bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preprocessing, normalization and integration of the Illumina HumanMethylationEPIC array
Authors: Fortin Jean-Philippe , Triche Timothy J. , Hansen Kasper D. 
Published: July 2016

AbstractTheminfipackage is widely used for analyzing Illumina DNA methylation array data. Here we describe modifications to theminfipackage required to support the HumanMethylationEPIC (”EPIC”) array from Illumina. We discuss methods for the joint analysis and normalization of data from the HumanMethylation450 (”450k”) and EPIC platforms. We also introduce the single-sample Noob (ssNoob) method, a normalization procedure suitable for incremental preprocessing of individual Human-Methylation arrays. Our results recommend thessNoobmethod when integrating data from multiple generations of Infinium methylation arrays. Finally, we show how to use reference 450k datasets to estimate cell type composition of samples on EPIC arrays. The cumulative effect of these updates is to ensure thatminfiprovides the tools to best integrate existing and forthcoming Illumina methylation array data.
Numerical aspect of Predator-Pray Model
Authors: Nir Monika Justyna , Majumdar Sarangam 
Published: July 2016

AbstractIn a closed eco-system, there are only two types of animals: the predator and the prey. They form a simple food-chain where the predator species hunts the prey species, while the prey grazes vegetation. The size of the two populations can be described by a simple system of two nonlinear first order differential equations formally known as the Lotka-Volterra equations, which originated in the study of fish populations of the Mediterranean during and immediately after World War I. Here, we study numerically this nonlinear parabolic evolution problem and compare the result of various numerical schemes.
TelomereHunter: telomere content estimation and characterization from whole genome sequencing data
Authors: Feuerbach Lars , Sieverling Lina , Deeg Katharina I. , Ginsbach Philip , Hutter Barbara , Buchhalter Ivo , Northcott Paul A. , Lichter Peter , Pfister Stefan M. , Jones David T.W. , Rippe Karsten , Brors Benedikt 
Published: July 2016

AbstractSummary:Telomere shortening plays an important role in cellular aging and tumor suppression. The availability of large next-generation sequencing cohorts of matched tumor and control samples enables a computational high-throughput analysis of changes in telomere content and composition in cancer. Here we describe a novel software tool specifically tailored for the processing of large data collections.Availability and Implementation:TelomereHunter is implemented as a python package. It is freely available online at:http://www.dkfz.de/en/applied-bioinformatics/telomerehunter/telomerehunter.html.
Cost-effectiveness of pharmacogenetic-guided treatment: are we there yet?
Authors: Verbelen Moira , Weale Michael E , Lewis Cathryn M 
Published: July 2016

AbstractPharmacogenetics (PGx) has the potential to personalize pharmaceutical treatments. Many relevant gene-drug associations have been discovered, but PGx guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard healthcare. Progress in this area can be assessed by reviewing economic evaluations to determine the cost-effectiveness of PGx testing versus standard treatment. We performed a review of economic evaluations for PGx associations listed in the US Food and Drug Administration (FDA) Table of Pharmacogenomic Biomarkers in Drug Labeling (http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm). We determined the proportion of evaluations that found PGx guided treatment to be cost-effective or dominant over the alternative strategies, and we estimated the impact on this proportion of removing the cost of genetic testing. Of the 130 PGx associations in the FDA table, 44 economic evaluations, relating to 10 drugs, were identified. Of these evaluations, 57% drew conclusions in favour of PGx testing, of which 30% were cost-effective and 27% were dominant (cost-saving). If genetic information was freely available, 75% of economic evaluations would support PGx guided treatment, of which 25% would be cost-effective and 50% would be dominant. Thus, PGx guided treatment can be a cost-effective and even cost-saving strategy. Having genetic information readily available in the clinical health record is a realistic future prospect, and would make more genetic tests economically worthwhile. However, few drugs with PGx associations have been studied and more economic evaluations are needed to underpin the uptake of genetic testing in clinical practice.
Enhanced representation of space by prefrontal neuronal ensembles and its dependence on cognitive states
Authors: Dehaqani Mohammad-Reza A. , Vahabie Abdol-Hossein , Parsa Mohammadbagher , Noudoost Behard , Soltani Alireza 
Published: July 2016

