bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns
Authors: Sanchez-Mut J V , Heyn H , Vidal E , Moran S , Sayols S , Delgado-Morales R , Schultz M D , Ansoleaga B , Garcia-Esparcia P , Pons-Espinal M , de Lagran M M , Dopazo J , Rabano A , Avila J , Dierssen M , Lott I , Ferrer I , Ecker J R , Esteller M 
Published: January 2016

AbstractDifferent neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease and Alzheimer-like neurodegenerative profile associated with Down’s syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies.
Embeddedness levels in Central and East European countries as revealed by patent-related indicators
Authors: Inzelt Annamária 
Published: January 2016

Central and East European countries (CEECs) still show many features of the Soviet era. Consequently, the region seems, in several ways, to have been shaped by a single universal phase of transformation. This explains, at least in part, the relatively weak patenting activities and innovation performance of these countries. This paper deals with quantitative information originating from a newly created databank and investigates CEECs, employing various patent indicators in a Triple Helix context.
New member states of the European Union (EU) from CEECs accounted for less than 1% of European patents between 1990 and 2006. This figure does not improve if patent applications are normalised according to population, and the number of patents registered in the region has evolved very little over the years. Analysing the relationships among old and new member states of the EU and their regions in terms of citations shows the pattern of intellectual linkages within Europe quite clearly. Even if CEECs feature relatively rarely in cited European publications, there are still 43 CEE affiliations recorded among the top 500 in Europe (ranked by performance). Intellectual linkages are still weak (both within the CEE area and among old and new EU member states and their regions), and the citation pattern clearly shows the importance of externally derived knowledge for CEE countries. Self-citation highlights the weakness of scientific impulses from the immediate environment to patenting activity. A very low level of self-citation may be indicative not only of low capabilities in terms of knowledge production, but also of a basic weakness in knowledge dissemination and absorption. In this respect, CEE universities have not yet shown themselves to be strong regional innovation organisers.
Hepatitis E Virus Infection Among Solid Organ Transplant Recipients at a North American Transplant Center
Authors: Sue Paul K. , Pisanic Nora , Heaney Christopher D. , Forman Michael , Valsamakis Alexandra , Jackson Annette M. , Ticehurst John R. , Montgomery Robert A. , Schwarz Kathleen B. , Nelson Kenrad E. , Karnsakul Wikrom 
Published: January 2016

Abstract
Background.  Autochthonous hepatitis E virus (HEV) infection has been reported in over 200 solid organ transplant (SOT) recipients since 2006, yet little is known about the burden of HEV among SOT recipients in North America. We performed a retrospective, cross-sectional study to investigate the prevalence and risk factors associated with HEV infection among SOT recipients at our institution.
Methods.  Children and adults (n = 311) who received allografts between 1988 and 2012 at the Johns Hopkins Hospital were assessed for evidence of HEV infection by testing posttransplantation serum samples for HEV antibody by enzyme immunoassay and HEV RNA by reverse transcription quantitative polymerase chain reaction. Individuals with evidence of posttransplant HEV infection (presence of anti-HEV immunoglobulin [Ig]M antibody, anti-HEV IgG seroconversion, or HEV RNA) were compared with individuals without evidence of infection and assessed for risk factors associated with infection.
Results.  Twelve individuals (4%) developed posttransplant HEV infection. Posttransplant HEV infection was associated with an increased risk for graft rejection (odds ratio, 14.2; P = .03). No individuals developed chronic infection.
Conclusions.  Solid organ transplant recipients in the United States are at risk for posttransplant HEV infection. Further studies are needed to characterize environmental risk factors and the risk of HEV infection after SOT in North America.
Relative Weighting of Semantic and Syntactic Cues in Native and Non-Native Listeners’ Recognition of English Sentences
Authors: Shi Lu-Feng , Koenig Laura L. 
Published: January 2016

Objective:
Non-native listeners do not recognize English sentences as effectively as native listeners, especially in noise. It is not entirely clear to what extent such group differences arise from differences in relative weight of semantic versus syntactic cues. This study quantified the use and weighting of these contextual cues via Boothroyd and Nittrouer’s j and k factors. The j represents the probability of recognizing sentences with or without context, whereas the k represents the degree to which context improves recognition performance.

