bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse drug event rates in pediatric pulmonary hypertension: a comparison of real-world data sources
Authors: Geva Alon , Abman Steven H , Manzi Shannon F , Ivy Dunbar D , Mullen Mary P , Griffin John , Lin Chen , Savova Guergana K , Mandl Kenneth D 
Published: October 2019

AbstractObjectiveReal-world data (RWD) are increasingly used for pharmacoepidemiology and regulatory innovation. Our objective was to compare adverse drug event (ADE) rates determined from two RWD sources, electronic health records and administrative claims data, among children treated with drugs for pulmonary hypertension.Materials and MethodsTextual mentions of medications and signs/symptoms that may represent ADEs were identified in clinical notes using natural language processing. Diagnostic codes for the same signs/symptoms were identified in our electronic data warehouse for the patients with textual evidence of taking pulmonary hypertension-targeted drugs. We compared rates of ADEs identified in clinical notes to those identified from diagnostic code data. In addition, we compared putative ADE rates from clinical notes to those from a healthcare claims dataset from a large, national insurer.ResultsAnalysis of clinical notes identified up to 7-fold higher ADE rates than those ascertained from diagnostic codes. However, certain ADEs (eg, hearing loss) were more often identified in diagnostic code data. Similar results were found when ADE rates ascertained from clinical notes and national claims data were compared.DiscussionWhile administrative claims and clinical notes are both increasingly used for RWD-based pharmacovigilance, ADE rates substantially differ depending on data source.ConclusionPharmacovigilance based on RWD may lead to discrepant results depending on the data source analyzed. Further work is needed to confirm the validity of identified ADEs, to distinguish them from disease effects, and to understand tradeoffs in sensitivity and specificity between data sources.
Dietary supplementation of a fiber-prebiotic and saccharin-eugenol blend in extruded diets fed to dogs
Authors: Nogueira Juliana Paschoalin De Souza , He Fei , Mangian Heather F , Oba Patricia Massae , De Godoy Maria R C 
Published: October 2019

AbstractPrebiotics and dietary fibers are nondigestible ingredients that may confer benefits to the host by selectively stimulating beneficial intestinal bacteria and microbial-derived metabolites that support gut and host health. This experiment evaluated the effects of a blend of prebiotics and dietary fibers on apparent total tract digestibility (ATTD) and fecal metabolites related to gastrointestinal health in adult dogs. Four diets containing either 5% cellulose (control; CT), 5% dietary fiber and prebiotic blend (FP), 0.02% saccharin and eugenol (SE), or 5% fiber blend plus 0.02% saccharin and eugenol (FSE) were formulated to meet or exceed the AAFCO (2017) nutritional requirements for adult dogs. Eight adult female beagles (mean age 4.2 ± 1.1 yr; mean BW = 10.8 ± 1.4 kg; mean BCS = 5.8 ± 0.6) were randomly assigned to 1 of the 4 dietary treatments using a replicated 4 × 4 Latin square design. Each experimental period consisted of 14 d (10 d of diet adaptation and 4 d of total and fresh fecal and total urine collection). All animals remained healthy throughout the study, with serum metabolites being within reference ranges for adult dogs. All diets were well accepted by the dogs, resulting in similar (P > 0.05) daily food intakes among treatments. Likewise, fecal output and scores did not differ (P > 0.05) among dietary treatments, with the latter being within the ideal range (2.5–2.9) in a 5-point scale. All diets were highly digestible and had similar (P > 0.05) ATTD of dry matter (81.6%–84.4%), organic matter (86.4%–87.3%), and crude protein (86.6%–87.3%). However, total dietary fiber (TDF) digestibility was greater for dogs fed the FSE diet (P < 0.05) in contrast with dogs fed the CT and SE diets, whereas dogs fed FP diets had intermediate TDF digestibility, but not different from all other treatments. Fecal acetate and propionate concentrations were greater (P < 0.05) for dogs fed FP and FSE diets. Fecal concentrations of isobutyrate and isovalerate were greater for dogs fed CT (P < 0.05) compared with dogs fed the other three treatments. No shifts in fecal microbial richness and diversity were observed among dietary treatments. Overall, the data suggest that dietary supplementation of fiber and prebiotic blend was well tolerated by dogs, did not cause detrimental effects on fecal quality or nutrient digestibility, and resulted in beneficial shifts in fecal metabolites that may support gut health.
A comparative assessment of salt marsh crabs (Decapoda: Brachyura) across the National Estuarine Research Reserves in New England, USA
Authors: Raposa Kenneth B , Goldstein Jason S , Grimes Kristin Wilson , Mora Jordan , Stacey Paul E , Mckinney Richard A 
Published: October 2019

