bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of Gender Differences in Proton Pump Inhibitor Dose Requirements for GERD
Authors: Helgadóttir Hólmfridur , Metz David C. , Lund Sigrún H. , Gizurarson Sveinbjorn , Jacobsen Elin I. , Asgeirsdóttir Gudrún A. , Yngadóttir Yrsa , Björnsson Einar S. 
Published: May 2016

Goals:
To determine the proportion of patients with gastroesophageal reflux disease who are on proton pump inhibitors (PPIs) who could reduce their prior dosage by half, and identify predictors of successful step-down.

Background:
Appropriate hypergastrinemia results from gastric acid inhibition. A gender difference in fasting gastrin with higher levels among women than among men on long-term PPI therapy has been demonstrated.

Study:
Patients with endoscopically verified erosive esophagitis on long-term PPI therapy were randomized double blindly to step down their dose by half or continue with the same dose for 8 weeks. Fasting gastrin levels were measured before and after treatment. The primary endpoint was successful step-down throughout the study period.

Results:
Overall, 100 patients were randomized, 49 (24 females) to continue with the same dose as before and 51 (25 females) to step down. Female patients had higher gastrin levels compared with male patients: 78 pg/mL (IQR, 50 to 99) versus 50 pg/mL (IQR, 36 to 74) (P=0.007). Among those randomized to the step-down intervention only 3/25 (12%) women failed to complete the 2 months of lower-dose therapy versus 9/25 (36%) men (P=0.09). Female gender (P=0.048) was the strongest predictor for successful step-down (odds ratio=1.27; 95% CI, 1.01-1.60). The chance of failing to maintain symptom control was twice as high in the reduction group (24%) as compared with the control group (13%) (P=0.2).

Conclusions:
Female patients on long-term PPI therapy were 3 times more likely to tolerate half of their prior dose. Female gender had higher probability for successful step-down. These results indicate that women with gastroesophageal reflux disease might manage with lower doses of PPIs as compared with men.
European Clinical Trial Database (https://eudract.ema.europa.eu/), number 2013-002067-26.
Potential impact of novel diagnostics and treatments on the burden of antibiotic resistant inEscherichia coli
Authors: Nouvellet Pierre , Robotham J.V. , Naylor N.R. , Woodford N. , Ferguson Neil M. 
Published: May 2016

AbstractThe rising threat of antibiotic resistance in Europe and beyond is of increasing concern and is prompting renewed effort to better understand and mitigate their impact.Escherichia Coliblood stream infections are a more major concern in Europe given their incidence and severe associated outcomes. Additionally the level of 3rdgeneration cephalosporins and carbapenems resistance among those bacteraemia has significantly increased, limiting available treatment options. We estimated the current burden associated withE. coliblood stream infections in Europe at 17,000 (95%CI [8,000; 30,000]) excess deaths and 960,000 (95%CI [600,000; 1,450,000]) extra hospital bed days. From those, the contribution due to 3rdgeneration cephalosporins and carbapenems resistant strains reached 6,000 (95%CI [2,000; 12,000]) excess deaths, and 200,000 (95%CI [76,000; 420,000]) extra hospital bed stay. In the worst case scenario, we estimated the burden ofE. coliblood stream infection in 2026 could increase over 4-fold, mostly resulting from an increase in the level of resistance rather than an increase in the incidence of blood stream infections. Finally, we estimated that the impact of combined novel diagnostics and treatments could substantially reduce the excess mortality by 18.5% to 55.5%, and length of stay by 13.2% to 75.6%.
Multiscale quantification of tissue behavior during amniote embryo axis elongation
Authors: Bénazéraf Bertrand , Beaupeux Mathias , Tchernookov Martin , Wallingford Allison , Salisbury Tasha , Shirtz Amelia , Shirtz Andrew , Huss Dave , Pourquié Olivier , François Paul , Lansford Rusty 
Published: May 2016

SummaryEmbryonic axis extension is a complex multi-tissue morphogenetic process responsible for the formation of the posterior part of the amniote body. Cells located in the caudal part of the embryo divide and rearrange to participate in the elongation of the different embryonic tissues (e.g. neural tube, axial and paraxial mesoderm, lateral plate, ectoderm, endoderm). We previously identified the paraxial mesoderm as a crucial player of axis elongation, but how movements and growth are coordinated between the different posterior tissues to drive morphogenesis remain largely unknown. Here we use the quail embryo as a model system to quantify cell behavior and movements in the various tissues of the elongating embryo. We first quantify the tissue-specific contribution to axis elongation by using 3D volumetric techniques, then quantify tissue-specific parameters such as cell density and proliferation at different embryonic stages. To be able to study cell behavior at a multi-tissue scale we used high-resolution 4D imaging of transgenic quail embryos expressing constitutively expressed fluorescent proteins. We developed specific tracking and image analysis techniques to analyze cell motion and compute tissue deformations in 4D. This analysis reveals extensive sliding between tissues during axis extension. Further quantification of “tissue tectonics” showed patterns of rotations, contractions and expansions, which are coherent with the multi-tissue behavior observed previously. Our results confirm the central role of the PSM in axis extension; we propose that the PSM specific cell proliferation and migration programs control the coordination of elongation between tissues during axis extension.
Cell-to-cell spread of microsporidia causesC. elegansorgans to form syncytia
Authors: Balla Keir M. , Luallen Robert J. , Bakowski Malina A. , Troemel Emily R. 
Published: May 2016

