bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cavernous Sinus and Parasellar Region: An Endoscopic Endonasal Anatomic Cadaver Dissection
Authors: Erdogan Umut , Turhal Goksel , Kaya Isa , Biceroglu Huseyin , Midilli Rasit , Gode Sercan , Karci Bulent 
Published: October 2018

Abstract
The aim of this study was to investigate the neurovascular structures of the cavernous sinus with the endonasal endoscopic transpterygoid approach on fresh human cadavers. Additionally, the course of internal carotid artery (ICA) and relevant anatomy was thoroughly investigated to refine the anatomical landmarks, exposure difficulties, potential complications, and limitations using the endonasal endoscopic technique. This study was carried out at an otolaryngology department of a tertiary medical center between June 2014 and June 2015. The surgical dissection was performed on 10 fresh human cadaver specimens using paranasal sinus and skull base endoscopic instruments. Cavernous sinuses and parasellar area were explored via an endoscopic endonasal transpterygoid approach. Dehiscence was present in 5 (25%) cavernous ICAs. Projection of the cavernous ICA on the whole lateral sphenoid wall was prominent in 6 (%30) sphenoid sinuses. Anterior curve was prominent in 12 (60%) cavernous ICAs, whereas posterior was prominent in 7 (35%). Mean distance between the lateral wall of eustachian tube orifice and petrous ICA was 19.50 ± 1.05 mm (range 18–22 mm). Cranial nerves of the cavernous sinus showed no variation. Control of the ICA is critical during the endonasal endoscopic approach to the cavernous sinus and skull base. The vidian nerve is a reliable and important landmark to the petrous ICA in the transpterygoid approach. Dissection of the eustachian tube and its relation to the ICA has to be kept in mind during nasopharyngeal surgery.
The Role of Mitochondrial DNA in the Development of Ischemia Reperfusion Injury
Authors: Hu Qiongyuan , Zhou Quan , Wu Jie , Wu Xiuwen , Ren Jianan 
Published: October 2018

Abstract
Ischemia/reperfusion (I/R) injury is a common occurrence resulting from acute mesenteric ischemia, traumatic or septic shock, burns, and surgical procedures that can lead to multiple organ failure and high mortality in critically ill patients. Mitochondria are often considered the cellular power factory via their capacity for ATP generation. Recently, mitochondria have been further identified as vital regulators of cell death, inflammation, and oxidative stress, all of which can aggravate I/R injury. Studies have indicated that mitochondrial DNA (mtDNA) damage leads to mitochondrial dysfunction and aggravates I/R injury. mtDNA is emerging as an agonist of the innate immune system that influences inflammatory pathology during I/R injury. In addition, when mtDNA is released into the cytoplasm, extracellular milieu, or circulation, it can activate multiple pattern-recognition receptors to trigger type I interferon and pro-inflammatory responses. Here, we review the emerging role of mtDNA in I/R injury to highlight novel mechanistic insights and discuss the pathophysiological relevance of mitochondrial biology.
Stimulation of N-methyl-D-aspartate receptors by exogenous and endogenous ligands improves outcome of brain injury
Authors: Biegon Anat , Liraz-Zaltsman Sigal , Shohami Esther 
Published: October 2018

Purpose of review
The failure of N-methyl-D-aspartate receptor (NMDAR) antagonists as a treatment for human traumatic brain injury (TBI) and stroke, along with preclinical findings of a persistent hypofunctional state of these receptors after brain injury, resulted in a new focus on NMDAR agonists, specifically those acting via the glycine site of the NMDAR. This article reviews the recent literature on positive modulators of the glycine site as a new modality for improving cognitive function in central nervous system pathology, including traumatic and ischemic brain injuries, neuroinflammation, and neuropsychiatric disorders.

Recent findings
A sustained cognitive decline and NMDAR downregulation were reported in rodent models of TBI, developmental TBI, stroke, and lipopolysaccharide-induced neuroinflammation. Activation of the glycine/serine site by D-cycloserine (DCS) or D-serine ameliorated these cognitive deficits. Recent reviews and reports on the use of DCS and D-serine to modify memory function in a wide range of psychiatric conditions are generally positive.