AbstractAlthough individual neurons can be highly selective to particular stimuli and certain upcoming actions, they can provide a complex representation of stimuli and actions at the level of population. The ability to dynamically allocate neural resources is crucial for cognitive flexibility. However, it is unclear whether cognitive flexibility emerges from changes in activity at the level of individual neurons, population, or both. By applying a combination of decoding and encoding methods to simultaneously recorded neural data, we show that while maintaining their stimulus selectivity, neurons in prefrontal cortex alter their correlated activity during various cognitive states, resulting in an enhanced representation of visual space. During a task with various cognitive states, individual prefrontal neurons maintained their limited spatial sensitivity between visual encoding and saccadic target selection whereas the population selectively improved its encoding of spatial locations far from the neurons' preferred locations. This 'encoding expansion' relied on high-dimensional neural representations and was accompanied by selective reductions in noise correlation for non-preferred locations. Our results demonstrate that through recruitment of less-informative neurons and reductions of noise correlation in their activity, the representation of space by neuronal ensembles can be dynamically enhanced, and suggest that cognitive flexibility is mainly achieved by changes in neural representation at the level of population of prefrontal neurons rather than individual neurons.
Hereditary lactate dehydrogenase M‐subunit deficiency with late‐developing pustular psoriasis‐like lesions
Authors: Takeo Naoko , Fujiwara Sakuhei , Sakai Takashi , Saito‐Shono Tomoko , Ishikawa Kazushi , Hatano Yutaka 
Published: July 2016

AbstractHereditary lactate dehydrogenase (LDH) M‐subunit deficiency is very rare and we have found reports of close to a dozen cases in the published work, two of which were associated with pustular psoriasis‐like lesions. We report a third case of pustular psoriasis‐like eruptions associated with LDH M‐subunit deficiency, which occurred 24 years after the diagnosis of LDH M‐subunit deficiency. These cases indicate that abnormal activity of LDH can induce pustular psoriatic lesions in the long term. Some patients with symptoms of hereditary LDH M‐subunit deficiency have antecedent annular scaly plaque lesions, that resemble psoriatic lesions. We discuss a hypothesis to explain this scenario.
Direct and indirect genetic and fine‐scale location effects on breeding date in song sparrows
Authors: Germain Ryan R. , Wolak Matthew E. , Arcese Peter , Losdat Sylvain , Reid Jane M. 
Published: July 2016

SummaryQuantifying direct and indirect genetic effects of interacting females and males on variation in jointly expressed life‐history traits is central to predicting microevolutionary dynamics. However, accurately estimating sex‐specific additive genetic variances in such traits remains difficult in wild populations, especially if related individuals inhabit similar fine‐scale environments.Breeding date is a key life‐history trait that responds to environmental phenology and mediates individual and population responses to environmental change. However, no studies have estimated female (direct) and male (indirect) additive genetic and inbreeding effects on breeding date, and estimated the cross‐sex genetic correlation, while simultaneously accounting for fine‐scale environmental effects of breeding locations, impeding prediction of microevolutionary dynamics.We fitted animal models to 38 years of song sparrow (Melospiza melodia) phenology and pedigree data to estimate sex‐specific additive genetic variances in breeding date, and the cross‐sex genetic correlation, thereby estimating the total additive genetic variance while simultaneously estimating sex‐specific inbreeding depression. We further fitted three forms of spatial animal model to explicitly estimate variance in breeding date attributable to breeding location, overlap among breeding locations and spatial autocorrelation. We thereby quantified fine‐scale location variances in breeding date and quantified the degree to which estimating such variances affected the estimated additive genetic variances.The non‐spatial animal model estimated nonzero female and male additive genetic variances in breeding date (sex‐specific heritabilities: 0·07 and 0·02, respectively) and a strong, positive cross‐sex genetic correlation (0·99), creating substantial total additive genetic variance (0·18). Breeding date varied with female, but not male inbreeding coefficient, revealing direct, but not indirect, inbreeding depression. All three spatial animal models estimated small location variance in breeding date, but because relatedness and breeding location were virtually uncorrelated, modelling location variance did not alter the estimated additive genetic variances.Our results show that sex‐specific additive genetic effects on breeding date can be strongly positively correlated, which would affect any predicted rates of microevolutionary change in response to sexually antagonistic or congruent selection. Further, we show that inbreeding effects on breeding date can also be sex specific and that genetic effects can exceed phenotypic variation stemming from fine‐scale location‐based variation within a wild population.
Intracellular movement of protein aggregates reveals heterogeneous inactivation and resuscitation dynamics in stressed populations of Escherichia coli
Authors: Govers Sander K. , Gayan Elisa , Aertsen Abram 
Published: July 2016

