bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity of Simulation-Based Assessment for Accreditation Council for Graduate Medical Education Milestone Achievement
Authors: Isaak Robert S. , Chen Fei , Martinelli Susan M. , Arora Harendra , Zvara David A. , Hobbs Gene , Stiegler Marjorie P. 
Published: January 2018

Introduction
The Accreditation Council for Graduate Medical Education requires biannual evaluation of anesthesiology residents on 25 subcompetency milestones. Some milestone domains are particularly challenging to repeatedly and reliably observe during clinical care. Simulation-Based Milestones Assessment (SBMA) may help overcome these challenges. However, few studies have examined the external validation of simulation assessment scores (ie, the relationships between simulation-based assessment scores and other standard measures of ability) for milestones. This study analyzed whether SBMA scores (1) discriminate by postgraduate year, (2) improve over time, and (3) correlate with traditional measures of performance.

Methods
This is a retrospective analysis of 55 residents' SBMA data from 30 scenarios for two academic years. Each scenario was evaluated for time-in-training discrimination. Scenarios were then analyzed for SBMA scoring trends over time, and SBMA scores were compared with residents' clinical evaluations.

Results
Twenty-four SBMA scenarios discriminated by postgraduate year. Repeated measure analysis of variance showed statistically significant between-session score improvements (F (3, 54) = 17.79, P < 0.001). Pearson correlation coefficients demonstrated moderate to strong correlation between SBMA and clinical evaluations: January 2015 r = 0.67, P < 0.01 (n = 27); May 2015 r = 0.43, P = 0.09 (n = 17); November 2015 r = 0.70, P < 0.01 (n = 24); and April 2016 r = 70, P < 0.01 (n = 27).

Conclusions
The associations between SBMA scores and experience level, time-in-training, and clinical performance evaluations provide evidence that SBMA may be used as metrics of residents' Accreditation Council for Graduate Medical Education milestone competencies.
Factors Associated With Pediatric Hospital-Acquired Pressure Injuries
Authors: Razmus Ivy 
Published: January 2018

PURPOSE:
The purpose of this study was to identify associations among pediatric patient characteristics (age and gender), hospital characteristics, inpatient unit characteristics (unit type, pressure injury prevention practices, and nurse staffing measures), and hospital-acquired pressure injuries (HAPIs) in a group of pediatric patients and in those determined to be at risk for pressure injury.

DESIGN:
A descriptive, correlational analysis of data from a large dataset.

SUBJECTS AND SETTING:
The sample comprised 39,984 children aged 1 day to 18 years of age from 678 pediatric units in 271 participating hospitals across the United States.

METHODS:
Data related to pressure injuries and prevention among pediatric patients from the National Database of Nursing Quality Indicators (NDNQI) were analyzed. All data were collected during the year 2012. Descriptive statistics were used to summarize the study sample. Hierarchical logistic regression analysis was used to analyze patient age and gender, unit type, pressure injury risk, prevention and staffing measures, and hospital characteristics associated with HAPI.

RESULTS:
The likelihood of a HAPI was more than 9 times higher among patients who were determined to be at risk for pressure injuries (odds ratio [OR]: 9.42, 95% confidence interval [CI]: 7.28-12.17, P < .001) compared to patients deemed not at risk. Hospital-acquired pressure injury was more likely to occur on pediatric critical care units (OR: 2.59, 95% CI: 1.28-5.26, P = .009) and rehabilitation units (OR: 4.05, 95% CI: 1.21-13.55, P = .02). Patients from hospitals that only provided care for children (OR: 2.6, 95% CI: 1.42-4.78, P = .002) were also more likely to be associated with HAPI compared to hospitals that provided care for adults and children. Among the 11,203 pediatric patients deemed at risk for pressure injuries, 95.8% received one or more prevention interventions. There were no prevention interventions associated with a lower occurrence of HAPI.

