bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Protocolized Versus Usual Care Rehabilitation for Pediatric Neurocritical Care Patients: A Randomized Controlled Trial
Authors: Fink Ericka L. , Beers Sue R. , Houtrow Amy J. , Richichi Rudolph , Burns Cheryl , Doughty Lesley , Ortiz-Aguayo Roberto , Madurski Catherine A. , Valenta Cynthia , Chrisman Maddie , Golightly Lynn , Kiger Michelle , Patrick Cheryl , Treble-Barna Amery , Pollon Dorothy , Smith Craig M. , Kochanek Patrick 
Published: February 2019

Objective
s: Few feasibility, safety, and efficacy data exist regarding ICU-based rehabilitative services for children. We hypothesized that early protocolized assessment and therapy would be feasible and safe versus usual care in pediatric neurocritical care patients.

Design:
Randomized controlled trial.

Setting:
Three tertiary care PICUs in the United States.

Patients:
Fifty-eight children between the ages of 3–17 years with new traumatic or nontraumatic brain insult and expected ICU admission greater than 48 hours.

Interventions:
Early protocolized (consultation of physical therapy, occupational therapy, and speech and language therapy within 72 hr ICU admission, n = 26) or usual care (consultation per treating team, n = 32).

Measurements and Main Results:
Primary outcomes were consultation timing, treatment type, and frequency of deferrals and safety events. Secondary outcomes included patient and family functional and quality of life outcomes at 6 months. Comparing early protocolized (n = 26) and usual care groups (n = 32), physical therapy was consulted during the hospital admission in 26 of 26 versus 28 of 32 subjects (p = 0.062) on day 2.4 ± 0.8 versus 7.7 ± 4.8 (p = 0.001); occupational therapy in 26 of 26 versus 23 of 32 (p = 0.003), on day 2.3 ± 0.6 versus 6.9 ± 4.8 (p = 0.001); and speech and language therapy in 26 of 26 versus 17 of 32 (p = 0.011) on day 2.3 ± 0.7 versus 13.0 ± 10.8 (p = 0.026). More children in the early protocolized group had consults and treatments occur in the ICU versus ward for all three services (all p < 0.001). Eleven sessions were discontinued early: nine during physical therapy and two during occupational therapy, none impacting patient outcome. There were no group differences in functional or quality of life outcomes.

Conclusions:
A protocol for early personalized rehabilitation by physical therapy, occupational therapy, and speech and language therapy in pediatric neurocritical care patients could be safely implemented and led to more ICU-based treatment sessions, accelerating the temporal profile and changing composition of interventions versus usual care, but not altering the total dose of rehabilitation.
UKAEA capabilities to address the challenges on the path to delivering fusion power
Authors: Chapman I. T. , Morris A. W. 
Published: February 2019

Fusion power could be one of very few sustainable options to replace fossil fuels as the world's primary energy source. Fusion offers the potential of predictable, safe power with no carbon emissions and fuel sources lasting for millions of years. However, it is notoriously difficult to achieve in a controlled, steady-state fashion. The most promising path is via magnetic confinement in a device called a tokamak. A magnetic confinement fusion (MCF) power plant requires many different science, technology and engineering challenges to be met simultaneously. This requires an integrated approach from the outset; advances are needed in individual areas but these only bring fusion electricity closer if the other challenges are resolved in harmony. The UK Atomic Energy Authority (UKAEA) has developed a wide range of skills to address many of the challenges and hosts the JET device, presently the only MCF facility capable of operating with both the fusion fuels, deuterium and tritium. Recently, several major new UKAEA facilities have been funded and some have started operation, notably a new spherical tokamak (MAST Upgrade), a major robotics facility (RACE), and a materials research facility (MRF). Most recently, work has started on Hydrogen-3 Advanced Technology (H3AT) for tritium technology and a group of Fusion Technology Facilities.
This article is part of a discussion meeting issue ‘Fusion energy using tokamaks: can development be accelerated?’
Compact steady-state tokamak performance dependence on magnet and core physics limits
Authors: Menard J. E. 
Published: February 2019

