bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Tear Film Lipid Layer Thickness and Blinking Pattern on Tear Film Instability After Corneal Refractive Surgery
Authors: Chen Qingzhong , Li Min , Yuan Ying , Me Rao , Yu Yunjie , Shi Guangsen , Wang Xin , Ke Bilian 
Published: April 2017

Purpose:
To investigate associations between changes in tear film instability and the lipid layer thickness (LLT) and blink pattern after corneal refractive surgery (CRS).

Methods:
Forty patients were enrolled in this study. The LLT and blink pattern were evaluated 1 week before and 30 days after CRS using a novel interferometer and an ocular surface disease index (OSDI) questionnaire, and other tear film stability markers were also evaluated.

Results:
Mean OSDI scores increased from 5.52 to 8.54 (P = 0.016), corneal fluorescence staining scores increased from 0.05 to 0.25 (P = 0.034), first noninvasive tear breakup time (NIBUT-F) decreased from 9.66 to 7.33 seconds (P = 0.014), and average noninvasive tear breakup time (NIBUT-Ave) decreased from 12.32 to 10.26 seconds (P = 0.047) 1 month after CRS. Meanwhile, mean total blink frequency in 20 seconds decreased significantly from 12.62 to 6.31 (P < 0.001); LLT did not change significantly (P = 0.447). The change in NIBUT-Ave was positively correlated with that in LLT (P = 0.003) and negatively correlated with that in the partial blink rate (P = 0.013). The changes in the OSDI questionnaire, NIBUT, LLT, and blink pattern were not different between the laser-assisted in situ keratomileusis and laser-assisted subepithelial keratomileusis groups.

Conclusions:
A decrease in tear film stability occurs 1 month after CRS, the change in the blink pattern and unchanged LLT preoperatively and postoperatively suggesting that these parameters play a role in maintaining tear film stability after CRS.
Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin–Tazobactam Safety in Infants
Authors: Salerno Sara , Hornik Christoph P. , Cohen-Wolkowiez Michael , Smith P. Brian , Ku Lawrence C. , Kelly Matthew S. , Clark Reese , Gonzalez Daniel 
Published: April 2017

Background:
Piperacillin, in combination with tazobactam, is frequently used in infants for treating nosocomial infections, although safety data in this population are limited. Electronic health record (EHR) data can be used to evaluate drug safety in infants, but measures of drug exposure are lacking.

Methods:
To relate simulated piperacillin exposure with adverse events (AEs) in infants using EHR data, we identified infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012. Using a previously published population pharmacokinetic model in the target population, we simulated piperacillin steady state area under the concentration versus time curve from zero to τ (AUCss,0-τ
) and steady state maximal drug concentration (Cmaxss). Next, we used multivariable logistic regression to evaluate the association between simulated AUCss,0-τ
and Cmaxss with clinical AEs (seizure and rash) and laboratory AEs controlling for gestational age. The odds ratios (95% confidence intervals) comparing the third versus the first tertiles for AUCss,0-τ
and Cmaxss were reported.

Results:
We identified 746 infants with a median (interquartile range) gestational age of 30 weeks (26–33) and postnatal age of 11 days (6–25). The median (interquartile range) piperacillin dose was 225 mg/kg/d (176–300). No significant associations were found between simulated piperacillin exposure (AUCss,0-τ
and Cmaxss) and clinical and laboratory AEs.

Conclusions:
We found no associations between predicted piperacillin exposures and the occurrence of AEs. This study confirms the feasibility of using population pharmacokinetics and EHR to relate drug exposure with safety.
HIV Transmission to Premature Very Low Birth Weight Infants
Authors: Levin Candyce , Le Roux David M. , Harrison Michael C. , Tooke Lloyd 
Published: April 2017

Abstract:There is sparse literature about HIV transmission in preterm infants. Eighty-two HIV-exposed preterm infants received birth polymerase chain reactions (PCRs). Five (6.1%) were HIV positive with all 5 mothers receiving inadequate antiretrovirals. Of the PCR-negative infants, 9 died and 87% of the survivors received further PCR testing which remained negative. With correct care, intrapartum transmission of HIV can virtually be eliminated.
Bayesian inference of cancer driver genes using signatures of positive selection
Authors: Zapata Luis , Susak Hana , Drechsel Oliver , Friedländer Marc R. , Estivill Xavier , Ossowski Stephan 
Published: April 2017

