bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining Trainee Competence: Value Is in the Eye of the Stakeholder
Authors: Yarris Lalena M. 
Published: February 2019

In this issue of Academic Medicine, Lundsgaard and colleagues present “Embracing Multiple Stakeholder Perspectives in Defining Trainee Competence,” a qualitative exploration of how various stakeholders contribute to the understanding of trainee competence. Drawing on stakeholder theory from business management, the authors of that report explore how the perceptions of key stakeholders (leaders/administrators, nurses/nurse practitioners, trainees, and patients) either confirm, enhance, or complicate the picture of competence that emerges from the perspectives of senior physician supervisors.
In this Invited Commentary, the author considers the potential effects of applying stakeholder theory to educational assessment and elaborates on Lundsgaard and colleagues’ findings that additional stakeholder perceptions may be redundant in some instances and present conflicting understandings of competence in others. She also emphasizes the importance of a process of defining competence, and ultimately developing assessment programs, that includes measuring and illuminating conflicting perceptions of what constitutes competence. Finally, the author considers potential applications of Lundsgaard and colleagues’ results for educators and assessors with comprehensive assessment programs already in place.
There are limitations and risks to applying a conceptual framework that aims to increase value for a company to the training of physicians. However, with thoughtful application, incorporating multiple stakeholders into instrument development and workplace-based assessment may provide educators with a more nuanced picture of competence that incorporates the values of those ultimately impacted by trainee performance.
Posttraumatic Stress Symptoms Mediate the Effects of Trauma Exposure on Clinical Indicators of Central Sensitization in Patients With Chronic Pain
Authors: McKernan Lindsey C. , Johnson Benjamin N. , Crofford Leslie J. , Lumley Mark A. , Bruehl Stephen , Cheavens Jennifer S. 
Published: February 2019

Objective:
Evidence supports high rates of co-occurrence of posttraumatic stress disorder (PTSD) and chronic pain disorders involving central sensitization (CS). The nature of this relationship, however, remains relatively unexplored. In this study, we aimed to (1) assess how both trauma exposure and current PTSD symptoms are related to clinical manifestations of CS, and (2) test whether PTSD symptoms explain the relationship between trauma exposure and CS. Because experiential avoidance has been shown to impact the relationship between trauma and health outcomes, we (3) explored experiential avoidance as a possible mediator or moderator of the trauma-CS relationship.

Methods:
A sample of 202 adult patients (79% female) with chronic pain completed validated self-report measures of trauma exposure, current PTSD symptoms, experiential avoidance, and 3 manifestations of CS: widespread pain, greater pain severity, and polysomatic symptom reporting. We used path analysis and multivariate regression to assess our study aims.

Results:
Both trauma exposure and PTSD symptoms were significantly associated with all 3 clinical indicators of CS. PTSD symptoms partially explained the relationship between trauma exposure and widespread pain, pain intensity, and polysomatic symptoms. Experiential avoidance did not mediate or moderate the trauma-CS relationship.

Conclusions:
Our findings suggest that trauma exposure is linked to elevated clinical markers of CS but a critical factor in this relationship is the mediating effect of current PTSD symptoms.
Brain tissue properties and morphometry assessment after chronic complete spinal cord injury
Authors: Hug Andreas , Bernini Adriano , Wang Haili , Lutti Antoine , Jende Johann M.E. , Böttinger Markus , Weber Marc-André , Weidner Norbert , Lang Simone 
Published: February 2019

