bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Affordable Care Act–related insurance expansion policies on mortality and access to post-discharge care for trauma patients: an analysis of the National Trauma Data Bank
Authors: Scott John W. , Neiman Pooja U. , Uribe-Leitz Tarsicio , Scott Kirstin W. , Zogg Cheryl K. , Salim Ali , Haider Adil H. 
Published: November 2018

BACKGROUND
Uninsured trauma patients have worse outcomes and worse access to post-discharge care that is critically important for recovery after injury. Little is known regarding the impact of the insurance coverage expansion policies of the Affordable Care Act (ACA), most notably state-level Medicaid expansion, on trauma patients. In this study, we examine the national impact of these policies on payer mix, inpatient mortality, and access to post-acute care for trauma patients.

METHODS
We used the 2011–2016 National Trauma Data Bank to evaluate for changes in insurance coverage among trauma patients 18–64 years old. Our pre-/post-expansion models defined 2011–2013 as the pre-policy period, 2015–2016 as the post-policy period, and 2014 as a washout year. To evaluate for policy-associated changes in inpatient mortality and discharge disposition among the policy-eligible sample, we leveraged multivariable linear regression techniques to adjust for year-to-year variation in patient demographics, injury characteristics, and facility traits. We then examined the relationship between the magnitude of facility-level reductions in uninsured patients and access to post-acute care after policy implementation.

RESULTS
We identified 1,656,469 patients meeting inclusion criteria between 2011 and 2016. The pre-policy uninsured rate of 23.4% fell by 5.9 percentage-points after coverage expansion (p < 0.001), with a corresponding 7.5 percentage-point increase in Medicaid coverage (p < 0.001). After policy implementation, there were no significant changes in inpatient mortality. However, there was a >30% relative increase in discharge to a post-acute care facility and a similar increase in discharge with home health services (p < 0.001 for both). The greatest gains in access to post-acute services were seen among facilities with the greatest reductions in their uninsured rate (p = 0.003).

CONCLUSION
ACA-related coverage expansion policies, most notably Medicaid expansion, were associated with a >25% reduction in the uninsured rate among non-elderly adult trauma patients. Although no immediate impact on inpatient mortality was seen, insurance coverage expansion was associated with a higher proportion of patients receiving critically important post-discharge care.

LEVEL OF EVIDENCE
Epidemiological, level III.
A Randomized Controlled Trial of Naloxone for Optimization of Hypoxemia in Lung Donors After Brain Death
Authors: Dhar Rajat , Stahlschmidt Emily , Paramesh Anil , Marklin Gary 
Published: November 2018

Background.
Persistent hypoxemia is the principal reason lungs from otherwise eligible brain dead (BD) organ donors are not transplanted. Experimental models and retrospective studies have suggested that naloxone attenuates neurogenic pulmonary edema and reverses hypoxemia after brain death. We undertook a multisite, randomized, placebo-controlled trial to evaluate whether naloxone is able to improve oxygenation in BD donors with hypoxemia.

Methods.
BD organ donors at 4 organ procurement organizations were randomized in a blinded manner to naloxone 8 mg or saline placebo if lung were being considered for allocation but exhibited hypoxemia (partial pressure of oxygen in arterial blood to fraction of inspired oxygen ratio [PFR] below 300 mm Hg). The primary outcome was change in PFR from baseline to final arterial blood gas. Secondary outcomes included early improvement in PFR and proportion of lungs transplanted.

Results.
A total of 199 lung-eligible BD donors were randomized to naloxone (n = 98) or placebo (n = 101). Groups were comparable at baseline. Both groups exhibited similar improvements in oxygenation (median improvement in PFR of 81 with naloxone versus 80 with saline, P = 0.68), with 37 (39%) versus 38 (40%) exhibiting reversal of hypoxemia. There was no difference in the rate of lungs transplanted (19% in both groups, P = 0.97) although it was significantly higher in those with reversal of hypoxemia (32/69 versus 2/111, P < 0.001).

