bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Controlled Trial Comparing Learners' Decision-making, Anxiety, and Task Load During a Simulated Airway Crisis Using Two Difficult Airway Aids
Authors: Ambardekar Aditee P. , Rosero Eric B. , Bhoja Ravi , Green Jerry , Rebal Brett A. , Minhajuddin Abu T. , Kosemund Matthew S. , Guttman Oren T. , Mercier David W. 
Published: March 2019

Introduction
The American Society of Anesthesiologists (ASA) difficult airway algorithm and the Vortex approach are difficult airway aids. Our objective was to demonstrate that a simpler cognitive model would facilitate improved decision-making during a process such as difficult airway management. We hypothesized the simpler Vortex approach would be associated with less anxiety and task load.

Methods
Medical students were randomized to the ASA algorithm (n = 33) or Vortex approach (n = 34). All learned basic airway techniques on day 1 of their rotation. Next, they watched a video of their respective aid then managed a simulated airway crisis. We assessed decision-making using a seven-point airway management score and a completeness score. Completeness was at least one attempt at each of four techniques (mask ventilation, supraglottic airway, intubation, and cricothyrotomy). Two validated tools, the State-Trait Anxiety Inventory Form Y and the National Aeronautics and Space Administration Task Load Index, were used to assess anxiety and task load.

Results
Students in the Vortex group had higher airway management scores [4.0 (interquartile range = 4.0 to 5.0) vs. 4.0 (3.0 to 4.0), P = 0.0003] and completeness (94.1% vs. 63.6%, P = 0.003). In the ASA group, the means (SD) of National Aeronautics and Space Administration Task Load Index scores of 55 or higher were observed in mental [61.4 (14.4)], temporal [62.3 (22.9)], and effort [57.1 (15.6)] domains. In the Vortex group, only the temporal load domain was 55 or higher [mean (SD) = 57.8 (25.4)]. There was no difference in anxiety.

Conclusions
Medical students perform better in a simulated airway crisis after training in the simpler Vortex approach to guide decision-making. Students in the ASA group had task load scores indicative of high cognitive load.
Tranexamic acid administration following head trauma in a combat setting: Does tranexamic acid result in improved neurologic outcomes?
Authors: Morte Douglas , Lammers Daniel , Bingham Jason , Kuckelman John , Eckert Matthew , Martin Matthew 
Published: March 2019

BACKGROUND
Tranexamic acid (TXA) has been shown to decrease mortality and blood product requirements in severely injured patients. Tranexamic acid has also been hypothesized to prevent secondary brain injury in patients with traumatic brain injury. While prior studies have demonstrated improved neurologic outcomes associated with TXA administration in severely injured pediatric patients, no such studies have been performed in adults.

METHODS
A retrospective review of all adult trauma admissions to North Atlantic Treaty Organization hospitals in Iraq and Afghanistan between 2008 and 2015. Univariate and multivariate analysis was used to identify factors associated with TXA administration. Patients without a documented head Abbreviated Injury Scale (AIS) were excluded. Patients were propensity matched based on demographics, mechanism of injury, Injury Severity Score (AIS/ISS), presenting Glasgow Coma Scale (GCS) score, initial vitals/laboratory values, and initial transfusion requirement. Primary outcomes were in-hospital mortality and neurologic outcomes measured by discharge GCS scores. Secondary outcomes were respiratory failure and rates of thromboembolic events.

RESULTS
Four thousand four hundred seventy-six injured patients 18 years or older were evaluated. Two hundred sixty-five (5.9%) of these patients required a massive transfusion in the first 24 hours, and 174 (3.9%) received TXA. The TXA patients had significantly higher ISS, more penetrating injuries, lower presenting GCS, higher incidence of severe head injury (AIS > 3), and higher transfusion requirements. Ninety-two patients were included in the propensity matched cohort. Of these, patients who received TXA had significantly lower mortality rate (0% vs. 10.1%, p = 0.02) and improvement of GCS score to 14 to 15, irrespective of admission GCS compared with patients who did not receive TXA (100% vs. 87%, p = 0.01). There were no significant differences in number of thromboembolic events recorded between the two groups.

