bluuebunny/crossref_metadata_2025_split huggingface dataset:
Helping GPs to extrapolate guideline recommendations to patients for whom there are no explicit recommendations, through the visualization of drug properties. The example of AntibioHelp® in bacterial diseases
Authors: Tsopra Rosy , Sedki Karima , Courtine Mélanie , Falcoff Hector , De Beco Antoine , Madar Ronni , Mechaï Frédéric , Lamy Jean-Baptiste 
Published: April 2019

Abstract

Introduction
Clinical decision support systems (CDSS) implementing clinical practice guidelines (CPGs) have 2 main limitations: they target only patients for whom CPGs provide explicit recommendations, and their rationale may be difficult to understand. These 2 limitations result in poor CDSS adoption. We designed AntibioHelp® as a CDSS for antibiotic treatment. It displays the recommended and nonrecommended antibiotics, together with their properties, weighted by degree of importance as outlined in the CPGs. The aim of this study was to determine whether AntibioHelp® could increase the confidence of general practitioners (GPs) in CPG recommendations and help them to extrapolate guidelines to patients for whom CPGs provide no explicit recommendations.

Materials and Methods
We carried out a 2-stage crossover study in which GPs responded to clinical cases using CPG recommendations either alone or with explanations displayed through AntibioHelp®. We compared error rates, confidence levels, and response times.

Results
We included 64 GPs. When no explicit recommendation existed for a particular situation, AntibioHelp® significantly decreased the error rate (−41%, P value = 6x10−13), and significantly increased GP confidence (+8%, P value = .02). This CDSS was considered to be usable by GPs (SUS score = 64), despite a longer interaction time (+9–22 seconds). By contrast, AntibioHelp® had no significant effect if there was an explicit recommendation.

Discussion/Conclusion
The visualization of weighted antibiotic properties helps GPs to extrapolate recommendations to patients for whom CPGs provide no explicit recommendations. It also increases GP confidence in their prescriptions for these patients. Further evaluations are required to determine the impact of AntibioHelp® on antibiotic prescriptions in real clinical practice.
Dehydration-Stress Resistance in Two Sister, Cryptic Rhodnius Species—Rhodnius prolixus and Rhodnius robustus Genotype I (Hemiptera: Reduviidae)
Authors: Brito Raíssa N , Souza Rita C M , Abad-Franch Fernando 
Published: April 2019

Abstract
Rhodnius prolixus Stål, a major Chagas disease vector, often colonizes in houses, whereas its sister species, Rhodnius robustus Larrousse genotype I, does not colonize in houses and has little medical relevance. Factors potentially underlying this crucial difference remain largely uncharted. The ‘microclimate-adaptation hypothesis’ notes that R. prolixus is adapted to the dry microclimate of small-crowned Copernicia palms, whereas R. robustus I exploits the high-moisture microclimate of large-crowned Attalea and Acrocomia. Hence, R. prolixus, but not R. robustus I, would be (pre)adapted to the relatively dry microclimate typical of man-made habitats. This hypothesis predicts that, while severe dehydration should harm both species similarly, R. prolixus should withstand moderate-to-mild dehydration stress better than R. robustus I. To test this prediction, we compared fitness metrics of genotyped R. prolixus and R. robustus I kept at 28°C and under severe (20% relative humidity, RH), moderate (40% RH), or mild dehydration stress (75% RH). Egg-hatching success increased with decreasing dehydration stress in R. robustus I (0% → 19% → 100%), but was high across treatments in R. prolixus (78% → 100% → 100%). Both species underwent high, early mortality under severe dehydration; under moderate and mild stress, R. prolixus experienced less mortality and survived longer than R. robustus I. Our results suggest that adaptation to distinct palm-crown microclimates may partly underlie the so far unexplained differences in house-colonization ability among Rhodnius Stål species. Experimental replication across additional species/populations will be required to further probe this adaptive hypothesis—which, if supported, may also provide insight into the likely responses of Chagas disease vectors to climate change.
Can the Design of Electoral Institutions Improve Perceptions of Democracy in Fragile States? Evidence from Afghanistan
Authors: Jochem Torsten , Murtazashvili Ilia , Murtazashvili Jennifer 
Published: April 2019