AbstractTumors are composed of an evolving population of cells subjected to tissue-specific selection, which fuels tumor heterogeneity and ultimately complicates cancer driver gene identification. Here, we integrate cancer cell fraction, population recurrence, and functional impact of somatic mutations as signatures of selection into a Bayesian inference model for driver prediction. In an in-depth benchmark, we demonstrate that our model, cDriver, outperforms competing methods when analyzing solid tumors, hematological malignancies, and pan-cancer datasets. Applying cDriver to exome sequencing data of 21 cancer types from 6,870 individuals revealed 98 unreported tumor type-driver gene connections. These novel connections are highly enriched for chromatin-modifying proteins, hinting at a universal role of chromatin regulation in cancer etiology. Although infrequently mutated as single genes, we show that chromatin modifiers are altered in a large fraction of cancer patients. In summary, we demonstrate that integration of evolutionary signatures is key for identifying mutational driver genes, thereby facilitating the discovery of novel therapeutic targets for cancer treatment.
Describing the Local Structure of Sequence Graphs
Authors: Rosen Yohei , Eizenga Jordan , Paten Benedict 
Published: April 2017

AbstractAnalysis of genetic variation using graph structures is an emerging paradigm of genomics. However, defining genetic sites on sequence graphs remains an open problem. Paten’s invention of theultra-bubbleandsnarl, special subgraphs of sequence graphs which can identified with efficient algorithms, represents important first step to segregating graphs into genetic sites. We extend the theory of ultrabubbles to a special subclass where every detail of the ultrabubble can be described in a series and parallel arrangement of genetic sites. We furthermore introduce the concept ofbundlestructures, which allows us to recognize the graph motifs created by additional combinations of variation in the graph, including but not limited to runs of abutting single nucleotide variants. We demonstrate linear-time identification of bundles in a bidirected graph. These two advances build on initial work on ultrabubbles in bidirected graphs, and define a more granular concept of genetic site.
Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos
Authors: Joseph Shai R. , Pálfy Máté , Hilbert Lennart , Kumar Mukesh , Karschau Jens , Zaburdaev Vasily , Shevchenko Andrej , Vastenhouw Nadine L. 
Published: April 2017

SUMMARYUpon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA bound core histones sets the time for the onset of transcription. The reduction in nuclear histone concentration that coincides with genome activation does not affect nucleosome density on DNA, but allows transcription factors to compete successfully for DNA binding. In agreement with this, transcription factor binding is sensitive to histone levels and the concentration of transcription factors also affects the time of transcription. Our results demonstrate that the relative levels of histones and transcription factors regulate the onset of transcription in the embryo.
Genome-Wide Mechanisms of Lifespan Extension by Dietary Restriction in Yeast
Authors: Campos Sergio E. , Garay Erika , Avelar-Rivas J. Abraham , Juárez-Reyes Alejandro , DeLuna Alexander 
Published: April 2017

SUMMARYDietary restriction is arguably the most promising non-pharmacological intervention to extend human life and health span. Yet, only few genetic regulators mediating the cellular response to dietary restriction are known, and the question remains which other transcription factors and regulatory pathways are involved. To gain a comprehensive view of how lifespan extension under dietary restriction is elicited, we screened the chronological lifespan of most gene deletions ofSaccharomyces cerevisiaeunder two dietary regimens, restricted and non-restricted. We identified 472 mutants with enhanced or diminished extension of lifespan by dietary restriction. Functional analysis of such dietary-restriction genes revealed novel processes underlying longevity specifically by dietary restriction. Importantly, this set of genes allowed us to generate a prioritized catalogue of transcription factors orchestrating the dietary-restriction response, which underscored the relevance of cell-cycle arrest control as a key mechanism of chronological longevity in yeast. We show that the transcription factor Ste12 is needed for full lifespan extension and cell-cycle arrest in response to nutrient limitation; linking the pheromone/invasive growth pathway with cell survivorship. Strikingly,STE12overexpression was sufficient to extend chronological lifespan under non-restricted conditions. Our global picture of the genetic players of longevity by dietary restriction highlights intricate regulatory cross-talks in aging cells.
Limited contribution of rare, noncoding variation to autism spectrum disorder from sequencing of 2,076 genomes in quartet families
Authors: Werling Donna M. , Brand Harrison , An Joon-Yong , Stone Matthew R. , Glessner Joseph T. , Zhu Lingxue , Collins Ryan L. , Dong Shan , Layer Ryan M. , Markenscoff-Papadimitriou Eirene , Farrell Andrew , Schwartz Grace B. , Currall Benjamin B. , Dea Jeanselle , Duhn Clif , Erdman Carolyn , Gilson Michael , Handsaker Robert E. , Kashin Seva , Klei Lambertus , Mandell Jeffrey D. , Nowakowski Tomasz J. , Liu Yuwen , Pochareddy Sirisha , Smith Louw , Walker Michael F. , Wang Harold Z. , Waterman Mathew J. , He Xin , Kriegstein Arnold R. , Rubenstein John L. , Sestan Nenad , McCarroll Steven A. , Neale Ben M. , Coon Hilary , Willsey A. Jeremy , Buxbaum Joseph D. , Daly Mark J. , State Matthew W. , Quinlan Aaron , Marth Gabor T. , Roeder Kathryn , Devlin Bernie , Talkowski Michael E. , Sanders Stephan J. 
Published: April 2017