Compact tokamak fusion reactors using advanced high-temperature superconducting magnets for the toroidal field coils have received considerable recent attention due to the promise of more compact devices and more economical fusion energy development. Facilities with combined fusion nuclear science and Pilot Plant missions to provide both the nuclear environment needed to develop fusion materials and components while also potentially achieving sufficient fusion performance to generate modest net electrical power are considered. The performance of the tokamak fusion system is assessed using a range of core physics and toroidal field magnet performance constraints to better understand which parameters most strongly influence the achievable fusion performance.
This article is part of a discussion meeting issue ‘Fusion energy using tokamaks: can development be accelerated?’.
Shielding materials in the compact spherical tokamak
Authors: Humphry-Baker Samuel A. , Smith George D. W. 
Published: February 2019

Neutron shielding materials are a critical area of development for nuclear fusion technology. In the compact spherical tokamak, shielding efficiency improvements are particularly needed because of severe space constraints. The most spatially restricted component is the central column shield. It must protect the superconducting magnets from excessive radiation-induced degradation, but also from associated heating, so that energy consumption of the cryogenic systems is kept to an acceptable level. Recent simulations show that tungsten carbide and its composites form an attractive class of neutron-attenuating materials. In this paper, the key structure–property relationships of these materials are assessed, as they relate to generic materials challenges for plasma-facing materials. We first consider some fundamental materials properties of monolithic tungsten carbide including thermal transport, mechanical properties and plasma interaction. WC is found to have generally favourable properties compared to metallic tungsten shields. We then report progress on the development of a new candidate cermet material, WC-FeCr. Recent results on its accident safety, thermo-mechanical properties, and irradiation behaviour are presented. This review also highlights the need for further study, particularly in the areas of irradiation damage and hydrogen trapping.
This article is part of a discussion meeting issue ‘Fusion energy using tokamaks: can development be accelerated?’.
Evolution of the nonsense mediated decay (NMD) pathway is associated with decreased cytolytic immune infiltration
Authors: Zhao Boyang , Pritchard Justin R. 
Published: February 2019

AbstractBackgroundThe somatic co-evolution of tumors and the cellular immune responses that combat them drives the diversity of immune-tumor interactions. This includes tumor mutations that generate neo-antigenic epitopes that elicit cytotoxic T-cell activity and subsequent pressure to select for genetic loss of antigen presentation. Most studies have focused on how tumor missense mutations can drive tumor immunity, but frameshift mutations have the potential to create far greater antigenic diversity. However, expression of this antigenic diversity is potentially regulated by Nonsense Mediated Decay (NMD) and NMD has been shown to be of variable efficiency in cancers.MethodsUsing TCGA datasets, we derived novel patient-level metrics of ‘NMD burden’ and interrogated how different mutation and most importantly NMD burdens influence cytolytic activity using machine learning models and survival outcomes.ResultsWe find that NMD is a significant and independent predictor of immune cytolytic activity. Different indications exhibited varying dependence on NMD and mutation burden features. We also observed significant co-alteration of genes in the NMD pathway, with a global increase in NMD efficiency in patients with NMD co-alterations. Finally, NMD burden also stratified patient survival in multivariate regression models.ConclusionsOur work suggests that beyond selecting for mutations that elicit NMD in tumor suppressors, tumor evolution may react to the selective pressure generated by inflammation to globally enhance NMD through coordinated amplification and/or mutation.
A new comprehensive Eye-Tracking Test Battery concurrently evaluating the Pupil Labs Glasses and the EyeLink 1000
Authors: Ehinger Benedikt V. , Groß Katharina , Ibs Inga , König Peter 
Published: February 2019