AbstractLiberal peace-building efforts in fragile states often suffer from low levels of public support for democracy. This article explores whether changes in the design of electoral institutions improves perceptions of democracy in states seeking to transition from conflict to a democratic order. We do so by embedding a vignette experiment in a nationally representative survey of households in Afghanistan. Our experiment varies the method of selecting members to the national legislature, which allows us to examine how changes to status quo electoral institutions influence perceptions of democracy. We find that support for democracy depends on the choice of electoral institutions, particularly among those respondents who express sympathy for the Taliban insurgency. These results show how electoral system design improves citizen support for democracy and helps explain why democracy struggles to live up to its promise in these challenging contexts.
Space configurations for empowering university-community interactions
Authors: Dorland Jens , Clausen Christian , Jørgensen Michael Søgaard 
Published: April 2019

AbstractSome see universities as a possible source of solutions to enable a sustainable transition and overcome societal challenges. Findings from three multisite case studies of Desis Labs, FabLabs, and Science Shops shed light on how universities can help empower communities and solve societal challenges locally. Adopting a sociotechnical and flat relational perspective inspired by science and technology studies (STS), we focus on the material and spatial aspects of how these spaces are configured, thereby ensuring practical relevance for policy makers and practitioners. Applying an analytical generalization methodology, we condense the qualitative data into a typology of three ideal space-types (i.e. affording, mediating, and impact-oriented) that represent specific configurations of actors, researchers, students, communities, spaces, infrastructure, equipment, facilitators, etc. The ideal space-types empower communities in different ways, require different resources to create and operate, and translate differently into specific local contexts.
Developing a couple typology: A qualitative study of couple dynamics around physical activity
Authors: Griesemer Ida , Phillips Ashley , Khan Cynthia , Bahorski Stephanie , Altpeter Mary , Callahan Leigh F , Porter Laura S , Rini Christine 
Published: April 2019

Abstract
Partner-based social support can motivate engagement in physical activity (PA); however, couples approach exchanging support in different ways. This study aimed to elucidate the role of relationship dynamics in couple-based support for PA, with the goal of informing intervention strategies that will effectively leverage couple characteristics to increase support for PA. We conducted a qualitative study of couples who completed a longitudinal study of social support for PA. Participants were people with osteoarthritis who were not meeting PA recommendations and their cohabitating partners (n = 19 couples). We conducted in-depth, semistructured interviews and analyzed transcripts using narrative analysis. Participants were 76% non-Hispanic White and, on average, 62 years old. Themes in the data included (a) attitudes about working together to be more active (ranging from positive to negative) and (b) couples’ narrative concordance (high to low shared reality). We developed a couple typology with four categories: “Working together works” (positive attitudes/high shared reality; n = 4 couples), “Doing our own thing” (range of attitudes with practical/preferential barriers to working together/high shared reality; n = 5 couples), “Conscious conflict” (discrepant attitudes/high shared reality; n = 5 couples), and “Different realities” (discrepant attitudes/low shared reality; n = 5 couples). We describe examples of each type. In a sample of 19 couples, there were observable differences in participants’ attitudes about working together to be more active and in couples’ shared reality around those attitudes. Future research should investigate implications for the efficacy of interventions and, if warranted, develop methods to identify couple types and offer appropriate intervention strategies.
Simulation of model overfit in variance explained with genetic data
Authors: Derringer Jaime 
Published: April 2019

AbstractTwo recent papers, and an author response to prior commentary, addressing the genetic architecture of human temperament and character claimed that “The identified SNPs explained nearly all the heritability expected”. The authors’ method for estimating heritability may be summarized as: Step 1: Pre-select SNPs on the basis of GWAS p<0.01 in the target sample. Step 2: Enter target sample genotypes (the pre-selected SNPs from Step 1) and phenotypes into an unsupervised machine learning algorithm (Phenotype-Genotype Many-to-Many Relations Analysis, PGMRA) for further reduction of the set of SNPs. Step 3: Test the sum score of the SNPs identified from Step 2, weighted by the GWAS regression weights estimated in Step 1, within the same target sample. The authors interpreted the linear regression model R2 obtained from Step 3 as a measure of successfully identified heritability. Regardless of the method applied to select SNPs in Step 2, the combination of Steps 1 and 3, as described, causes inflation of the estimated effect size. The extent of this inflation is demonstrated here, where random SNP selection and polygenic scoring from simulated random data recovered effect sizes similar to those reported in the original empirical papers.
Systematically understanding the key roles of microglia in AD development
Authors: Ji Zhiwei , Liu Changan , Zhao Weiling , Soto Claudio , Zhou Xiaobo 
Published: April 2019

