bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost Associated With Pediatric Delirium in the ICU
Authors: Traube Chani , Mauer Elizabeth A. , Gerber Linda M. , Kaur Savneet , Joyce Christine , Kerson Abigail , Carlo Charlene , Notterman Daniel , Worgall Stefan , Silver Gabrielle , Greenwald Bruce M. 
Published: August 2016

Objective:
To determine the costs associated with delirium in critically ill children.

Design:
Prospective observational study.

Setting:
An urban, academic, tertiary-care PICU in New York city.

Patients:
Four-hundred and sixty-four consecutive PICU admissions between September 2, 2014, and December 12, 2014.

Interventions:
None.

Measurements and Main Results:
All children were assessed for delirium daily throughout their PICU stay. Hospital costs were analyzed using cost-to-charge ratios, in 2014 dollars. Median total PICU costs were higher in patients with delirium than in patients who were never delirious ($18,832 vs $4,803; p < 0.0001). Costs increased incrementally with number of days spent delirious (median cost of $9,173 for 1 d with delirium, $19,682 for 2–3 d with delirium, and $75,833 for > 3 d with delirium; p < 0.0001); this remained highly significant even after adjusting for PICU length of stay (p < 0.0001). After controlling for age, gender, severity of illness, and PICU length of stay, delirium was associated with an 85% increase in PICU costs (p < 0.0001).

Conclusions:
Pediatric delirium is associated with a major increase in PICU costs. Further research directed at prevention and treatment of pediatric delirium is essential to improve outcomes in this population and could lead to substantial healthcare savings.
Safety of Immediate-Release Nifedipine
Authors: Means Laura , Benken Scott T. , Tesoro Eljim P. 
Published: August 2016

Abstract:
Nifedipine immediate release (IR) is a short-acting dihydropyridine calcium channel blocker historically used for hypertensive crisis, but its use has decreased because of reports of adverse reactions such as myocardial infarction (MI), arrhythmias, and stroke. This was a retrospective evaluation of the safety of nifedipine IR in 122 patients at an academic medical center from January 1, 2009, to December 31, 2014. Patients were separated into high- and low-risk groups. High risk was defined as a medical history significant for arrhythmia, MI, or stroke. The primary outcome was a comparison of the composite incidence of nifedipine-associated adverse events including the following: new cardiology consultation, sentinel arrhythmia, stroke, MI, need for blood pressure support, transition to higher levels of care, or death. A per-dose incidence of 2.4% and per-patient incidence of 7.3% in this composite endpoint were found, with no differences between the groups. Patients received median doses of 10 mg and follow-up within 2.8 hours. There were no cases of death in either group. Although nifedipine IR may cause major adverse events, the incidence seems lower than previously believed. Future research is warranted to evaluate whether nifedipine IR may be an option to treat elevated blood pressure in hospitalized patients.
Enhanced Platelet Response to Clopidogrel in Abcc3-deficient Mice Due to Its Increased Bioactivation
Authors: Tai Ting , Mi Qiong-Yu , Ji Jin-Zi , Yin Qian , Pan Yu-Qin , Zhang Meng-Ran , Huang Bei-Bei , Xie Hong-Guang 
Published: August 2016

Abstract:
Resistance of the patient to clopidogrel (an inactive prodrug) has been recently reported to be associated with increased messenger RNA expression of ABCC3 that encodes MRP3 (multidrug resistance–associated protein 3). However, there is no evidence showing the effects of MRP3 on altered platelet responses to clopidogrel and their underlying mechanisms. To further clarify whether the presence or absence of Mrp3 could affect the formation of and response to clopidogrel active metabolite (CAM) in Abcc3 knockout (KO) versus wild-type (WT) mice, we determined pharmacokinetic profiles of clopidogrel and CAM and measured inhibition of adenosine diphosphate–induced platelet aggregation by clopidogrel after administration of a single oral dose of clopidogrel to KO and WT mice, respectively. Results indicated that Abcc3 KO mice exhibited increased formation of CAM and greater systemic exposure to clopidogrel and enhanced inhibition of adenosine diphosphate–induced platelet aggregation ex vivo by clopidogrel when compared with well-matched WT mice. We conclude that Abcc3 KO mice have enhanced platelet response to clopidogrel due to increased formation of CAM.
Common prepubertal vulvar conditions
Authors: Vilano Samantha E. , Robbins Cynthia L. 
Published: August 2016

Purpose of review
The purpose of this article is to provide an update for the GP on selected common vulvar concerns in prepubertal girls. Presentation, diagnostic criteria, and management of common vulvar conditions will be described. The following conditions are frequently encountered and may pose diagnostic or management challenges if unrecognized.