Conclusions.
Naloxone does not improve oxygenation more than placebo in hypoxemic organ donors. However, reversal of hypoxemia was a powerful predictor of lung utilization regardless of drug therapy. Further organ procurement organization–led research is needed to assess optimal interventions to improve oxygenation in BD donors with hypoxemia.
Investigating causal relationships between sleep traits and risk of breast cancer: a Mendelian randomization study
Authors: Richmond Rebecca C. , Anderson Emma L. , Dashti Hassan S. , Jones Samuel E. , Lane Jacqueline M. , Strand Linn Beate , Brumpton Ben , Rutter Martin , Wood Andrew R. , Relton Caroline L. , Munafò Marcus , Frayling Timothy M. , Martin Richard M. , Saxena Richa , Weedon Michael N. , Lawlor Debbie A. , Davey Smith George 
Published: November 2018

AbstractObjectiveTo examine whether sleep traits have a causal effect on risk of breast cancer.DesignMultivariable regression, one- and two-sample Mendelian randomization.SettingThe UK Biobank prospective cohort study and the Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.Participants156,848 women in the multivariable regression and one-sample Mendelian randomization analysis in UK Biobank (7,784 with a breast cancer diagnosis) and 122,977 breast cancer cases and 105,974 controls from BCAC in the two-sample Mendelian randomization analysis.ExposuresSelf-reported chronotype (morning/evening preference), insomnia symptoms and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits.Main outcome measuresBreast cancer (prevalent and incident cases in UK Biobank, prevalent cases only in BCAC).ResultsIn multivariable regression analysis using data on breast cancer incidence in UK Biobank, morning preference was inversely associated with breast cancer (HR 0.95, 95% CI 0.93, 0.98 per category increase) while there was little evidence for an association with sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated sleep duration and 57 SNPs associated with insomnia symptoms, one-sample MR analysis in UK Biobank provided some supportive evidence for a protective effect of morning preference on breast cancer risk (HR 0.85, 95% 0.70, 1.03 per category increase) but imprecise estimates for sleep duration and insomnia symptoms. Two-sample MR using data from BCAC supported findings for a protective effect of morning preference (OR 0.88, 95% CI 0.82, 0.93 per category increase) and adverse effect of increased sleep duration (OR 1.19, 95% CI 1.02, 1.39 per hour increase) on breast cancer (both estrogen receptor positive and negative), while there was inconsistent evidence for insomnia symptoms. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy.ConclusionsWe found consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of sleep duration on breast cancer risk.
In Silico Analysis of Non Synonymous Single Nucleotide Polymorphisms (nsSNPs) of SMPX Gene in Hearing Impairment
Authors: Arifuzzaman Md. , Mitra Sarmistha , Hamza Amir , Das Raju , Absar Nurul , Dash Raju 
Published: November 2018

ABSTRACTBackgroundMutations in SMPX gene can disrupt the normal activity of the SMPX protein which is involved in hearing process.ObjectiveIn this study, deleterious non-synonymous single nucleotide polymorphisms were isolated from the neutral variants by using several bioinformatics tools.MethodFirstly, dbSNP database hosted by NCBI was used to retrieve the SNPs of SMPX gene, secondly, SIFT was used primarily to screen the damaging SNPs. Further, for validation PROVEAN, PredictSNP and PolyPhen 2 were used. I-Mutant 3 was utilized to analyze the protein stability change and MutPred predicted the molecular mechanism of protein stability change. Finally evolutionary conservation was done to study their conservancy by using ConSurf server.ResultsA total of 26 missense (0.6517%) and 3 nonsense variants (0.075%) were retrieved and among them 4 mutations were found deleterious by all the tools of this experiment and are also highly conserved according to ConSurf server. rs772775896, rs759552778, rs200892029 and rs1016314772 are the reference IDs of deleterious mutations where the substitutions are S71L, N19D, A29T and K54N. Loss of Ubiquitination, loss of methylation, loss of glycosylation, and loss of MoRF binding motifs are the root causes of protein stability change.ConclusionThis is the first study regarding nsSNPs of SMPX gene where the most damaging SNPs were screened that are associated with the SMPX gene and can be used for further research to study their effect on protein structure and function, their dynamic behavior and how they actually affect protein’s flexibility.
Nitric oxide is important for sensing and survival under hypoxia in Arabidopsis
Authors: Wany Aakanksha , Gupta Alok Kumar , Brotman Yariv , Pandey Sonika , Vishwakarma Abhay Pratap , Kumari Aprajita , Singh Pooja , Pathak Pradeep K , Igamberdiev Abir U. , Gupta Kapuganti Jagadis 
Published: November 2018

