foxa2eGFPreporter mouse line, we performed deep single-cell RNA sequencing on 1,966 individual cells, including nascent hepatic and gallbladder cells, isolated from the endoderm and hepatic regions from ten embryonic stages, ranging from day E7.5 to E15.5. We identified the embryonic liver developmental trajectory from primitive streak to hepatoblasts and characterized the transcriptome of the hepatic lineage. During pre-hepatogenesis (5-6 somite stage), we have identified two groups of foregut endoderm cells, one derived from visceral endoderm and the second derived from primitive streak via a mesenchymal-epithelial transition (MET). During the liver specification stages, liver primordium was identified to share both foregut and liver features. We also documented dynamic gene expression during the epithelial-hepatic transition (EHT). Six gene groups were found to switch on or off at different stages during liver specification. Importantly, we found that RXR complex signaling and newly identified transcription factors associated with liver specification. Moreover, we revealed the gallbladder primordium cells at E9.5 and found genes that transcriptionally distinguish them from the liver primordium. The present data provides a high-resolution resource and critical insights for understanding the emergence of the endoderm, liver and gallbladder development.