AbstractAlzheimer’s disease (AD) is the leading cause of age-related dementia, affecting over 5 million people in the United States. Unfortunately, current therapies are largely palliative and several potential drug candidates have failed in late-stage clinical trials. Studies suggest that microglia-mediated neuroinflammation might be responsible for the failures of various therapies. Microglia contribute to Aβ clearance in the early stage of neurodegeneration and may contribute to AD development at the late stage by releasing pro-inflammatory cytokines. However, the activation profile and phenotypic changes of microglia during the development of AD are poorly understood. To systematically understand the key role of microglia in AD progression and predict the optimal therapeutic strategyin silico, we developed a 3D multi-scale model of AD (MSMAD) by integrating multi-level experimental data, to manipulate the neurodegeneration in a simulated system. Based on our analysis, we revealed how TREM2-related signal transduction leads to an imbalance in the activation of different microglia phenotypes, thereby promoting AD development. Our MSMAD model also provides an optimal treatment strategy for improving the outcome of AD treatment.
Role of host genetic diversity for susceptibility-to-infection in the evolution of virulence of a plant virus
Authors: González Rubén , Butković Anamarija , Elena Santiago F. 
Published: April 2019

AbstractPredicting viral emergence is difficult due to the stochastic nature of the underlying processes and the many factors that govern pathogen evolution. Environmental factors affecting the host, the pathogen and the interaction between both are key in emergence. In particular, infectious disease dynamics are affected by spatiotemporal heterogeneity in their environments. A broad knowledge of these factors will allow better estimating where and when viral emergence is more likely to occur. Here we investigate how the population structure for susceptibility-to-infection genes of the plantArabidopsis thalianashapes the evolution ofTurnip mosaic virus(TuMV). For doing so we have evolved TuMV lineages in two radically different host population structures: (i) multiple genetically homogeneousA. thalianasubpopulations and (ii) a single maximally genetically heterogeneous population. We found faster adaptation of TuMV to homogeneous than to heterogeneous host populations. However, viruses evolved in heterogeneous host populations were more pathogenic and infectious than viruses evolved in the homogeneous population. Furthermore, the viruses evolved in homogeneous populations showed stronger signatures of local specialization than viruses evolved in heterogeneous populations. These results illustrate how the genetic diversity of hosts in an experimental ecosystem favors the evolution of virulence of a pathogen.
Integrative taxonomy confirms the species status of the Himalayan langurs, Semnopithecus schistaceus Hodgson 1840
Authors: Arekar Kunal , Sathyakumar S. , Karanth K. Praveen 
Published: April 2019

AbstractTaxonomy is replete with groups where the species identity and classification remain unresolved. One such group is the widely distributed Hanuman langur (Colobinae: Semnopithecus). For most part of the last century, Hanuman langur was considered to be a single species with multiple subspecies. Nevertheless, recent studies using an integrative taxonomy approach suggested that this taxon is a complex, with at least three species. However, these studies did not include the Himalayan population of the Hanuman langur whose taxonomic status remains unresolved. The Himalayan population of Hanuman langurs have been classified as a distinct species with multiple subspecies or have been subsumed into other species. These classification schemes are wholly based on morphological characters and which are sometimes insufficient to delimit different species. Here, we have integrated data from multiple sources viz. morphology, DNA, and ecology to resolve the taxonomy of the Himalayan langur and to understand its distribution limit. Our results with three lines of evidence corresponding to three different species concepts show that Himalayan langur is a distinct species from S. entellus of the plains. Additionally, these results did not show any support for splitting of the Himalayan langur into multiple subspecies. Our study supports the classification proposed by Hill (1939) and we recommend Semnopithecus schistaceus, Hodgson 1840 as species name for the Himalayan langur and subsume all the known subspecies into it.
Evaluating the quorum quenching potential of bacteria associated toAurelia auritaandMnemiopsis leidyi
Authors: Prasse Daniela , Weiland-Bräuer Nancy , Jaspers Cornelia , Reusch Thorsten B.H. , Schmitz Ruth A. 
Published: April 2019