Recent findings
The article is a review of current literature on pediatric vulvar conditions and was conducted through searching PubMed and published books on this topic. Areas of interest frequently encountered by providers are presented, including vulvovaginitis, genital ulcers, lichen sclerosus, and labial adhesions along with the most recent North American Society for Pediatric and Adolescent Gynecology recommendations for diagnosis and management.

Summary
Vulvar complaints in prepubertal girls are common. Many present with nonspecific symptoms and consequently, the diagnosis may be missed or delayed. Prompt recognition improves long-term outcomes and importantly, provides a positive introduction to longitudinal women's health for young girls.
Evaluation of an Amino Acid−Based Formula in Infants Not Responding to Extensively Hydrolyzed Protein Formula
Authors: Vanderhoof Jon , Moore Nancy , de Boissieu Delphine 
Published: August 2016

ABSTRACTNearly 2% to 3% of infants and children younger than 3 years have confirmed cow's milk protein allergy with multiple clinical presentations including atopic dermatitis (AD), diarrhea, and vomiting/spitting up. Although most infants with cow's milk protein allergy experience clinical improvement with the use of an extensively hydrolyzed (EH) formula, highly sensitive infants may require an amino acid−based formula. In this observational, prospective study, 30 infants (1–12 months of age) with a history of weight loss and persistent allergic manifestations while on an EH formula were provided an amino acid−based formula for 12 weeks. Mean weight gain (z score change) improved +0.43 ± 0.28 (mean ± standard deviation) after the 12‐week feeding period. Improvement was observed for many allergic symptoms including significant decreases in AD severity (P = 0.02). These results indicate the new amino acid–based infant formula supported healthy weight gain and improvement in allergic manifestations in infants not responding to EH formulas.
Lingering representations of stimulus history at encoding influence recall organization
Authors: Chan Stephanie C.Y. , Applegate Marissa C. , Morton Neal W , Polyn Sean M. , Norman Kenneth A. 
Published: August 2016

AbstractSeveral prominent theories posit that information about recent experiences lingers in the brain and organizes memories for current experiences, by forming a temporal context that is linked to those memories at encoding. According to these theories, if the thoughts preceding an experience X resemble the thoughts preceding an experience Y, then X and Y should show an elevated probability of being recalled together. We tested this prediction by using multi-voxel pattern analysis (MVPA) of fMRI data to measure neural evidence for lingering processing of preceding stimuli. As predicted, memories encoded with similar lingering thoughts (about the category of preceding stimuli) were more likely to be recalled together, thereby showing that the “fading embers” of previous stimuli help to organize recall.
Gene expression markers of Tumor Infiltrating Leukocytes
Authors: Danaher Patrick , Warren Sarah , Dennis Lucas , D’Amico Leonard , White Andrew , Disis Mary L. , Geller Melissa A. , Odunsi Kunle , Beechem Joseph , Fling Steven P. 
Published: August 2016