Abstract
Salt marsh degradation and loss is accelerating in many regions of the United States as well as worldwide. Multiple stressors are often responsible, sometimes including crab burrowing and herbivory. A recent national assessment identified stark differences in crab indicators between northern and southern New England, with the latter exhibiting intense signs of impacts by crabs, but more details on crab patterns across the entire region are needed beyond this “broad-brush” assessment. Our study used green crab (Carcinus maenas (Linnaeus, 1758)) traps, intensive marsh platform burrow counts, and a new multi-metric index of relative crab abundance to examine patterns in marsh crabs across four National Estuarine Research Reserves in New England. Crab indicators from the multi-metric index and burrow counts were higher in southern New England marshes; patterns from trapping of green crabs were less clear. At the marshes examined, green crabs were very abundant in Maine, lower in New Hampshire, and intermediate in southern New England. Our study confirms that abundance and impacts by crabs vary dramatically between sites in northern and southern New England, and provides improved context for managers and researchers when considering impacts to marshes from multiple crab species across New England and elsewhere.
Evolutionary significance of the embryological development of the daphniid cladocerans Ceriodaphnia Dana, 1853 and Scapholeberis Schoedler, 1858 (Branchiopoda: Cladocera: Daphniidae)
Authors: Uhlik Marcin Edward 
Published: October 2019

Abstract
The embryological development of Ceriodaphnia reticulataDumont & Pensaert, 1983 and Scapholeberis rammneriJurine, 1820 were investigated using scanning electron microscopy. A carapace spine did not develop and there was no fusion of the first antennae. These are apparent apomorphies of DaphniaMüller, 1785, which suggests that the common ancestor of Daphniidae Straus, 1820 did not have a carapace spine during its embryological development, and its first antennae were short and separated during embryogenesis. Morphological evidence thus appears congruent with molecular interpretations showing that ScapholeberisSchoedler, 1858 is basal to other genera of Daphniidae, Ceriodaphnia being a sister taxon to Daphnia.
Recovering Decimation-Based Cryptographic Sequences by Means of Linear CAs
Authors: Cardell Sara D , Aranha Diego F , Fúster-Sabater Amparo 
Published: October 2019

Abstract
The sequences produced by the cryptographic sequence generator known as the shrinking generator can be modelled as the output sequences of linear elementary cellular automata (CA). These sequences are composed of interleaved m-sequences produced by linear structures based on feedback shifts. This profitable characteristic can be used in the cryptanalysis of this generator. In this work we propose an algorithm that takes advantage of the inherent linearity of these CA and the interleaved m-sequences. Although irregularly decimated generators have been conceived and designed as non-linear ones, in practice they can be easily analysed in terms of simple linear structures.
Proteoglycan (Keratan Sulfate) Barrier in Developing Human Forebrain Isolates Cortical Epileptic Networks From Deep Heterotopia, Insulates Axonal Fascicles, and Explains Why Axosomatic Synapses Are Inhibitory
Authors: Sarnat Harvey B 
Published: October 2019