AbstractThere is much controversy about the potential impact of spinal cord injury (SCI) on brain’s anatomy and function, which is mirrored in the substantial divergence of findings between animal models and human imaging studies. Given recent advances in quantitative magnetic resonance imaging (MRI) we sought to tackle the unresolved question about the link between the presumed injury associated volume differences and underlying brain tissue property changes in a cohort of chronic complete SCI patients. Using the established computational anatomy methods of voxel-based morphometry (VBM) and voxel-based quantification (VBQ) we performed statistical analyses of grey matter volume and parameter maps indicative for brain’s myelin, iron and free tissue water content in complete SCI patients (n=14) and healthy individuals (n=14). Our whole-brain analysis showed significant white matter volume loss in the rostral and dorsal part of the spinal cord consistent with Wallerian degeneration of proprioceptive axons in the lemniscal tract in SCI subjects, which correlated with spinal cord atrophy assessed with quantification of the spinal cord cross-sectional area at cervical level. The latter finding suggests that Wallerian degeneration of the lemniscal tract represents a main contributor to the observed spinal cord atrophy, which is highly consistent with preclinical ultrastructural/histological evidence of remote changes in the central nervous system secondary to SCI. Structural changes in the brain representing remote changes in the course of chronic SCI could not be confirmed with conventional VBM or VBQ statistical analysis. Whether and how MRI based brain morphometry and brain tissue property analysis will inform clinical decision making and clinical trial outcomes in spinal cord medicine remains to be determined.
Nuclear hormone receptor NHR-49 shapes immuno-metabolic response ofCaenorhabditis elegans to Enterococcus faecalisinfection
Authors: Dasgupta Madhumanti , Shashikanth Meghana , Bojanala Nagagireesh , Gupta Anjali , Javed Salil , Singh Varsha 
Published: February 2019

ABSTRACTImmune responses to pathogenic microbes include activation of resistance and tolerance mechanisms in the host both of which are energetically expensive. In this study, we show thatC. elegansexposed to Gram positive bacteriaEnterococcus faecalisandStaphylococcus aureus, rapidly utilizes lipid droplets, the major energy reserve in the nematode. Feeding onE. faecaliscauses developmental arrest inC. eleganslarvae and growth arrest in adults, pointing to starvation response. We find that nematode’s early response to infection entails upregulation of 25 genes involved in lipid hydrolysis and downregulation of 13 lipid synthesis genes as early as 8 hours following exposure. We also show that lipid droplets play a protective role inC. elegansduring infection. NHR-49, a PPARα ortholog, is required forE. faecalisinduced beta-oxidation of fatty acids and immune effector production. It regulates an immunometabolic axis required for survival of the nematode onE. faecalis.Our findings reveal a facet of nutritional immunity wherein lipid droplet homeostasis plays a central role in nematode microbe interactions.
Dynamic Aha1 Co-Chaperone Binding to Human Hsp90
Authors: Oroz Javier , Blair Laura J. , Zweckstetter Markus 
Published: February 2019

AbstractHsp90 is an essential chaperone that requires large allosteric changes to determine its ATPase activity and client binding. Because of the inherent low ATPase activity of human Hsp90, the co-chaperone Aha1, which is the only known ATPase stimulator in eukaryotes, is important for regulation of Hsp90’s allosteric timing. Little is known, however, about the structure of the Hsp90/Aha1 full-length complex. Here, we characterize the solution structure of unmodified human Hsp90 in complex with Aha1 using NMR spectroscopy. We show that the 214 kDa complex adopts multiple conformations in the absence of nucleotide. Interaction with Aha1 induces structural changes near the nucleotide-binding site in Hsp90’s N-terminal domain, providing a basis for its ATPase-enhancing activity. Moreover, the E67K mutation in Aha1 strongly diminishes the interaction, supporting a two-step binding mechanism. Our data reveal important aspects of this pivotal chaperone/co-chaperone interaction and emphasize the relevance of characterizing dynamic chaperone structures in solution.
Allergic inflammation hinders synergistic viral-bacterial co-infection in C57BL/6 mice
Authors: LeMessurier Kim S. , Iverson Amy R. , Chang Ti-Cheng , Palipane Maneesha , Vogel Peter , Rosch Jason W. , Samarasinghe Amali E. 
Published: February 2019

