bluuebunny/crossref_metadata_2025 huggingface dataset:
GDISC: a web portal for integrative analysis of gene–drug interaction for survival in cancer
Authors: Spainhour John Christian Givhan , Lim Juho , Qiu Peng
Published: January 2017

Survival analysis has been applied to The Cancer Genome Atlas (TCGA) data. Although drug exposure records are available in TCGA, existing survival analyses typically did not consider drug exposure, partly due to naming inconsistencies in the data. We have spent extensive effort to standardize the drug exposure data, which enabled us to perform survival analysis on drug-stratified subpopulations of cancer patients. Using this strategy, we integrated gene copy number data, drug exposure data and patient survival data to infer gene–drug interactions that impact survival. The collection of all analyzed gene–drug interactions in 32 cancer types are organized and presented in a searchable web-portal called gene–drug Interaction for survival in cancer (GDISC). GDISC allows biologists and clinicians to interactively explore the gene-drug interactions identified in the context of TCGA, and discover interactions associated to their favorite cancer, drug and/or gene of interest. In addition, GDISC provides the standardized drug exposure data, which is a valuable resource for developing new methods for drug-specific analysis.

Availability and Implementation

GDISC is available at https://gdisc.bme.gatech.edu/.
A comprehensive quality control workflow for paired tumor-normal NGS experiments
Authors: Schroeder Christopher M , Hilke Franz J , Löffler Markus W , Bitzer Michael , Lenz Florian , Sturm Marc
Published: January 2017

Quality control (QC) is an important part of all NGS data analysis stages. Many available tools calculate QC metrics from different analysis steps of single sample experiments (raw reads, mapped reads and variant lists). Multi-sample experiments, as sequencing of tumor-normal pairs, require additional QC metrics to ensure validity of results. These multi-sample QC metrics still lack standardization. We therefore suggest a new workflow for QC of DNA sequencing of tumor-normal pairs. With this workflow well-known single-sample QC metrics and additional metrics specific for tumor-normal pairs can be calculated. The segmentation into different tools offers a high flexibility and allows reuse for other purposes. All tools produce qcML, a generic XML format for QC of -omics experiments. qcML uses quality metrics defined in an ontology, which was adapted for NGS.

Availability and Implementation

All QC tools are implemented in C ++ and run both under Linux and Windows. Plotting requires python 2.7 and matplotlib. The software is available under the ‘GNU General Public License version 2’ as part of the ngs-bits project: https://github.com/imgag/ngs-bits

Supplementary information

Supplementary data are available at Bioinformatics online.
Hierarchical sets: analyzing pangenome structure through scalable set visualizations
Authors: Pedersen Thomas Lin
Published: January 2017

Motivation

The increase in available microbial genome sequences has resulted in an increase in the size of the pangenomes being analyzed. Current pangenome visualizations are not intended for the pangenome sizes possible today and new approaches are necessary in order to convert the increase in available information to increase in knowledge. As the pangenome data structure is essentially a collection of sets we explore the potential for scalable set visualization as a tool for pangenome analysis.

Results

We present a new hierarchical clustering algorithm based on set arithmetics that optimizes the intersection sizes along the branches. The intersection and union sizes along the hierarchy are visualized using a composite dendrogram and icicle plot, which, in pangenome context, shows the evolution of pangenome and core size along the evolutionary hierarchy. Outlying elements, i.e. elements whose presence pattern do not correspond with the hierarchy, can be visualized using hierarchical edge bundles. When applied to pangenome data this plot shows putative horizontal gene transfers between the genomes and can highlight relationships between genomes that is not represented by the hierarchy. We illustrate the utility of hierarchical sets by applying it to a pangenome based on 113 Escherichia and Shigella genomes and find it provides a powerful addition to pangenome analysis.

Availability and Implementation

The described clustering algorithm and visualizations are implemented in the hierarchicalSets R package available from CRAN (https://cran.r-project.org/web/packages/hierarchicalSets)

Supplementary information

Supplementary data are available at Bioinformatics online.
Extracting morphologies from third harmonic generation images of structurally normal human brain tissue
Authors: Zhang Zhiqing , Kuzmin Nikolay V , Groot Marie Louise , de Munck Jan C
Published: January 2017

Motivation

The morphologies contained in 3D third harmonic generation (THG) images of human brain tissue can report on the pathological state of the tissue. However, the complexity of THG brain images makes the usage of modern image processing tools, especially those of image filtering, segmentation and validation, to extract this information challenging.

Results

We developed a salient edge-enhancing model of anisotropic diffusion for image filtering, based on higher order statistics. We split the intrinsic 3-phase segmentation problem into two 2-phase segmentation problems, each of which we solved with a dedicated model, active contour weighted by prior extreme. We applied the novel proposed algorithms to THG images of structurally normal ex-vivo human brain tissue, revealing key tissue components—brain cells, microvessels and neuropil, enabling statistical characterization of these components. Comprehensive comparison to manually delineated ground truth validated the proposed algorithms. Quantitative comparison to second harmonic generation/auto-fluorescence images, acquired simultaneously from the same tissue area, confirmed the correctness of the main THG features detected.

Availability and Implementation

The software and test datasets are available from the authors.