AbstractAxons from deep heterotopia do not extend through U-fibers, except transmantle dysplasias. Keratan sulfate (KS) in fetal spinal cord/brainstem median septum selectively repels glutamatergic axons while enabling GABAergic commissural axons. Immunocytochemical demonstration of KS in neocortical resections and forebrain at autopsy was studied in 12 fetuses and neonates 9–41 weeks gestational age (GA), 9 infants, children, and adolescents and 5 patients with focal cortical dysplasias (FCD1a). From 9 to 15 weeks GA, no KS is seen in the cortical plate; 19-week GA reactivity is detected in the molecular zone. By 28 weeks GA, patchy granulofilamentous reactivity appears in extracellular matrix and adheres to neuronal somata with increasing intensity in deep cortex and U-fibers at term. Perifascicular KS surrounds axonal bundles of both limbs of the internal capsule and within basal ganglia from 9 weeks GA. Thalamus and globus pallidus exhibit intense astrocytic reactivity from 9 weeks GA. In FCD1a, U-fiber reactivity is normal, discontinuous or radial. Ultrastructural correlates were not demonstrated; KS is not electron-dense. Proteoglycan barrier of the U-fiber layer impedes participation of deep heterotopia in cortical epileptic networks. Perifascicular KS prevents aberrant axonal exit from or entry into long and short tracts. KS adhesion to neuronal somatic membranes may explain inhibitory axosomatic synapses.
Differences in seed properties and germination between native and introduced populations of Triadica sebifera
Authors: Zhang Jialiang , Siemann Evan , Tian Baoliang , Huang Wei , Ding Jianqing 
Published: October 2019

Abstract

Aims
Seeds of many invasive plants germinate more quickly than those of native species, likely facilitating invasion success. Assessing the germination traits and seed properties simultaneously for introduced and native populations of an invasive plant is essential to understanding biological invasions. Here, we used Triadica sebifera as a study organism to examine intraspecific differences in seed germination together with seed characteristics.

Methods
We measured physical (volume, mass, coat hardness and coat thickness of seeds) and chemical (crude fat, soluble protein, sugar, gibberellins [GA] and abscisic acid [ABA] of kernels) properties of T. sebifera seeds collected in 2017 from 12 introduced (United States) populations and 12 native (China) populations and tested their germination rates and timing in a greenhouse experiment in China. Furthermore, we conducted an extra experiment in the United States using seeds collected in 2016 and 2017 to compare the effects of study sites (China vs. United States) and seed collection time (2016 vs. 2017) on seed germination.

Important Findings
Seeds from the introduced range germinated faster than those from the native range. Physical and chemical measurements showed that seeds from the introduced range were larger, had higher GA concentrations and GA:ABA ratio, but lower crude fat concentrations compared to those from the native range. There were no significant differences in seed mass, coat hardness and coat thickness or kernel ABA, soluble protein or sugar concentrations between seeds from introduced vs. native ranges. Germination rates were correlated between United States and China greenhouses but germination rates for populations varied between collection years. Our results suggest that larger seeds and higher GA likely contribute to faster germination, potentially facilitating T. sebifera invasion in the introduced range.
Sigma factor 1 in chloroplast gene transcription and photosynthetic light acclimation
Authors: Macadlo Lauren A , Ibrahim Iskander M , Puthiyaveetil Sujith 
Published: October 2019

Abstract
Sigma factors are dissociable subunits of bacterial RNA polymerase that ensure efficient transcription initiation from gene promoters. Owing to their prokaryotic origin, chloroplasts possess a typical bacterial RNA polymerase together with its sigma factor subunit. The higher plant Arabidopsis thaliana contain as many as six sigma factors for the hundred or so of its chloroplast genes. The role of this relatively large number of transcription initiation factors for the miniature chloroplast genome, however, is not fully understood. Using two Arabidopsis T-DNA insertion mutants, we show that sigma factor 1 (SIG1) initiates transcription of a specific subset of chloroplast genes. We further show that the photosynthetic control of PSI reaction center gene transcription requires complementary regulation of the nuclear SIG1 gene at the transcriptional level. This SIG1 gene regulation is dependent on both a plastid redox signal and a light signal transduced by the phytochrome photoreceptor.
Arabidopsis thaliana SEED DORMANCY 4-LIKE regulates dormancy and germination by mediating the gibberellin pathway
Authors: Cao Hong , Han Yi , Li Jingyi , Ding Meng , Li Yu , Li Xiaoying , Chen Fengying , Soppe Wim Jj , Liu Yongxiu 
Published: October 2019