AbstractAsthma is a chronic airways disease that can be exacerbated during respiratory infections. Our previous findings that the inflammatory state of allergic airways at the time of influenza A virus (IAV) infection in combination with epidemiologic findings that asthmatics were less likely to suffer from severe influenza during the 2009 pandemic suggest that additional complications of influenza, such as increased susceptibility to bacterial superinfection, may be mitigated in the allergic host. To test this hypothesis, we developed a murine model of ‘triple-disease’ in which mice were first rendered allergic toAspergillus fumigatusand co-infected with IAV andStreptococcus pneumoniaeseven days apart. Significant alterations to known synergistic effects of co-infection were noted in the allergic mice including reduced morbidity and mortality, bacterial burden, maintenance of alveolar macrophages, and reduced lung inflammation and damage. The lung microbiome of allergic mice differed from that of non-allergic mice during co-infection. To investigate the impact of the microbiome on the pathogenesis of lung disease, we induced a perturbation with a short course of fluoroquinolone antibiotic that is often prescribed for lung infections. A significant change in the microbiome was complemented with alterations to the inflammatory profile and a drastic increase in pro-inflammatory cytokines in allergic mice which were now susceptible to severe disease from IAV andS. pneumoniaeco-infection. Our data suggest that responses to co-infection in allergic hosts likely depends on the immune and microbiome states and that antibiotics should be used with caution in individuals with underlying chronic lung disease.Author SummaryAsthma is a condition of the lungs that affects millions worldwide. Traditionally, respiratory infections are considered to have a negative impact on asthmatics. However, epidemiological data surrounding the 2009 influenza pandemic suggest that asthmatics may be better equipped to counter severe influenza including bacterial pneumonia. Herein, we introduce a novel mouse model system designed to recapitulate an influenza virus and Streptococcal co-infection in a host with fungal asthma. We found that underlying allergic asthma protects against severe disease induced by co-infection. Mice with underlying allergic inflammation had reduced damage to the lungs and did not show signs of respiratory distress. Among the differences noted in the allergic mice that were protected from viral and bacterial co-infection, was the lung microbiome. Allergic mice lost their protection from co-infection after we perturbed their lung microbiome with antibiotics suggesting that the lung microbiome plays a role in host immunity against invading pathogens.
Identification of circadian rhythms inNannochloropsisspecies using bioluminescence reporter lines
Authors: Poliner Eric , Cummings Cameron , Newton Linsey , Farré Eva M. 
Published: February 2019

SummaryCircadian clocks allow organisms to predict environmental changes caused by the rotation of the Earth. Although circadian rhythms are widespread among different taxa, the core components of circadian oscillators are not conserved and differ between bacteria, plants, animals and fungi. Stramenopiles are a large group of organisms in which circadian rhythms have been only poorly characterized and no clock components have been identified. We have investigated cell division and molecular rhythms inNannochloropsisspecies. In the four strains tested, cell division occurred principally during the night period under diel conditions, however, rhythms dampened within 2-3 days after transfer to constant light. We developed firefly luciferase reporters for long-term monitoring ofin vivotranscriptional rhythms in twoNannochlropsisspecies,N. oceanicaCCMP1779 andN. salinaCCMP537. The reporter lines express free-running bioluminescence rhythms with periods of ~21-31 h that dampen within ~3-4 days under constant light. Using different entrainment regimes, we demonstrate that these rhythms are regulated by a circadian-type oscillator. In addition, the phase of free-running luminescence rhythms can be modulated pharmacologically using a CK1 ε/δ inhibitor, suggesting a role of this kinase in theNannochloropsisclock. Together with the molecular and genomic tools available forNannochloropsisspecies, these reporter lines represent an excellent system for future studies on the molecular mechanisms of stramenopile circadian oscillators.Significance statementStramenopiles are a large and diverse line of eukaryotes in which circadian rhythms have been only poorly characterized and no clock components have been identified. We have developed bioluminescence reporter lines inNannochloropsisspecies and provide evidence for the presence of a circadian oscillator in stramenopiles; these lines will serve as tools for future studies to uncover the molecular mechanisms of circadian oscillations in these species.
multiPhATE: bioinformatics pipeline for functional annotation of phage isolates
Authors: Ecale Zhou Carol L. , Malfatti Stephanie , Kimbrel Jeffrey , Philipson Casandra , McNair Katelyn , Hamilton Theron , Edwards Robert , Souza Brian 
Published: February 2019