ABSTRACTEye-tracking experiments rely heavily on good data quality of eye-trackers. Unfortunately, it is often that only the spatial accuracy and precision values are available from the manufacturers. These two values alone are not sufficient enough to serve as a benchmark for an eye-tracker: Eye-tracking quality deteriorates during an experimental session due to head movements, changing illumination or calibration decay. Additionally, different experimental paradigms require the analysis of different types of eye movements, for instance smooth pursuit movements, blinks or microsaccades, which themselves cannot readily be evaluated by using spatial accuracy or precision alone. To obtain a more comprehensive description of properties, we developed an extensive eye-tracking test battery. In 10 different tasks, we evaluated eye-tracking related measures such as: the decay of accuracy, fixation durations, pupil dilation, smooth pursuit movement, microsaccade detection, blink detection, or the influence of head motion. For some measures, true theoretical values exist. For others, a relative comparison to a gold standard eye-tracker is needed. Therefore, we collected our gaze data simultaneously from a gold standard remote EyeLink 1000 eye-tracker and compared it with the mobile Pupil Labs glasses.As expected, the average spatial accuracy of 0.57° for the EyeLink 1000 eye-tracker was better than the 0.82° for the Pupil Labs glasses (N=15). Furthermore, we detected less fixations and shorter saccade durations for the Pupil Labs glasses. Similarly, we found fewer microsaccades using the Pupil Labs glasses. The accuracy over time decayed only slightly for the EyeLink 1000, but strongly for the Pupil Labs glasses. Finally we observed that the measured pupil diameters differed between eye-trackers on the individual subject level but not the group level.To conclude, our eye-tracking test battery offers 10 tasks that allow us to benchmark the many parameters of interest in stereotypical eye-tracking situations, or addresses a common source of confounds in measurement errors (e.g. yaw and roll head movements).All recorded eye-tracking data (including Pupil Labs’ eye video files), the stimulus code for the test battery and the modular analysis pipeline are available (https://github.com/behinger/etcomp).BVE, KG, IIandPKconceived the experiment.IIandBVEcreated the experiment and recorded the gaze data.BVEandKGperformed the analysis.BVE, KGandPKreviewed the manuscript critically.
Hypothesis-Testing Improves the Predicted Reliability of Neuroscience Research
Authors: Alger Bradley E. 
Published: February 2019

AbstractCritics often cite statistical problems as prime contributors to the “reproducibility crisis” of science, expressing great concern about research that bases major conclusions on single p-valued statistical tests. The critics also argue that the predicted reliability of neuroscience research in particular is low because much of the work depends heavily on small experimental sample sizes and, hence, its statistical tests lack adequate “power.”It isn’t known how common the practice of basing major conclusions on single tests is in neuroscience or how the statistical criticisms affect the validity of conclusions drawn by laboratory research that evaluates hypotheses via multiple tests. I review a sample of neuroscience publications to estimate the prevalence and extensiveness of hypothesis-testing research. I then apply R.A. Fisher’s method for combining test results to show that the practice of testing multiple predictions of hypotheses increases the predicted reliability of neuroscience research.
Systematic mapping of drug metabolism by the human gut microbiome
Authors: Chankhamjon Pranatchareeya , Javdan Bahar , Lopez Jaime , Hull Raphaella , Chatterjee Seema , Donia Mohamed S. 
Published: February 2019

ABSTRACTThe human gut microbiome harbors hundreds of bacterial species with diverse biochemical capabilities, making it one of nature’s highest density, highest diversity bioreactors. Several drugs have been previously shown to be directly metabolized by the gut microbiome, but the extent of this phenomenon has not been systematically explored. Here, we develop a systematic screen for mapping the ability of the complex human gut microbiome to biochemically transform small molecules (MDM-Screen), and apply it to a library of 575 clinically used oral drugs. We show that 13% of the analyzed drugs, spanning 28 pharmacological classes, are metabolized by a single microbiome sample. In a proof-of-principle example, we show that microbiome-derived metabolism occursin vivo, identify the genes responsible for it, and provide a possible link between its consequences and clinically observed features of drug bioavailability and toxicity. Our findings reveal a previously underappreciated role for the gut microbiome in drug metabolism, and provide a comprehensive framework for characterizing this important class of drug-microbiome interactions.
Generalization as diffusion: human function learning on graphs
Authors: Wu Charley M. , Schulz Eric , Gershman Samuel J. 
Published: February 2019