Design:
Four groups of 13 normal-hearing young adult listeners participated. One group consisted of native English monolingual (EMN) listeners, whereas the other three consisted of non-native listeners contrasting in their language dominance and first language: English-dominant Russian-English, Russian-dominant Russian-English, and Spanish-dominant Spanish-English bilinguals. All listeners were presented three sets of four-word sentences: high-predictability sentences included both semantic and syntactic cues, low-predictability sentences included syntactic cues only, and zero-predictability sentences included neither semantic nor syntactic cues. Sentences were presented at 65 dB SPL binaurally in the presence of speech-spectrum noise at +3 dB SNR. Listeners orally repeated each sentence and recognition was calculated for individual words as well as the sentence as a whole.

Results:
Comparable j values across groups for high-predictability, low-predictability, and zero-predictability sentences suggested that all listeners, native and non-native, utilized contextual cues to recognize English sentences. Analysis of the k factor indicated that non-native listeners took advantage of syntax as effectively as EMN listeners. However, only English-dominant bilinguals utilized semantics to the same extent as EMN listeners; semantics did not provide a significant benefit for the two non-English-dominant groups. When combined, semantics and syntax benefitted EMN listeners significantly more than all three non-native groups of listeners.

Conclusions:
Language background influenced the use and weighting of semantic and syntactic cues in a complex manner. A native language advantage existed in the effective use of both cues combined. A language-dominance effect was seen in the use of semantics. No first-language effect was present for the use of either or both cues. For all non-native listeners, syntax contributed significantly more to sentence recognition than semantics, possibly due to the fact that semantics develops more gradually than syntax in second-language acquisition. The present study provides evidence that Boothroyd and Nittrouer’s j and k factors can be successfully used to quantify the effectiveness of contextual cue use in clinically relevant, linguistically diverse populations.
Practitioner Perceptions of Patients Wearing Decorative Contact Lenses Purchased Through Unauthorized Sellers
Authors: Gaiser Hilary , Ho Connie , Janier Nicole , Wee Amy , Johnson Catherine , Watanabe Ronald 
Published: January 2016

Objectives:
To describe practitioner experiences regarding ocular complications in patients wearing decorative contact lenses, and to investigate the compliance of unauthorized distributors of decorative contact lenses to current Food and Drug Administration (FDA) and Federal Trade Commission (FTC) regulations. Also, to provide data to support a more targeted public health approach to reducing the incidence of illegal contact lens sales and associated ocular complications.

Methods:
An institutional review board–approved online survey was distributed through mass email to a list of 98 optometrists in the Boston, MA area. Concurrently, an empirical evaluation of independent, online decorative contact lens sellers who were not associated with FDA-approved contact lens manufacturers was performed to determine their adherence to FDA and FTC guidelines. The first 18 noncoincidental websites that resulted from a Google search for “costume contact lens sellers” and “cosmetic contact lens sellers” were examined as to the brands and parameters of lenses being sold, whether or not a valid prescription was required or verified, and if consumer education was provided.

Results:
Twenty-two optometrists completed the online survey. Seventy-seven percent of respondents reported having patients with complications from decorative contact lenses that were purchased both legally and illegally. The most common age group for complications was 18 to 25 years (61%). One third of complications were seen in first-time lens wearers, half of whom never received proper care instructions or were unaware that care instructions existed. One quarter of the lenses were purchased illegally with unlicensed stores being the most common place of purchase. Of the 18 online sites examined, 72% of sellers failed to adhere to FTC and FDA regulations.

