bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANKRD22 promotes progression of non-small cell lung cancer through transcriptional up-regulation of E2F1
Authors: Yin Jun , Fu Wenfan , Dai Lu , Jiang Zeyong , Liao Hongying , Chen Wenbin , Pan Lei , Zhao Jian 
Published: June 2017

AbstractLung cancer is the leading cause of death among all malignancies due to rapid tumor progression and relapse; however, the underlying molecular mechanisms of tumor progression are unclear. In the present study, we identified ANKRD22 as a novel tumor-associated gene in non-small cell lung cancer (NSCLC). According to the clinical correlation analysis, ANKRD22 was highly expressed in primary cancerous tissue compared with adjacent cancerous tissue, and high expression levels of ANKRD22 were significantly correlated with relapse and short overall survival time. Knockdown and overexpression analysis revealed that ANKRD22 promoted tumor progression by increasing cell proliferation. In xenograft assays, knockdown of ANKRD22 or in vivo treatment with ANKRD22 siRNA inhibited tumor growth. Furthermore, ANKRD22 was shown to participate in the transcriptional regulation of E2F1, and ANKRD22 promoted cell proliferation by up-regulating the expression of E2F1 which enhanced cell cycle progression. Therefore, our studies indicated that ANKRD22 up-regulated the transcription of E2F1 and promoted the progression of NSCLC by enhancing cell proliferation. These findings suggest that ANKRD22 could potentially act as a novel therapeutic target for NSCLC.
Sedimentation and mobility of PDCs: a reappraisal of ignimbrites’ aspect ratio
Authors: Giordano Guido , Doronzo Domenico M. 
Published: June 2017

AbstractThe aspect ratio of ignimbrites is a commonly used parameter that has been related to the energy of the parent pyroclastic density currents (PDCs). However this parameter, calculated as the ratio between the average thickness and the average lateral extent of ignimbrites, does not capture fundamental differences in pyroclastic flow mobility nor relates to lithofacies variations of the final deposits. We herein introduce the “topological aspect ratio” (ARt) as the ratio of the local deposit thickness (Ht) to the distance between the local site and the maximum runout distance (Lt), where Ht is a proxy for the PDC tendency to deposit, and Lt a proxy for the PDC mobility or its tendency to further transport the pyroclastic material. The positive versus negative spatial gradient d(ARt)/dx along flow paths discriminate zones where PDCs are forced (i.e. where they transport the total energy under the action of mass discharge rate) from zones where they are inertial (i.e. where they transport the total energy under the action of viscous or turbulent fluidization). Though simple to apply, the topological aspect ratio and its spatial gradient are powerful descriptors of the interplay between sedimentation and mobility of PDCs, and of the resulting lithofacies variations.
Strategies for the Synthesis of N-Arylammonium Salts
Authors: Diesendruck Charles , Arava Shlomy 
Published: June 2017

The N-arylation of tertiary amines to provide sp3 quaternary ammonium salts is a challenge in organic chemistry. To date, no general method for such arylations has been established. Here, we summarize a variety of strategies that have been tested, starting with harsh nucleophilic aromatic substitutions, through to the use of copper catalysis and the application of strong electrophiles, such as phenyl cations and benzynes. The achievements and limitations of each method are summarized, and the challenges yet to be met in the synthesis of charged ammonium compounds are described.1 Introduction2 Alkylation of Anilines: The Menshutkin Reaction3 Arylations3.1 Nucleophilic Aromatic Substitutions by Tertiary Amines3.2 Preparation of N-Arylpyridinum Salts from Zincke and Pyrylium Salts3.3 Arylations Using Phenyl Cations3.4 Copper-Catalyzed Arylation of N-Heteroarenes3.5 Benzynes as Aryl Electrophiles4 Conclusions and Perspective
Angles, Traction, and Time after Delivery of Fetal Head: Interobserver Variation of Novel Visual Analogs
Authors: Ankumah Nana-Ama , Chauhan Vidya , Pedroza Claudia , McLaren Rodney , Blackwell Sean , Chauhan Suneet 
Published: June 2017