SummaryInactivation of bacterial pathogens is of critical importance in fields ranging from antimicrobial therapy to food preservation. The efficacy of an antimicrobial treatment is often experimentally determined through viable plate counts that inherently provide a poor focus on the mechanisms and distribution of (sub)lethal injury and subsequent inactivation or resuscitation behavior of the stressed cells, which are increasingly important features for the proper understanding and design of inactivation strategies. In this report, we employ a live cell biology approach focusing on the energy‐dependent motion of intracellular protein aggregates to investigate the heterogeneity within heat stressed Escherichia coli populations. As such, we were able to identify differential dynamics of cellular resuscitation and inactivation that are impossible to distinguish using more traditional approaches. Moreover, our data indicate the existence of late‐resuscitating cells that remain physiologically active and are able to persist in the presence of antibiotics before resuscitation.
Pediatric obesity is associated with an altered gut microbiota and discordant shifts in Firmicutes populations
Authors: Riva Alessandra , Borgo Francesca , Lassandro Carlotta , Verduci Elvira , Morace Giulia , Borghi Elisa , Berry David 
Published: July 2016

SummaryAn altered gut microbiota has been linked to obesity in adulthood, although little is known about childhood obesity. The aim of this study was to characterize the composition of the gut microbiota in obese (n = 42) and normal‐weight (n = 36) children aged 6 to 16. Using 16S rRNA gene‐targeted sequencing, we evaluated taxa with differential abundance according to age‐ and sex‐normalized body mass index (BMI z‐score). Obesity was associated with an altered gut microbiota characterized by elevated levels of Firmicutes and depleted levels of Bacteroidetes. Correlation network analysis revealed that the gut microbiota of obese children also had increased correlation density and clustering of operational taxonomic units (OTUs). Members of the Bacteroidetes were generally better predictors of BMI z‐score and obesity than Firmicutes, which was likely due to discordant responses of Firmicutes OTUs. In accordance with these observations, the main metabolites produced by gut bacteria, short chain fatty acids (SCFAs), were higher in obese children, suggesting elevated substrate utilisation. Multiple taxa were correlated with SCFA levels, reinforcing the tight link between the microbiota, SCFAs and obesity. Our results suggest that gut microbiota dysbiosis and elevated fermentation activity may be involved in the etiology of childhood obesity.
Identification of an iron permease, cFTR1, in cyanobacteria involved in the iron reduction/re‐oxidation uptake pathway
Authors: Xu Ning , Qiu Guo‐Wei , Lou Wen‐Jing , Li Zheng‐Ke , Jiang Hai‐Bo , Price Neil M. , Qiu Bao‐Sheng 
Published: July 2016

SummaryCyanobacteria are globally important primary producers and abundant in many iron‐limited aquatic environments. The ways in which they take up iron are largely unknown, but reduction of Fe3+ is an important step in the process. Here we report a special iron permease in Synechocystis, cFTR1, that is required for Fe3+ uptake following Fe2+ re‐oxidation. The expression of cFTR1 is induced by iron starvation, and a mutant lacking the gene is abnormally sensitive to iron starvation. The cFTR1 protein localizes to the plasma membrane and contains the iron‐binding motif “REXXE”. Point‐directed mutagenesis of the REXXE motif results in a sensitivity to Fe‐deficiency. Measurements of iron (55Fe) uptake rate show that cFTR1 takes up Fe3+ rather than Fe2+. The function of cFTR1 in Synechocystis could be genetically complemented by the iron permease, Ftr1p, of Saccharomyces cerevisiae, that is known to transport Fe3+ produced by the oxidation of Fe2+ via a multicopper oxidase. Unlike yeast Ftr1p, cyanobacterial cFTR1 probably obtains Fe3+ primarily from the oxidation of Fe2+ by oxygen. Growth assays show that the cFTR1 is required during oxygenic, photoautotrophic growth but not when oxygen production is inhibited during photoheterotrophic growth. In cyanobacteria, iron reduction/re‐oxidation uptake pathway may represent their adaptation to oxygenated environments.
Mating behavior of Psammotettix alienus (Hemiptera: Cicadellidae)
Authors: Derlink Maja , Abt Isabelle , Mabon Romain , Julian Charlotte , Virant‐Doberlet Meta , Jacquot Emmanuel 
Published: July 2016