Supplementary information

Supplementary data are available at Bioinformatics online.
ANAQUIN: a software toolkit for the analysis of spike-in controls for next generation sequencing
Authors: Wong Ted , Deveson Ira W , Hardwick Simon A , Mercer Tim R
Published: January 2017

Spike-in controls are synthetic nucleic-acid sequences that are added to a user’s sample and constitute internal standards for subsequent steps in the next generation sequencing workflow.

The Anaquin software toolkit can be used to analyze the performance of spike-in controls at multiple steps during RNA sequencing or genome sequencing analysis, providing useful diagnostic statistics, data visualization and sample normalization.

Availability and Implementation

The software is implemented in C ++/R and is freely available under BSD license. The source code is available from github.com/student-t/Anaquin, binaries and user manual from www.sequin.xyz/software and R package from bioconductor.org/packages/Anaquin

Supplementary information

Supplementary data are available at Bioinformatics online.
Genome-wide analysis of DNA methylation profiles in a senescence-accelerated mouse prone 8 brain using whole-genome bisulfite sequencing
Authors: Zhang Shuai , Qin Chunxia , Cao Guoqiong , Guo Limin , Feng Chengqiang , Zhang Wensheng
Published: January 2017

Motivation

The pathogenesis of AD is complex and contributed by both genetic and environmental factors. Recent work revealed a potential link between DNA methylation and AD. However, a genome-wide study to identify potential DNA methylation sites involved in AD is still at an early stage. WGBS, an up-to-date technology, was used in this study. We investigated mouse brain genome-wide DNA methylation profiles between seven-month-old SAMP8 and SAMR1 models through deep WGBS.

Results

According to the results, the global ML slightly decreased in the SAMP8 mice than in the SAMR1 mice (4.12% versus 4.19%). A total of 1 307 172 280 clean reads were obtained. Subsequently, we identified 63 DMRs from all cases in SAMP8 mice relative to SAMR1 mice. In addition, 26 DMR-related genes were detected. GO analyses revealed that these DMR-related genes were involved in regulating the development of AD from different aspects. Finally, three differentially expressed DMR-related genes (Dlgap1, TMEM51 and Eif2ak2) that were most likely involved in AD were summarized and listed in detail. Our study provided a systematic exploration of DNA methylation profiles in SAMP8 mouse brain for the first time. These novel methylation sites may be considered strong future candidates to combat this life-threatening disease.

Availability and Implementation

The WGBS sequencing clean data and RNA-seq clean data have been deposited in the NCBI Sequence Read Archive (SRA).The accession number of WGBS is SRP097054. The accession number of RNA-seq is SRP096779.

Supplementary information

Supplementary data are available at Bioinformatics online.
Classification of RNA structure change by ‘gazing’ at experimental data
Authors: Woods Chanin Tolson , Laederach Alain
Published: January 2017

Motivation

Mutations (or Single Nucleotide Variants) in folded RiboNucleic Acid structures that cause local or global conformational change are riboSNitches. Predicting riboSNitches is challenging, as it requires making two, albeit related, structure predictions. The data most often used to experimentally validate riboSNitch predictions is Selective 2′ Hydroxyl Acylation by Primer Extension, or SHAPE. Experimentally establishing a riboSNitch requires the quantitative comparison of two SHAPE traces: wild-type (WT) and mutant. Historically, SHAPE data was collected on electropherograms and change in structure was evaluated by ‘gel gazing.’ SHAPE data is now routinely collected with next generation sequencing and/or capillary sequencers. We aim to establish a classifier capable of simulating human ‘gazing’ by identifying features of the SHAPE profile that human experts agree ‘looks’ like a riboSNitch.

Results

We find strong quantitative agreement between experts when RNA scientists ‘gaze’ at SHAPE data and identify riboSNitches. We identify dynamic time warping and seven other features predictive of the human consensus. The classSNitch classifier reported here accurately reproduces human consensus for 167 mutant/WT comparisons with an Area Under the Curve (AUC) above 0.8. When we analyze 2019 mutant traces for 17 different RNAs, we find that features of the WT SHAPE reactivity allow us to improve thermodynamic structure predictions of riboSNitches. This is significant, as accurate RNA structural analysis and prediction is likely to become an important aspect of precision medicine.

Availability and Implementation

The classSNitch R package is freely available at http://classsnitch.r-forge.r-project.org.

Supplementary information

Supplementary data are available at Bioinformatics online.
Detection of the pedogenic magnetic fraction in volcanic soils developed on basalts using frequency-dependent magnetic susceptibility: comparison of two instruments
Authors: Grison Hana , Petrovsky Eduard , Kapicka Ales , Hanzlikova Hana
Published: January 2017