CONCLUSION
The TXA administration in adult combat trauma patients was independently associated with decreased mortality and improved neurologic outcomes, with no increase in thromboembolic events. Further study of the possible mechanisms and effect of TXA on brain injury and neurologic outcomes is warranted.

LEVEL OF EVIDENCE
Therapeutic, level IV.
Management of acute appendicitis in adults: A practice management guideline from the Eastern Association for the Surgery of Trauma
Authors: Rushing Amy , Bugaev Nikolay , Jones Christian , Como John J. , Fox Nicole , Cripps Michael , Robinson Bryce , Velopulos Catherine , Haut Elliott R. , Narayan Mayur 
Published: March 2019

BACKGROUNDAcute appendicitis (AA) has been considered one of the most common acute surgical conditions in the world. Recent studies, however, have suggested that nonoperative management (NOM) with a course of antibiotics (ABX) may be as effective as surgery in treating appendicitis. As there are evolving perspectives regarding the optimal therapy for appendicitis, we sought to provide recommendations regarding the role of NOM with the administration of antibiotics (antibiotics-first approach) in uncomplicated AA as well as the need for routine interval appendectomy (RIA) in those presenting with appendiceal abscess or phlegmon (AAP) initially managed without appendectomy.METHODSA writing group from the Guidelines Committee of the Eastern Association for the Surgery of Trauma (EAST) performed a systematic review and meta-analysis of the current literature regarding appendicitis in adult populations. The Grading of Recommendations Assessment, Development and Evaluation methodology was applied and meta-analyses and evidence profiles generated.RESULTSWhen comparing antibiotics-first therapy to surgery for uncomplicated AA in adult populations, we found that perforation and recurrence of disease were the only outcomes consistently represented in the literature. For perforation, we were unable to make a definitive conclusion based on the degree of heterogeneity among the six randomized controlled trials reviewed. The risk of recurrence at 1 year with antibiotics-first treatment was 15.8% (95% confidence interval, 12.05–118.63). Critical outcomes could not be evaluated with the current literature. In NOM patients for AAP, the risk of recurrence was 24.3% if RIA was not performed (95% confidence interval, 2.74–73.11).CONCLUSIONBased on the completed meta-analysis and Grading of Recommendations Assessment, Development and Evaluation profiles, we were unable to make a recommendation for or against the antibiotics-first approach as primary treatment for uncomplicated AA. For NOM with AAP, we conditionally recommend against RIA in an otherwise asymptomatic patient. This review reveals multiple limitations of the published literature, leaving ample opportunities for additional research on this topic.LEVEL OF EVIDENCESystematic review, level II.
Electroconvulsive Therapy Practice in the Kingdom of Denmark
Authors: Bjørnshauge Didde , Hjerrild Simon , Videbech Poul 
Published: March 2019

Objectives
The aim of this study was to survey and describe the contemporary practice of electroconvulsive therapy (ECT) in the Kingdom of Denmark (Denmark, Greenland, and the Faroe Islands).

Methods
Data regarding number of ECTs and number of patients with different diagnoses treated with ECT were retrieved from the Danish National Patient Registry. In addition, a 45-item questionnaire was sent to all psychiatric departments practicing ECT in Denmark (n = 26), Greenland (n = 1), and the Faroe Islands (n = 1).

Results
According to the Danish National Patient Registry, a total of 21,730 ECTs were administered to 1891 unique patients in 2017. All departments responded to the survey. The psychiatric departments' attitude toward ECT was generally favorable and in accord with official guidelines. Maintenance ECT was used in all departments but one. Bilateral electrode placement was preferred. All departments used a preselected age-based dosing strategy. Involuntary ECT was performed in 96% of the psychiatric departments, but infrequently (3% of all treatments). All departments used a Thymatron (brief pulse) device, and in 71% of the departments, ECT was given in a specialized ECT unit and preanesthetic evaluation was carried out in all departments. The departments reported several different practices regarding documentation and monitoring of treatment effect, patient consent, screening for side effects (including cognitive side effects), and guidelines for the discharge of ECT patients.