AbstractThe growth of pathogens is dictated by their interactions with the host environment. Many obligate intracellular pathogens undergo several cellular decisions as they progress through their life cycles inside of host cells. We studied this process for several species of microsporidia in the genusNematocidain their co-evolved animal hostCaenorhabditis elegans. We found that microsporidia can restructure multicellular host tissues into a single contiguous multinucleate cell. In particular, we found that all threeNematocidaspecies we studied were able to spread across the cells ofC. eleganstissues before forming spores, with two species causing syncytial formation in the intestine, and one species causing syncytial formation in the muscle. We also found that the decision to switch from replication to differentiation inN. parisiiwas altered by the density of infection, suggesting that environmental cues influence the dynamics of the pathogen life cycle. These findings show how microsporidia can maximize the use of host space for growth, and that environmental cues in the host can regulate a developmental switch in the pathogen.
Corticosteroid and progesterone transactivation of mineralocorticoid receptors from Amur sturgeon and tropical gar
Authors: Sugimoto Akira , Oka Kaori , Sato Rui , Adachi Shinji , Baker Michael E. , Katsu Yoshinao 
Published: May 2016

AbstractThe response to a panel of steroids by the mineralocorticoid receptor (MR) from Amur sturgeon and tropical gar, two basal ray-finned fish, expressed in HEK293 cells was investigated. Half-maximal responses (EC50s) for transcriptional activation of sturgeon MR by 11-deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol and aldosterone, and progesterone were between 13 pM and 150 pM. For gar MR, EC50s were between 8 pM and 55 pM. Such low EC50s support physiological regulation by these steroids of the MR in sturgeon and gar. Companion studies with human MR and zebrafish MR found higher EC50s compared to EC50s for sturgeon and gar MR, with EC50s for zebrafish MR closer to gar and sturgeon MR than was human MR. For zebrafish MR, EC50s were between 75 pM and 740 pM; for human MR, EC50s were between 65 pM and 2 nM. In addition to progesterone, spironolactone and 19nor-progesterone were agonists for all three fish MRs, in contrast to their antagonist activity for human MR, which is hypothesized to involve serine-810 in human MR because all three steroids are agonists for a mutant human Ser810Leu-MR. Paradoxically, sturgeon, gar and zebrafish MRs contain a serine corresponding to serine-810 in human MR. Our data suggests alternative mechanism(s) for progesterone, spironolactone and 19nor-progesterone as MR agonists in these three ray-finned fishes and the need for caution in applying data for progesterone signaling in zebrafish to human physiology.
Genome sequencing of a single tardigrade Hypsibius dujardini individual
Authors: Arakawa Kazuharu , Yoshida Yuki , Tomita Masaru 
Published: May 2016

AbstractTardigrades are ubiquitous microscopic animals that play an important role in the study of metazoan phylogeny. Most terrestrial tardigrades can withstand extreme environments by entering an ametabolic desiccated state termed anhydrobiosis. Due to their small size and the non-axenic nature of laboratory cultures, molecular studies of tardigrades are prone to contamination. To minimize the possibility of microbial contaminations and to obtain high-quality genomic information, we have developed an ultra-low input library sequencing protocol to enable the genome sequencing of a single tardigradeHypsibius dujardiniindividual. Here, we describe the details of our sequencing data and the ultra-low input library preparation methodologies.
Exact Bayesian lineage tree-based inference identifies Nanog negative autoregulation in mouse embryonic stem cells
Authors: Feigelman Justin , Ganscha Stefan , Hastreiter Simon , Schwarzfischer Michael , Filipczyk Adam , Schroeder Timm , Theis Fabian J. , Marr Carsten , Claassen Manfred 
Published: May 2016