In studies of the magnetic properties of soils, the frequency-dependent magnetic susceptibility percentage (χFD%) is often used for the identification of ultrafine magnetically superparamagnetic/stable single-domain (SP/SSD) particles. This parameter is commonly used as an indicator for increased pedogenesis. In strongly magnetic soils, the SP/SSD magnetic signal (mostly bio-pedogenic) may be masked by lithological signals; making pedogenesis hard to detect. In this study, we compare results for the detection of ultrafine SP/SSD magnetic particles in andic soils using two instruments: a Bartington MS2B dual-frequency meter and an AGICO Kappabridge MFK1-FA. In particular, the study focuses on the effect of pedogenesis by investigating the relationship between specific soil magnetic and chemical properties (soil organic carbon and pHH2O). The values of χFD% obtained with the MS2B varied from 2.4 to 5.9 per cent, and mass-specific magnetic susceptibility (χLF) from 283 to 1688 × 10−8 m3 kg−1, while values of χFD% and χLF obtained with the MFK1-FA varied from 2.7 to 8.2 per cent and from 299 to 1859 × 10−8 m3 kg−1, respectively. Our results suggest that the detection of the SP/SSD magnetic fraction can be accomplished by comparing relative trends of χFD% along the soil profile. Moreover, the discrimination between bio-pedogenic and lithogenic magnetic contributions in the SP/SSD fraction is possible by comparing the χFD% and χLF data determined in the fine earth (<2 mm) and the coarse fraction (4–10 mm) samples down the soil profile.
PHARYNGEAL ISOLATIONS OF ADENOVIRUS 31 FROM A FAMILY POPULATION
Authors: WANG STEPHEN S. , FELDMAN HARRY A.
Published: February 2017

During a 14-month period in 1965 and 1966, adenovirus type 31 was isolated from 26 pharyngeal swabs obtained on a routine schedule from children and adults during a study of respiratory viruses among members of a family population. Eighteen isolations were made in a four-day period, seven within the preceding five months, and the last, eight months earlier. A significant association between the isolation of adenovirus 31 and respiratory or gastrointestinal illnesses was not demonstrable. Limited tests demonstrated neutralizing antibody increases in a few paired sera of infected adults. The virus is antigenically related to adenoviruses 12 and 18 and is capable of inducing soft tissue tumors in mice.
NOSOCOMIAL INFECTION WITH HIGHLY RESISTANT
Authors: KASLOW RICHARD A. , LINDSEY JAMES O. , BISNO ALAN L. , PRICE ANN
Published: February 2017

Over 22-1/2 months an epidemic of at least 127 cases of nosocomial infection developed from a strain of Proteus rettgeri resistant to all antibiotics commonly tested in hospital laboratories. Although there were at least four cases of septicemia and one related death, the majority of cases consisted of asymptomatic bacteriuria or clinically mild urinary tract infection. Indwelling urinary tract devices and antibiotic therapy were important predisposing factors. Data supported an association between increasing use of gentamicin and increasing rates of resistant infection. No common source was found, and contact spread appeared more likely. Control measures included efforts to reduce unnecessary exposure to the incriminated risk factors and to improve asepsis in the management of catheterized patients. An additional 36 cases and one related death were identified in the 7-1/2 months following the investigation and institution of control measures. Nosocomial infection with extremely resistant organisms may pose a serious hazard wherever indwelling urinary tract devices and antibiotics are used together intensively.
Spontaneous development of cerebrovascular pathology and microinfarcts in a mouse model of sickle cell disease
Authors: Hyacinth Hyacinth I. , Sugihara Cortney L. , Spencer Thomas L. , Archer David R. , Shih Andy Y.
Published: January 2017

Stroke is a dramatic complication of sickle cell disease (SCD) and is associated with aneurysms, moya moya, intravascular thrombi, cerebral hyperemia and increased vessel tortuosity. We show that aged SCD mice spontaneously develop the characteristics features of cerebral vasculopathy seen in human SCD. Thirteen month old Townes SCD mice and age-matched controls had a cranial windows implanted over the somatosensory cortex. Cortical capillaries were imaged usingin vivotwo-photon microscopy after the blood plasma was labeled with a fluorescent dye. Results showed that SCD mice compared to controls, had significantly higher red blood cell (RBC) velocity and capillary vessel diameter. SCD mice also had a significantly higher number of occlusive events in the capillary bed, resulting in more stalling of RBC flow. Microvascular topology was also altered, as SCD mice had significantly higher vessel tortuosity and shorter capillary branch lengths. Finally,post-mortemanalyses revealed a greater number of cortical microinfarcts, likely caused by vascular occlusion since local tissue hypoxia and blood-brain barrier leakage was prominent. We concluded that aged Townes sickle cell mice spontaneously develop SCD-associated cerebral vasculopathy, and thatin vivotwo-photon imaging is a powerful approach to investigate the mechanisms of vascular complications in SCD.
Health Information Needs and Health Seeking Behavior during the 2014-2016 Ebola Outbreak: A Twitter Content Analysis
Authors: Odlum Michelle L. , Yoon Sunmoo
Published: January 2017

Introduction

For effective public communication during major disease outbreaks like the 2014-2016 Ebola epidemic, health information needs of the population must be adequately assessed. Through content analysis of social media data, like tweets, public health information needs can be effectively assessed and in turn provide appropriate health information to effectively address such needs. The aim of the current study was to assess health information needs about Ebola, at distinct epidemic time points, through longitudinal tracking.

Methods

Natural language processing was applied to explore public response to Ebola over time from the beginning of the outbreak (July 2014) to six month post outbreak (March 2015). A total 155,647 tweets (unique 68,736, retweet 86,911) mentioning Ebola were analyzed and visualized with infographics.

Results

Public fear, frustration, and health information seeking regarding Ebola-related global priorities were observed across time. Our longitudinal content analysis revealed that due to ongoing health information deficiencies, resulting in fear and frustration, social media was at times an impediment and not a vehicle to support health information needs.

