bluuebunny/crossref_metadata_2025_split huggingface dataset:
A manipulative thermal challenge protocol for adult salmonids in remote field settings
Authors: Donnelly Daniel S , von Biela Vanessa R , McCormick Stephen D , Laske Sarah M , Carey Michael P , Waters Shannon , Bowen Lizabeth , Brown Randy J , Larson Sean , Zimmerman Christian E 
Published: September 2020

Abstract
Manipulative experiments provide stronger evidence for identifying cause-and-effect relationships than correlative studies, but protocols for implementing temperature manipulations are lacking for large species in remote settings. We developed an experimental protocol for holding adult Chinook salmon (Oncorhynchus tshawytscha) and exposing them to elevated temperature treatments. The goal of the experimental protocol was to validate heat stress biomarkers by increasing river water temperature from ambient (~14°C) to a treatment temperature of 18°C or 21°C and then maintain the treatment temperature over 4 hours within a range of ±1.0°C. Our protocol resulted in a mean rate of temperature rise of 3.71°C h-1 (SD = 1.31) to treatment temperatures and mean holding temperatures of 18.0°C (SD = 0.2) and 21.0°C (SD = 0.2) in the low- and high-heat treatments, respectively. Our work demonstrated that manipulative experiments with large, mobile study species can be successfully developed in remote locations to examine thermal stress.
Continuous growth through winter correlates with increased resting metabolic rate but does not affect daily energy budgets due to torpor use
Authors: Boratyński Jan S , Iwińska Karolina , Szafrańska Paulina A , Chibowski Piotr , Bogdanowicz Wiesław 
Published: September 2020

AbstractSmall mammals that are specialists in homeothermic thermoregulation reduce their self-maintenance costs of normothermy to survive the winter. By contrast, heterothermic ones that are considered generalists in thermoregulation can lower energy expenditure by entering torpor. It is well known that different species vary the use of their strategies to cope with harsh winters in temperate zones; however, little is still known about the intraspecific variation within populations and the associated external and internal factors. We hypothesized that yellow-necked mice Apodemus flavicollis decrease their resting metabolic rate (RMR) from autumn to winter, and then increase it during spring. However, since the alternative for seasonal reduction of RMR could be the development of heterothermy, we also considered the use of this strategy. We measured body mass (mb), RMR, and body temperature (Tb) of mice during 2 consecutive years. In the 1st year, mice decreased whole animal RMR in winter, but did not do so in the 2nd year. All mice entered torpor during the 2nd winter, whereas only a few did so during the first one. Mice showed a continuous increase of mb, which was steepest during the 2nd year. The relationship between RMR and mb varied among seasons and years most likely due to different mouse development stages. The mb gain at the individual level was correlated positively with RMR and heterothermy. This indicates that high metabolism in winter supports the growth of smaller animals, which use torpor as a compensatory mechanism. Isotope composition of mice hair suggests that in the 1st year they fed mainly on seeds, while in the 2nd, they likely consumed significant amounts of less digestible herbs. The study suggests that the use of specialist or generalist thermoregulatory strategies can differ with environmental variation and associated differences in developmental processes.
Do key innovations unlock diversification? A case-study on the morphological and ecological impact of pharyngognathy in acanthomorph fishes
Authors: Larouche Olivier , Hodge Jennifer R , Alencar Laura R V , Camper Benjamin , Adams Danielle S , Zapfe Katerina , Friedman Sarah T , Wainwright Peter C , Price Samantha A 
Published: September 2020