AbstractBackgroundAssays of the abundance of immune cell populations in the tumor microenvironment promise to inform immune oncology research and the choice of immunotherapy for individual patients. We propose to measure the intratumoral abundance of various immune cells populations with gene expression. In contrast to IHC and flow cytometry, gene expression assays yield high information content from a clinically practical workflow. Previous studies of gene expression in purified immune cells have reported hundreds of genes showing enrichment in a single cell type, but the utility of these genes in tumor samples is unknown. We describe a novel statistical method for using co-expression patterns in large tumor gene expression datasets to validate previously reported candidate cell type marker genes, and we use this method to winnow previously published gene lists down to a subset of high confidence marker genes.MethodsWe use co-expression patterns in 9986 samples from The Cancer Genome Atlas (TCGA) to validate previously reported cell type marker genes. We compare immune cell scores derived from these genes to measurements from flow cytometry and immunohistochemistry. We characterize the reproducibility of our cell scores in replicate runs of RNA extracted from FFPE tumor tissue.ResultsWe identify a list of 60 marker genes whose expression levels quantify 14 immune cell populations. Cell type scores calculated from these genes are concordant with flow cytometry and IHC readings, show high reproducibility in replicate RNA samples from FFPE tissue, and reveal an intricate picture of the immune infiltrate in TCGA. Most genes previously reported to be enriched in a single cell type have co-expression patterns inconsistent with cell type specificity.ConclusionsDue to their concise gene set, computational simplicity and utility in tumor samples, these cell type gene signatures may be useful in future discovery research and clinical trials to understand how tumors and therapeutic intervention shape the immune response.
Exploring evolutionary relationships across the genome using topology weighting
Authors: Martin Simon H. , Van Belleghem Steven M. 
Published: August 2016

AbstractWe introduce the concept of topology weighting, a method for quantifying relationships between taxa that are not necessarily monophyletic, and visualising how these relationships change across the genome. A given set of taxa can be related in a limited number of ways, but if each taxon is represented by multiple sequences, the number of possible topologies becomes very large. Topology weighting reduces this complexity by quantifying the contribution of each ‘taxon topology’ to the full tree. We describe our method for topology weighting by iterative sampling of sub-trees (Twisst), and test it on both simulated and real genomic data. Overall, we show that this is an informative and versatile approach, suitable for exploring relationships in almost any genomic dataset.Scripts to implement the method described are available atgithub.com/simonhmartin/twisst.
iELVis: An open source MATLAB toolbox for localizing and visualizing human intracranial electrode data
Authors: Groppe David M. , Bickel Stephan , Dykstra Andrew R. , Wang Xiuyuan , Mégevand Pierre , Mercier Manuel R. , Lado Fred A. , Mehta Ashesh D. , Honey Christopher J. 
Published: August 2016

AbstractBackgroundIntracranial electrical recordings (iEEG) and brain stimulation (iEBS) are invaluable human neuroscience methodologies. However, the value of such data is often unrealized as many laboratories lack tools for localizing electrodes relative to anatomy. To remedy this, we have developed a MATLAB toolbox for intracranial electrode localization and visualization, iELVis.New MethodiELVis uses existing tools (BioImage Suite, FSL, and FreeSurfer) for preimplant magnetic resonance imaging (MRI) segmentation, neuroimaging coregistration, and manual identification of electrodes in postimplant neuroimaging.Subsequently, iELVis implements methods for correcting electrode locations for postimplant brain shift with millimeter-scale accuracy and provides interactive visualization on 3D surfaces or in 2D slices with optional functional neuroimaging overlays. iELVis also localizes electrodes relative to FreeSurfer-based atlases and can combine data across subjects via the FreeSurfer average brain.ResultsIt takes 30-60 minutes of user time and 12-24 hours of computer time to localize and visualize electrodes from one brain. We demonstrate iELVis’s functionality by showing that three methods for mapping primary hand somatosensory cortex (iEEG, iEBS, and functional MRI) provide highly concordant results.Comparison with Existing MethodsiELVis is the first public software for electrode localization that corrects for brain shift, maps electrodes to an average brain, and supports neuroimaging overlays. Moreover, its interactive visualizations are powerful and its tutorial material is extensive.ConclusionsiELVis promises to speed the progress and enhance the robustness of intracranial electrode research. The software and extensive tutorial materials are freely available as part of the EpiSurg software project:https://github.com/episurg/episurg
Biotinylation by antibody recognition - A novel method for proximity labeling
Authors: Bar Daniel Z , Atkatsh Kathleen , Tavarez Urraca , Erdos Michael R , Gruenbaum Yosef , Collins Francis S 
Published: August 2016