Summary
Taken together, the preclinical and clinical studies provide new, additional support for the notion that activation of the glycine/serine site should be considered a novel therapeutic approach to cognitive impairments. Specifically, as DCS is an approved drug, its translation into clinical practice should be advocated.
Role of amino-tracer PET for decision-making in neuro-oncology
Authors: Suchorska Bogdana , Albert Nathalie L. , Tonn Jörg-Christian 
Published: October 2018

Purpose of review
To give an overview on the current development in PET imaging as an additional tool in brain tumor management.

Recent findings
The rising emphasis on molecular tumor characteristics both in primary and in metastatic brain disease leads to an increased demand for noninvasive ‘molecular’ grading as well as treatment planning and surveillance of therapy effects. Metabolic imaging using amino acid PET provides further insights into tumor metabolism; current novelties comprise the use of hybrid PET/MRI scanners as well as development of new tracers. Furthermore, treatment monitoring and prognostication on the basis of amino acid PET is gaining further importance in neuro-oncological decision-making.

Summary
Due to its unique properties in visualization of tumor biology, amino acid PET will continue to gain further importance in primary and secondary brain tumors.
Current and future tools for determination and monitoring of isocitrate dehydrogenase status in gliomas
Authors: Picca Alberto , Di Stefano Anna L. , Sanson Marc 
Published: October 2018

Purpose of review
Hotspot mutations of isocitrate dehydrogenase 1 (R132) or 2 (R172) genes affect 40% of diffuse gliomas, mostly grades II and III. The mutant enzyme produces high quantities of d-2-hydroxyglutarate (D2HG), which reshapes the epigenetic of the cell leading to gliomagenesis. For the clinician, the isocitrate dehydrogenase (IDH) mutation is a major biomarker with diagnostic, prognostic, and predictive consequences. With the development of specific inhibitors and vaccination, it appears also a potential actionable target.

Recent findings
IDH status is routinely determined on tumor sample by sequencing and immunohistochemistry detecting the most common mutant protein (IDH1R132H). Recently noninvasive diagnostic approaches have been developed based on the detection of the mutant DNA or the D2HG in body fluids, and the detection of D2HG by magnetic resonance spectroscopy of the brain.

Summary
These new techniques open avenues for non invasive diagnostic of glioma in patients not amenable to biopsy, in the preoperative setting and also duringpatients follow-up for evaluation of treatment response and prediction of recurrence.
Movement Disorders After Exposure to Antipsychotic Drugs in Patients With Depressive Disorders
Authors: Rey María Verónica , Molina Luis , Recinos Byron , Paz Bezner , Rovelo Mauricio , Rodriguez Elias Fanny Elizabeth , Calderón José , Arellano Arturo , Perez-Lloret Santiago 
Published: October 2018

Objectives
The aims of the study were to explore the frequency of movement disorders (MDs) in depressive patients exposed to antipsychotic drugs (APDs) and to compare it with nonexposed depressive patients and APDs-treated schizophrenic patients.

Methods
Four hundred fifty-two depressive patients not exposed to APDs (group A), 156 depressives exposed to APDs (group B), and 75 patients with schizophrenia on APDs (group C) were recruited. Presence of MDs was explored by the Simpson-Angus and UKU scales (Registration: NCT02409823).

Results
Movement disorders were observed in 5%, 9%, and 13% of patients in groups A to C, respectively (P < 0.001, χ2 for linear trend). A logistic multivariate analysis revealed that male sex (odds ratio = 2.26, 95% confidence interval = 1.13–4.49, P < 0.01), exposure to first-generation (vs second-generation) APDs (odds ratio = 5.71, 95% confidence interval = 2.08–15.66, P < 0.01), and exposure to lithium (odds ratio = 3.99, 95% confidence interval = 1.74–9.14, P < 0.01) were independently and significantly associated with MDs.