AbstractNitric oxide (NO) is a free radical molecule that plays an important role in hypoxic stress. We studied the impact of hypoxia-induced NO production on the expression of genes and production of metabolites involved in carbon, oxygen sensing, nitrogen, and antioxidant metabolism using wild type (WT), non-symbiotic haemoglobin-overexpressing (Hb+) and nitrate reductase double mutant (nia1,2) of Arabidopsis. Futher application of NO scavenger cPTIO was used to confirm NO role. We found that imposing hypoxia leads to the increaseof NO and reactive oxygen species (ROS) levels in WT, while the reduced levels of NO and higher levels of ROS were observed in roots of Hb+andnia1,2mutant. Expression of the genes encoding oxygen sensing and the enzymes involved in fermentative pathways, their activities and metabolite levels were highly induced in WT suggesting that NO plays a role in the induction of fermentation. Several genes and metabolites involved in the TCA cycle were also induced in WT in comparison to Hb+andniamutant line suggesting that NO can accelerate TCA cycle to regenerate reducing equivalents under hypoxia. Interestingly, we found that the genes and metabolites involved in the ascorbate-glutathione cycle were modulated by NO under hypoxia. The alternative oxidasegene (AOX1A) was induced under hypoxia in WTdue to increased levels of NO rather than ROS. Futher, we found that NO improves plant survival. Overall these findings suggest that NO is a major player in plant survival under hypoxia by modulating gene expression and metabolite levels of carbon, nitrogen, oxygen sensing and antioxidant metabolism.HighlightHypoxia-induced nitric oxide plays a central role in activation of genes and metabolites involved in fermentation, TCA cycle, nitrogen and antioxidant metabolism
Individualised MRI training for paediatric neuroimaging in autism spectrum disorders: A child-focused approach
Authors: Kiat Pua Emmanuel Peng , Barton Sarah , Williams Katrina , Craig Jeffrey M , Seal Marc L 
Published: November 2018

AbstractMagnetic Resonance Imaging (MRI) in paediatric cohorts is often complicated by reluctance to enter the scanner and head motion-related imaging artefacts. The MRI scanner environment is highly unusual and may distress younger cohorts, especially in children with sensory sensitivity and separation anxiety. The issue is particularly challenging in children with Autism Spectrum Disorders (ASD), where delivery of instructions for novel task demands in an unfamiliar setting may be limited or less effective due to communication disorder or intellectual disability. These issues together often give rise to excessive head motion that can significantly reduce the quality of images acquired, or render data unusable. Here we report an individualised MRI training procedure that enables young children with ASD to better tolerate the MRI scanner environment based on a child-focused approach and an individualised familiarisation strategy. The training procedure was implemented in a locally recruited study of monozygotic twins (n=12; 6 twin pairs; age range 7.1 to 12.85 years) concordant or discordant for ASD. MRI image quality indices were better or comparable to images acquired from an independent multi-centre ASD cohort. The success of these findings is promising and may be useful to improve the quality of paediatric neuroimaging in similar clinical populations.
High resolution protein-protein interaction mapping using all-versus-all sequencing (AVA-seq)
Authors: Andrews Simeon S. , Schaefer-Ramadan Stephanie , Al-Thani Nayra M. , Ahmed Ikhlak , Mohamoud Yasmin A. , Malek Joel A. 
Published: November 2018

