bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal Viral Dynamics in Semen During Early HIV Infection
Authors: Morris Sheldon R. , Zhao Mitchell , Smith Davey M. , Vargas Milenka V. , Little Susan J. , Gianella Sara 
Published: November 2016

Abstract

Background.
Multiple viruses coinfect the male genital tract, influencing each other’s replication and perhaps affecting human immunodeficiency virus (HIV) pathogenesis and disease progression.

Methods.
This study included 453 longitudinal seminal samples from 195 HIV-infected men from the San Diego Primary Infection Resource Consortium and 67 seminal samples from HIV-negative healthy controls. Seminal HIV RNA and DNA from 7 human herpesviruses (HHVs) were measured by real-time polymerase chain reaction. Longitudinal shedding rates were determined by Kaplan-Meier survival analysis. Predictors of viral shedding were determined using backwards selection in a multivariable generalized estimating equation model.

Results.
HIV-infected participants presented significantly increased rates of seminal HHV shedding compared with HIV-uninfected controls. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were the most commonly detected HHV in semen of HIV-infected participants. Persistent shedding was more common for CMV and EBV when compared to other HHVs. With exception of HHV-7, HHV shedding was not significantly influenced by HIV RNA levels, CD4+ cell counts, or antiretroviral therapy. Presence of CMV, EBV, and herpes simplex virus (HSV) were independent predictors of genital HIV RNA shedding after adjusting for plasma HIV RNA and longitudinal measurements.

Conclusions.
Seminal replication of multiple HHVs is common in our HIV primary infection cohort. Genital replication of CMV and EBV was the most common and was significantly associated with seminal HIV RNA shedding. Prevalence of HSV shedding was lower and mostly intermittent, but its association with seminal HIV RNA was the strongest. Understanding the complex viral milieu in semen is important for HIV transmission but might also play a role in HIV pathogenesis and disease progression.
Efficacy and Safety of Praziquantel Against Light Infections of Opisthorchis viverrini: A Randomized Parallel Single-Blind Dose-Ranging Trial
Authors: Sayasone Somphou , Meister Isabel , Andrews Jason R. , Odermatt Peter , Vonghachack Youthanavanh , Xayavong Syda , Senggnam Kanpaseuth , Phongluxa Khampheng , Hattendorf Jan , Bogoch Isaac I. , Keiser Jennifer 
Published: November 2016

Abstract

Background.
The liver fluke Opisthorchis viverrini, highly prevalent in Southeast Asia, is an important public health burden, including a risk factor for developing an aggressive bile duct cancer, cholangiocarcinoma, in chronically infected patients. Praziquantel, administered at a single 40 mg/kg dose in preventive chemotherapy programs and 3 × 25 mg/kg for individual treatment, is the drug of choice, yet information on the nature of the dose-response relationship is lacking.

Methods.
We performed a randomized, parallel, single-blind dose-ranging phase 2 trial in the Lao People’s Democratic Republic in O. viverrini–infected adults. Patients were randomly assigned to 30 mg/kg, 40 mg/kg, 50 mg/kg, or 3 × 25 mg/kg praziquantel or placebo. Adverse events were recorded at baseline, 3 hours, and 24 hours posttreatment. Cure rates (CRs) and egg reduction rates (ERRs) were estimated 3 weeks after drug administration using available case analysis. Dose-response curves were predicted using Emax models.

Results.
Two-hundred seventeen O. viverrini–infected patients were assigned to the 5 treatment arms. The majority (94.3%) of patients harbored light infections. The Emax model predicted a high efficacy among the observed dose range. We observed CRs ranging from 92.7% to 95.5% and ERRs &gt;99.5% for all praziquantel treatment groups. Adverse events were mild but higher in the standard treatment group (3 × 25 mg/kg) than in the single-dose treatment arms.

Conclusions.
Single-dose praziquantel appears to be as efficacious as the standard 3 × 25 mg/kg regimen for the treatment of O. viverrini infections, while presenting fewer adverse events. Further studies are necessary in moderate and heavy O. viverrini infections.