AbstractThe Wheat dwarf virus, the causal agent of the wheat dwarf disease, is transmitted by leafhoppers from the genus Psammotettix and currently the main protection strategy is based on the use of insecticide treatments. Sustainable management strategies for insect vectors should include methods that are targeted to disrupt reproductive behavior and here we investigated the mating behavior of Psammotettix alineus (Dahlbom 1850) in order to determine the role of vibrational signals in intra‐specific communication and pair formation. Both genders spontaneously emit species‐ and sex‐specific calling songs that consisted of regularly repeated pulse trains and differ primarily in pulse train duration and pulse repetition time. Females preferred the conspecific male calling song. After a coordinated exchange of pulse trains, the male approached the stationary female. During the close range courtship and also immediately prior to copulatory attempts distinct male vibrational signals associated with wing flapping and wing vibrations were recorded from the substrate. In the presence of a receptive female, competing males emitted vibrational signals most likely aimed to interfere with male‐female interaction. Mated females regained sexual receptivity after they laid eggs. Although results suggest that the viruliferous status of insects may have an effect on vibrational songs, our current results did not reveal a significant effect of virus on leafhopper performance in mating behavior. However, this study also suggests, that detailed understanding of plant–vector–virus interactions relevant for vector mating behavior is essential for trying new approaches in developing future control practices against plant viruses transmitted by insect vectors.
Treatment efficacy and safety of low‐dose azathioprine in chronic active ulcerative colitis patients: A meta‐analysis and systemic review
Authors: Luan Zi Jian , Li Yue , Zhao Xin Yu , Wang Li , Sun Ying Hao , Wang Shi Yao , Qian Jia Ming 
Published: July 2016

ObjectiveTo evaluate the efficacy and safety of low‐dose azathioprine (AZA) in treating patients with chronic active ulcerative colitis (UC).MethodsA literature search of Medline, Embase, the Cochrane Library, Web of Science, Wanfang Database, CNKI, SinoMed, VIP Chinese Science and the Technology Journals Database was conducted to identify eligible studies that evaluated the efficacy and safety of low‐dose azathioprine (AZA) in treating patients with chronic active UC published up to 15 July 2015. Data were extracted from the studies, including clinical efficacy (response rate, adverse drug reaction [ADR] rate, steroid withdrawal rate and relapse rate) and endoscopic improvement (endoscopic remission rate and mucosal healing rate).ResultsSix studies with 211 patients were eligible for the analysis. The overall response rates after 6 and 12 months of treatment were 78.0% (95% confidence interval [CI] 71.0–85.0%) and 88.0% (95% CI 80.0–96.0%), respectively. The overall ADR rate was 25.0% (95% CI 18.0–31.0%). Endoscopic response rate was around 85.0%, while the endoscopic remission rates and mucosal healing rates after 6 and 12 months of treatment were above 60.0% and 70.0%, respectively. The steroid withdrawal rate and relapse rate were in moderate to high heterogeneity. Egger's test indicated that there was no publication bias for studies regarding the 6‐month response rate and ADR rate.ConclusionsLow‐dose AZA is effective and safe in the treatment of chronic active UC patients. However, randomized controlled trials with large sample sizes are needed to draw definitive conclusions.
FAST MRI breast screening revisited
Authors: Jain Manish , Jain Arushi , Hyzy Marek D , Werth Graziella 
Published: July 2016