ABSTRACTSummaryTo address the need for improved phage annotation tools that scale, we created an automated throughput annotation pipeline: multiple-genome Phage Annotation Toolkit and Evaluator (multiPhATE). multiPhATE is a throughput pipeline driver that invokes an annotation pipeline (PhATE) across a user-specified set of phage genomes. This tool incorporates a de novo phage gene-calling algorithm and assigns putative functions to gene calls using protein-, virus-, and phage-centric databases. multiPhATE’s modular construction allows the user to implement all or any portion of the analyses by acquiring local instances of the desired databases and specifying the desired analyses in a configuration file. We demonstrate multiPhATE by annotating two newly sequenced Yersinia pestis phage genomes. Within multiPhATE, the PhATE processing pipeline can be readily implemented across multiple processors, making it adaptable for throughput sequencing projects. Software documentation assists the user in configuring the system.Availability and implementationmultiPhATE was implemented in Python 3.7, and runs as a command-line code under Linux or Unix. multiPhATE is freely available under an open-source BSD3 license from https://github.com/carolzhou/multiPhATE. Instructions for acquiring the databases and third-party codes used by multiPhATE are included in the distribution README file. Users may report bugs by submitting to the github issues page associated with the multiPhATE distribution.Contactzhou4@llnl.gov or carol.zhou@comcast.net.Supplementary informationData generated during the current study are included as supplementary files available for download at https://github.com/carolzhou/PhATE_docs.
Unique structural features of the mitochondrial AAA+ protease AFG3L2 reveal the molecular basis for activity in health and disease
Authors: Puchades Cristina , Ding Bojian , Song Albert , Wiseman R. Luke , Lander Gabriel C. , Glynn Steven E. 
Published: February 2019

AbstractMitochondrial AAA+ quality control proteases regulate diverse aspects of mitochondrial biology through specialized protein degradation, but the underlying molecular mechanisms that define the diverse activities of these enzymes remain poorly defined. The mitochondrial AAA+ protease AFG3L2 is of particular interest, as genetic mutations localized throughout AFG3L2 are linked to diverse neurodegenerative disorders. However, a lack of structural data has limited our understanding of how mutations impact enzymatic activity. Here, we used cryo-EM to determine a substrate-bound structure of the catalytic core of human AFG3L2. This structure identifies multiple specialized structural features within AFG3L2 that integrate with conserved structural motifs required for hand-over-hand ATP-dependent substrate translocation to engage, unfold and degrade targeted proteins. Mapping disease-relevant AFG3L2 mutations onto our structure demonstrates that many of these mutations localize to these unique structural features of AFG3L2 and distinctly influence its activity and stability. Our results provide a molecular basis for neurological phenotypes associated with different AFG3L2 mutations, and establish a structural framework to understand how different members of the AAA+ superfamily achieve specialized, diverse biological functions.
Genome-wide identification and analysis of A-to-I RNA editing events in the malignantly transformed cell lines from BEP2D induced by α-particles radiation
Authors: Liu Qiaowei , Li Hao , You Lukuan , Li Tao , Li Lingling , Zhou Pingkun , Bo Xiaochen , Chen Hebing , Chen Xiaohua , Hu Yi 
Published: February 2019

AbstractAdenosine (A) to inosine (I) RNA editing is the most prevalent RNA editing mechanism in humans and play critical roles in tumorigenesis. However, the effects of radiation on RNA editing and the mechanisms of radiation-induced cancer were poorly understood. Here, we analyzed human bronchial epithelial BEP2D cells and radiation-induced malignantly transformed cells with next generation sequencing. By performing an integrated analysis of A-to-I RNA editing, we found that genome-encoded single-nucleotide polymorphisms (SNPs) might induce the downregulation of ADAR2 enzymes, and further caused the abnormal occurrence of RNA editing in malignantly transformed cells. These editing events were significantly enriched in differentially expressed genes between normal cells and cancer cells. In addition, oncogenes CTNNB1 and FN1 were highly edited and significantly overexpressed in cancer cells, thus may be responsible for the lung cancer progression. Our work provides a systematic analysis of RNA editing from lung tumor specimens with high-throughput RNA sequencing and DNA sequencing. Moreover, these results demonstrate further evidence for RNA editing as an important tumorigenesis mechanism.
PRDM14 controls X-chromosomal and global epigenetic reprogramming of H3K27me3 in migrating mouse primordial germ cells
Authors: Mallol Anna , Guirola Maria , Payer Bernhard 
Published: February 2019