Discussion

Content analysis of tweets effectively assessed Ebola information needs. Our study also demonstrates the use of Twitter as a method for capturing real-time data to assess ongoing information needs, fear, and frustration over time.

All authors have seen and approved the manuscript.
aBayesQR: A Bayesian method for reconstruction of viral populations characterized by low diversity
Authors: Ahn Soyeon , Vikalo Haris
Published: January 2017

RNA viruses replicate with high mutation rates, creating closely related viral populations. The heterogeneous virus populations, referred to as viral quasispecies, rapidly adapt to environmental changes thus adversely affecting efficiency of antiviral drugs and vaccines. Therefore, studying the underlying genetic heterogeneity of viral populations plays a significant role in the development of effective therapeutic treatments. Recent high-throughput sequencing technologies have provided invaluable opportunity for uncovering the structure of quasispecies populations (i.e., reconstruction of viral sequences and discovery of their relative frequencies). However, accurate reconstruction of viral quasispecies remains difficult due to limited read-lengths and presence of sequencing errors. The problem is particularly challenging when the strains in a population are highly similar, i.e., the sequences are characterized by low mutual genetic distances, and further exacerbated if some of those strains are relatively rare; this is the setting where state-of-the-art methods struggle. In this paper, we present a novel viral quasispecies reconstruction algorithm, aBayesQR, that employs a maximum-likelihood framework to infer individual sequences in a mixture from high-throughput sequencing data. The search for the most likely quasispecies is conducted on long contigs that our method constructs from the set of short reads via agglomerative hierarchical clustering; operating on contigs rather than short reads enables identification of close strains in a population and provides computational tractability of the Bayesian method. Results on both simulated and real HIV-1 data demonstrate that the proposed algorithm generally outperforms state-of-the-art methods; aBayesQR particularly stands out when reconstructing a set of closely related viral strains (e.g., quasispecies characterized by low diversity).
A miRNA catalogue and ncRNA annotation of the short-living fishNothobranchius furzeri
Authors: Baumgart Mario , Barth Emanuel , Savino Aurora , Groth Marco , Koch Philipp , Petzold Andreas , Arisi Ivan , Platzer Matthias , Marz Manja , Cellerino Alessandro
Published: January 2017

Background:The short-lived fishNothobranchius furzeriis the shortest-lived vertebrate that can be cultured in captivity and was recently established as a model organism for aging research. Small non-coding RNAs, especially miRNAs, are implicated in age-dependent control of gene expression.

Results:Here, we present a comprehensive catalogue of miRNAs and several other non-coding RNA classes (ncRNAs) forNothobranchius furzeri. Analyzing multiple small RNA-Seq libraries, we show most of these identified miRNAs are expressed in at least one of sevenNothobranchiusspecies. Additionally, duplication and clustering ofN. furzerimiRNAs was analyzed and compared to the four fish speciesDanio rerio,Oryzias latipes,Gasterosteus aculeatusandTakifugu rubripes. A peculiar characteristic ofN. furzerias compared to other teleosts was a duplication of the miR-29 cluster.

Conclusion:The completeness of the catalogue we provide is comparable to that of zebrafish. This catalogue represents a basis to investigate the role of miRNAs in aging and development in this species.

Availability:All supplementary material can be found online athttp://www.rna.uni-jena.de/en/supplements/nothobranchius-furzeri-mirnome/.
A Fast Approximate Algorithm for Mapping Long Reads to Large Reference Databases
Authors: Jain Chirag , Dilthey Alexander , Koren Sergey , Aluru Srinivas , Phillippy Adam M.
Published: January 2017

Emerging single-molecule sequencing technologies from Pacific Biosciences and Oxford Nanopore have revived interest in long read mapping algorithms. Alignment-based seed-and-extend methods demonstrate good accuracy, but face limited scalability, while faster alignment-free methods typically trade decreased precision for efficiency. In this paper, we combine a fast approximate read mapping algorithm based on minimizers with a novel MinHash identity estimation technique to achieve both scalability and precision. In contrast to prior methods, we develop a mathematical framework that defines the types of mapping targets we uncover, establish probabilistic estimates of p-value and sensitivity, and demonstrate tolerance for alignment error rates up to 20%. With this framework, our algorithm automatically adapts to different minimum length and identity requirements and provides both positional and identity estimates for each mapping reported. For mapping human PacBio reads to the hg38 reference, our method is 290x faster than BWA-MEM with a lower memory footprint and recall rate of 96%. We further demonstrate the scalability of our method by mapping noisy PacBio reads (each ≥ 5 kbp in length) to the complete NCBI RefSeq database containing 838 Gbp of sequence and > 60, 000 genomes.
Dealing with false‐positive and false‐negative errors about species occurrence at multiple levels
Authors: Guillera‐Arroita Gurutzeta , Lahoz‐Monfort José Joaquín , van Rooyen Anthony R. , Weeks Andrew R. , Tingley Reid
Published: January 2017

Accurate knowledge of species occurrence is fundamental to a wide variety of ecological, evolutionary and conservation applications. Assessing the presence or absence of species at sites is often complicated by imperfect detection, with different mechanisms potentially contributing to false‐negative and/or false‐positive errors at different sampling stages. Ambiguities in the data mean that estimation of relevant parameters might be confounded unless additional information is available to resolve those uncertainties.