AbstractKey innovations may allow lineages access to new resources and facilitate the invasion of new adaptive zones, potentially influencing diversification patterns. Many studies have focused on the impact of key innovations on speciation rates, but far less is known about how they influence phenotypic rates and patterns of ecomorphological diversification. We use the repeated evolution of pharyngognathy within acanthomorph fishes, a commonly cited key innovation, as a case study to explore the predictions of key innovation theory. Specifically, we investigate whether transitions to pharyngognathy led to shifts in the rate of phenotypic evolution, as well as shifts and/or expansion in the occupation of morphological and dietary space, using a dataset of 8 morphological traits measured across 3,853 species of Acanthomorpha. Analyzing the 6 evolutionarily independent pharyngognathous clades together, we found no evidence to support pharyngognathy as a key innovation; however, comparisons between individual pharyngognathous lineages and their sister clades did reveal some consistent patterns. In morphospace, most pharyngognathous clades cluster in areas that correspond to deeper-bodied morphologies relative to their sister clades, while occupying greater areas in dietary space that reflects a more diversified diet. Additionally, both Cichlidae and Labridae exhibited higher univariate rates of phenotypic evolution compared with their closest relatives. However, few of these results were exceptional relative to our null models. Our results suggest that transitions to pharyngognathy may only be advantageous when combined with additional ecological or intrinsic factors, illustrating the importance of accounting for lineage-specific effects when testing key innovation hypotheses. Moreover, the challenges we experienced formulating informative comparisons, despite the ideal evolutionary scenario of multiple independent evolutionary origins of pharyngognathous clades, illustrates the complexities involved in quantifying the impact of key innovations. Given the issues of lineage specific effects and rate heterogeneity at macroevolutionary scales we observed, we suggest a reassessment of the expected impacts of key innovations may be warranted.
Whole genome sequencing identifies allelic ratio distortion in sperm involving genes related to spermatogenesis in a swine model
Authors: Gòdia Marta , Casellas Joaquim , Ruiz-Herrera Aurora , Rodríguez-Gil Joan E , Castelló Anna , Sánchez Armand , Clop Alex 
Published: September 2020

Abstract
Transmission Ratio Distortion (TRD), the uneven transmission of an allele from a parent to its offspring, can be caused by allelic differences affecting gametogenesis, fertilization or embryogenesis. However, TRD remains vaguely studied at a genomic scale. We sequenced the diploid and haploid genomes of three boars from leukocytes and spermatozoa at 50x to shed light into the genetic basis of spermatogenesis-caused Allelic Ratio Distortion (ARD). We first developed a Binomial model to identify ARD by simultaneously analysing all three males. This led to the identification of 55 ARD SNPs, most of which were animal-specific. We then evaluated ARD individually within each pig by a Fisher’s exact test and identified two shared genes (TOP3A and UNC5B) and four shared genomic regions harbouring distinct ARD SNPs in the three boars. The shared genomic regions contained candidate genes with functions related to spermatogenesis including AK7, ARID4B, BDKRB2, GSK3B, NID1, NSMCE1, PALB2, VRK1 and ZC3H13. Using the Fisher’s test, we also identified 378 genes containing variants with protein damaging potential in at least one boar, a high proportion of which, including FAM120B, TDRD15, JAM2 or AOX4 among others, are associated to spermatogenesis. Overall, our results show that sperm is subjected to ARD with variants associated to a wide variety of genes involved in different stages of spermatogenesis.
Accuracy of Achalasia Quality of Life and Eckardt scores for assessment of clinical improvement post treatment for achalasia
Authors: Slone Samuel , Kumar Ambuj , Jacobs John , Velanovich Vic , Richter Joel E 
Published: September 2020