Objective The objective was to ascertain interobserver variability for assessment of Angles of fetal head manipulation, Traction exerted on the fetal head, and Time interval from the emergence of the head to the feet (ATT) at vaginal delivery.
Materials and Methods Singleton pregnancies of ≥36 weeks with vaginal delivery were included. Visual analogs were created to assess angles and traction, and mobile phone stopwatch was used to assess the time interval. The intraclass coefficient (ICC) was calculated to determine interobserver variability.
Results Thirty-seven deliveries were analyzed. For the two observers, the median angle for downward manipulation was –5° vs –20° (interquartile range [IQR], –5 to –5 vs –30 to –10), ICC of 0.09 (poor agreement; 95% confidence interval [CI] –0.09, 0.32), and that for upward manipulation was 10° vs 20° (IQR, 10–15 vs 10–30), ICC of 0.25 (poor agreement; 95% CI –0.05, 0.52). ICC for lateral manipulation could not be calculated as it was not noted in 98% of deliveries. Mean traction was 2.5 versus 5.0, ICC of 0.36 (poor agreement; 95% CI –0.09, 0.72). The mean time intervals were 14.9 versus 14.0 seconds, ICC of 0.94 (excellent agreement, 95% CI 0.88–0.97).
Conclusion With exception of time interval, interobserver agreement was poor in estimation of fetal head manipulation and traction.
S2k-Leitlinie: Tuberkulose im Erwachsenenalter
Authors: Schaberg Tom , Bauer Torsten , Brinkmann Folke , Diel Roland , Feiterna-Sperling Cornelia , Haas Walter , Hartmann Pia , Hauer Barbara , Heyckendorf Jan , Lange Christoph , Nienhaus Albert , Otto-Knapp Ralf , Priwitzer Martin , Richter Elvira , Rumetshofer Rudolf , Schenkel Karl , Schoch Otto , Schönfeld Nicolas , Stahlmann Ralf 
Published: June 2017

ZusammenfassungIn Deutschland ist seit 2015 ein deutlicher Anstieg der gemeldeten Tuberkulosefälle zu verzeichnen. Zurückzuführen ist dieser vor allem auf die aktuell vermehrte Migration. Durch die niedrige Inzidenz in den vorhergehenden Jahren konzentriert sich die Erfahrung im Umgang mit Tuberkulose immer mehr auf spezialisierte Zentren. Pneumologen wie auch andere Fachbereiche sind nun aber wieder häufiger an der Behandlung einer Tuberkulose beteiligt, sodass Fachwissen zur Standardtherapie wie auch zu selteneren Therapiesituationen benötigt wird. Die aktuelle Leitlinie zur Diagnostik und Therapie, einschließlich Chemoprävention und -prophylaxe im Erwachsenenalter fasst den derzeitigen Wissensstand zusammen und passt die Empfehlungen an die Situation in Deutschland an. Realisiert wurde die AWMF S2k-Leitlinie durch das Deutsche Zentralkomitee zur Bekämpfung der Tuberkulose e. V. (DZK) im Auftrag der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V. (DGP). Zur Behandlung der Tuberkulose im pädiatrischen Bereich wird in Kürze eine eigenständige Leitlinie der entsprechenden Fachgesellschaften veröffentlicht. Im Vergleich zu den Empfehlungen von 2012 sind eigenständige Kapitel zur Labordiagnostik und zum therapeutischen Medikamentenmanagement entstanden. Die Kapitel Mehrfachresistenzen gegen Medikamente der Standardtherapie, HIV-Koinfektion und die Übersicht der Arzneimittel wurden erweitert. Die umfangreiche Überarbeitung der Empfehlungen soll Ärzten und auch anderen Beschäftigten im Gesundheitswesen helfen, den aktuellen Herausforderungen im Umgang mit dem selten gewordenen Tuberkuloseerreger zu begegnen.
Relationship of Radiographic Osteoarthritis Severity with Treatment Outcomes after Imaging-Guided Knee Injections: A Prospective Outcomes Study
Authors: Miletic Ivan , Agten Christoph , Sutter Reto , Pfirrmann Christian , Peterson Cynthia 
Published: June 2017