CONCLUSIONS:
Study findings support pressure injury risk assessment among pediatric patients and elucidates important information regarding pediatric unit and hospital characteristics associated with HAPI.
TuBA: Tunable Biclustering Algorithm Reveals Clinically Relevant Tumor Transcriptional Profiles in Breast Cancer
Authors: Singh Amartya , Bhanot Gyan , Khiabanian Hossein 
Published: January 2018

ABSTRACTBackgroundTraditional clustering approaches for gene expression data are not well adapted to address the complexity and heterogeneity of tumors, where small sets of genes may be aberrantly co-expressed in specific subsets of tumors. Biclustering algorithms that perform local clustering on subsets of genes and conditions help address this problem. We propose a graph-based Tunable Biclustering Algorithm (TuBA) based on a novel pairwise proximity measure, examining the relationship of samples at the extremes of genes’ expression profiles to identify similarly altered signatures.ResultsTuBA’s predictions are consistent in 3,940 Breast Invasive Carcinoma (BRCA) samples from three independent sources, employing different technologies for measuring gene expression (RNASeq and Microarray). Over 60% of biclusters identified independently in each dataset had significant agreement in their gene sets, as well as similar clinical implications. About 50% of biclusters were enriched in the ER-/HER2- (or basal-like) subtype, while more than 50% were associated with transcriptionally active copy number changes. Biclusters representing gene co-expression patterns in stromal tissue were also identified in tumor specimens.ConclusionTuBA offers a simple biclustering method that can identify biologically relevant gene co-expression signatures not captured by traditional unsupervised clustering approaches. It complements biclustering approaches that are designed to identify constant or coherent submatrices in gene expression datasets, and outperforms them in identifying a multitude of altered transcriptional profiles that are associated with observed genomic heterogeneity of diseased states in breast cancer, both within and across tumor subtypes, a promising step in understanding disease heterogeneity, and a necessary first step in individualized therapy.
Toxoplasma gondiiinfection triggers chronic cachexia and sustained commensal dysbiosis in mice
Authors: Hatter Jessica A. , Kouche Yue Moi , Melchor Stephanie J. , Ng Katherine , Bouley Donna M. , Boothroyd John C. , Ewald Sarah E. 
Published: January 2018

AbstractToxoplasma gondiiis a protozoan parasite with a predation-mediated transmission cycle between rodents and felines. Intermediate hosts acquireToxoplasmaby eating parasite cysts which invade the small intestine, disseminate systemically and finally establish host life-long chronic infection in brain and muscles. Here we show thatToxoplasmainfection can trigger a severe form of sustained cachexia: a disease of progressive weight loss that is a causal predictor of mortality in cancer, chronic disease and many infections.Toxoplasmacachexia is characterized by acute anorexia, systemic inflammation and loss of 20% body mass. Although mice recover from symptoms of peak sickness they fail to regain muscle mass or visceral adipose depots. We asked whether the damage to the intestinal microenvironment observed at acute time points was sustained in chronic infection and could thereby play a role the sustaining cachexia. We found that parasites replicate in the same region of the distal jejunum/proximal ileum throughout acute infection, inducing the development of secondary lymphoid structures and severe, regional inflammation. Small intestine pathology was resolved by 5 weeks post-infection. However, changes in the commensal populations, notably an outgrowth ofClostridia spp., were sustained in chronic infection. Importantly, uninfected animals co-housed with infected mice display similar changes in commensal microflora but never display symptoms of cachexia, indicating that altered commensals are not sufficient to explain the cachexia phenotype alone. These studies indicate thatToxoplasmainfection is a novel and robust model to study the immune-metabolic interactions that contribute chronic cachexia development, pathology and potential reversal.
Markov Katana: a Novel Method for Bayesian Resampling of Parameter Space Applied to Phylogenetic Trees
Authors: Pollard Stephen T. , Fukushima Kenji , Wang Zhengyuan O. , Castoe Todd A. , Pollock David D. 
Published: January 2018