Clinical Trials Registration.
Randomized Controlled Trials (ISRCTN77186750).
High glucose facilitated endothelial heparanase transfer to the cardiomyocyte modifies its cell death signature
Authors: Wang Fulong , Jia Jocelyn , Lal Nathaniel , Zhang Dahai , Chiu Amy Pei-Ling , Wan Andrea , Vlodavsky Israel , Hussein Bahira , Rodrigues Brian 
Published: November 2016

Aims
The secretion of enzymatically active heparanase (HepA) has been implicated as an essential metabolic adaptation in the heart following diabetes. However, the regulation and function of the enzymatically inactive heparanase (HepL) remain poorly understood. We hypothesized that in response to high glucose (HG) and secretion of HepL from the endothelial cell (EC), HepL uptake and function can protect the cardiomyocyte by modifying its cell death signature.

Methods and results
HG promoted both HepL and HepA secretion from microvascular (rat heart micro vessel endothelial cells, RHMEC) and macrovascular (rat aortic endothelial cells, RAOEC) EC. However, only RAOEC were capable of HepL reuptake. This occurred through a low-density lipoprotein receptor-related protein 1 (LRP1) dependent mechanism, as LRP1 inhibition using small interfering RNA (siRNA), receptor-associated protein, or an LRP1 neutralizing antibody significantly reduced uptake. In cardiomyocytes, which have a negligible amount of heparanase gene expression, LRP1 also participated in the uptake of HepL. Exogenous addition of HepL to rat cardiomyocytes produced a dramatically altered expression of apoptosis-related genes, and protection against HG and H2O2 induced cell death. Cardiomyocytes from acutely diabetic rats demonstrated a robust increase in LRP1 expression and levels of heparanase, a pro-survival gene signature, and limited evidence of cell death, observations that were not apparent following chronic and progressive diabetes.

Conclusion
Our results highlight EC-to-cardiomyocyte transfer of heparanase to modulate the cardiomyocyte cell death signature. This mechanism was observed in the acutely diabetic heart, and its interruption following chronic diabetes may contribute towards the development of diabetic cardiomyopathy.
Polarized emission from an off-centred dipole
Authors: Pétri J. 
Published: November 2016

Abstract
Radio polarization measurements of pulsed emission from pulsars offer a valuable insight into the basic geometry of the neutron star: inclination angle between the magnetic and rotation axis and inclination of the line of sight. So far, all studies about radio polarization focused on the standard rotating vector model with the underlying assumption of a centred dipole. In this Letter, we extend this model to the most general off-centred dipole configuration and give an exact closed analytic expression for the phase-resolved polarization angle. It is shown that contrary to the rotating vector model, for an off-centred dipole, the polarization angle also depends on the emission altitude. Although the fitting parameter space increases from two to six (position of the dipole, altitude and shift of the zero phase), statistical analysis should remain tractable. Observations revealing an evolution of the polarization angle with frequency would undeniably furnish a strong hint for the presence of a decentred magnetic dipole in neutron stars.
Projected axis ratios of galaxy clusters in the Horizon-AGN simulation: Impact of baryon physics and comparison with observations
Authors: Suto Daichi , Peirani Sébastien , Dubois Yohan , Kitayama Tetsu , Nishimichi Takahiro , Sasaki Shin , Suto Yasushi 
Published: November 2016