SummaryGenomic studies to date in autism spectrum disorder (ASD) have largely focused on newly arising mutations that disrupt protein coding sequence and strongly influence risk. We evaluate the contribution of noncoding regulatory variation across the size and frequency spectrum through whole genome sequencing of 519 ASD cases, their unaffected sibling controls, and parents. Cases carry a small excess ofde novo(1.02-fold) noncoding variants, which is not significant after correcting for paternal age. Assessing 51,801 regulatory classes, no category is significantly associated with ASD after correction for multiple testing. The strongest signals are observed in coding regions, including structural variation not detected by previous technologies and missense variation. While rare noncoding variation likely contributes to risk in neurodevelopmental disorders, no category of variation has impact equivalent to loss-of-function mutations. Average effect sizes are likely to be smaller than that for coding variation, requiring substantially larger samples to quantify this risk.
Gamma oscillations in the rat ventral striatum originate in the piriform cortex
Authors: Carmichael James E. , Gmaz Jimmie M. , van der Meer Matthijs A. A. 
Published: April 2017

AbstractLocal field potentials (LFP) recorded from the human and rodent ventral striatum (vStr) exhibit prominent, behaviorally relevant gamma-band oscillations. These oscillations are related to local spiking activity and transiently synchronize with anatomically related areas, suggesting a possible role in organizing vStr activity. However, the origin of vStr gamma is unknown. We recorded vStr gamma oscillations across a 1.4mm2grid spanned by 64 recording electrodes as rats rested and foraged for rewards, revealing a highly consistent power gradient originating in the adjacent piriform cortex. Phase differences across the vStr were consistently small (<10°) and current source density analysis further confirmed the absence of local sink-source pairs in the vStr. Reversible occlusions of the ipsilateral (but not contralateral) nostril, known to abolish gamma oscillations in the piriform cortex, strongly reduced vStr gamma power and the occurrence of transient gamma-band events. These results imply that local circuitry is not a major contributor to gamma oscillations in the vStr LFP, and that piriform cortex is an important driver of gamma-band oscillations in the vStr and associated limbic areas.Significance StatementThe ventral striatum is an area of anatomical convergence in circuits underlying motivated behavior, but it remains unclear how its inputs from different sources interact. One of the major proposals of how neural circuits may dynamically switch between convergent inputs is through temporal organization reflected in local field potential (LFP) oscillations. Our results show that in the rat, the mechanisms controlling vStr gamma oscillations are primarily located in the in the adjacent piriform cortex, rather than vStr itself. This provides a novel interpretation of previous rodent work on gamma oscillations in the vStr and related circuits, and an important consideration for future work seeking to use oscillations in these areas as biomarkers in rodent models of human behavioral and neurological disorders.
Comparison of NMR and crystal structures of membrane proteins and computational refinement to improve model quality
Authors: Leman Julia Koehler , D’Avino Andrew R. , Bhatnagar Yash , Gray Jeffrey J. 
Published: April 2017