Conclusions
Male sex, use first-generation APDs, and exposure to lithium were associated with MDs in depression. Therefore, caution is advised with the use of these drugs in depressive patients. Prospective studies are needed to confirm these results.
Efficient feature selection on gene expression data: Which algorithm to use?
Authors: Tsagris Michail , Papadovasilakis Zacharias , Lakiotaki Kleanthi , Tsamardinos Ioannis 
Published: October 2018

AbstractBackgroundFeature selection seeks to identify a minimal-size subset of features that is maximally predictive of the outcome of interest. It is particularly important for biomarker discovery from high-dimensional molecular data, where the features could correspond to gene expressions, Single Nucleotide Polymorphisms (SNPs), proteins concentrations, e.t.c. We evaluate, empirically, three state-of-the-art, feature selection algorithms, scalable to high-dimensional data: a novel generalized variant of OMP (gOMP), LASSO and FBED. All three greedily select the next feature to include; the first two employ the residuals re-sulting from the current selection, while the latter rebuilds a statistical model. The algorithms are compared in terms of predictive performance, number of selected features and computational efficiency, on gene expression data with either survival time (censored time-to-event) or disease status (case-control) as an outcome. This work attempts to answer a) whether gOMP is to be preferred over LASSO and b) whether residual-based algorithms, e.g. gOMP, are to be preferred over algorithms, such as FBED, that rely heavily on regression model fitting.ResultsgOMP is on par, or outperforms LASSO in all metrics, predictive performance, number of features selected and computational efficiency. Contrasting gOMP to FBED, both exhibit similar performance in terms of predictive performance and number of selected features. Overall, gOMP combines the benefits of both LASSO and FBED; it is computationally efficient and produces parsimonious models of high predictive performance.ConclusionsThe use of gOMP is suggested for variable selection with high-dimensional gene expression data, and the target variable need not be restricted to time-to-event or case control, as examined in this paper.
Genetic variants influence on the placenta regulatory landscape
Authors: Delahaye F. , Do C. , Kong Y. , Ashkar R. , Sala M. , Tycko B. , Wapner R. , Hughes F. 
Published: October 2018

AbstractBackgroundFrom genomic association studies, quantitative trait loci analysis, and epigenomic mapping, it is evident that significant efforts are necessary to define genetic-epigenetic interactions and understand their role in disease susceptibility and progression. For this reason, an analysis of the effects of genetic variation on gene expression and DNA methylation in human placentas at high resolution and whole-genome coverage will have multiple mechanistic and practical implications.ResultsBy producing and analyzing DNA sequence variation (n=303), DNA methylation (n=303) and mRNA expression data (n=80) from placentas from healthy women, we investigate the regulatory landscape of the human placenta and offer analytical approaches to integrate different types of genomic data and address some potential limitations of current platforms. We distinguish two profiles of interaction between expression and DNA methylation, revealing linear or bimodal effects, reflecting differences in genomic context, transcription factor recruitment, and possibly cell subpopulations.ConclusionsThese findings help to clarify the interactions of genetic, epigenetic, and transcriptional regulatory mechanisms in normal human placentas. They also provide strong evidence for genotype-driven modifications of transcription and DNA methylation in normal placentas. In addition to these mechanistic implications, the data and analytical methods presented here will improve the interpretability of genome-wide and epigenome-wide association studies for human traits and diseases that involve placental functions.Author summaryThe placenta is a critical organ playing multiple roles including oxygen and metabolite transfer from mother to fetus, hormone production, and vascular perfusion. With this study, we aimed to deliver a placenta-specific regulatory map based on a combination of publicly available and newly generated data. To complete this reference, we obtained genotype information (n=303), DNA methylation (n=303) and expression data (n=80) for placentas from healthy women. Our analysis of methylation and expression quantitative trait loci (QTLs) and correlations between methylation and expression data were designed to identify fundamental associations between genome, transcriptome, and epigenome in this key fetal organ. The results provide high-resolution genetic and epigenetic maps specific to the placenta based on a representative ethnically diverse cohort. As interest and efforts are growing to better understand the etiology of placental disease and the impact of the environment on placental function these data will provide a reference and enhance future investigations.
Novel Data Transformations for RNA-seq Data Analysis
Authors: Zhang Zeyu , Yu Danyang , Seo Minseok , Hersh Craig P. , Weiss Scott T. , Qiu Weiliang 
Published: October 2018