Abstract
We characterize the non-sphericity of galaxy clusters by the projected axis ratio of spatial distribution of star, dark matter, and X-ray surface brightness (XSB). We select 40 simulated groups and clusters of galaxies with mass larger than 5 × 1013 M⊙ from the Horizon simulation that fully incorporates the relevant baryon physics, in particular, the active galactic nucleus feedback. We find that the baryonic physics around the central region of galaxy clusters significantly affects the non-sphericity of dark matter distribution even beyond the central region, approximately up to half of the virial radius. Therefore it is very difficult to predict the probability density function (PDF) of the projected axis ratio of XSB from dark-matter-only N-body simulations as attempted in previous studies. Indeed, we find that the PDF derived from our simulated clusters exhibits much better agreement with that from the observed X-ray clusters. This indicates that our present methodology to estimate the non-sphericity directly from the Horizon simulation is useful and promising. Further improvements in both numerical modeling and observational data will establish the non-sphericity of clusters as a cosmological test complementary to more conventional statistics based on spherically averaged quantities.
Understanding the general feature of microvariability in Kepler blazar W2R 1926+42
Authors: Sasada Mahito , Mineshige Shin , Yamada Shinya , Negoro Hitoshi 
Published: November 2016

Abstract
We analyze the Kepler monitoring light curve of a blazar W2R 1926+42 to examine features of microvariability by means of the “shot analysis” technique. We select 195 intra-day, flare-like variations (shots) for the continuous light curve of Quarter 14 with a duration of 100 d. In the application of the shot analysis, an averaged profile of variations is assumed to converge with a universal profile which reflects a physical mechanism generating the microvariability in a blazar jet, although light-variation profiles of selected shots show a variety. A mean profile, which is obtained by aligning the peaks of the 195 shots, is composed of a spiky-shaped shot component at ± 0.1 d (with respect to the time of the peak), and two slow varying components ranging from −0.50 d to −0.15 d and from 0.10 d to 0.45 d of the peak time. The former spiky feature is well represented by an exponential rise of 0.043 ± 0.001 d and an exponential decay of 0.061 ± 0.002 d. These timescales are consistent with that corresponding to a break frequency of a power spectrum density calculated from the obtained light curve. After verification with the Monte Carlo method, the exponential shape, but not the observed asymmetry, of the shot component can be explained by noise variation. The asymmetry is difficult to explain through a geometrical effect (i.e., changes of the geometry of the emitting region), but is more likely to be caused by the production and dissipation of high-energy accelerated particles in the jet. Additionally, the durations of the detected shots show a systematic variation with a dispersion caused by a statistical randomness. A comparison with the variability of Cygnus X-1 is also briefly discussed.
Obscene Humour, Gender, and Sociability in Sixteenth-Century St Gallen*
Authors: Roth Carla 
Published: November 2016

Abstract
Over the last few decades, studies of early modern satires, Shrovetide plays and printed joke collections have gone a long way to establishing humour as a valid subject of historical research. Yet unfortunately these sources rarely shed any light on the role of jokes in everyday life. When writing about the social function of sexual humour, historians have therefore often relied on sociological and psychological studies which depict obscene jokes as a form of aggression, in particular against women. Through a detailed analysis of the obscene jokes recorded by the St. Gallen linen merchant Johannes Rï¿½tiner (1501-1556/7), this article shall propose an alternative perspective on sixteenth-century sexual humour. Based on the premise that in order to get the joke, we need to place it within both its social and cultural context, the analysis of Rï¿½tiner’s joke collection shall be twofold: first, the article will discuss obscene humour as an important element of sociability, in particular among the town’s educated elite. It will also examine how jokes circulated orally and in print, and highlight some of the creative processes and social skills involved in making a successful joke. Subsequently, Rï¿½tiner’s collection of jokes shall be analysed and placed within its broader cultural context. I shall argue that sexual and scatological jokes were closely linked through both medical discourse and a common set of metaphors, and that this type of humour primarily targeted the male body and his fluids. Rather than representing a safety valve for men’s aggressions against women, Rï¿½tiner’s obscene jokes first and foremost offered a platform on which acceptable forms of masculinity could be circumscribed and reaffirmed.
Esomeprazole FDA Approval in Children With GERD
Authors: Earp Justin C. , Mehrotra Nitin , Peters Kristina E. , Fiorentino Robert P. , Griebel Donna , Lee Sue C. , Mulberg Andrew , Röhss Kerstin , Sandström Marie , Taylor Amy , Tornøe Christoffer W. , Wynn Erica L. , Van der Walt Jan‐Stefan , Garnett Christine 
Published: November 2016