ABSTRACTPhylogenetic inference requires a means to search phylogenetic tree space. This is usually achieved using progressive algorithms that propose and test small alterations in the current tree topology and branch lengths. Current programs search tree topology space using branch-swapping algorithms, but proposals do not discriminate well between swaps likely to succeed or fail. When applied to datasets with many taxa, the huge number of possible topologies slows these programs dramatically. To overcome this, we developed a statistical approach for proposal generation in Bayesian analysis, and evaluated its applicability for the problem of searching phylogenetic tree space. The general idea of the approach, which we call ‘Markov katana’, is to make proposals based on a heuristic algorithm using bootstrapped subsets of the data. Such proposals induce an unintended sampling distribution that must be determined and removed to generate posterior estimates, but the cost of this extra step can in principle be small compared to the added value of more efficient parameter exploration in Markov chain Monte Carlo analyses. Our prototype application uses the simple neighbor-joining distance heuristic on data subsets to propose new reasonably likely phylogenetic trees (including topologies and branch lengths). The evolutionary model used to generate distances in our prototype was far simpler than the more complex model used to evaluate the likelihood of phylogenies based on the full dataset. This prototype implementation indicates that the Markov katana approach could be easily incorporated into existing phylogenetic search programs and may prove a useful alternative in conjunction with existing methods. The general features of this statistical approach may also prove useful in disciplines other than phylogenetics. We demonstrate that this method can be used to efficiently estimate a Bayesian posterior.
Structure, Asymmetry and Segmentation of the Human Parietal Aslant and Vertical Occipital Fasciculi
Authors: Panesar Sandip S , A Belo Joao Tiago , Yeh Fang-Cheng , Fernandez-Miranda Juan C 
Published: January 2018

AbstractWe previously proposed a bipartite ‘dorsal-ventral’ model of human arcuate fasciculus (AF) morphology. This model does not, however, account for the ‘vertical,’ temporoparietal subdivision of the AF described in earlier dissection and tractographic studies. In an effort to address the absence of the vertical AF (VAF) within the ‘dorsal-ventral’ model, we conducted a dedicated tractographic and white-matter dissection study of this tract and another short, vertical, posterior-hemispheric fascicle: the vertical occipital fasciculus (VOF). We conducted atlas-based, non-tensor, deterministic tractography in 30 single subjects from the Human Connectome Project database and verified our results using an average diffusion atlas comprising 842 separate normal subjects. We also performed white-matter dissection in 4 cadaveric hemispheres. Our tractographic results demonstrate that the VAF is in fact a bipartite system connecting the ventral-parietal and ventral-temporal regions, with variable connective and no volumetric lateralization. The VOF is a nonlateralized, non-segmented system connecting lateral occipital areas with basal-temporal regions. Importantly, the VOF was distinctly dissociated from the VAF. As the VAF demonstrates no overall connective or volumetric lateralization, we postulate its distinction from the AF system and propose its renaming to the ‘parietal aslant tract,’ (PAT) with unique dorsal and ventral subdivisions. Our tractography results were supported by diffusion atlas and white matter dissection findings.
Mind your gaps: Overlooking assembly gaps confounds statistical testing in genome analysis
Authors: Domanska Diana , Kanduri Chakravarthi , Simovski Boris , Sandve Geir Kjetil 
Published: January 2018

AbstractBackgroundThe difficulties associated with sequencing and assembling some regions of the DNA sequence result in gaps in the reference genomes that are typically represented as stretches of Ns. Although the presence of assembly gaps causes a slight reduction in the mapping rate in many experimental settings, that does not invalidate the typical statistical testing comparing read count distributions across experimental conditions. However, we hypothesize that not handling assembly gaps in the null model may confound statistical testing of co-localization of genomic features.ResultsFirst, we performed a series of explorative analyses to understand whether and how the public genomic tracks intersect the assembly gaps track (hg19). The findings rightly confirm that the genomic regions in public genomic tracks intersect very little with assembly gaps and the intersection was observed only at the beginning and end regions of the assembly gaps rather than covering the whole gap sizes. Further, we simulated a set of query and reference genomic tracks in a way that nullified any dependence between them to test our hypothesis that not avoiding assembly gaps in the null model would result in spurious inflation of statistical significance. We then contrasted the distributions of test statistics and p-values of Monte Carlo simulation-based permutation tests that either avoided or not avoided assembly gaps in the null model when testing for significant co-localization between a pair of query and reference tracks. We observed that the statistical tests that did not account for the assembly gaps in the null model resulted in a distribution of the test statistic that is shifted to the right and a distribu tion of p-values that is shifted to the left (leading to inflated significance).ConclusionOur results shows that not accounting for assembly gaps in statistical testing of co-localization analysis may lead to false positives and over-optimistic findings.
Developmental genetics of corolla tube formation: role of the tasiRNA-ARF pathway and a conceptual model
Authors: Ding Baoqing , Xia Rui , Lin Qiaoshan , Gurung Vandana , Sagawa Janelle M. , Stanley Lauren E. , Strobel Matthew , Diggle Pamela K. , Meyers Blake C. , Yuan Yao-Wu 
Published: January 2018