Here, we consider the analysis of species detection data with false‐positive and false‐negative errors at multiple levels. We develop and examine a two‐stage occupancy‐detection model for this purpose. We use profile likelihoods for identifiability analysis and estimation, and study the types of additional data required for reliable estimation. We test the model with simulated data, and then analyse data from environmental DNA (eDNA) surveys of four Australian frog species. In our case study, we consider that false positives may arise due to contamination at the water sample and quantitative PCR‐sample levels, whereas false negatives may arise due to eDNA not being captured in a field sample, or due to the sensitivity of laboratory tests. We augment our eDNA survey data with data from aural surveys and laboratory calibration experiments.

We demonstrate that the two‐stage model with false‐positive and false‐negative errors is not identifiable if only survey data prone to false positives are available. At least two sources of extra information are required for reliable estimation (e.g. records from a survey method with unambiguous detections, and a calibration experiment). Alternatively, identifiability can be achieved by setting plausible bounds on false detection rates as prior information in a Bayesian setting. The results of our case study matched our simulations with respect to data requirements, and revealed false‐positive rates greater than zero for all species.

We provide statistical modelling tools to account for uncertainties in species occurrence survey data when false negatives and false positives could occur at multiple sampling stages. Such data are often needed to support management and policy decisions. Dealing with these uncertainties is relevant for traditional survey methods, but also for promising new techniques, such as eDNA sampling.
Insufficient evidence for ‘shaken baby syndrome’ – a systematic review
Authors: Lynøe Niels , Elinder Göran , Hallberg Boubou , Rosén Måns , Sundgren Pia , Eriksson Anders
Published: January 2017

Shaken baby syndrome has typically been associated with findings of subdural haematoma, retinal haemorrhages and encephalopathy, which are referred to as the triad. During the last decade, however, the certainty with which the triad can indicate that an infant has been violently shaken has been increasingly questioned. The aim of this study was to determine the diagnostic accuracy of the triad in detecting that an infant had been shaken. The literature search was performed using PubMed, Embase and the Cochrane Library up to October 15, 2015. Relevant publications were assessed for the risk of bias using the QUADAS tool and were classified as having a low, moderate or high risk of bias according to predefined criteria. The reference standards were confessions or witnessed cases of shaking or accidents. The search generated 3773 abstracts, 1064 were assessed as possibly relevant and read as full texts, and 30 studies were ultimately included. Of these, 28 were assessed as having a high risk of bias, which was associated with methodological shortcomings as well as circular reasoning when classifying shaken baby cases and controls. The two studies with a moderate risk of bias used confessions and convictions when classifying shaken baby cases, but their different designs made a meta‐analysis impossible. None of the studies had a low risk of bias.

Conclusion: The systematic review indicates that there is insufficient scientific evidence on which to assess the diagnostic accuracy of the triad in identifying traumatic shaking (very low‐quality evidence). It was also demonstrated that there is limited scientific evidence that the triad and therefore its components can be associated with traumatic shaking (low‐quality evidence).
Retrospective study shows that doxapram therapy avoided the need for endotracheal intubation in most premature neonates
Authors: Flint Robert , Halbmeijer Nienke , Meesters Naomi , van Rosmalen Joost , Reiss Irwin , van Dijk Monique , Simons Sinno
Published: January 2017

Aim

Using doxapram to treat neonates with apnoea of prematurity might avoid the need for endotracheal intubation and invasive ventilation. We studied whether doxapram prevented the need for intubation and identified the predictors of the success.

Methods

This was a retrospective study of preterm infants born from January 2006 to August 2014 who received oral or intravenous doxapram. Success was defined as no need for endotracheal intubation, due to apnoea, during doxapram therapy. Univariable and multivariable logistic regression analyses identified predictors of success during the first 48 hours of doxapram therapy.

Results

Data on 203 patients with a median gestational age of 26.1 (interquartile range 25.1–27.4) weeks were analysed. During the first 48 hours of doxapram therapy, 157 (77%) patients did not need endotracheal intubation and 127 (63%) patients were successfully treated over the entire treatment course. The median postnatal age at the start of doxapram therapy was 20 days (interquartile range 12–30). Postnatal age and a lower fraction of inspired oxygen at the start of doxapram therapy were significant predictors of success (odds ratio 0.964, 95% confidence interval 0.938–0.991, p = 0.001).

Conclusion

Oral and intravenous doxapram effectively treated most cases of apnoea in preterm infants, avoiding the need for intubation.
Evaluation of single and multiple doses of a novel mGlu2 agonist, a potential antipsychotic therapy, in healthy subjects
Authors: McColm Juliet , Brittain Claire , Suriyapperuma Subha , Swanson Steven , Tauscher‐Wisniewski Sitra , Foster Joanne , Soon Danny , Jackson Kimberley
Published: February 2017

Aims

The safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of single and multiple doses of a novel mGlu2 agonist were assessed in healthy males.