Introduction To be able to predict which patients are more likely to have a positive treatment outcome, the purpose of this study is 1: To compare outcomes after intra-articular corticosteroid knee injections with the Kellgren and Lawrence (KL) 5 and 3 grading systems for knee osteoarthritis, the Osteoarthritis Research Society International (OARSI) grading system and actual joint space measurements; and 2: To compare the reliability of these grading systems.
Materials and Methods Knee radiographs of 117 patients who received intra-articular corticosteroid injections were independently evaluated by two radiologists blinded to the outcome. Evaluation included the KL5, KL3, OARSI systems and actual joint space widths. The numerical rating scale for pain was collected at baseline and along with the Patient’s Global Impression of Change on day 1, in week 1 and in month 1. The number of ‘improved’ patients was compared between the OA grades using the Chi-square test. Logistic regression determined which findings were predictive for improvement. Agreement was assessed using Kappa statistics and the intraclass correlation coefficient (ICC).
Results Patients with OARSI grade 2 reported the highest rates of ‘improvement’ at all time points, which was significant on day 1 (p = 0.004). No relationship with improvement was found with KL5, KL3 or actual joint space measurements. Patients with OARSI grade 2 were 8 times more likely to report improvement on day 1 (p = 0.024). Reliability was best for joint space measurements (ICC = 0.812 – 0.882), followed by the OARSI.
Conclusion The OARSI for joint space narrowing grade 2 (34 – 66 % narrowing) was linked with a better outcome on day 1 with trends in week 1 and month 1. The reliability of the OARSI was better than the KL5 or KL3 systems.
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Development of a High-Performance Liquid Chromatographic Method for Asiaticoside Quantification in Different Skin Layers after Topical Application of a Centella asiatica Extract
Authors: da Rocha Priscila , Souza Bruno , Andrade Lígia , Marreto Ricardo , Lima Eliana , Taveira Stephânia 
Published: June 2017

AbstractThe topical application of Centella asiatica extract has been commonly used for many different purposes but especially for cosmetic use in the treatment of gynoid lipodystrophy. Asiaticoside, the most active component in this extract, is responsible for its therapeutic activities. However, little is known to date about asiaticoside skin penetration. Thus, an analytical method for asiaticoside quantification in different skin layers after the topical application of C. asiatica extract was developed and skin permeation studies were performed with the plant extract to apply the analytical method developed. An extraction procedure to recover asiaticoside from the biological matrix was also developed. Asiaticoside was assayed by HPLC/UV (high-performance liquid chromatography-ultraviolet detection) using a gradient of ACN (acetonitrile) and 0.2% phosphoric acid (flow rate of 1.0 mL/min). The analytical procedure was validated according to U. S. Food and Drug Administration guidelines. Selectivity was shown, as endogenous skin components did not interfere with the asiaticoside peak. Analytical curve was linear (3 to 60 µg/mL) and the lower limit of quantification was determined (3 µg/mL). Asiaticoside recoveries from skin samples were 95.1% and 66.7% for the stratum corneum and remaining skin, respectively. After 48 h of in vitro permeation studies, a substantial amount of asiaticoside was quantified in the skin layers. The presence of asiaticoside was also detected in the receptor solution of Franz diffusion cells after 48 h (5.81 ± 1.00 µg/mL). The method was reliable and reproducible for asiaticoside quantification in skin samples, thereby making it possible to determine the cutaneous penetration profile of this drug in permeation studies.
On the status of functional categories (heads and phrases)
Authors: Cinque Guglielmo 
Published: June 2017

AbstractIn this article I would like to revisit one aspect of the structure of the functional sequence of the clause in light of certain recent developments, in particularKayne’s (2016)proposal that all heads are necessarily silent. I will also discuss the possibility that (certain) silent heads may be endowed with single features that denote complex notions taking progressive aspect as a case in point.
FALCON: a toolbox for the fast contextualization of logical networks
Authors: De Landtsheer Sébastien , Trairatphisan Panuwat , Lucarelli Philippe , Sauter Thomas 
Published: June 2017

Abstract

Motivation
Mathematical modelling of regulatory networks allows for the discovery of knowledge at the system level. However, existing modelling tools are often computation-heavy and do not offer intuitive ways to explore the model, to test hypotheses or to interpret the results biologically.

Results
We have developed a computational approach to contextualize logical models of regulatory networks with biological measurements based on a probabilistic description of rule-based interactions between the different molecules. Here, we propose a Matlab toolbox, FALCON, to automatically and efficiently build and contextualize networks, which includes a pipeline for conducting parameter analysis, knockouts and easy and fast model investigation. The contextualized models could then provide qualitative and quantitative information about the network and suggest hypotheses about biological processes.