ABSTRACTMore than 80,000 angiosperm species produce flowers with petals fused into a corolla tube. As an important element of the tremendous diversity of flower morphology, the corolla tube plays a critical role in many specialized interactions between plants and animal pollinators (e.g., beeflies, hawkmoths, hummingbirds, nectar bats), which in turn drives rapid plant speciation. Despite its clear significance in plant reproduction and evolution, the corolla tube remains one of the least understood plant structures from a developmental genetics perspective. Through mutant analyses and transgenic experiments, here we show that the tasiRNA-ARF pathway is required for corolla tube formation in the monkeyflower speciesMimulus lewisii. Loss-of-function mutations in theM. lewisiiorthologs ofARGONAUTE7andSUPPRESSOR OF GENE SILENCING 3cause a dramatic decrease in abundance ofTAS3-derived small RNAs and a moderate up-regulation ofAUXIN RESPONSE FACTOR 3(ARF3) andARF4, which lead to inhibition of lateral expansion of the bases of petal primordia and complete arrest of the upward growth of the inter-primordial regions, resulting in unfused corollas. By using an auxin reporter construct, we discovered that auxin distribution is continuous along the petal primordium base and the inter-primordial region during the critical stage of corolla tube formation in the wild-type, and that this auxin distribution is much weaker and more restricted in the mutant. Together, these results suggest a new conceptual model highlighting the central role of auxin directed synchronized growth of the petal primordium base and the inter-primordial region in corolla tube formation.
INSaFLU: an automated open web-based bioinformatics suite “from-reads” for influenza whole-genome-sequencing-based surveillance
Authors: Borges Vítor , Pinheiro Miguel , Pechirra Pedro , Guiomar Raquel , Gomes João Paulo 
Published: January 2018

AbstractA new era of flu surveillance has already started based on the genetic characterization and exploration of influenza virus evolution at whole-genome scale. Although this has been prioritized by national and international health authorities, the demanded technological transition to whole-genome sequencing (WGS)-based flu surveillance has been particularly delayed by the lack of bioinformatics infrastructures and/or expertise to deal with primary next-generation sequencing (NGS) data. Here, we launch INSaFLU (“INSide the FLU”), which, to the best of our knowledge, is the first influenza-specific bioinformatics free web-based suite that deals with primary data (reads) towards the automatic generation of the output data that are actually the core first-line “genetic requests” for effective and timely influenza laboratory surveillance (e.g., type and sub-type, gene and whole-genome consensus sequences, variants’ annotation, alignments and phylogenetic trees). By handling NGS data collected from any amplicon-based schema, the implemented pipeline enables any laboratory to perform advanced, multi-step software intensive analyses in a user-friendly manner without previous training in bioinformatics. INSaFLU gives access to user-restricted sample databases and projects’ management, being a transparent and highly flexible tool specifically designed to automatically update project outputs as more samples are uploaded. Data integration is thus completely cumulative and scalable, fitting the need for a continuous epidemiological surveillance during the flu epidemics. Multiple outputs are provided in nomenclature-stable and standardized formats that can be explored in situ or through multiple compatible downstream applications for fine-tune data analysis. This platform additionally flags samples as “putative mixed infections” if the population admixture enrolls influenza viruses with clearly distinct genetic backgrounds, and enriches the traditional “consensus-based” influenza genetic characterization with relevant data on influenza sub-population diversification through a depth analysis of intra-patient minor variants. This dual approach is expected to strengthen our ability not only to detect the emergence of antigenic and drug resistance variants, but also to decode alternative pathways of influenza evolution and to unveil intricate routes of transmission. In summary, INSaFLU supplies public health laboratories and influenza researchers with an open “one size fits all” framework, potentiating the operationalization of a harmonized multi-country WGS-based surveillance for influenza virus.INSaFLU can be accessed through https://insaflu.insa.pt (see homepage view in Figure 1).
Three-dimensional human axon tracts derived from cerebral organoids
Authors: Cullen D. Kacy , Struzyna Laura A. , Jgamadze Dennis , Gordián-Vélez Wisberty J. , Lim James , Wofford Kathryn L. , Browne Kevin D. , Chen H. Isaac 
Published: January 2018