Methods

In two, Phase 1 investigator‐ and subject‐blind, placebo‐controlled studies, oral doses of prodrug LY2979165 were evaluated: single doses (20–150 mg, N = 30) and multiple once‐daily (QD) doses (20–400 mg; N = 84), using a titration regimen. The plasma and urine PK of LY2979165 and active moiety, 2812223, were measured. Cerebrospinal fluid (CSF) was collected to determine PK and neurotransmitter levels. Safety parameters were assessed throughout.

Results

Nausea and vomiting were dose limiting following single doses; dose titration allowed higher doses to be tested over 14 days. The most common adverse events related to LY2979165 were dizziness, vomiting, nausea, somnolence and headache. The plasma PK of 2812223 were approximately linear with minimal accumulation with QD dosing. Conversion of LY2979165 to 2812223 was extensive, with minimal LY2979165 measurable in plasma. There was no effect of food on the PK of LY2979165 and 2812223. After 60 mg LY2979165 single‐dose, 2812223 exposure in CSF was approximately 2–6% and plasma exposure and peak concentrations were approximately four‐fold higher than the mGlu2 agonist in vitro EC50 value. No consistent effects were observed on CSF neurotransmitter levels.

Conclusions

Oral doses of LY2979165 up to 60 mg as a single dose and up to 400 mg given as multiple QD doses, using a titration regimen, were well tolerated with linear PK. Overall, these data support further clinical evaluation of LY2979165.
Math grades and intrinsic motivation in elementary school: A longitudinal investigation of their association
Authors: Weidinger Anne F. , Steinmayr Ricarda , Spinath Birgit
Published: February 2017

Background

It is often argued that the negative development of intrinsic motivation in elementary school strongly depends on the presence of school grades because grades represent extrinsic consequences and achievement feedback that are supposed to influence intrinsically motivated behaviour. However, only a few studies have tested this hypothesis.

Aims

Therefore, we investigated the role of school grades in inter‐ and intra‐individual changes in elementary school students’ intrinsic motivation from when grades were first introduced until the end of elementary school, when students in Germany receive recommendations for a secondary school type on the basis of their prior performance in school.

Sample

A sample of 542 German elementary school students (t1: M = 7.95 years, SD = 0.57) was followed for 2 years from the end of Grade 2 to the end of Grade 4.

Methods

At seven measurement occasions, children's math grades and their domain‐specific intrinsic motivation were assessed.

Results

Latent growth curve models showed differences in trajectories of intrinsic motivation across students rather than uniform development. Moreover, students’ trajectories of grades and intrinsic motivation were only weakly associated. A latent cross‐lagged model revealed that reciprocal effects between the two constructs over time were small at best.

Conclusions

Contrary to theoretical considerations, our results indicate that negative performance feedback in the form of grades does not necessarily lead to a decrease in intrinsic motivation. This calls into question the common opinion that a perception of being less competent, as reflected by poor grades, is responsible for weakening students’ intrinsic motivation.
Gaussian model‐based partitioning using iterated local search
Authors: Brusco Michael J. , Shireman Emilie , Steinley Douglas , Brudvig Susan , Cradit J. Dennis
Published: January 2017

The emergence of Gaussian model‐based partitioning as a viable alternative to K‐means clustering fosters a need for discrete optimization methods that can be efficiently implemented using model‐based criteria. A variety of alternative partitioning criteria have been proposed for more general data conditions that permit elliptical clusters, different spatial orientations for the clusters, and unequal cluster sizes. Unfortunately, many of these partitioning criteria are computationally demanding, which makes the multiple‐restart (multistart) approach commonly used for K‐means partitioning less effective as a heuristic solution strategy. As an alternative, we propose an approach based on iterated local search (ILS), which has proved effective in previous combinatorial data analysis contexts. We compared multistart, ILS and hybrid multistart–ILS procedures for minimizing a very general model‐based criterion that assumes no restrictions on cluster size or within‐group covariance structure. This comparison, which used 23 data sets from the classification literature, revealed that the ILS and hybrid heuristics generally provided better criterion function values than the multistart approach when all three methods were constrained to the same 10‐min time limit. In many instances, these differences in criterion function values reflected profound differences in the partitions obtained.
Response style analysis with threshold and multi‐process IRT models: A review and tutorial
Authors: Böckenholt Ulf , Meiser Thorsten
Published: January 2017

Two different item response theory model frameworks have been proposed for the assessment and control of response styles in rating data. According to one framework, response styles can be assessed by analysing threshold parameters in Rasch models for ordinal data and in mixture‐distribution extensions of such models. A different framework is provided by multi‐process item response tree models, which can be used to disentangle response processes that are related to the substantive traits and response tendencies elicited by the response scale. In this tutorial, the two approaches are reviewed, illustrated with an empirical data set of the two‐dimensional ‘Personal Need for Structure’ construct, and compared in terms of multiple criteria. Mplus is used as a software framework for (mixed) polytomous Rasch models and item response tree models as well as for demonstrating how parsimonious model variants can be specified to test assumptions on the structure of response styles and attitude strength. Although both frameworks are shown to account for response styles, they differ on the quantitative criteria of model selection, practical aspects of model estimation, and conceptual issues of representing response styles as continuous and multidimensional sources of individual differences in psychological assessment.
Complex Roles of Annexin A2 in Host Blood–Brain Barrier Invasion by Cryptococcus neoformans
Authors: Fang Wei , Fa Zhen‐Zong , Xie Qun , Wang Gui‐Zhen , Yi Jiu , Zhang Chao , Meng Guang‐Xun , Gu Ju‐Lin , Liao Wan‐Qing
Published: January 2017

Introduction

Fungal transversal across the brain microvascular endothelial cells (BMECs) is the essential step for the development of cryptococcal meningoencephalitis. Annexin A2 (AnxA2) is an important signaling protein involved in several intracellular processes such as membrane trafficking, endocytosis, and exocytosis.