Conclusions
Electroconvulsive therapy is frequently used in Denmark, Greenland, and the Faroe Islands in a relatively uniform way in adherence with clinical guidelines.
Electroconvulsive Treatment Utilization for the Inpatient Management of Severe Manic Episodes of Bipolar Disorder
Authors: Patel Rikinkumar S. , Jain Shailesh Bobby , Youssef Nagy A. 
Published: March 2019

Objective
Main objectives of the study are to (1) describe the utilization of electroconvulsive treatment (ECT) for the treatment of manic episodes (ME) and (2) examine the effect of early inpatient use of ECT (within 7 days of admission) compared with delayed use on length of stay and cost of inpatient care.

Method
The total sample of 14,005 inpatients with a principal diagnosis of bipolar disorder, ME (2012–2014), from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project were analyzed using univariate and logistic regressions. This represented data from 4411 hospitals from 45 states in the United States.

Results
The rate of ECT use was higher in young adults (<50 years), female patients, and whites from high-income families. Electroconvulsive treatment was preferred more in private, nonprofit, urban, and teaching hospitals. The percentages of overall hospitals where ECT was administered for mania by region were as follows: 22% in the Northeast, 23% in Midwest. 17% in the South, and 10% in the West. Approximately half (55.3%) of patients received initial ECT session within the first 7 days (median) after admission. Early ECT was associated with significantly shorter (−14.7 days) and less costly (−$41,976) inpatient care per patient.

Conclusions
Patients treated with ECT are generally sicker and more treatment resistant. However, ECT should not be considered only as a “last resort” in the treatment algorithm. Inpatient ECT for patients with MEs if initiated during the first 7 days of hospitalization reduces length of stay and cost.
Integrative analysis of epigenetics data identifies gene-specific regulatory elements
Authors: Schmidt Florian , Marx Alexander , Hebel Marie , Wegner Martin , Baumgarten Nina , Kaulich Manuel , Göke Jonathan , Vreeken Jilles , Schulz Marcel H. 
Published: March 2019

AbstractUnderstanding the complexity of transcriptional regulation is a major goal of computational biology. Because experimental linkage of regulatory sites to genes is challenging, computational methods considering epigenomics data have been proposed to create tissue-specific regulatory maps. However, we showed that these approaches are not well suited to account for the variations of the regulatory landscape between cell-types. To overcome these drawbacks, we developed a new method called STITCHIT, that identifies and links putative regulatory sites to genes. Within STITCHIT, we consider the chromatin accessibility signal of all samples jointly to identify regions exhibiting a signal variation related to the expression of a distinct gene. STITCHIToutperforms previous approaches in various validation experiments and was used with a genome-wide CRISPR-Cas9 screen to prioritize novel doxorubicin-resistance genes and their associated non-coding regulatory regions. We believe that our work paves the way for a more refined understanding of transcriptional regulation at the gene-level.
Genome-wide analysis of MIKC-type MADS-box genes in wheat: pervasive duplications may have facilitated adaptation to different environmental conditions
Authors: Schilling Susanne , Kennedy Alice , Pan Sirui , Jermiin Lars S. , Melzer Rainer 
Published: March 2019

AbstractBackgroundWheat (Triticum aestivum) is one of the most important crops worldwide. Given a growing global population coupled with increasingly challenging climate and cultivation conditions, facilitating wheat breeding by fine-tuning important traits such as stress resistance, yield and plant architecture is of great importance. Since they are involved in virtually all aspects of plant development and stress responses, prime candidates for improving these traits are MIKC-type (type II) MADS-box genes.ResultsWe present a detailed overview of number, phylogeny, and expression of 201 wheat MIKC-type MADS-box genes, which can be assigned to 15 subfamilies. Homoeolog retention is significantly above the average genome-wide retention rate for wheat genes, indicating that many MIKC-type homoeologs are functionally important and not redundant. Gene expression is generally in agreement with the expected subfamily-specific expression pattern, indicating broad conservation of function of MIKC-type genes during wheat evolution.We find the extensive expansion of some MIKC-type subfamilies to be correlated with their chromosomal location and propose a link between MADS-box gene duplications and the adaptability of wheat. A number of MIKC-type genes encode for truncated proteins that lack either the DNA-binding or protein-protein interaction domain and occasionally show novel expression patterns, possibly pointing towards neofunctionalization.ConclusionsConserved and neofunctionalized MIKC-type genes may have played an important role in the adaptation of wheat to a diversity of conditions, hence contributing to its importance as a global staple food. Therefore, we propose that MIKC-type MADS-box genes are especially well suited for targeted breeding approaches and phenotypic fine tuning.
Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC
Authors: Messerschmidt Clemens , Obermayer Benedikt , Klinghammer Konrad , Ochsenreither Sebastian , Treue Denise , Stenzinger Albrecht , Glimm Hanno , Fröhling Stefan , Kindler Thomas , Brandts Christian H. , Schulze-Osthoff Klaus , Weichert Wilko , Tinhofer Ingeborg , Klauschen Frederick , Keilholz Ulrich , Beule Dieter , Rieke Damian T. 
Published: March 2019