AbstractMembrane proteins are challenging to study and restraints for structure determination are typically sparse or of low resolution because the membrane environment that surrounds them leads to a variety of experimental challenges. When membrane protein structures are determined by different techniques in different environments, a natural question is “which structure is most biologically relevant?” Towards answering this question, we compiled a dataset of membrane proteins with known structures determined by both solution NMR and X-ray crystallography. By investigating differences between the structures, we found that RMSDs between crystal and NMR structures are below 5 Å in the membrane region, NMR ensembles have a higher convergence in the membrane region, crystal structures typically have a straighter transmembrane region, have higher stereo-chemical correctness, and are more tightly packed. After quantifying these differences, we used high-resolution refinement of the NMR structures to mitigate them, which paves the way for identifying and improving the structural quality of membrane proteins.
A Collection of 2,280 Public Domain (CC0) Curated Human Genotypes
Authors: Shaw Richard J. , Corpas Manuel 
Published: April 2017

AbstractCheap sequencing has driven the proliferation of big human genome data aggregation consortiums, providing extensive reference datasets for genome research. These datasets, however, may come with restrictive terms of use, conditioned by the consent frameworks within which individuals donate their data. Having an aggregated genome dataset with unrestricted use, analogous to public domain licensing, is therefore unusually rare. Yet public domain data is tremendously useful because it allows freedom to perform research with it. This comes with the price of donors surrendering their privacy and accepting the associated risks derived from publishing personal data. Using the Repositive platform (https://repositive.io/?23andMe), an indexing service for human genome datasets, we aggregated all deposited files in public data sources under a CC0 license from 23andMe, a leading Direct-to-Consumer genetic testing service. After downloading 3,137 genotypes, we filtered out those that were incomplete, corrupt or duplicated, ending up with a dataset of 2,280 curated files, each one corresponding to a unique individual. Although the size of this dataset is modest compared to current major genome data aggregation projects, its full access and licensing terms, which allows free reuse without attribution, make it a useful reference pool for validation purposes and control experiments.
Ras/MAPK modifier loci revealed by eQTL inC. elegans
Authors: Sterken Mark G. , van Bemmelen van der Plaat Linda , Riksen Joost A. G. , Rodriguez Miriam , Schmid Tobias , Hajnal Alex , Kammenga Jan E. , Snoek Basten L. 
Published: April 2017

ABSTRACTThe oncogenic Ras/MAPK pathway is evolutionarily conserved across metazoans. Yet, almost all our knowledge on this pathway comes from studies using single genetic backgrounds, whereas mutational effects can be highly background dependent. Therefore, we lack insight in the interplay between genetic backgrounds and the Ras/MAPK-signaling pathway. Here, we used aCaenorhabditis elegansRIL population containing a gain-of-function mutation in the Ras/MAPK pathway genelet-60and measured how gene expression regulation is affected by this mutation. We mapped eQTL and found that the majority (~73%) of the 1516 detectedcis-eQTL were not specific for thelet-60mutation, whereas most (~76%) of the 898 detectedtrans-eQTL were associated with thelet-60mutation. We detected 6 eQTLtrans-bands specific for the interaction between the genetic background and the mutation, one of which co-localized with the polymorphic Ras/MAPK modifieramx-2. Comparison between transgenic lines expressing allelic variants ofamx-2showed the involvement ofamx-2in 79% of thetrans-eQTL for genes mapping to thistrans-band. Together, our results have revealed loci hidden loci affecting Ras/MAPK signaling using sensitized backgrounds inC. elegans. These loci harbor putative polymorphic modifier genes that would not have been detected using mutant screens in single genetic backgrounds.
Just above chance: is it harder to decode information from human prefrontal cortex BOLD signals?
Authors: Bhandari Apoorva , Gagne Christopher , Badre David 
Published: April 2017

AbstractUnderstanding the nature and form of prefrontal cortex representations that support flexible behavior is an important open problem in cognitive neuroscience. In humans, multi-voxel pattern analysis (MVPA) of fMRI BOLD measurements has emerged as an important approach for studying neural representations. An implicit, untested assumption underlying many PFC MVPA studies is that the base rate of decoding information from PFC BOLD activity patterns is similar to that of other brain regions. Here we estimate these base rates from a meta-analysis of published MVPA studies and show that the PFC has a significantly lower base rate for decoding than visual sensory cortex. Our results have implications for the design and interpretation of MVPA studies of prefrontal cortex, and raise important questions about its functional organization.
Volumetric grey matter alterations in adolescents and adults born very preterm suggest accelerated brain maturation
Authors: Karolis Vyacheslav R. , Froudist-Walsh Sean , Kroll Jasmin , Brittain Philip J. , Tseng Chieh-En Jane , Nam Kie-Woo , Reinders Antje A. T. S. , Murray Robin M. , Williams Steven C. R. , Thompson Paul M. , Nosarti Chiara 
Published: April 2017