AbstractThe associated microbiota of marine invertebrates plays an important role to the host in relation to fitness, health and homeostasis of the metaorganism. As one key chemically-mediated interaction, Quorum sensing (QS) and interference with QS among colonizing bacteria ultimately affects the establishment and dynamics of the microbial community on the host. Aiming to address interspecies competition of cultivable microbes associated to merging model species of the basal animal phyla Cnidaria (Aurelia aurita) and Ctenophora (Mnemiopsis leidyi) as well as to evaluate their potential to shape the associated community by interfering with QS, we performed a classical isolation approach. Overall, 84 bacteria were isolated fromA. auritamedusae and polyps, 64 bacteria fromM. leidyi, and 83 bacteria from the ambient seawater, followed by taxonomically classification by full length 16S rRNA gene analysis. The results show that the moon jellyfishA. auritaand the comb jellyM. leidyiharbor a cultivable core microbiota consisting of typical marine and ubiquitously found bacteria (e.g.Chryseobacter, Microbacterium, Micrococcus, Olleya, Phaeobacter, Pseudoalteromonas, Pseudomonas, Rhodococcus, Shewanella, Staphylococcus, andVibrio) which can also be found in the ambient seawater. However, several bacteria were restricted to one host (e.g. forA. aurita: Bacillus, Glaciecola, Ruegeria, Luteococcus;forM. leidyi: Acinetobacter, Aeromonas, Colwellia, Exiguobacterium, Marinomonas, Pseudoclavibacter, Psychrobacter, Sagittula, Thalassomonas) suggesting host-specific microbial community patterns. Evaluating QQ activities, out of 231 isolates, 121 showed QS-interfering activity. They mainly interfered with the acyl homoserine lactone (AHL) based communication, whereas 21 showed simultaneous quorum quenching activities against AHL and autoinducer-2. Overall, this study provides insights into the cultivable part of the microbiota associated to two environmentally important marine non-model organisms and discloses their potential in synthesizing QS interfering compounds, potentially important in shaping a healthy and resilient microbiota.
Transcriptional response ofStreptomyces coelicolorto rapid chromosome relaxation or long-term supercoiling imbalance
Authors: Szafran MJ , Gongerowska M , Małecki T , Elliot MA , Jakimowicz D 
Published: April 2019

ABSTRACTNegative DNA supercoiling allows chromosome condensation within a cell and facilitates DNA unwinding, which is required for the occurrence of DNA transaction processes, i.e., DNA replication, transcription and recombination. In bacteria, changes in chromosome supercoiling impact global gene expression; however, the limited studies on the global transcriptional response have focused mostly on pathogenic species and have reported various fractions of affected genes. Furthermore, the transcriptional response to long-term supercoiling imbalance is still poorly understood. Here, we address the transcriptional response to both novobiocin-induced rapid chromosome relaxation or long-term topological imbalance, both increased and decreased supercoiling, in environmental antibiotic-producing bacteria belonging to theStreptomycesgenus. During theStreptomycescomplex developmental cycle, multiple copies of GC-rich linear chromosomes present in hyphal cells undergo profound topological changes, from being loosely condensed in vegetative hyphae, to being highly compacted in spores. InStreptomyces, chromosomal supercoiling changes may also be triggered by environmental stressors and have been suggested to be associated with the control of antibiotic production. Remarkably, inS. coelicolor, one of modelStreptomycesspecies, topoisomerase I (TopA) is solely responsible for the removal of negative DNA supercoils. Using aS. coelicolorstrain in whichtopAtranscription is under the control of an inducible promoter, we generated a long-term supercoiling imbalance, enabling us to identify genes involved in the supercoiling-sensitive transcriptional response. We observed that affected genes are preferentially organized in clusters, and among them, we identified a supercoiling-hypersensitive cluster (SHC) located in the core of theS. coelicolorchromosome. Moreover, using a gyrase inhibitor, we identified the directly affected novobiocin-sensitive genes and established that the AT content in their promoter regions was increased. Notably, genes whose expression was immediately impacted by gyrase inhibition encoded products associated with membrane transport or secondary metabolite synthesis. In contrast to the novobiocin-sensitive genes, the transcripts affected by long-term topological imbalance encompassed genes encoding nucleoid-associated proteins, DNA repair proteins and transcriptional regulators, including multiple developmental regulators. Collectively, our results show that long-term supercoiling imbalance globally regulates gene transcription and has the potential to impact development, secondary metabolism and DNA repair, amongst others.
High Throughput PET/CT Imaging Using a Multiple Mouse Imaging System
Authors: Greenwood Hannah E. , Nyitrai Zoltan , Mocsai Gabor , Hobor Sandor , Witney Timothy H. 
Published: April 2019