ABSTRACTIn order to prepare the genome for gametogenesis, primordial germ cells (PGCs) undergo extensive epigenetic reprogramming during migration towards the gonads in mammalian embryos. This includes changes on a genome-wide scale and additionally in females the remodeling of the inactive X-chromosome to enable X-chromosome reactivation (XCR). However, if global and X-chromosomal remodeling are related and which factors are important is unknown. Here we identify the germ cell determinant PR-domain containing protein 14 (PRDM14) as the first known factor that is instrumental for both global and X-chromosomal reprogramming in migrating mouse PGCs. We find that global upregulation of the repressive histone H3 lysine 27 trimethylation (H3K27me3) mark is PRDM14 dosage-dependent in PGCs of both sexes. When focusing on XCR, we observed that PRDM14 is required for removal of H3K27me3 from the inactive X-chromosome. Furthermore we show that global and X-chromosomal H3K27me3 reprogramming are functionally separable, despite their common regulation by PRDM14. Thereby we provide mechanistic insight and spatiotemporal resolution to the remodeling of the epigenome during mouse PGC migration and link epigenetic reprogramming to its developmental context in vivo.
Semi-quantitative characterisation of mixed pollen samples using MinION sequencing and Reverse Metagenomics (RevMet)
Authors: Peel Ned , Dicks Lynn V. , Heavens Darren , Percival-Alwyn Lawrence , Cooper Chris , Clark Matthew D. , Davies Richard G. , Leggett Richard M. , Yu Douglas W. 
Published: February 2019

Abstract1. The ability to identify and quantify the constituent plant species that make up a mixed-species sample of pollen has important applications in ecology, conservation, and agriculture. Recently, metabarcoding protocols have been developed for pollen that can identify constituent plant species, but there are strong reasons to doubt that metabarcoding can accurately quantify their relative abundances. A PCR-free, shotgun metagenomics approach has greater potential for accurately quantifying species relative abundances, but applying metagenomics to eukaryotes is challenging due to low numbers of reference genomes.2. We have developed a pipeline, RevMet (Reverse Metagenomics), that allows reliable and semi-quantitative characterization of the species composition of mixed-species eukaryote samples, such as bee-collected pollen, without requiring reference genomes. Instead, reference species are represented only by ‘genome skims’: low-cost, low-coverage, short-read sequence datasets. The skims are mapped to individual long reads sequenced from mixed-species samples using the MinION, a portable nanopore sequencing device, and each long read is uniquely assigned to a plant species.3. We genome-skimmed 49 wild UK plant species, validated our pipeline with mock DNA mixtures of known composition, and then applied RevMet to pollen loads collected from wild bees. We demonstrate that RevMet can identify plant species present in mixed-species samples at proportions of DNA ≥1%, with few false positives and false negatives, and reliably differentiate species represented by high versus low amounts of DNA in a sample.4. The RevMet pipeline could readily be adapted to generate semi-quantitative datasets for a wide range of mixed eukaryote samples, which could include characterising diets, quantifying allergenic pollen from air samples, quantifying soil fauna, and identifying the compositions of algal and diatom communities. Our per-sample costs were £90 per genome skim and £60 per pollen sample, and new versions of sequencers available now will further reduce these costs.
South African foodservice quality: inpatient’s perceptions
Authors: Ncube Lindiwe Julia , Nesamvuni Alufheli Edgar 
Published: February 2019

Purpose
The purpose of this paper is to assess patient perceptions regarding South African hospital foodservice quality.

Design/methodology/approach
In total, 419 questionnaires were administered to surgical and medical inpatients consuming a normal diet in six South African provinces. A number of 23 urban and 10 rural hospitals were sampled. Inpatients were surveyed for their opinions on hospital foodservice quality with a view to improving meals and food delivery processes.

Findings
Results revealed lower patient satisfaction with aspects relating to foodservice reliability. Among other issues, inpatients were not informed about meal times (overall median=0), had to wait longer than expected for their meals and were not informed about delays (overall median=2). Menu items were not explained to inpatients (overall median=0), and inpatients were not informed about nutritional values (overall median=0). Consequently, patients opined that they were not willing to use the hospital foodservice in future (overall median=2).

Originality/value
To identify South African healthcare issues that need improvement, it is necessary to establish where to act. These findings create awareness among authorities and hospital managers to consider patient perceptions when they review and try to improve public hospital foodservice quality, which could also assist in ensuring improvement in food consumption levels, thereby combating South African hospital malnutrition.