Conclusions:
A significant number of individuals who obtain contact lenses illegally from unauthorized sources are young adults. Most unauthorized sellers reviewed did not adhere to the proper protocol for selling contact lenses or instruct their customers on proper lens wear and care. A significant percentage of optometrists responding to the survey reported complications associated with contact lenses purchased through unauthorized sources, suggesting that the risk of contact lens–related complications increases when the lenses are purchased from one of these sources.
Substance Use Among Homeless Individuals With Schizophrenia and Bipolar Disorder
Authors: Maremmani Angelo G.I. , Bacciardi Silvia , Gehring Nicole D. , Cambioli Luca , Schütz Christian , Jang Kerry , Krausz Michael 
Published: January 2016

AbstractMental illness and substance use are overrepresented within urban homeless populations. This paper compared substance use patterns between homeless individuals diagnosed with schizophrenia spectrum (SS) and bipolar disorders (BD) using the Mini-International Neuropsychiatric Interview. From a sample of 497 subjects drawn from Vancouver, Canada who participated in the At Home/Chez Soi study, 146 and 94 homeless individuals were identified as BD and SS, respectively. In the previous 12 months, a greater proportion of BD homeless reported greater use of cocaine (χ2= 20.0,p= 0.000), amphetamines (χ2= 13,8,p= 0.000), opiates (χ2= 24.6,p= 0.000), hallucinogens (χ2= 11.7,p= 0.000), cannabinoids (χ2= 5.05,p= 0.034), and tranquilizers (χ2= 7.95,p= 0.004) compared to SS. Cocaine and opiates were significantly associated with BD homeless (χ2= 39.06,df= 2,p< 0.000). The present study illustrates the relationship between substance use and BD in a vulnerable urban population of homeless, affected by adverse psychosocial factors and severe psychiatric conditions.
Defining Quality in Health Care and Measuring Quality in Surgery
Authors: Yuan Frank , Chung Kevin C. 
Published: January 2016

Summary:
Quality in health care has been sluggish to adapt to the changing landscape, leading to lapses in the successful delivery of care. Consequently, quality of care has come under intense scrutiny in the past decade, resulting in the creation of various federally funded and nonprofit organizations aimed at assessing and implementing systematic quality improvements. In this article, the authors examine the evolution of quality in health care relative to established quality control measures in other sectors, different ways of assessing quality, and the current state of the health care system.
Quantitative assessment of eye phenotypes for functional genetic studies usingDrosophila melanogaster
Authors: Iyer Janani , Wang Qingyu , Le Thanh , Pizzo Lucilla , Grönke Sebastian , Ambegaokar Surendra S. , Imai Yuzuru , Srivastava Ashutosh , Troisí Beatriz Llamusí , Mardon Graeme , Artero Ruben , Jackson George R. , Isaacs Adrian M. , Partridge Linda , Lu Bingwei , Kumar Justin P. , Girirajan Santhosh 
Published: January 2016

AbstractAbout two-thirds of the vital genes in theDrosophilagenome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net), to quantitatively assess the morphological defects in theDrosophilaeye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown ofDrosophilaorthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers ofsine oculisobtained from two genome-wide deficiency screens ofDrosophilaand accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions.
Geographic cline analysis as a tool for studying genome-wide variation: a case study of pollinator-mediated divergence in a monkeyflower
Authors: Stankowski Sean , Sobel James M. , Streisfeld Matthew A. 
Published: January 2016

AbstractA major goal of speciation research is to reveal the genomic signatures that accompany the speciation process. Genome scans are routinely used to explore genome-wide variation and identify highly differentiated loci that may contribute to ecological divergence, but they do not incorporate spatial, phenotypic, or environmental data that might enhance outlier detection. Geographic cline analysis provides a potential framework for integrating diverse forms of data in a spatially-explicit framework, but it has not been used to study genome-wide patterns of divergence. Aided by a first-draft genome assembly, we combine anFCTscan and geographic cline analysis to characterize patterns of genome-wide divergence between divergent pollination ecotypes ofMimulus aurantiacus. FCTanalysis of 58,872 SNPs generated via RADseq revealed little ecotypic differentiation (meanFCT= 0.041), though a small number of loci were moderately to highly diverged. Consistent with our previous results from the geneMaMyb2, which contributes to differences in flower color, 130 loci have cline shapes that recapitulate the spatial pattern of trait divergence, suggesting that they reside in or near the genomic regions that contribute to pollinator isolation. In the narrow hybrid zone between the ecotypes, extensive admixture among individuals and low linkage disequlibrium between markers indicate that outlier loci are scattered throughout the genome, rather than being restricted to one or a few regions. In addition to revealing the genomic consequences of ecological divergence in this system, we discuss how geographic cline analysis is a powerful but under-utilized framework for studying genome-wide patterns of divergence.
Believer-Skeptic meets Actor-Critic: Rethinking the role basal ganglia pathways in decision-making and reinforcement learning
Authors: Dunovan Kyle , Verstynen Timothy 
Published: January 2016