AbstractPrevious research investigating structural neurodevelopmental alterations in individuals who were born very preterm demonstrated a complex pattern of grey matter changes that defy straightforward summary. Here we addressed this problem by characterising volumetric brain alterations in individuals who were born very preterm from adolescence to adulthood at three hierarchically related levels - global, modular and regional. We demarcated structural components that were either particularly resilient or vulnerable to the impact of very preterm birth. We showed that individuals who were born very preterm had smaller global grey matter volume compared to controls, with subcortical and medial temporal regions being particularly affected. Conversely, frontal and lateral parieto-temporal cortices were relatively resilient to the effects of very preterm birth, possibly indicating compensatory mechanisms. Exploratory analyses supported this hypothesis by showing a stronger association of lateral parieto-temporal volume with IQ in the very preterm group compared to controls. We then related these alterations to brain maturation processes. Very preterm individuals exhibited a higher maturation index compared to controls, indicating accelerated brain ageing and this was specifically associated with younger gestational age. We discuss how the findings of accelerated maturation might be reconciled with evidence of delayed maturation at earlier stages of development.
Comparison of equine platelet function and survival in whole blood collected in acid‐citrate‐dextrose solution or citrate‐phosphate‐dextrose‐adenine solution
Authors: Bozorgmanesh Rana , Sutton‐Burges Julie W. , Tablin Fern 
Published: April 2017

BackgroundEquine whole blood collection and storage methods have been evaluated to assess red blood cell viability; however, platelet (PLT) viability has not been comprehensively assessed.ObjectivesThe purpose of the study was to compare viability of PLTs collected in whole blood into 2 different anticoagulants.MethodsWhole blood from 6 healthy adult Thoroughbred horses was collected into citrate‐phosphate‐dextrose‐adenine (CPDA) or acid‐citrate‐dextrose (ACD). Platelet count, pH, and concentrations of glucose, lactate, carbon dioxide, oxygen, bicarbonate, sodium, potassium, and chloride were measured within 10 minutes of collection and then again one hour later at which time PLT aggregometry was performed to assess PLT function.ResultsAggregometry mean amplitudes were significantly higher in CPDA compared to ACD. Blood glucose, pH, bicarbonate, sodium, and lactate concentrations were significantly higher in CPDA compared to ACD. Lactate concentration was higher following one hour in either anticoagulant. Potassium, oxygen, and carbon dioxide concentrations were significantly higher in ACD compared to CPDA at collection.ConclusionsPlatelet aggregometry results suggest that CPDA is superior to ACD for maintaining PLT viability following whole blood collection. This may be associated with the higher, more neutral pH as well as an increase in glucose available for metabolism. Although lactate was increased in the CPDA samples it was not high enough to decrease pH and therefore may not have been high enough to cause morphologic lesions and loss of PLT viability.
Permanent Draft Genome Sequence of Desulfurococcus amylolyticus Strain Z-533
T
, a Peptide and Starch Degrader Isolated from Thermal Springs in the Kamchatka Peninsula and Kunashir Island, Russia
Authors: Susanti Dwi , Johnson Eric F. , Lapidus Alla , Han James , Reddy T. B. K. , Mukherjee Supratim , Pillay Manoj , Perevalova Anna A. , Ivanova Natalia N. , Woyke Tanja , Kyrpides Nikos C. , Mukhopadhyay Biswarup 
Published: April 2017

ABSTRACT

Desulfurococcus amylolyticus
Z-533
T
, a hyperthermophilic crenarcheon, ferments peptide and starch, generating acetate, isobutyrate, isovalerate, CO
2
, and hydrogen. Unlike
D. amylolyticus
Z-1312, it cannot use cellulose and is inhibited by hydrogen. The reported draft genome sequence of
D. amylolyticus
Z-533
T
will help to understand the molecular basis for these differences.