AbstractTwo-hybrid systems test for protein-protein interactions and can provide important information for genes with unknown function. Despite their success, two-hybrid systems have remained mostly untouched by improvements from next-generation DNA sequencing. Here we present a method for all-versus-all protein interaction mapping (AVA-seq) that utilizes next-generation sequencing to remove multiple bottlenecks of the two-hybrid process. The method allows for high resolution protein-protein interaction mapping of a small set of proteins, or the potential for lower-resolution mapping of entire proteomes. Features of the system include open-reading frame selection to improve efficiency, high bacterial transformation efficiency, a convergent fusion vector to allow paired-end sequencing of interactors, and the use of protein fragments rather than full-length genes to better resolve specific protein contact points. We demonstrate the system’s strengths and limitations on a set of proteins known to interact in humans and provide a framework for future large-scale projects.
Pectin digestion in herbivorous beetles: Impact of pseudoenzymes exceeds that of their active counterparts
Authors: Kirsch Roy , Kunert Grit , Vogel Heiko , Pauchet Yannick 
Published: November 2018

AbstractMany protein families harbor pseudoenzymes that have lost the catalytic function of their enzymatically active counterparts. Assigning alternative function and importance to these proteins is challenging [1]. Because the evolution towards pseudoenzymes is driven by gene duplication, they often accumulate in multigene families. Plant cell wall-degrading enzymes (PCWDEs) are prominent examples of expanded gene families. The pectolytic glycoside hydrolase family 28 (GH28) allows herbivorous insects to break down the PCW polysaccharide pectin. GH28 in the Phytophaga clade of beetles contains many active enzymes but also many inactive counterparts. Using functional characterization, gene silencing, global transcriptome analyses and recordings of life history traits, we found that not only catalytically active but also inactive GH28 proteins are part of the same pectin-digesting pathway. The robustness and plasticity of this pathway and thus its importance for the beetle is supported by extremely high steady-state expression levels and counter-regulatory mechanisms. Unexpectedly, the impact of pseudoenzymes on the pectin-digesting pathway in Phytophaga beetles exceeds even the influence of their active counterparts, such as a lowered efficiency of food-to-energy conversion and a prolongation of the developmental period.
Inferring biochemical reactions and metabolite structures to cope with metabolic pathway drift
Authors: Belcour Arnaud , Girard Jean , Aite Méziane , Delage Ludovic , Trottier Camille , Marteau Charlotte , Leroux Cédric , Dittami Simon M. , Sauleau Pierre , Corre Erwan , Nicolas Jacques , Boyen Catherine , Leblanc Catherine , Collén Jonas , Siegel Anne , Markov Gabriel V. 
Published: November 2018

AbstractInferring genome-scale metabolic networks in emerging model organisms is challenging because of incomplete biochemical knowledge and incomplete conservation of biochemical pathways during evolution. This limits the possibility to automatically transfer knowledge from well-established model organisms. Therefore, specific bioinformatic tools are necessary to infer new biochemical reactions and new metabolic structures that can be checked experimentally. Using an integrative approach combining both genomic and metabolomic data in the red algal modelChondrus crispus, we show that, even metabolic pathways considered as conserved, like sterol or mycosporine-like amino acids (MAA) synthesis pathways, undergo substantial turnover. This phenomenon, which we formally define as “metabolic pathway drift”, is consistent with findings from other areas of evolutionary biology, indicating that a given phenotype can be conserved even if the underlying molecular mechanisms are changing. We present a proof of concept with a new methodological approach to formalize the logical reasoning necessary to infer new reactions and new molecular structures, based on previous biochemical knowledge. We use this approach to infer previously unknown reactions in the sterol and MAA pathways.Author summaryGenome-scale metabolic models describe our current understanding of all metabolic pathways occuring in a given organism. For emerging model species, where few biochemical data are available about really occurring enzymatic activities, such metabolic models are mainly based on transferring knowledge from other more studied species, based on the assumption that the same genes have the same function in the compared species. However, integration of metabolomic data into genome-scale metabolic models leads to situations where gaps in pathways cannot be filled by known enzymatic reactions from existing databases. This is due to structural variation in metabolic pathways accross evolutionary time. In such cases, it is necessary to use complementary approaches to infer new reactions and new metabolic intermediates using logical reasoning, based on available partial biochemical knowledge. Here we present a proof of concept that this is feasible and leads to hypotheses that are precise enough to be a starting point for new experimental work.
Dynamic Electrical Stimulation of Sites in Visual Cortex Produces Form Vision in Sighted and Blind Humans
Authors: Beauchamp Michael S. , Bosking William , Sun Ping , Foster Brett , Niketeghad Soroush , Pouratian Nader , Yoshor Daniel 
Published: November 2018