Availability and implementation
FALCON is freely available for non-commercial users on GitHub under the GPLv3 licence. The toolbox, installation instructions, full documentation and test datasets are available at https://github.com/sysbiolux/FALCON. FALCON runs under Matlab (MathWorks) and requires the Optimization Toolbox.

Supplementary information
Supplementary data are available at Bioinformatics online.
ClusterSignificance: a bioconductor package facilitating statistical analysis of class cluster separations in dimensionality reduced data
Authors: Serviss Jason T , Gådin Jesper R , Eriksson Per , Folkersen Lasse , Grandér Dan 
Published: June 2017

Abstract

Summary
Multi-dimensional data generated via high-throughput experiments is increasingly used in conjunction with dimensionality reduction methods to ascertain if resulting separations of the data correspond with known classes. This is particularly useful to determine if a subset of the variables, e.g. genes in a specific pathway, alone can separate samples into these established classes. Despite this, the evaluation of class separations is often subjective and performed via visualization. Here we present the ClusterSignificance package; a set of tools designed to assess the statistical significance of class separations downstream of dimensionality reduction algorithms. In addition, we demonstrate the design and utility of the ClusterSignificance package and utilize it to determine the importance of long non-coding RNA expression in the identity of multiple hematological malignancies.

Availability and implementation
ClusterSignificance is an R package available via Bioconductor (https://bioconductor.org/packages/ClusterSignificance) under GPL-3.

Supplementary information
Supplementary data are available at Bioinformatics online.
Genomic evidence of globally widespread admixture from polar bears into brown bears during the last ice age
Authors: Cahill James A. , Heintzman Peter D. , Harris Kelley , Teasdale Matthew , Kapp Joshua , E Rodrigues Soares André , Stirling Ian , Bradley Daniel , Edwards Ceiridwen J. , Kisleika Aliaksandr A. , Malev Alexander V. , Monaghan Nigel , Green Richard E. , Shapiro Beth 
Published: June 2017

AbstractRecent genomic analyses have provided substantial evidence for past periods of gene flow from polar bears (Ursus maritimus) into Alaskan brown bears (Ursus arctos), with some analyses suggesting a link between climate change and genomic introgression. However, because it has only been possible to sample bears from the present day, the timing, frequency, and evolutionary significance of this admixture remains unknown. Here, we analyze genomic DNA from three additional and geographically distinct brown bear populations, including two that lived temporally close to the peak of the last ice age. We find evidence of admixture in all three populations, suggesting that admixture between these species has been common in their recent evolutionary history. In addition, analyses of ten fossil bears from the now-extinct Irish population indicate that admixture peaked during the last ice age, when brown bear and polar bear ranges overlapped. Following this peak, the proportion of polar bear ancestry in Irish brown bears declined rapidly until their extinction. Our results support a model in which ice age climate change created geographically widespread conditions conducive to admixture between polar bears and brown bears, as is again occurring today. We postulate that this model will be informative for many admixing species pairs impacted by climate change. Our results highlight the power of paleogenomes to reveal patterns of evolutionary change that are otherwise masked with only contemporary data.
Learning Edge Rewiring in EMT From Single Cell Data
Authors: Krishnaswamy Smita , Zivanovic Nevena , Sharma Roshan , Pe’er Dana , Bodenmiller Bernd 
Published: June 2017

AbstractCellular regulatory networks are not static, but continuously reconfigure in response to stimuli via alterations in gene expression and protein confirmations. However, typical computational approaches treat them as static interaction networks derived from a single experimental time point. Here, we provide a method for learning the dynamic modulation, orrewiringof pairwise relationships (edges) from a static single-cell data. We use the epithelial-to-mesenchymal transition (EMT) in murine breast cancer cells as a model system, and measure mass cytometry data three days after induction of the transition by TGFβ. We take advantage of transitional rate variability between cells in the data by deriving a pseudo-time EMT trajectory. Then we propose methods for visualizing and quantifying time-varying edge behavior over the trajectory and use these methods: TIDES (Trajectory Imputed DREMI scores), and measure of edge dynamism (3DDREMI) to predict and validate the effect of drug perturbations on EMT.
Mapping the drivers of within-host pathogen evolution using massive data sets
Authors: Palmer Duncan S. , Turner Isaac , Fidler Sarah , Frater John , Goulder Philip , Goedhals Dominique , Huang Kuan-Hsiang Gary , Oxenius Annette , Phillips Rodney , Shapiro Roger , van Vuuren Cloete , McLean Angela R. , McVean Gil 
Published: June 2017