AbstractImmune checkpoint inhibition leads to response in some patients with head and neck squamous cell carcinoma (HNSCC). Robust biomarkers are lacking to date.We analyzed viral status, gene expression signatures, mutational load and mutational signatures in whole exome and RNA-sequencing data of the HNSCC TCGA dataset (N = 496) and a validation set (DKTK MASTER cohort, N = 10). Public single-cell gene expression data from 17 HPV-negative HNSCC were separately re-analyzed.Among HPV-negative HNSCC, APOBEC3-associated TCW motif mutations but not total single nucleotide variant burden were significantly associated with inflammation. APOBEC3-enriched HPV-negative HNSCC showed higher T-cell inflammation and immune checkpoint expression. Mutations in immune-evasion pathways were enriched in these tumors. APOBEC3B and 3C expression was identified in tumor cells and correlated with tumor inflammation.We identified an APOBEC-enriched subgroup of HPV-negative HNSCC with a distinct immunogenic phenotype, potentially mediating response to immunotherapy.
The TCR/peptide/MHC complex with a superagonist peptide shows similar interface and reduced flexibility compared to the complex with a self-peptide
Authors: Salutari Ilaria , Martin Roland , Caflisch Amedeo 
Published: March 2019

ABSTRACTT-cell receptor (TCR) recognition of myelin basic protein (MBP) peptide presented by major histocompatibility complex (MHC) protein HLA-DR2a, one of the MHC class II alleles associated with multiple sclerosis, is highly variable. Interactions in the trimolecular complex between the TCR of MBP83-99-specific T cell clone 3A6 with the MBP-peptide/HLA-DR2a (abbreviated TCR/pMHC) lead to substantially different proliferative responses when comparing the wild-type decapeptide MBP90-99 and a superagonist peptide which differs mainly in the residues that point towards the TCR. Here we investigate the influence of the peptide sequence on the interface and intrinsic plasticity of the TCR/pMHC trimolecular and pMHC bimolecular complexes by molecular dynamics simulations. The intermolecular contacts at the TCR/pMHC interface are similar for the complexes with the superagonist and the MBP self-peptide. The orientation angle between TCR and pMHC fluctuates less in the complex with the superagonist peptide. Thus, the higher structural stability of the TCR/pMHC tripartite complex with the superagonist peptide, rather than a major difference in binding mode with respect to the self-peptide, seems to be responsible for the stronger proliferative response.
Metabolic labeling of RNAs uncovers hidden features and dynamics of the Arabidopsis thaliana transcriptome
Authors: Szabo Emese Xochitl , Reichert Philipp , Lehniger Marie-Kristin , Ohmer Marilena , de Francisco Amorim Marcella , Gowik Udo , Schmitz-Linneweber Christian , Laubinger Sascha 
Published: March 2019