AbstractThe autoregulatory motif of Nanog, a heterogeneously expressed core pluripotency factor in mouse embryonic stem cells, remains debated. Although recent time-lapse microscopy data provide the unparalleled ability to monitor Nanog expression at the single-cell level, the extraction of mechanistic knowledge is precluded by the lack of inference techniques suitable for noisy, incomplete and heterogeneous data obtained from proliferating cell populations.This work identifies Nanog’s autoregulatory motif from quantified time-lapse fluorescence line-age trees with STILT (Stochastic Inference on Lineage Trees), a novel particle-filter based algorithm for exact Bayesian parameter inference and model selection of stochastic models. We first verify STILT’s ability to accurately infer parameters and select the correct autoregulatory motif from simulated data. We then apply STILT to time-lapse microscopy movies of a fluorescent Nanog fusion protein reporter and reject the possibility of positive autoregulation. Finally, we use STILT for experimental design, performin silicooverexpression simulations, and experimentally validate model predictions via exogenous Nanog overexpression. We finally conclude that the protein expression dynamics and overexpression experiments strongly suggest a weak negative feedback from the protein on the DNA activation rate.We find that a simple autoregulatory mechanism can explain the observed heterogeneous Nanog dynamics. This finding has implications on the understanding of the core pluripotency network, such as supporting the ability of mESC populations to diversify their proteomic profile to respond to a spectrum of differentiation cues. Beyond this application STILT constitutes a generally applicable fully Bayesian approach for model selection of gene regulatory models on the basis of time-lapse imaging data of proliferating cell populations. STILT is freely available at:http://www.imsb.ethz.ch/research/claassen/Software/stilt—stochastic-inference-on-lineage-trees.html
The multiple testing burden in sequencing-based disease studies of global populations
Authors: Pulit Sara L. , de With Sera A.J. , de Bakker Paul I.W. 
Published: May 2016

AbstractGenome-wide association studies (GWAS) of common disease have been hugely successful in implicating loci that modify disease risk. The bulk of these associations have proven robust and reproducible, in part due to community adoption of statistical criteria for claiming significant genotype-phenotype associations. Currently, studies of common disease are rapidly shifting towards the use of sequencing technologies. As the cost of sequencing drops, assembling large samples in global populations is becoming increasingly feasible. Sequencing studies interrogate not only common variants, as was true for genotyping-based GWAS, but variation across the full allele frequency spectrum, yielding many more (independent) statistical tests. We sought to empirically determine genome-wide significance for various analysis scenarios. Using whole-genome sequence data, we simulated sequencing-based disease studies of varying sample size and ancestry. We determined that future sequencing efforts in>2,000 samples should practically employ a genome-wide significance threshold of of p <5 ×10−9, though the threshold does vary with ancestry. Studies of European or East Asian ancestry should set genome-wide significance at approximately p <5×10−9, but similar studies of African or South Asian samples should be more stringent (p <1×10−9). Because sequencing analysis brings with it many challenges (especially for rare variants), appropriate adoption of a revised multiple test correction will be crucial to avoid irreproducible claims of association.
PIVOT: Platform for Interactive Analysis and Visualization of Transcriptomics Data
Authors: Zhu Qin , Fisher Stephen A , Dueck Hannah , Middleton Sarah , Khaladkar Mugdha , Kim Junhyong 
Published: May 2016

AbstractMany R packages have been developed for transcriptome analysis but their use often requires familiarity with R and integrating results of different packages is difficult. Here we present PIVOT, an R-based application with a uniform user interface and graphical data management that allows non-programmers to conveniently access various bioinformatics tools and interactively explore transcriptomics data. PIVOT supports many popular open source packages for transcriptome analysis and provides an extensive set of tools for statistical data manipulations. A graph-based visual interface is used to represent the links between derived datasets, allowing easy tracking of data versions. PIVOT further supports automatic report generation, publication-quality plots, and program/data state saving, such that all analysis can be saved, shared and reproduced.
The proteasome acts as a hub for local and systemic plant immunity inArabidopsis thalianaand constitutes a virulence target ofPseudomonas syringaetype-III effector proteins
Authors: Üstün Suayib , Sheikh Arsheed , Gimenez-Ibanez Selena , Jones Alexandra , Ntoukakis Vardis , Börnke Frederik 
Published: May 2016