AbstractVisual cortical prosthetics (VCPs) offer the promise of restoring sight to blind patients. Electrical stimulation of a single site in visual cortex can reliably produce a percept of a spot of light in a fixed visual field location, known as a phosphene. Researchers developing VCPs have assumed that multiple phosphenes produced by concurrent stimulation of multiple sites in visual cortex can combine to form a coherent form, like pixels in a visual display. However, existing data do not support this assumption. Therefore, we developed a novel stimulation paradigm for VCPs termeddynamic current steeringin which the visual form to be conveyed is traced on the surface of visual cortex by electrically stimulating electrodes in a dynamic sequence. When tested in sighted and blind subjects, this method of stimulating visual cortex allowed for the immediate recognition of a variety of letter shapes without training and with high accuracy.One Sentence SummaryStimulating human visual cortex using dynamic patterns of activity allows both blind and sighted patients to perceive visual percepts of useful forms.
PSL-Recommender: Protein Subcellular Localization Prediction using Recommender System
Authors: Jamali Ruhollah , Eslahchi Changiz , Jahangiri-Tazehkand Soheil 
Published: November 2018

AbstractIdentifying a protein’s subcellular location is of great interest for understanding its function and behavior within the cell. In the last decade, many computational approaches have been proposed as a surrogate for expensive and inefficient wet-lab methods that are used for protein subcellular localization. Yet, there is still much room for improving the prediction accuracy of these methods.PSL-Recommender (Protein subcellular location recommender) is a method that employs neighborhood regularized logistic matrix factorization to build a recommender system for protein subcellular localization. The effectiveness of PSL-Recommender method is benchmarked on one human and three animals datasets. The results indicate that the PSL-Recommender significantly outperforms state-of-the-art methods, improving the previous best method up to 31% in F1 – mean, up to 28% in ACC, and up to 47% in AVG. The source of datasets and codes are available at:https://github.com/RJamali/PSL-Recommender
Single cell analysis reveals dynamics of transposable element transcription following epigenetic de-repression
Authors: Brocks David , Chomsky Elad , Mukamel Zohar , Lifshitz Aviezer , Tanay Amos 
Published: November 2018

ABSTRACTSpontaneous or pharmacological loss of epigenetic repression exposes thousands of promoters encoded in transposable elements (TEs) for pervasive transcriptional activation. How TE responses differ between epigenetically relaxed cancer cells and what factors govern such variation remains however largely unknown. By quantifying TE transcription initiation at single cell and locus resolution in epigenetically targeted cancer cells, we characterize specific groups of co-regulated loci that drive over ten-fold variation in TE load per single cell. Such variable activity patterns are largely linked to cell cycle stages, stress response signatures, and immune pathways. Furthermore, cells with high levels of specific transcription factors show increased TE expression, while within such cells, multi-copy families are differentially regulated in response to local sequence divergence of binding sites and the locus’ repressive or active chromosomal contexts. Our data thereby implicates the regulation of potent promoters within TEs as an underestimated source of transcriptional heterogeneity following epigenetic therapy.
A chemogenetic approach for optical monitoring of voltage in neurons
Authors: Sundukova Mayya , Prifti Efthymia , Bucci Annalisa , Kirillova Kseniia , Serrao Joana , Reymond Luc , Umebayashi Miwa , Hovius Ruud , Riezman Howard , Johnsson Kai , Heppenstall Paul A. 
Published: November 2018

AbstractOptical monitoring of neuronal voltage using fluorescent indicators is a powerful approach for interrogation of the cellular and molecular logic of the nervous system. Here we describe a Semisynthetic Tethered Voltage Indicator (STeVI1) based upon Nile Red that displays voltage sensitivity when genetically targeted to neuronal membranes. This environmentally sensitive probe allows for wash-free imaging and faithfully detects supra- and subthreshold activity in neurons.