Abstract
Achalasia Quality of Life (ASQ) and Eckardt scores are two patient-reported instruments widely used to assess symptom severity in achalasia patients. ASQ is validated and reliable. Although Eckardt is commonly used, it has not been rigorously assessed for validity or reliability. This study aims to evaluate (i) the accuracy of Eckardt and ASQ for assessing improvement post-treatment (predictive validity), (ii) accuracy of Eckardt and ASQ for assessing improvement post-treatment with pneumatic dilatation (PD) versus surgical myotomy (predictive validity), and (iii) convergent validity of Eckardt and ASQ tools. Patients with achalasia treated between 2011 and 2018 were eligible. Both instruments were administered by telephone. Treatment failure was determined by the review of medical records by two clinicians. The predictive ability of ASQ and Eckardt instruments in identifying treatment successes and failures was determined using receiver operating characteristics analysis and summarized as area under the curve (AUC). A total of 106 patients met inclusion criteria with 39 PD, 51 Heller myotomy, and 16 per-oral endoscopic myotomy. A review of medical records and esophageal testing revealed 13 failures (12%). AUC for Eckardt was 0.96 (95% confidence interval [CI] 0.87–0.99] and ASQ 0.97 (95% CI 0.92–0.99). The Eckardt cutoff 4, and ASQ, cutoff 15, were 94% and 87% accurate in identifying treatment successes versus failures, respectively. The correlation coefficient between the two tools was 0.85. In conclusions, (i) ASQ and Eckardt scores are valid and reliable tools to assess symptom severity in achalasia patients, (ii) both instruments accurately classify treatment successes versus failures, and (iii) the choice of tool should be informed by the physicians and patients’ values and preferences and repeat physiologic testing may be reserved for treatment failures with either instrument and patients classified, as treatment successes may be spared routine physiologic testing in the long term.
The Colour of a Free Ride
Authors: Mujcic Redzo , Frijters Paul 
Published: September 2020

Abstract
We use a natural field experiment to estimate the causal effect of race on discretionary favours in the marketplace. Test customers are randomly assigned to board public buses with no money to purchase a fare, leaving the bus driver to voluntarily decide whether to offer them a free ride. Based on 1,552 transactions, we uncover strong evidence of racial bias: bus drivers were twice as willing to let white testers ride free as black testers (72% vs. 36% of the time). Signals of wealth and patriotism improve minority testers’ outcomes. Our results show that white privilege extends to unregulated daily interactions.
Global Earnings Inequality, 1970–2018
Authors: Hammar Olle , Waldenström Daniel 
Published: September 2020

Abstract
We estimate trends in global earnings dispersion across occupational groups by constructing a new database that covers 68 developed and developing countries between 1970 and 2018. Our main finding is that global earnings inequality has fallen, primarily during the 2000s and 2010s, when the global Gini coefficient dropped by 15 points and the earnings share of the world's poorest half doubled. Decomposition analyses show earnings convergence between countries and within occupations, while within-country earnings inequality has increased. Moreover, the falling global inequality trend was driven mainly by real wage growth, rather than changes in hours worked, taxes or occupational employment.
A systematic strategy using a reconstructed genome-scale metabolic network for pathogenStreptococcuspneumoniaeD39 to find novel potential drug targets
Authors: Pedram Narges , Rashedi Hamid , Motamedian Ehsan 
Published: September 2020

ABSTRACTStreptococcus pneumoniae is a Gram-positive bacterium that is one of the major causes of various infections such as pneumonia, meningitis, otitis media and endocarditis. Since antibiotic resistance of S. pneumoniae is pointed out as a challenge in the treatment of these infections, more studies are required to focus on disease prevention. In this research, a first manually curated genome-scale metabolic network of the pathogen S. pneumoniae D39 was reconstructed based on its genome annotation data, and biochemical knowledge from literature and databases. The model was validated by amino acid auxotrophies, gene essentiality analysis, and different carbohydrate sources. Then, a two-stage strategy was developed to find target genes for growth reduction of the pathogen and their importance in the various infection sites. In the first stage, growth-associated genes were identified by integration of transcriptomic data with the model and in the second stage, the importance of each gene in the metabolism for growth was evaluated using principal component analysis. The reports presented in the literature confirm the effect of some found genes on the growth of S. pneumoniae.
Transcriptomic biomarkers for predicting response to neoadjuvant treatment in oesophageal cancer
Authors: Lavery Anita , Turkington Richard C 
Published: September 2020