ABSTRACTObjectives:Food and Drug Administration approval of proton‐pump inhibitors for infantile gastroesophageal reflux disease has been limited by intrapatient variability in the clinical assessment of gastroesophageal reflux disease. For children 1 to 17 years old, extrapolating efficacy from adults for IV esomeprazole was accepted. The oral formulation was previously approved in children. Exposure‐response and exposure matching analyses were sought to identify approvable pediatric doses.Methods:Intragastric pH biomarker comparisons between children and adults were conducted. Pediatric doses were selected to match exposures in adults and were based on population pharmacokinetic (PK) modeling and simulations with pediatric esomeprazole data. Observed IV or oral esomeprazole PK data were available from 50 and 117 children, between birth and 17 years, respectively, and from 65 adults, between 20 and 48 years. A population PK model developed using these data was used to simulate steady‐state esomeprazole exposures for children at different doses to match the observed exposures in adults.Results:Exposure‐response relationships of intragastric pH measures were similar between children and adults. The PK simulations identified a dosing regimen for children that results in comparable steady‐state area under the curve to that observed after 20 mg in adults. For IV esomeprazole, increasing the infusion duration to 10 to 30 minutes in children achieves matching Cmax values with adults.Conclusions:The exposure‐matching analysis permitted approval of an esomeprazole regimen not studied directly in clinical trials. Exposure‐response for intragastric pH‐permitted approval for the treatment of gastroesophageal reflux disease in children in whom it was not possible to evaluate the adult primary endpoint, mucosal healing assessed by endoscopy.
Plant growth regulators ameliorate or exacerbate abiotic and biotic stress effects on Zea mays kernel weight in a genotype-specific manner
Authors: Stutts Lauren , Wang Yishi , Stapleton Ann E. 
Published: November 2016

ABSTRACTPlant growth regulators have documented roles in plant responses to single stresses. In combined-stress environments, plants display novel genetic architecture for growth traits and the response to growth regulators is unclear. We investigated the role of plant growth regulators in combined-stress responses in Zea mays. Twelve maize inbreds were exposed to all combinations of the following stressors: drought, nitrogen, and density stress. Chemical treatments were utilized to alter balances of the hormones abscisic acid, gibberellic acid, and brassinosteroids. We found a significant difference between the seed weights of plants given different chemical treatments after accounting for differences in genotype and stress environments. We conclude that plant growth regulators have targets in combined-stress response pathways in Zea mays.HIGHLIGHTPlant growth regulators can ameliorate effects of combinations of abiotic and biotic stress in maize, in certain genotypes and under specific stress conditions.
A unified characterization of population structure and relatedness
Authors: Weir Bruce S. , Goudet Jérôme 
Published: November 2016

AbstractMany population genetic activities, ranging from evolutionary studies to association mapping to forensic identification, rely on appropriate estimates of population structure or relatedness. All applications require recognition that quantities with an underlying meaning of allelic identity by descent are not defined in an absolute sense, but instead are made “relative to” some set of alleles other than the target set. The early Weir and CockerhamFSTestimate made explicit that the reference set of alleles was across independent populations. Standard kinship estimates have an implicit assumption that pairs of individuals in a study sample, other than the target pair, are unrelated, whereas other estimates assume alleles within individuals are not identical by descent. However, populations lose independence when there is migration between them, and when individuals in a study are related it is difficult to see how they can also be non-inbred. We have therefore re-cast our treatments of population structure, relatedness and inbreeding to make explicit that the parameters of interest involve differences of probabilities of identity by descent in the target and the reference sets of alleles and so can be negative. We take the reference set to be for the population from which study individuals have been sampled. We provide simple moment estimates of these parameters, phrased in terms of allele matching within and between individuals for relatedness and inbreeding, or within and between populations for population structure. A multi-level hierarchy of alleles within individuals, alleles between individuals within populations, and alleles between populations allows a unified treatment of relatedness and population structure. Our new estimates appear to be sensitive to rare or private variants, to give indications of the effects of natural selection, and to be appropriate for use in association studies.
GLASS: assisted and standardized assessment of gene variations from Sanger sequence trace data
Authors: Pal Karol , Bystry Vojtech , Reigl Tomas , Demko Martin , Krejci Adam , Touloumenidou Tasoula , Stalika Evangelia , Tichy Boris , Ghia Paolo , Stamatopoulos Kostas , Pospisilova Sarka , Malcikova Jitka , Darzentas Nikos ,   European Research Initiative on CLL (ERIC) – TP53 Network
Published: November 2016