Aim

To investigate the roles and mechanism of AnxA2 during cryptococcal transversal of BMECs.

Results

Cryptococcus neoformans infection initiated upregulation of AnxA2 in mouse BMECs. Blockade with anti‐AnxA2 antibody led to a reduction in fungal transcytosis activity but no change in its adhesion efficiency. Intriguingly, AnxA2 depletion caused a significant increase in fungal association activity but had no effect on their transcytosis. AnxA2 suppression resulted in marked reduction in its partner protein S100A10, and S100A10 suppression in BMECs significantly reduced the cryptococcal transcytosis efficiency. Furthermore, AnxA2 dephosphorylation at Tyr23 and dephosphorylation of downstream cofilin were required for cryptococcal transversal of BMECs, both of which might be primarily involved in the association of C. neoformans with host cells.

Conclusions

Our work indicated that AnxA2 played complex roles in traversal of C. neoformans across host BMECs, which might be dependent on downstream cofilin to inhibit fungal adhesion but rely on its partner S100A10 to promote cryptococcal transcytosis.
False‐positive cytopathology results for papillary thyroid carcinoma: A trap for thyroid surgeons
Authors: Yi K.‐I. , Ahn S. , Park D.Y. , Lee J.‐C. , Lee B.‐J. , Wang S.‐G. , Cha W.
Published: January 2017

Objectives

Current preoperative diagnosis of thyroid nodules remains imperfect despite recent advances in cytopathology and molecular diagnostics. False positivity in preoperative fine‐needle aspiration cytology (FNAC) may lead to overtreatment of patients, including total thyroidectomy, and sometimes to lawsuits for misdiagnosis and malpractice. In this study, we analysed clinical characteristics and pathologic findings in patients with false positivity for papillary thyroid carcinoma (PTC) in FNAC.

Methods

We retrospectively reviewed permanent pathology results from 3788 patients who underwent thyroid surgery. Among them, 48 patients had lesions that were deemed suspicious or positive (Bethesda class V or VI) for PTC in preoperative FNAC. We reviewed clinic–pathologic data, radiologic findings and surgical planning in these patients.

Results

The prevalence of pathologic thyroiditis was significantly higher among patients with false‐positive FNAC results than in those with confirmed PTC (54.2% vs 9.2%, P<.001). The analysis of the permanent pathology reports showed that 26 patients had chronic lymphocytic thyroiditis and 22 patients had no evidence of thyroiditis. Among the patients without pathologic thyroiditis, 19 patients (86.4%) had nodular hyperplasia and three (13.6%) had follicular adenoma, while among the patients with pathologic thyroiditis, seven (26.9%) had no nodule, 14 (53.8%) had nodular hyperplasia, two (7.7%) had hyalinized nodules, two (7.7%) had follicular adenoma and one (3.8%) had a hyalinizing trabecular tumour. In 42 patients, the extent of surgery (total thyroidectomy or hemithyroidectomy) was to be determined according to the intra‐operative frozen section biopsy results. Among them, four (10.5%) had inconclusive frozen section results, and 38 (90.5%) had benign results on frozen section.

Conclusions

Patient counselling about the possibility of false positivity is still important. And the presence of thyroiditis might create confusion in the interpretation of cytopathologic results.
Expanding access to transplantation with hepatitis C‐positive donors: A new perspective on an old issue
Authors: Kling Catherine E. , Limaye Ajit P. , Landis Charles S. , Sibulesky Lena
Published: January 2017

With the need for organs far exceeding supply, donors previously exposed to hepatitis B (HBV) and hepatitis C (HCV) viral infections should be considered for transplantation. Although many centers have protocols for transplanting organs from HBV core antibody‐positive (HBcAb+) donors into select recipients, in the era of direct‐acting antivirals (DAAs), a new focus should be placed on HCV‐positive donors. The transmission rate from HCV antibody‐positive (HCVAb+) nucleic acid testing negative (HCV NAT‐) donors is expected to be very low, and we encourage use of such organs in HCV recipients provided a normal biopsy, appropriate counseling, and careful post‐transplant monitoring. While transmission of HCV from HCV NAT+ donors is universal, the success of DAA in obtaining a sustained viral response in post‐transplant recipients should make the use of these organs more appealing. We herein provide information to help guide the use of organs from HCV donors.
Doppler vocal fremitus
Authors: Fiser Wesley , Pai Balakrishna , Vallurupalli Srikanth
Published: January 2017