AbstractIntroductionScreening for breast cancer in high‐risk women takes about 40 minutes to acquire an MRI scan and is time‐intensive to report. There is recent interest in the performance of an abbreviated MRI protocol (FAST) in the screening setting. FAST scans have a reported negative predictive value of 99.8%. This study evaluates the false positive rates (FPR) and recall rates for FAST scans as compared to full diagnostic studies (FD).MethodsA database of all screening breast MRI scans performed at our institution between 30 June 2013 and 1 July 2014 (n = 591) was created by one of the researchers, who did not subsequently analyse the MRI scans. The T1W and first post‐contrast and subtracted images from each of these scans (FAST protocol) were assessed by experienced breast MRI radiologists, blinded to the final diagnosis. The findings were then compared with the FD result.ResultsThe recall rates were 6.6% for FAST scans and 5.8% for FD scans. FPR rates were 4.7% and 3.9% respectively. There is no statistically significant difference in the recall rates or FPR of FAST scans in comparison with full diagnostic studies.ConclusionsGiven the absence of statistically significant difference in the FPR and recall rates in comparison with FD, FAST scans can replace FD for screening of breast cancer.
Contesting the Divided City: Arts of Resistance in Skopje
Authors: Véron Ophélie 
Published: July 2016

AbstractThis paper examines issues of power and resistance in “divided cities”. Basing my analysis on fieldwork I carried out in Skopje, Macedonia, I look at how urban space may be constructed and used by hegemonic groups as a means of asserting their power and how, in turn, the city may be a place of resistance where power is contested and public space reappropriated. Drawing on Lefebvre's perspective on the production of space, I compare the conceived city to the lived city and examine how urban inhabitants may resist the division of the city and challenge hegemonic representations. I also draw on Debord's psychogeography to define an artistic, active and participatory approach to urban space through which the inhabitants may re‐conquer their right to the œuvre and to the city. I argue that the city as a lived environment may offer narratives other than division and that there are alternatives to the divided city.
Application of the integrated glucose–insulin model for cross‐study characterization of T2DM patients on metformin background treatment
Authors: Parkinson Joanna , Hamrén Bengt , Kjellsson Maria C. , Skrtic Stanko 
Published: July 2016

AimThe integrated glucose–insulin (IGI) model is a semi‐mechanistic physiological model which can describe the glucose–insulin homeostasis system following various glucose challenge settings. The aim of the present work was to apply the model to a large and diverse population of metformin‐only‐treated type 2 diabetes mellitus (T2DM) patients and identify patient‐specific covariates.MethodsData from four clinical studies were pooled, including glucose and insulin concentration–time profiles from T2DM patients on stable treatment with metformin alone following mixed‐meal tolerance tests. The data were collected from a wide range of patients with respect to the duration of diabetes and level of glycaemic control.ResultsThe IGI model was expanded by four patient‐specific covariates. The level of glycaemic control, represented by baseline glycosylated haemoglobin was identified as a significant covariate for steady‐state glucose, insulin‐dependent glucose clearance and the magnitude of the incretin effect, while baseline body mass index was a significant covariate for steady‐state insulin levels. In addition, glucose dose was found to have an impact on glucose absorption rate. The developed model was used to simulate glucose and insulin profiles in different groups of T2DM patients, across a range of glycaemic control, and it was found accurately to characterize their response to the standard oral glucose challenge.ConclusionsThe IGI model was successfully applied to characterize differences between T2DM patients across a wide range of glycaemic control. The addition of patient‐specific covariates in the IGI model might be valuable for the future development of antidiabetic treatment and for the design and simulation of clinical studies.
Somewhere I belong: Long‐term increases in adolescents’ resilience are predicted by perceived belonging to the in‐group
Authors: Scarf Damian , Moradi Saleh , McGaw Kate , Hewitt Joshua , Hayhurst Jillian G. , Boyes Mike , Ruffman Ted , Hunter John A. 
Published: July 2016

This study sought to examine the role of belonging in the increases in resilience observed following an adventure education programme (AEP). First, we demonstrate that group belonging makes a significant contribution to the improvement in resilience participants’ experienced over the course of the AEP. Second, we demonstrate that this increase in resilience is maintained 9 months following the AEP and that group belonging maintained a significant contribution when controlling for participants’ initial resilience level and other psychosocial variables (i.e., centrality of identity and social support). Our findings accord well with recent research on the Social Cure or Social Identity Approach to Health and add to a growing body of work identifying the mechanisms underlying this phenomenon.