Abstract
Oesophageal cancer is a devastating disease with poor outcomes and is the sixth leading cause of cancer death worldwide. In the setting of resectable disease, there is clear evidence that neoadjuvant chemotherapy and chemoradiotherapy result in improved survival. Disappointingly, only 15%–30% of patients obtain a histopathological response to neoadjuvant therapy, often at the expense of significant toxicity. There are no predictive biomarkers in routine clinical use in this setting and the ability to stratify patients for treatment could dramatically improve outcomes. In this review, we aim to outline current progress in evaluating predictive transcriptomic biomarkers for neoadjuvant therapy in oesophageal cancer and discuss the challenges facing biomarker development in this setting. We place these issues in the wider context of recommendations for biomarker development and reporting. The majority of studies focus on messenger RNA (mRNA) and microRNA (miRNA) biomarkers. These studies report a range of different genes involved in a wide variety of pathways and biological processes, and this is explained to a large extent by the different platforms and analysis methods used. Many studies are also vastly underpowered so are not suitable for identifying a candidate biomarker. Multiple molecular subtypes of oesophageal cancer have been proposed, although little is known about how these relate to clinical outcomes. We anticipate that the accumulating wealth of genomic and transcriptomic data and clinical trial collaborations in the coming years will provide unique opportunities to stratify patients in this poor-prognosis disease and recommend that future biomarker development incorporates well-designed retrospective and prospective analyses.
Frailty Is Associated With Neutrophil Dysfunction Which Is Correctable With Phosphoinositol-3-Kinase Inhibitors
Authors: Wilson Daisy , Drew William , Jasper Alice , Crisford Helena , Nightingale Peter , Newby Paul , Jackson Thomas , Lord Janet M , Sapey Elizabeth 
Published: September 2020

AbstractNeutrophil dysfunction has been described with age, appears exaggerated in infection, with altered phosphoinositol signaling a potential mechanism. However, functional aging is heterogeneous. Frailty is a negative health status and is more common in older adults. We hypothesized that neutrophil migration may be compromised in frailty, associated with the degree of frailty experienced by the older person. We compared measures of frailty, neutrophil function, and systemic inflammation in 40 young and 77 older community-dwelling adults in the United Kingdom. Systemic neutrophils exhibited an age-associated reduction in the accuracy of migration (chemotaxis) which was further blunted with frailty. The degree of migratory inaccuracy correlated with physical (adjusted hand grip strength) and cognitive (Stroop test) markers of frailty. Regression analysis demonstrated that age, Charlson comorbidity index, and frailty index were able to predict neutrophil chemotaxis. Reduced chemotaxis of neutrophils from frail adults could be reversed using selective PI3K inhibitors. Exposure of neutrophils from young adults to plasma from chronically inflamed frail older adults could not recapitulate the migratory deficit in vitro, and there were no relationships with systemic inflammation and neutrophil dysfunction. Frailty exaggerated the neutrophil deficits seen with advanced age but aspects of the frailty-associated deficit in neutrophil function are rescuable and thus potentially form a therapeutic target to improve outcomes from infection in older adults.
Normative Labels in Slovene Dictionaries: Users’ and Lexicographers’ Perspectives
Authors: Šipka Danko , Vrbinc Alenka , Vrbinc Marjeta 
Published: September 2020

AbstractThis paper discusses normative labels in the Dictionary of Standard Slovene from the point of view of users and lexicographers. Using a questionnaire distributed to the students of the University of Ljubljana, we wanted to learn how native speakers of Slovene interpret select normative labels. Additionally, five Slovene lexicographers were interviewed to get an insight into their views on labeling lemmata or their senses. The problems they encounter when assigning the labels were assessed in the interviews. The results of the student survey show that the presence of normative labels and their type has an effect on the users’ perceived degree of acceptability of the word in the standard language variety. Though still marking inadequate forms, the lexicographers interviewed strive to stay away from prescriptivism by trying to give reasons for a less adequate form. This is a new development that diverges from traditional, strongly prescriptive, attitude of Slovene linguists.
A convergent finite element scheme for a fourth-order liquid crystal model
Authors: Metzger Stefan 
Published: September 2020