AbstractThe flexibility of behavioral control is a testament to the brain’s capacity for dynamically resolving uncertainty during goal-directed actions. This ability to select actions and learn from immediate feedback is driven by the dynamics of basal ganglia (BG) pathways. A growing body of empirical evidence conflicts with the traditional view that these pathways act as independent levers for facilitating (i.e., direct pathway) or suppressing (i.e., indirect pathway) motor output, suggesting instead that they engage in a dynamic competition during action decisions that computationally captures action uncertainty. Here we discuss the utility of encoding action uncertainty as a dynamic competition between opposing control pathways and provide evidence that this simple mechanism may have powerful implications for bridging neurocomputational theories of decision making and reinforcement learning.
A virtual B cell lymphoma model to predict effective combination therapy
Authors: Du Wei , Goldstein Rebecca , Jiang Yanwen , Aly Omar , Cerchietti Leandro , Melnick Ari , Elemento Olivier 
Published: January 2016

AbstractThe complexity of cancer signaling networks limits the efficacy of most single agent treatments and brings about challenges in identifying effective combinatorial therapies. Using chronic active B cell receptor (BCR) signaling in diffuse large B cell lymphoma (DLBCL) as a model system, we established a computational framework to optimize combinatorial therapyin silico.We constructed a detailed kinetic model of the BCR signaling network, which captured the known complex crosstalk between the NFκB, ERK and AKT pathways; and multiple feedback loops. Combining this signaling model with a data-derived tumor growth model we predicted viability responses of many single drug and drug combinations that are in agreement with experimental data. Under this framework, we exhaustively predicted and ranked the efficacy and synergism of all possible combinatorial inhibitions of eleven currently targetable kinases in the BCR signaling network. Our work established a detailed kinetic model of the core BCR signaling network and provides the means to explore the large space of possible drug combinations.Author SummaryUsing chronic active B cell receptor (BCR) signaling in diffuse large B cell lymphoma(DLBCL) as a model system, we developed a kinetic-modeling based computational framework for predicting effective combination therapyin silico.By integrative modeling of signal transduction, drug kinetics and tumor growth, we were able to directly predict drug-induced cell viability response at various dosages, which were in agreement with published cell line experimental data. We implemented computational screening methods that identified potent and synergistic combinationsin silicoand validated our independent predictionsin vitro.
Phenotypic switching can speed up biological evolution of microbes
Authors: Tadrowski Andrew C. , Evans Martin R. , Waclaw Bartłomiej 
Published: January 2016

AbstractStochastic phenotype switching has been suggested to play a beneficial role in microbial populations by leading to the division of labour among cells, or ensuring that at least some of the population survives an unexpected change in environmental conditions. Here we use a computational model to investigate an alternative possible function of stochastic phenotype switching – as a way to adapt more quickly even in a static environment. We show that when a genetic mutation causes a population to become less fit, switching to an alternative phenotype with higher fitness (growth rate) may give the population enough time to develop compensatory mutations that increase the fitness again. The possibility of switching phenotypes can reduce the time to adaptation by orders of magnitude if the “fitness valley” caused by the deleterious mutation is deep enough. Our work has important implications for the emergence of antibiotic-resistant bacteria. In line with recent experimental findings we hypothesise that switching to a slower growing but less sensitive phenotype helps bacteria to develop resistance by exploring a larger set of beneficial mutations while avoiding deleterious ones.
Analysis of Two-State Folding Using Parabolic Approximation II: Temperature-Dependence
Authors: Sade Robert S. 
Published: January 2016

ABSTRACTEquations that govern the temperature-dependence of the rate constants, Gibbs energies, enthalpies, entropies and heat capacities of activation for folding and unfolding of spontaneously-folding fixed two-state systems have been derived using a procedure that treats the denatured and the native conformers as being confined to harmonic Gibbs energy wells. The notion that a two-state system is physically defined only for a set temperature range is introduced. The implications of this novel treatment for protein folding are discussed.