AbstractThe molecular mechanisms underlying seed dormancy and germination are not fully understood. Here, we show that Arabidopsis thaliana SEED DORMANCY 4-LIKE (AtSdr4L) is a novel specific regulator of dormancy and germination. AtSdr4L encodes a protein with an unknown biochemical function that is localized in the nucleus and is expressed specifically in seeds. Loss of function of AtSdr4L results in increased seed dormancy. The germination of freshly harvested seeds of the Atsdr4l mutant is insensitive to gibberellin (GA). After-ripened mutant seeds are hypersensitive to the GA biosynthesis-inhibitor paclobutrazol but show unaltered sensitivity to abscisic acid. Several GA biosynthesis genes and GA-regulated cell wall remodeling genes are down-regulated in the mutant in both dormant and after-ripened seeds. These results suggest that the Atsdr4l mutation causes both decreased GA biosynthesis and reduced responses. In addition, a genetic analysis indicated that AtSdr4L is epistatic to DELAY OF GERMINATION1 (DOG1) for dormancy and acts upstream of RGA-LIKE 2 (RGL2) in the GA pathway. We propose that AtSdr4L regulates seed dormancy and germination by mediating both the DOG1 and GA pathways.
Xylem embolism in leaves does not occur with open stomata: evidence from direct observations using the optical visualization technique
Authors: Creek Danielle , Lamarque Laurent J , Torres-Ruiz José M , Parise Camille , Burlett Regis , Tissue David T , Delzon Sylvain 
Published: October 2019

AbstractDrought represents a major abiotic constraint to plant growth and survival. On the one hand, plants keep stomata open for efficient carbon assimilation while, on the other hand, they close them to prevent permanent hydraulic impairment from xylem embolism. The order of occurrence of these two processes (stomatal closure and the onset of leaf embolism) during plant dehydration has remained controversial, largely due to methodological limitations. However, the newly developed optical visualization method now allows concurrent monitoring of stomatal behaviour and leaf embolism formation in intact plants. We used this new approach directly by dehydrating intact saplings of three contrasting tree species and indirectly by conducting a literature survey across a greater range of plant taxa. Our results indicate that increasing water stress generates the onset of leaf embolism consistently after stomatal closure, and that the lag time between these processes (i.e. the safety margin) rises with increasing embolism resistance. This suggests that during water stress, embolism-mediated declines in leaf hydraulic conductivity are unlikely to act as a signal for stomatal down-regulation. Instead, these species converge towards a strategy of closing stomata early to prevent water loss and delay catastrophic xylem dysfunction.
From antagonist to protagonist: ‘Democracy’ and ‘people’ in British parliamentary debates, 1775–1885
Authors: Bonin Hugo 
Published: October 2019

Abstract
‘Democracy’ is a central word of our current political lexicon, often defined as ‘the power of the people’. However, in 19th century Britain, ‘democracy’ was not characterized by the rule of the ‘people’ but by the power of lower classes, of the ‘populace’ and the ‘mob’. In political discourse, and especially in parliamentary debates, the ‘people’ were an antagonist of ‘democracy’, not its protagonist. To support these statements, this article analyses British parliamentary debates between 1775 and 1885, through both a ‘distant reading’ with the help of corpus linguistics tools and a closer examination of certain key debates and actors. After a brief overview of the methodology, three crucial periods of British political history are analysed. (1) The end of the 18th century, where the impact of the French Revolution on democratic vocabulary is measured. (2) The debates surrounding the 1832 Reform Act, in which the explicit differentiation between the constitutional ‘people’ and the democratic ‘mob’ is drawn out by Whigs and Tories alike. (3) The Second Reform Act (1867), also presented as a ‘popular’ measure, and not a step towards ‘democracy’. In conclusion, the adoption of the democratic vocabulary by British Members of Parliament is traced to the 1880s, notably with the emergence of the idea of ‘Tory democracy’.
Orbital dynamics of circumbinary planets
Authors: Chen Cheng , Franchini Alessia , Lubow Stephen H , Martin Rebecca G 
Published: October 2019