AbstractA considerable limitation of current small animal positron emission tomography/computed tomography (PET/CT) imaging is the low throughput of image acquisitions. Subsequently, to design sufficiently-powered studies, high costs accumulate. Together with Mediso Medical Imaging Systems, a four-bed mouse ‘hotel’ was developed to simultaneously image up to four mice, thereby reducing the cost and maximising radiotracer usage when compared to scans performed with a single mouse bed.MethodsFor physiological evaluation of the four-bed mouse hotel, temperature and anaesthesia were tested for uniformity, followed by [18F]fluorodeoxyglucose (FDG) PET/CT imaging of ‘mini’ image quality (IQ) phantoms specifically designed to fit the new imaging system. Post-reconstruction, National Electrical Manufacturers Association (NEMA) NU-4 tests examined uniformity, recovery coefficients (RCs) and spill-over ratios (SORs). To evaluate the bed under standard in vivo imaging conditions, four mice were simultaneously scanned by dynamic [18F]FDG PET/CT over 60 minutes using the four-bed mouse hotel, with quantified images compared to those acquired using a single mouse bed.ResultsThe bed maintained a constant temperature of 36.8°C ± 0.4°C (n = 4), with anaesthesia distributed evenly to each nose cone (2.9 ± 0.1 L/min, n = 4). The NEMA tests performed on reconstructed mini IQ phantom images acquired using the four-bed mouse hotel revealed values within the tolerable limits for uniformity, RC values in >2mm rods, and SORs in the non-radioactive water- and air-filled chambers. There was low variability in radiotracer uptake in all major organs of mice scanned using the four-animal bed versus those imaged using a single bed imaging platform.ConclusionAnalysis of images acquired using the four-bed mouse hotel confirmed its utility to increase the throughput of small animal PET imaging without considerable loss of image quality and quantitative precision. In comparison to a single mouse bed, the cost and time associated with each scan were substantially reduced.
Evolved resistance to GAPDH inhibition results in loss of the Warburg Effect but retains a different state of glycolysis
Authors: Liberti Maria V. , Allen Annamarie E. , Ramesh Vijyendra , Dai Ziwei , Singleton Katherine R. , Guo Zufeng , Liu Jun O. , Wood Kris C. , Locasale Jason W. 
Published: April 2019

SUMMARYAerobic glycolysis or the Warburg Effect (WE) is characterized by increased glucose uptake and incomplete oxidation to lactate. Although ubiquitous, the biological role of the WE remains controversial and whether glucose metabolism is functionally different during fully oxidative glycolysis or during the WE is unknown. To investigate this question, we evolved resistance to koningic acid (KA), a natural product shown to be a specific inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a rate-controlling glycolytic enzyme during the WE. We find that KA-resistant cells lose the WE but conduct glycolysis and surprisingly remain dependent on glucose and central carbon metabolism. Consequentially this altered state of glycolysis leads to differential metabolic activity and requirements including emergent activities in and dependencies on fatty acid metabolism. Together, these findings reveal that, contrary to some recent reports, aerobic glycolysis is a functionally distinct entity from conventional glucose metabolism and leads to distinct metabolic requirements and biological functions.