AbstractRecent evidence suggests that the ubiquitin-proteasome system (UPS) is involved in several aspects of plant immunity and a range of plant pathogens subvert the UPS to enhance their virulence. Here, we show that proteasome activity is strongly induced during basal defense in Arabidopsis and mutant lines defective in proteasome subunitsRPT2aandRPN12asupport increased bacterial growth of virulentPseudomonas syringaeDC3000 (Pst), strains in local leaves. Both proteasome subunits are required for PTI events such as production of reactive oxygen species and mitogen-activated protein kinases signaling as well as for defense gene expression. Furthermore, analysis of bacterial growth after a secondary infection of systemic leaves revealed that the establishment of systemic-acquired resistance (SAR) is impaired in proteasome mutants, suggesting that the proteasome plays an important role in defense priming and SAR. In addition, we show thatPstinhibits proteasome activity in a type-III secretion dependent manner. A systematic screen for type-III effector proteins fromPstfor their ability to interfere with proteasome activity revealed HopM1, HopAO1, HopA1 and HopG1 as candidates. Identification of proteins interacting with HopM1 by mass-spectrometry indicate that HopM1 resides in a complex together with several E3 ubiquitin ligases and proteasome subunits, supporting the hypothesis that HopM1 associates with the proteasome leading to its inhibition. We conclude that the proteasome is an essential component of the plant immune system and that some pathogens have developed a general strategy to overcome proteasome-mediated defense.One sentence summaryThe proteasome is required for local and systemic immune responses and is targeted by Pseudomonas type-III effectors
Land use change on U.S. floodplain buyout sites, 1990-2000
Authors: Zavar Elyse , Hagelman III Ronald R. 
Published: May 2016

Purpose– The Federal Emergency Management Agency provides guidelines for the management of open space created through property acquisition (buyouts); however, land use decisions are primarily left to local governments manifesting in a variety of uses. The purpose of this paper is to provide a land use assessment of buyout sites, to describe the changes in those uses that have occurred during a ten-year period from 1990 to 2000, and to offer an assessment of management approaches employed across these sites.Design/methodology/approach– Using a mixed-methods approach consisting of a land use classification survey and a semi-structured questionnaire of floodplain managers, this study explores the land use trends at buyout sites, diverse approaches local governments take in managing the open spaces created through floodplain buyout programs, and the successes and challenges communities face in open space management.Findings– Results indicate strong support from floodplain managers for property acquisition and several cases emerged where communities put their newly acquired public land to creative uses. However, the opportunity to leverage these properties for greater public values is largely being missed, primarily because of limited funding.Practical implications– The analysis indicates strong support among floodplain managers for the buyout approach; however, additional resource-sharing and funding opportunities are needed to increase the utility of buyout properties.Originality/value– By evaluating the long-term management strategies floodplain managers utilize on buyout sites, this study adds to an underrepresented area of scholarship and is of value to practitioners, government officials, and academics.
Informational capital and disaster resilience: the case of Jalin Merapi
Authors: Tasic Justyna , Amir Sulfikar 
Published: May 2016

Purpose– The purpose of this paper is to present a concept of informational capital to explain the interplay between social capital and information technology in community-based disaster management. It aims to discuss the role and formation of informational capital in community disaster resilience.Design/methodology/approach– Based on an exploratory case study focusing on the 2010 eruption of Merapi volcano in Central Java, Indonesia, the paper seeks to analyse the emergence of disaster response fully organized by grassroots groups in Yogyakarta. In advancing the concept of informational capital, this paper analyses how the grassroots groups were able to mobilize resources for disaster mitigation, through which social capital became the foundation of community-based disaster response and recovery. Furthermore, the mobilization of social capital was significantly enhanced by mutual interactions facilitated by the use of information technology. This is evident in the role of Jalin Merapi, a web-based organization formed to respond to the crisis after the volcano eruption.Findings– The concept of informational capital revolves around the ways in which social capital and information act as crucial assets when a disaster strikes. Through informational capital, strong community bonds and ties are transformed into organized information that effectively facilitates collective action to face the emergency crisis.Originality/value– This paper presents a new concept of informational capital and highlights its key role in facilitating disaster management processes and contribution to community disaster resilience.
Sequential expansion in a foreign market
Authors: Pehrsson Anders 
Published: May 2016

PurposeA multinational firm’s expansion in a foreign market is a key issue of international business. The purpose of this study is to extend the understanding of essential drivers that will facilitate firm’s assessment of alternative modes of sequential expansion.Design/methodology/approachThe study applies the knowledge-based view and explores a multinational firm’s sequential post-entry expansion in a foreign market. Event histories of Swedish industrial firms’ establishments of wholly owned subsidiaries in Germany, the UK and the USA were explored using Cox regression.FindingsBroad market experiences stemming from corporate strategy and deep experiences from the preceding subsidiary increase the likelihood of a sequential investment. Effects of broad experiences are contingent on the context specified by the geographic scope of the firm and its general subsidiary experience.Research limitations/implicationsThe study contributes to international expansion theory and integrates sources of knowledge originating from strategy theory and internationalization theory. The study shows that the dual approach is needed to understand international expansion.Practical implicationsIn evaluating a further subsidiary investment in a foreign market, the multinational firm is advised to assess whether it possesses enough market experiences to justify the investment. The experiences should be associated with corporate strategy, the previous wholly owned subsidiary and the context specifications identified in the study.Originality/valueThe study is unique, as it addresses the simultaneous impact of broad and deep market experiences. Also, the inclusion of central context specifications makes the study novel.