A young woman with metastatic breast cancer was found to have a regular spectral Doppler event spanning multiple cardiac cycles and timing to her tachypneic respiratory rate, which suggested an extracardiac source. A chest CT confirmed a large mediastinal mass causing a postobstructive pneumonia. This Doppler signal reflected increased turbulence across the obstructed bronchus due to sound wave conduction through a pulmonary consolidation—a Doppler equivalent of “vocal fremitus” elicited by physical examination of a patient with a lung mass or pneumonia. Careful attention to the timing of Doppler abnormalities is required to avoid misdiagnosis.
A new and simple method for clarifying the severity of tricuspid regurgitation
Authors: Izgi Ibrahim Akin , Acar Emrah , Kilicgedik Alev , Guler Ahmet , Cakmak Ender Ozgun , Demirel Muhittin , Izci Servet , Yilmaz Mehmet Fatih , Inanir Mehmet , Kirma Cevat
Published: January 2017

Background

No gold standard exists for grading tricuspid regurgitation (TR) severity. We developed a simple parameter, the right ventricular (RV) early inflow‐outflow (RVEIO) index, using the early diastolic filling velocity and RV outflow velocity integrated over the systolic ejection period. We hypothesized that this index would help identify severe TR in clinical practice.

Methods

We obtained data from routine transthoracic echocardiograms. All records reporting moderate (n=395) or severe (n=395) TR were reanalyzed to measure vena contracta (VC) width, TR jet area, effective regurgitant orifice (EROA) derived with the proximal isovelocity surface area method, RVEIO index, and right‐sided chamber volumes.

Results

Significant linear trends were demonstrated for right atrial volume index, end‐diastolic volume index, E‐wave velocity, RV velocity time integral, TR jet area, VC width, and EROA with increasing TR severity. Independent predictors of severe RT included RVEIO index ≥ 10, VC width ≥ 0.7 cm, TR jet area>10 cm2, and EROA ≥ 0.4 cm2.

Conclusion

RVEIO index is a useful, simple, accurate, and independent predictor of severe TR that adds incrementally to traditional methods of quantifying TR severity. Accurate quantification and classification of TR severity is critical for clinical decision‐making and management; therefore, the incorporation of RVEIO index into the integrative approach to grading TR severity should be considered.
Twist deformation for predicting postoperative left ventricular function in patients with mitral regurgitation: A speckle tracking echocardiography study
Authors: Candan Ozkan , Hatipoglu Akpinar Suzan , Dogan Cem , Demirkıran Aykut , Dindar Barış , Bayram Zubeyde , Yılmaz Fatih , Kaymaz Cihangir , Ozdemir Nihal
Published: January 2017

Purpose

Postoperative LV dysfunction is associated with poor prognosis and increased mortality in patient with mitral regurgitation undergoing surgery. With this study, we aimed to investigate the predictive value of classic and speckle tracking echocardiographic (STE) LV deformational parameters for estimating postoperative LV dysfunction.

Methods

Fifty‐nine asymptomatic patients with severe mitral regurgitation (MR) due to mitral valve prolapse, who had sinus rhythm and LV ejection fraction (EF) ≥50%, were included. Patients underwent comprehensive and speckle tracking echocardiographic examination before and 6 months after the surgical procedure. Patients were divided into two groups according to postoperative LV function: group A postoperative LV EF≥50% and group B postoperative LV EF<50%.

Results

Patients in group A were found to have higher LV twist (19.7±6.8° vs 11.9±4.2°; P<.001), LV global longitudinal peak strain (GLPS) (−21.7±4 vs −16.5±3.4%; P<.001), and circumferential strain (−19.5±5.2 vs −14.4±5.1%; P=.004) values but lower end‐systolic diameter (ESD) (3.2±0.6 vs 4.1±0.9 cm; P<.001) when compared to group B. Multivariate logistic regression analysis revealed that GLPS, ESD, and twist were independent predictors of postoperative LV functions. In the ROC analysis, GLPS ≥18.4% and twist>14.4° predicted postoperative LVEF ≥50%.

Conclusion

GLPS and twist measured by 2DSTE are predictors of LV preservation after surgery in severe MR. These parameters may also be used as prognostic predictors and optimal timing of operation in this patient population.
Assessing the inclusion of seafood in the sustainable diet literature
Authors: Farmery Anna K , Gardner Caleb , Jennings Sarah , Green Bridget S , Watson Reg A
Published: January 2017

The literature on sustainable diets is broad in its scope, and application yet is consistently supportive of a move away from animal‐based diets towards more plant‐based diets. The positioning of seafood within the sustainable diet literature is less clear. A literature review was conducted to examine how the environmental impacts of seafood consumption are assessed and what conclusions are being drawn about the inclusion of seafood in a sustainable diet. Seafood is an essential part of the global food system but is not adequately addressed in most of the sustainable diet literature. Aquaculture, the world's fastest growing food sector, was considered by very few papers. Seafood consumption was commonly presented as a dilemma due to the perceived trade‐offs between positive health outcomes from eating seafood and concerns of overfishing. A number of studies included seafood as part of their sustainable diet scenario, or as part of a diet that had lower impacts than current consumption. Most of the indicators used were biophysical, with a strong focus on greenhouse gas emissions, and very few studies addressed biological or ecological impacts. The assessment of seafood was limited in many studies due to relevant data sets not being incorporated into the models used. Where they were used, data sources and methodological choices were often not stated thereby limiting the transparency of many studies. Both farmed and wild‐capture production methods need to be integrated into research on the impacts of diets and future food scenarios to better understand and promote the benefits of sustainable diets.