AbstractDifferences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Identifying such interactions can potentially be achieved through genetic association studies. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses. Moreover, the multiple testing burden of interaction scanning can potentially limit power. To address these problems, we have developed a Bayesian approach for detecting host influences on pathogen evolution that makes use of vast existing data sets of pathogen diversity to improve power and control for stratification. The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors. Using simulations and empirical analysis of drug-induced selection on the HIV-1 genome we demonstrate the power of the method to recover known associations and show greatly improved precision-recall characteristics compared to other approaches. We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.
Distinct contributions of three GABAergic interneuron populations to a mouse model of Rett Syndrome
Authors: Mossner James M. , Batista-Brito Renata , Pant Rima , Cardin Jessica A. 
Published: June 2017

AbstractBackgroundRett Syndrome is a devastating neurodevelopmental disorder resulting from mutations in the gene MeCP2. MeCP2 is a transcriptional regulator active in many cell types throughout the brain. However, mutations of MeCP2 restricted to GABAergic cell types largely replicate the behavioral phenotypes associated with mouse models of Rett Syndrome, suggesting a key role for inhibitory interneurons in the pathophysiology underlying this disorder.MethodsWe generated conditional deletions of MeCP2 from each of three major classes of GABAergic interneurons, the parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP)-expressing cells, along with a pan-interneuron deletion from all three GABAergic populations. We examined seizure incidence, mortality, and performance on several key behavioral assays.ResultsWe find that each interneuron class makes a contribution to the seizure phenotype associated with Rett Syndrome. PV, SOM, and VIP interneurons made partially overlapping contributions to deficits in motor behaviors. We find little evidence for elevated anxiety associated with any of the conditional deletions. However, MeCP2 deletion from VIP interneurons causes a unique deficit in marble burying. Furthermore, VIP interneurons make a distinct contribution to deficits in social behavior.ConclusionsWe find an unanticipated contribution of VIP interneuron dysfunction to the MeCP2 loss-of-function model of Rett Syndrome. Together, our findings suggest a complex interaction between GABAergic dysfunction and behavioral phenotypes in this neurodevelopmental disorder.
Positively Selected Enhancer Elements Endow Tumor Cells with Metastatic Competence
Authors: Morrow James J. , Bayles Ian , Funnell Alister PW , Miller Tyler E. , Saiakhova Alina , Lizardo Michael M. , Bartels Cynthia F. , Kapteijn Maaike Y. , Hung Stevephen , Mendoza Arnulfo , Chee Daniel R. , Myers Jay T. , Allen Frederick , Gambarotti Marco , Righi Alberto , DiFeo Analisa , Rubin Brian P. , Huang Alex Y. , Meltzer Paul S. , Helman Lee J. , Picci Piero , Versteeg Henri , Stamatoyannopoulos John , Khanna Chand , Scacheri Peter C. 
Published: June 2017

AbstractMetastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumorigenesis. Here, we investigate the contribution of enhancer elements to the metastatic phenotype of osteosarcoma. Through epigenomic profiling, we identify substantial differences in enhancer activity between primary and metastatic tumors in human patients as well as nearisogenic pairs of high and low lung-metastatic osteosarcoma cells. We term these regions Metastatic Variant Enhancer Loci (Met-VELs). We demonstrate that these Met-VELs drive coordinated waves of gene expression during metastatic colonization of the lung. Met-VELs cluster non-randomly, indicating that activity of these enhancers and their associated gene targets are positively selected. As evidence of this causal association, osteosarcoma lung metastasis is inhibited by global interruptions of Met-VEL-associated gene expression via pharmacologic BET inhibition, by knockdown of AP-1 transcription factors that occupy Met-VELs, and by knockdown or functional inhibition of individual genes activated by Met-VELs, such as F3. We further show that genetic deletion of a single Met-VEL at theF3locus blocks metastatic cell outgrowth in the lung. These findings indicate that Met-VELs and the genes they regulate play a functional role in metastasis and may be suitable targets for anti-metastatic therapies.