AbstractFrom social networks to public transportation, graph structures are a ubiquitous feature of life. Yet little is known about how humans learn functions on graphs, where relationships are defined by the connectivity structure. We adapt a Bayesian framework for function learning to graph structures, and propose that people perform generalization by diffusing observed function values across the graph. We test the predictions of this model by asking participants to make predictions about passenger volume in a virtual subway network. The model captures both generalization and confidence judgments, and is a quantitatively superior account relative to several heuristic models. Our work suggests that people exploit graph structure to make generalizations about functions in complex discrete spaces.
Genome-wide expression analysis identifies core components during iron starvation in hexaploid wheat
Authors: Kaur Gazaldeep , Shukla Vishnu , Kumar Anil , Kaur Mandeep , Goel Parul , Singh Palvinder , Shukla Anuj , Kaur Jaspreet , Singh Jagtar , Mantri Shrikant , Rouached Hatem , Pandey Ajay Kumar 
Published: February 2019

AbstractIron is one of essential micronutrient for all organisms. Its deficiency causes a severe loss in crops yield. Nevertheless, our current understanding on major crops response to Fe deficiency remains limited. Herein, we investigated the effect of Fe deprivation at both transcriptomic and metabolic levels in hexaploid wheat. A genome-wide gene expression reprogramming was observed with a total of 5854 genes showing differential expression in roots of wheat subjected to Fe-starved medium. Subsequent, analysis revealed a predominance of strategy-II mode of Fe uptake, with induced genome bias contribution from the A and B genomes. In general, the predominance of genes encoding for nicotianamine synthase, yellow stripe like transporters, metal transporters, ABC transporters and zinc-induced facilitator-like protein was noticed. Our transcriptomic data were in agreement with the GC-MS analysis that showed an enhancement of accumulation of various metabolites such as fumarate, malonate, succinate and xylofuranose, which could be linked for enhancing Fe-mobilization. Interestingly, Fe starvation causes a significant temporal increase of glutathione-S-transferase both at transcriptional and enzymatic activity, which indicate the important role of glutathione in the response to Fe starvation in wheat roots. Taken together, our result provides new insight on wheat response to Fe starvation and lays foundation to design strategies to improve Fe nutrition in crops.
Unlocking a signal of introgression from codons in Lachancea kluyveri using a mutation-selection model
Authors: Landerer Cedric , O’Meara Brian C. , Zaretzki Russell , Gilchrist Michael A. 
Published: February 2019

AbstractFor decades, codon usage has been used as a measure of adaptation for translational efficiency and translation accuracy of a gene’s coding sequence. These patterns of codon usage reflect both the selective and mutational environment in which the coding sequences evolved. Over this same period, gene transfer between lineages has become widely recognized as an important biological phenomenon. Nevertheless, most studies of codon usage implicitly assume that all genes within a genome evolved under the same selective and mutational environment, an assumption violated when introgression occurs. In order to better understand the effects of introgression on codon usage patterns and vice versa, we examine the patterns of codon usage in Lachancea kluyveri, a yeast which has experienced a large introgression. We quantify the effects of mutation bias and selection for translation efficiency on the codon usage pattern of the endogenous and introgressed exogenous genes using a Bayesian mixture model, ROC SEMPPR, which is built on mechanistic assumptions about protein synthesis and grounded in population genetics.We find substantial differences in codon usage between the endogenous and exogenous genes, and show that these differences can be largely attributed to differences in mutation bias favoring A/T ending codons in the endogenous genes while favoring C/G ending codons in the exogenous genes. Recognizing the two different signatures of mutation bias and selection improves our ability to predict protein synthesis rate by 42% and allowed us to accurately assess the decaying signal of endogenous codon mutation and preferences. In addition, using our estimates of mutation bias and selection, we identify Eremothecium gossypii as the closest relative to the exogenous genes, providing an alternative hypothesis about the origin of the exogenous genes, estimate that the introgression occurred ∼ 6 × 108 generation ago, and estimate its historic and current selection against mismatched codon usage.Our work illustrates how mechanistic, population genetic models like ROC SEMPPR can separate the effects of mutation and selection on codon usage and provide quantitative estimates from sequence data.
Quantifying bacterial fitness in intracellular dynamics
Authors: Paupério Francisco F. S. , Gjini Erida 
Published: February 2019