AbstractTranscriptome analysis by RNA sequencing (RNA-seq) has become an indispensable core research tool in modern plant biology. Virtually all RNA-seq studies provide a snapshot of the steady-state transcriptome, which contains valuable information about RNA populations at a given time, but lacks information about the dynamics of RNA synthesis and degradation. Only a few specialized sequencing techniques, such as global run-on sequencing (GRO-seq), have been applied in plants and provide information about RNA synthesis rates. Here, we demonstrate that RNA labeling with a modified, non-toxic uridine analog, 5-ethynyl uridine (5-EU), in Arabidopsis thaliana seedlings provides insight into the dynamic nature of a plant transcriptome. Pulse-labeling with 5-EU allowed the detection and analysis of nascent and unstable RNAs, of RNA processing intermediates generated by splicing, and of chloroplast RNAs. We also conducted pulse-chase experiments with 5-EU, which allowed us to determine RNA stabilities without the need for chemical inhibition of transcription using compounds such as actinomycin and cordycepin. Genome-wide analysis of RNA stabilities by 5-EU pulse-chase experiments revealed that this inhibitor-free RNA stability measurement results in RNA half-lives much shorter than those reported after chemical inhibition of transcription. In summary, our results show that the Arabidopsis nascent transcriptome contains unstable RNAs and RNA processing intermediates, and suggest that half-lives of plant RNAs are largely overestimated. Our results lay the ground for an easy and affordable nascent transcriptome analysis and inhibitor-free analysis of RNA stabilities in plants.
Proteinarium: Multi-Sample Protein-Protein Interaction Analysis and Visualization Tool
Authors: Armanious David , Schuster Jessica , Tollefson George F. , Agudelo Anthony , DeWan Andrew T. , Istrail Sorin , Padbury James , Uzun Alper 
Published: March 2019

AbstractBackgroundData analysis has become crucial in the post genomic era where the accumulation of genomic information is mounting exponentially. Analyzing protein-protein interactions in the context of the interactome is a powerful approach to understanding disease phenotypes.ResultsWe describe Proteinarium, a multi-sample protein-protein interaction network analysis and visualization tool. Proteinarium can be used to analyze data for samples with dichotomous phenotypes, multiple samples from a single phenotype or a single sample. Then, by similarity clustering, the network-based relations of samples are identified and clusters of related samples are presented as a dendrogram. Each branch of the dendrogram is built based on network similarities of the samples. The protein-protein interaction networks can be analyzed and visualized on any branch of the dendrogram. Proteinarium’s input can be derived from transcriptome analysis, whole exome sequencing data or any high-throughput screening approach. Its strength lies in use of gene lists for each sample as a distinct input which are further analyzed through protein interaction analyses. Proteinarium output includes the gene lists of visualized networks and PPI interaction files where users can analyze the network(s) on other platforms such as Cytoscape. In addition, since the dendrogram is written in Newick tree format, users can visualize it in other software platforms like Dendroscope, ITOL.ConclusionsProteinarium, through the analysis and visualization of PPI networks, allows researchers to make important observations on high throughput data for a variety of research questions. Proteinarium identifies significant clusters of patients based on their shared network similarity for the disease of interest and the associated genes. Proteinarium is a command-line tool written in Java with no external dependencies and it is freely available athttps://github.com/Armanious/Proteinarium.
DDX3 depletion represses translation of mRNAs with complex 5′ UTRs
Authors: Calviello Lorenzo , Venkataramanan Srivats , Rogowski Karol J. , Wyler Emanuel , Wilkins Kevin , Tejura Malvika , Thai Bao , Krol Jacek , Filipowicz Witold , Landthaler Markus , Floor Stephen N. 
Published: March 2019

AbstractDDX3 is an RNA chaperone of the DEAD-box family that regulates translation. Ded1, the yeast ortholog of DDX3, is a global regulator of translation, whereas DDX3 is thought to preferentially affect a subset of mRNAs. However, the set of mRNAs that are regulated by DDX3 are unknown, along with the relationship between DDX3 binding and activity. Here, we use ribosome profiling, RNA-seq, and PAR-CLIP to define the set of mRNAs that are regulated by DDX3 in human cells. We find that while DDX3 binds highly expressed mRNAs, depletion of DDX3 particularly affects the translation of a small subset of the transcriptome. We further find that DDX3 binds a site on helix 16 of the human ribosome, placing it immediately adjacent to the mRNA entry channel. Translation changes caused by depleting DDX3 levels or expressing an inactive point mutation are different, consistent with different association of these genetic variant types with disease. Taken together, this work defines the subset of the transcriptome that is responsive to DDX3 inhibition, with relevance for basic biology and disease states where DDX3 is altered.