AbstractIdentification of protein-protein interactions is a major goal of biological research. Despite technical advances over the last two decades, important but still largely unsolved challenges include the high-throughput detection of interactions directly from primary tissue and the identification of interactors of insoluble proteins that form higher-order structures. We have developed a novel, proximity-based labeling approach that uses antibodies to guide biotin deposition onto adjacent proteins in fixed cells and primary tissues. We used this method to profile the dynamic interactome of lamin A/C in multiple cell and tissue types under various treatment conditions. Our results suggest a considerable variation in the composition of the nuclear envelope of different tissues. Of note, DNA damage response proteins Ku70 and Ku80 are more abundant in the vicinity of lamin A/C after thermal stress. This increased affinity also applies to the progerin isoform, potentially contributing to the premature aging phenotype of Hutchinson-Gilford progeria syndrome. The ability to detect protein-protein interactions in intact tissues, and to compare affinities quantitatively under different conditions or in the presence of disease mutations, can provide a new window into cell biology and disease pathogenesis.
FUN-LDA: A LATENT DIRICHLET ALLOCATION MODEL FOR PREDICTING TISSUE-SPECIFIC FUNCTIONAL EFFECTS OF NONCODING VARIATION
Authors: Backenroth Daniel , He Zihuai , Kiryluk Krzysztof , Boeva Valentina , Pethukova Lynn , Khurana Ekta , Christiano Angela , Buxbaum Joseph D. , Ionita-Laza Iuliana 
Published: August 2016

ABSTRACTWe describe here a new method based on a latent Dirichlet allocation model for predicting functional effects of noncoding genetic variants in a cell type and tissue specific way (FUN-LDA) by integrating diverse epigenetic annotations for specific cell types and tissues from large scale epige-nomics projects such as ENCODE and Roadmap Epigenomics. Using this unsupervised approach we predict tissue-specific functional effects for every position in the human genome. We demonstrate the usefulness of our predictions using several validation experiments. Using eQTL data from several sources, including the Genotype-Tissue Expression project, the Geuvadis project and Twin-sUK cohort, we show that eQTLs in specific tissues tend to be most enriched among the predicted functional variants in relevant tissues in Roadmap. We further show how these integrated functional scores can be used to derive the most likely cell/tissue type causally implicated for a complex trait using summary statistics from genome-wide association studies, and estimate a tissue-based correlation matrix of various complex traits. We find large enrichment of heritability in functional components of relevant tissues for various complex traits, with FUN-LDA yielding the highest enrichment estimates relative to existing methods. Finally, using experimentally validated functional variants from the literature and variants possibly implicated in disease by previous studies, we rigorously compare FUN-LDA to state-of-the-art functional annotation methods such as GenoSky-line, ChromHMM, Segway, and IDEAS, and show that FUN-LDA has better prediction accuracy and higher resolution compared to these methods. In summary, we describe a new approach and perform rigorous comparisons with the most commonly used functional annotation methods, providing a valuable resource for the community interested in the functional annotation of noncoding variants. Scores for each position in the human genome and for each ENCODE/Roadmap tissue are available fromhttp://www.columbia.edu/~ii2135/funlda.html.
Neuronal firing rates diverge during REM and homogenize during non-REM
Authors: Miyawaki Hiroyuki , Watson Brendon , Diba Kamran 
Published: August 2016

AbstractNeurons fire at highly variable innate rates and recent evidence suggests that low and high firing rate neurons display different plasticity and dynamics. Furthermore, recent publications imply possibly differing rate-dependent effects in hippocampus versus neocortex, but those analyses were carried out separately and with possibly important differences. To more effectively synthesize these questions, we analyzed the firing rate dynamics of populations of neurons in both hippocampal CA1 and frontal cortex under one framework that avoids pitfalls of previous analyses and accounts for regression-to-the-mean. We observed remarkably consistent effects across these regions. While rapid eye movement (REM) sleep was marked by decreased hippocampal firing and increased neocortical firing, in both regions firing rates distributions widened during REM due to differential changes in high-firing versus low-firing cells in parallel with increased interneuron activity. In contrast, upon non-REM (NREM) sleep, firing rate distributions narrowed while interneuron firing decreased. Interestingly, hippocampal interneuron activity closely followed the patterns observed in neocortical principal cells rather than the hippocampal principal cells, suggestive of long-range interactions. Following these undulations in variance, the net effect of sleep was a decrease in firing rates. These decreases were greater in lower-firing hippocampal neurons but higher-firing frontal cortical neurons, suggestive of greater plasticity in these cell groups. Our results across two different regions and with statistical corrections indicate that the hippocampus and neocortex show a mixture of differences and similarities as they cycle between sleep states with a unifying characteristic of homogenization of firing during NREM and diversification during REM.Significance StatementMiyawaki and colleagues analyze firing patterns across low-firing and high-firing neurons in the hippocampus and the frontal cortex throughout sleep in a framework that accounts for regression-to-the-mean. They find that in both regions REM sleep activity is relatively dominated by high-firing neurons and increased inhibition, resulting in a wider distribution of firing rates. On the other hand, NREM sleep produces lower inhibition, and results in a more homogenous distribution of firing rates. Integration of these changes across sleep results in net decrease of firing rates with largest drops in low-firing hippocampal pyramidal neurons and high-firing neocortical principal neurons. These findings provide insights into the effects and functions of different sleep stages on cortical neurons.
Inferring Fitness Landscapes and Selection on Phenotypic States from Single-Cell Genealogical Data
Authors: Nozoe Takashi , Kussell Edo , Wakamoto Yuichi 
Published: August 2016