Abstract
In this manuscript we propose and analyse a fully discrete, unconditionally stable finite element scheme for a recently developed director model for liquid crystalline flows (Metzger, S. (2020) On a novel approach for modeling liquid crystalline flows. Commun. Math. Sci., 18, 359–378). The model consists of nonlinear fourth-order partial differential equations describing the evolution of the director field and Navier–Stokes equations governing the velocity field. We employ a stable splitting approach to reduce the computational complexity by decoupling the update of the director field from the update of the velocity field. We also perform a rigorous passage to the limit as the spatial and temporal discretization parameters simultaneously tend to zero, and show that a subsequence of finite element approximations converges towards a weak solution of the original model. Passing to the limit in the nonlinear terms requires us to derive the strong convergence of the gradient of the director field from uniform bounds for its discrete Laplacian. Furthermore, we present simulations underlining the practicability of the proposed scheme, investigate its convergence properties and discuss the differences between the underlying model and already established Ericksen–Leslie-type models.
An energy-stable parametric finite element method for simulating solid-state dewetting
Authors: Zhao Quan , Jiang Wei , Bao Weizhu 
Published: September 2020

Abstract
We propose an energy-stable parametric finite element method for simulating solid-state dewetting of thin films in two dimensions via a sharp-interface model, which is governed by surface diffusion and contact line (point) migration together with proper boundary conditions. By reformulating the relaxed contact angle condition into a Robin-type boundary condition and then treating it as a natural boundary condition, we obtain a new variational formulation for the problem, in which the interface curve and its contact points are evolved simultaneously. Then the variational problem is discretized in space by using piecewise linear elements. A full discretization is presented by adopting the backward Euler method in time, and the well-posedness and energy dissipation of the full discretization are established. The numerical method is semi-implicit (i.e., a linear system to be solved at each time step and thus efficient), unconditionally energy-stable with respect to the time step and second-order in space measured by a manifold distance between two curves. In addition, it demonstrates equal mesh distribution when the solution reaches its equilibrium, i.e., long-time dynamics. Numerical results are reported to show accuracy and efficiency as well as some good properties of the proposed numerical method.
Adverse drug event presentation and tracking (ADEPT): semiautomated, high throughput pharmacovigilance using real-world data
Authors: Geva Alon , Stedman Jason P , Manzi Shannon F , Lin Chen , Savova Guergana K , Avillach Paul , Mandl Kenneth D 
Published: September 2020

AbstractObjectiveTo advance use of real-world data (RWD) for pharmacovigilance, we sought to integrate a high-sensitivity natural language processing (NLP) pipeline for detecting potential adverse drug events (ADEs) with easily interpretable output for high-efficiency human review and adjudication of true ADEs.Materials and methodsThe adverse drug event presentation and tracking (ADEPT) system employs an open source NLP pipeline to identify in clinical notes mentions of medications and signs and symptoms potentially indicative of ADEs. ADEPT presents the output to human reviewers by highlighting these drug-event pairs within the context of the clinical note. To measure incidence of seizures associated with sildenafil, we applied ADEPT to 149 029 notes for 982 patients with pediatric pulmonary hypertension.ResultsOf 416 patients identified as taking sildenafil, NLP found 72 [17%, 95% confidence interval (CI) 14–21] with seizures as a potential ADE. Upon human review and adjudication, only 4 (0.96%, 95% CI 0.37–2.4) patients with seizures were determined to have true ADEs. Reviewers using ADEPT required a median of 89 s (interquartile range 57–142 s) per patient to review potential ADEs.DiscussionADEPT combines high throughput NLP to increase sensitivity of ADE detection and human review, to increase specificity by differentiating true ADEs from signs and symptoms related to comorbidities, effects of other medications, or other confounders.ConclusionADEPT is a promising tool for creating gold standard, patient-level labels for advancing NLP-based pharmacovigilance. ADEPT is a potentially time savings platform for computer-assisted pharmacovigilance based on RWD.