ABSTRACT
We investigate the dynamics of a non-zero mass, circular orbit planet around an eccentric orbit binary for various values of the binary eccentricity, binary mass fraction, planet mass, and planet semimajor axis by means of numerical simulations. Previous studies investigated the secular dynamics mainly by approximate analytic methods. In the stationary inclination state, the planet and binary precess together with no change in relative tilt. For both prograde and retrograde planetary orbits, we explore the conditions for planetary orbital libration versus circulation and the conditions for stationary inclination. As was predicted by analytic models, for sufficiently high initial inclination, a prograde planet’s orbit librates about the stationary tilted state. For a fixed binary eccentricity, the stationary angle is a monotonically decreasing function of the ratio of the planet-to-binary angular momentum j. The larger j, the stronger the evolutionary changes in the binary eccentricity and inclination. We also calculate the critical tilt angle that separates the circulating from the librating orbits for both prograde and retrograde planet orbits. The properties of the librating orbits and stationary angles are quite different for prograde versus retrograde orbits. The results of the numerical simulations are in very good quantitative agreement with the analytic models. Our results have implications for circumbinary planet formation and evolution.
JexoSim: a time-domain simulator of exoplanet transit spectroscopy with JWST
Authors: Sarkar Subhajit , Madhusudhan Nikku , Papageorgiou Andreas 
Published: October 2019

ABSTRACT
The James Webb Space Telescope (JWST) will perform exoplanet transit spectroscopy in the coming decade, promising transformative science results. All four instruments onboard can be used for this technique that reconstructs the atmospheric transmission or emission spectrum of an exoplanet from wavelength-dependent light-curve measurements. Astrophysical and instrumental noise and systematics can affect the precision and accuracy of the final spectrum, and hence, the atmospheric properties derived from the spectrum. Correlated noise and time-dependent systematics that can bias the measured signal must be accounted for in the final uncertainties. However, quantifying these effects can be difficult with real data or simple analytic tools. Existing publicly available simulators for JWST do not adequately simulate complex time-domain processes on exoplanetary transit observations. We report JexoSim, a dedicated time-domain simulator for JWST including all the four instruments for exoplanet transit spectroscopy. JexoSim models both the astrophysics and the instrument, generating 2D images in simulated time akin to a real observation. JexoSim can capture correlated noise and systematic biases on the light curve, giving it great versatility. Potential applications of JexoSim include performance testing of JWST instruments, assessing science return, and testing data reduction pipelines. We describe JexoSim, validate it against other simulators, and present examples of its utility.
Reliable Confidence Intervals for RelTime Estimates of Evolutionary Divergence Times
Authors: Tao Qiqing , Tamura Koichiro , Mello Beatriz , Kumar Sudhir 
Published: October 2019

AbstractConfidence intervals (CIs) depict the statistical uncertainty surrounding evolutionary divergence time estimates. They capture variance contributed by the finite number of sequences and sites used in the alignment, deviations of evolutionary rates from a strict molecular clock in a phylogeny, and uncertainty associated with clock calibrations. Reliable tests of biological hypotheses demand reliable CIs. However, current non-Bayesian methods may produce unreliable CIs because they do not incorporate rate variation among lineages and interactions among clock calibrations properly. Here, we present a new analytical method to calculate CIs of divergence times estimated using the RelTime method, along with an approach to utilize multiple calibration uncertainty densities in dating analyses. Empirical data analyses showed that the new methods produce CIs that overlap with Bayesian highest posterior density intervals. In the analysis of computer-simulated data, we found that RelTime CIs show excellent average coverage probabilities, that is, the actual time is contained within the CIs with a 94% probability. These developments will encourage broader use of computationally efficient RelTime approaches in molecular dating analyses and biological hypothesis testing.
Molecular Biology and Evolution of Cancer: From Discovery to Action
Authors: Somarelli Jason A , Gardner Heather , Cannataro Vincent L , Gunady Ella F , Boddy Amy M , Johnson Norman A , Fisk Jeffrey Nicholas , Gaffney Stephen G , Chuang Jeffrey H , Li Sheng , Ciccarelli Francesca D , Panchenko Anna R , Megquier Kate , Kumar Sudhir , Dornburg Alex , DeGregori James , Townsend Jeffrey P 
Published: October 2019

AbstractCancer progression is an evolutionary process. During this process, evolving cancer cell populations encounter restrictive ecological niches within the body, such as the primary tumor, circulatory system, and diverse metastatic sites. Efforts to prevent or delay cancer evolution—and progression—require a deep understanding of the underlying molecular evolutionary processes. Herein we discuss a suite of concepts and tools from evolutionary and ecological theory that can inform cancer biology in new and meaningful ways. We also highlight current challenges to applying these concepts, and propose ways in which incorporating these concepts could identify new therapeutic modes and vulnerabilities in cancer.