SummaryReestablishing cerebral connectivity is a critical part of restoring neuronal network integrity and brain function after trauma, stroke, and neurodegenerative diseases. Creating transplantable axon tracts in the laboratory is a novel strategy for overcoming the common barriers limiting axon regeneration in vivo, including growth-inhibiting factors and the limited outgrowth capacity of mature neurons in the brain. We describe the generation and phenotype of three-dimensional human axon tracts derived from cerebral organoid tissue. These centimeter-long constructs are encased in an agarose shell that permits physical manipulation and are composed of discrete cellular regions spanned by axon tracts and dendrites, mirroring the separation of grey and white matter in the brain. Features of cerebral cortex also are emulated, as evidenced by the presence of neurons with different cortical layer phenotypes. This engineered neural tissue has the translational potential to reconstruct brain circuits by physically replacing discrete cortical neuron populations as well as long-range axon tracts in the brain.eTOC BlurbRestoring axonal connectivity after brain damage is crucial for improving neurological and cognitive function. Cullen, et al. have generated anatomically inspired, three-dimensional human axon tracts projecting from cerebral organoids in a transplantable format that may facilitate the reconstruction of large-scale brain circuits.HighlightsA neural tissue engineering approach is applied to human cerebral organoids.Three-dimensional axon tracts are generated in a transplantable format.The growth characteristics of the engineered axons are examined.The cellular phenotypes of the organoid tissue and axons are characterized.
Influenza Virus Infection Model With Density Dependence Supports Biphasic Viral Decay
Authors: Smith Amanda P. , Moquin David J. , Bernhauerova Veronika , Smith Amber M. 
Published: January 2018

AbstractMathematical models that describe infection kinetics help elucidate the time scales, effectiveness, and mechanisms underlying viral growth and infection resolution. For influenza A virus (IAV) infections, the standard viral kinetic model has been used to investigate the effect of different IAV proteins, immune mechanisms, antiviral actions, and bacterial coinfection, among others. We sought to further define the kinetics of IAV infections by infecting mice with influenza A/PR8 and measuring viral loads with high frequency and precision over the course of infection. The data highlighted dynamics that were not previously noted, including viral titers that remain elevated for several days during mid-infection and a sharp 4-5 log10decline in virus within one day as the infection resolves. The standard viral kinetic model, which has been widely used within the field, could not capture these dynamics. Thus, we developed a new model that could simultaneously quantify the different phases of viral growth and decay with high accuracy. The model suggests that the slow and fast phases of virus decay are due to the infected cell clearance rate changing as the density of infected cells changes. To characterize this model, we fit the model to the viral load data, examined the parameter behavior, and connected the results and parameters to linear regression estimates. The resulting parameters and model dynamics revealed that the rate of viral clearance during resolution occurs 25 times faster than the clearance during mid-infection and that small decreases to this rate can significantly prolong the infection. This likely reflects the high efficiency of the adaptive immune response. The new model provides a well-characterized representation of IAV infection dynamics, is useful for analyzing and interpreting viral load dynamics in the absence of immunological data, and gives further insight into the regulation of viral control.