AbstractMotivationSanger sequencing remains the reference method for sequence variant detection, especially in a clinical setting. However, chromatogram interpretation often requires manual inspection and in some cases considerable expertise. Additionally, variant reporting and nomenclature is typically left to the user, which can lead to inconsistencies.ResultsWe introduce GLASS, a tool built to assist with the assessment of gene variations in Sanger sequencing data. Critically, it provides a standardized variant output as recommended by the Human Genome Variation Society.AvailabilityThe program is freely available online athttp://bat.infspire.org/genomepd/glass/.Contactnikos.darzentas@gmail.com,malcikova.jitka@fnbrno.czSupplementary informationSupplementary data are available at Bioinformatics online.
Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs
Authors: Melé Marta , Mattioli Kaia , Mallard William , Shechner David M , Gerhardinger Chiara , Rinn John 
Published: November 2016

ABSTRACTWhile long intergenic noncoding RNAs (lincRNAs) and mRNAs share similar biogenesis pathways, these transcript classes differ in many regards. LincRNAs are less evolutionarily conserved, less abundant, and more tissue-specific, suggesting that their pre‐ and post-transcriptional regulation is different from that of mRNAs. Here, we perform an in-depth characterization of the features that contribute to lincRNA regulation in multiple human cell lines. We find that lincRNA promoters are depleted of transcription factor (TF) binding sites, yet enriched for some specific factors such as GATA and FOS relative to mRNA promoters. Surprisingly, we find that H3K9me3—a histone modification typically associated with transcriptional repression—is more enriched at the promoters of active lincRNA loci than at those of active mRNAs. Moreover, H3K9me3-marked lincRNA genes are more tissue-specific. The most discriminant differences between lincRNAs and mRNAs involve splicing. LincRNAs are less efficiently spliced, which cannot be explained by differences in U1 binding or the density of exonic splicing enhancers, but may be partially attributed to lower U2AF65 binding and weaker splicing–related motifs. Conversely, the stability of lincRNAs and mRNAs is similar, differing only with regard to the location of stabilizing protein binding sites. Finally, we find that certain transcriptional properties are correlated with higher evolutionary conservation in both DNA and RNA motifs, and are enriched in lincRNAs that have been functionally characterized.
A SIMPLE pipeline for mapping point mutations
Authors: Wachsman Guy , Modliszewski Jennifer L. , Valdes Manuel , Benfey Philip N. 
Published: November 2016

AbstractA forward genetic screen is one of the best methods for revealing the regulatory functions of genes. In plants, this technique is highly efficient since it is relatively easy to grow and screen the phenotypes of hundreds or thousands of individuals. The cost-efficiency and ease of data production afforded by next-generation sequencing techniques have created new opportunities for mapping induced mutations. The principles of genetic mapping remain the same. However, the details have changed, which allows for rapid mapping of causal mutations. Current mapping tools are often not user-friendly and complicated or require extensive preparation steps. To simplify the process of mapping new mutations, we developed a pipeline that takes next generation sequencing fastq files as input, calls on several well-established and freely available genome-analysis tools, and outputs the most likely causal DNA change(s). The pipeline has been validated in Arabidopsis and can be readily applied to other species.