AbstractUnderstanding bacterial infection is challenging because it involves a complex interplay of host, pathogen, and intervention factors. To design successful control measures, mathematical models that quantify such interplay at the level of populations and phenotypes are needed. Here, we study a key aspect of intracellular infection: the interaction dynamics between bacteria and target cells, applicable to pathogens such as Salmonella, E. coli or Listeria monocytogenes. Our mathematical model focuses on the macrophage-bacteria system, implicitly accounting for host immunity, and illustrates three infection scenarios driven by the balance between bacterial growth and death processes. Our analysis reveals critical parameter combinations for the intracellular vs. extracellular fitness advantage of persistent bacteria, and the drivers of overall infection success across acute and persistent regimes. Our results provide quantitative insights on transitions from persistent, to acute, to containment of infection, and suggest biological parameters, such as infected macrophage apoptosis rate and burst size, as suitable intervention targets.
Enhancer locus in ch14q23.1 modulates brain asymmetric temporal regions involved in language processing
Authors: Le Guen Yann , Leroy François , Philippe Cathy ,   IMAGEN consortium, Mangin Jean-François , Dehaene-Lambertz Ghislaine , Frouin Vincent 
Published: February 2019

AbstractIdentifying the genes that contribute to the variability in brain regions involved in language processing may shed light on the evolution of brain structures essential to the emergence of language in Homo sapiens. The superior temporal asymmetrical pit (STAP), which is not observed in chimpanzees, represents an ideal phenotype to investigate the genetic variations that support human communication. The left STAP depth was significantly associated with a predicted enhancer annotation located in the 14q23.1 locus, between DACT1 and KIAA0586, in the UK Biobank British discovery sample (N=16,515). This association was replicated in the IMAGEN cohort (N=1,726) and the UK Biobank non-British validation sample (N=2,161). This genomic region was also associated to a lesser extent with the right STAP depth and the formation of sulcal interruptions, plis de passage, in the bilateral STAP but not with other structural brain MRI phenotypes, highlighting its notable association with the superior temporal regions. Diffusion MRI emphasized an association with the fractional anisotropy of the left auditory fibers of the corpus callosum and with networks involved in linguistic processing in resting-state functional MRI. Overall, this evidence demonstrates a specific relationship between this locus and the establishment of the superior temporal regions that support human communication.
Molecular dissection of the cellular response to mechanical stress
Authors: Zuela-Sopilniak Noam , Dorfman Jehudith , Gruenbaum Yosef 
Published: February 2019

AbstractThe response of cells to mechanical stress is crucial for many cellular functions, yet its molecular mechanisms are not yet fully understood. Previous studies of the cellular response to mechanical stress were performed on cultured cells or isolated muscle fibers devoid of cell and/or tissue contexts. Thus, the emerging results were limited to the specific cell types or tissues analyzed and dependent on the growth matrix elasticity. In the present study, we looked for changes in early gene expression in response to mechanical whole body stretching of livingC. elegans. Our transcriptome analysis revealed upregulation of genes involved in cuticle development, stress response and several signaling pathways such as WNT, TGFβ, AMPK and Hedgehog signaling. These findings indicate that protecting against mechanical insults entails providing additional support to the mechanically resilient protective cuticle, and that proper recovery from mechanical stretching requires an intact Hedgehog signaling pathway. Recent findings suggest an important role for the nuclear lamina in mediating cellular mechanical response. The nuclear lamina is composed mainly of lamins, which are nuclear intermediate filament-type proteins needed, among other functions to maintain nuclear integrity. One particular area of interest are laminopathies, which are caused by mutations in lamin. Stretched animals expressing the Emery Dreifuss Muscular Dystrophy (EDMD) linked L535P lamin mutation, showed further upregulation of cytoskeleton organization, cellular respiration and mitochondrial protein-unfolding stress response genes, most likely to compensate for aberrant muscle tissue function. These findings provide a broad multi-dimensional picture of thein vivogenetic response of live animals to mechanical stress, highlighting previously unreported mechano-sensitive genes and molecular pathways.