AbstractRecent advances in single-cell time-lapse microscopy have revealed non-genetic heterogeneity and temporal fluctuations of cellular phenotypes. While different phenotypic traits such as abundance of growth-related proteins in single cells may have differential effects on the reproductive success of cells, rigorous experimental quantification of this process has remained elusive due to the complexity of single cell physiology within the context of a proliferating population. We introduce and apply a practical empirical method to quantify the fitness landscapes of arbitrary phenotypic traits, using genealogical data in the form of population lineage trees which can include phenotypic data of various kinds. Our inference methodology for fitness landscapes determines how reproductivity is correlated to cellular phenotypes, and provides a natural generalization of bulk growth rate measures for single-cell histories. Using this technique, we quantify the strength of selection acting on different cellular phenotypic traits within populations, which allows us to determine whether a change in population growth is caused by individual cells’ response, selection within a population, or by a mixture of these two processes. By applying these methods to single-cell time-lapse data of growing bacterial populations that express a resistance-conferring protein under antibiotic stress, we show how the distributions, fitness landscapes, and selection strength of single-cell phenotypes are affected by the drug. Our work provides a unified and practical framework for quantitative measurements of fitness landscapes and selection strength for any statistical quantities definable on lineages, and thus elucidates the adaptive significance of phenotypic states in time series data. The method is applicable in diverse fields, from single cell biology to stem cell differentiation and viral evolution.
The Chloroplast Protease AMOS1/EGY1 Affects Phosphate Homeostasis under Phosphate Stress
Authors: Yu Fang Wei , Zhu Xiao Fang , Li Guang Jie , Kronzucker Herbert J. , Shi Wei Ming 
Published: August 2016

Abstract
Plastid intramembrane proteases in Arabidopsis (Arabidopsis thaliana) are involved in jasmonic acid biosynthesis, chloroplast development, and flower morphology. Here, we show that Ammonium-Overly-Sensitive1 (AMOS1), a member of the family of plastid intramembrane proteases, plays an important role in the maintenance of phosphate (P) homeostasis under P stress. Loss of function of AMOS1 revealed a striking resistance to P starvation. amos1 plants displayed retarded root growth and reduced P accumulation in the root compared to wild type (Col-0) under P-replete control conditions, but remained largely unaffected by P starvation, displaying comparable P accumulation and root and shoot growth under P-deficient conditions. Further analysis revealed that, under P-deficient conditions, the cell wall, especially the pectin fraction of amos1, released more P than that of wild type, accompanied by a reduction of the abscisic acid (ABA) level and an increase in ethylene production. By using an ABA-insensitive mutant, abi4, and applying ABA and ACC exogenously, we found that ABA inhibits cell wall P remobilization while ethylene facilitates P remobilization from the cell wall by increasing the pectin concentration, suggesting ABA can counteract the effect of ethylene. Furthermore, the elevated ABA level and the lower ethylene production also correlated well with the mimicked P deficiency in amos1. Thus, our study uncovers the role of AMOS1 in the maintenance of P homeostasis through ABA-antagonized ethylene signaling.