AbstractWe propose eight data transformations for RNA-seq data analysis aiming to make the transformed sample mean to be representative of the distribution center since it is not always possible to transform count data to satisfy the normality assumption. Simulation studies showed that limma based on transformed data by using the rv transformation (denoted as limma+rv) performed best compared with limma based on transformed data by using other transformation methods in term of high accuracy and low FNR, while keeping FDR at the nominal level. For large sample size, limma based on transformed data by using the 8 proposed transformation methods had similar performance to limma based on transformed data by using existing transformation methods for equal library size scenarios. Otherwise, limma based on transformed data by using the rv, lv, rv2, or lv2 transformation, or by using the existing voom transformation performed better than limma based on data from other transformation methods. Real data analysis results showed that limma+ l2 performed best, while limma+ rv also had good performance.
The geography of the Anthropocene differs between the land and the sea
Authors: Bowler D.E. , Bjorkman A.D. , Dornelas M. , Myers-Smith I.H. , Navarro L. M. , Niamir A. , Supp S.R. , Waldock C. , Vellend M. , Blowes S. A. , Böhning-Gaese K. , Bruelheide H. , Elahi R. , Antão L.H. , Hines J. , Isbell F. , Jones H.P. , Magurran A.E. , Cabral J. S. , Winter M. , Bates A.E. 
Published: October 2018

AbstractClimate change and other anthropogenic drivers of biodiversity change are unequally distributed across the world. The geographic patterns of different drivers, and the spatial overlap among these drivers, have important implications for the direction and pace of biodiversity change, yet are not well documented. Moreover, it is unknown if the geographic patterns of drivers differ between the terrestrial and marine realm, as expected due to marked differences in how humans interact with the land and ocean.We compiled global gridded datasets on climate change, land-use, resource exploitation, pollution, species invasions, and human population density. We used multivariate statistics to examine the spatial relationships among the datasets and to characterize the typical combinations of drivers experienced by different parts of the world.We found stronger positive correlations among drivers in the terrestrial than in the marine realm, leading to areas of high intensities of multiple drivers on land. Climate change tended to be negatively correlated with other drivers in the terrestrial realm (e.g., in the tundra and boreal forest with high climate change but low human use and pollution) whereas the opposite was true in the marine realm (e.g., in the Indo-Pacific with high climate change and high fishing).We show that different regions of the world can be defined by anthropogenic threat complexes (ATCs), distinguished by different sets of drivers with varying intensities. The ATCs can be used to test hypothesis about the pattern of biodiversity change, especially the joint effects of multiple drivers. More generally, our global analysis highlights the broad conservation priorities needed to mitigate the effects of anthropogenic change on biodiversity responses, with different priorities emerging on land and in the ocean, and in different parts of the world.
Viral RNA-dependent RNA polymerase inhibitor 7-deaza-2′-C-methyladenosine prevents death in a mouse model of West Nile virus infection
Authors: Eyer Luděk , Fojtíková Martina , Nencka Radim , Rudolf Ivo , Hubálek Zdeněk , Ruzek Daniel 
Published: October 2018

AbstractWest Nile virus (WNV) is a medically important emerging arbovirus causing serious neuroinfections in humans against which no approved antiviral therapy is currently available. In this study, we demonstrate that 2′-C- methyl- or 4′-azido-modified nucleosides are highly effective inhibitors of WNV replication, showing nanomolar or low micromolar anti-WNV activity and negligible cytotoxicity in cell culture. One representative ofC2′-methylated nucleosides, 7-deaza-2′-C- methyladenosine, significantly protected WNV-infected mice from disease progression and mortality. Twice daily treatment at 25 mg/kg starting at the time of infection resulted in 100% survival of the mice. This compound was highly effective, even if the treatment was initiated 3 days post-infection, at the time of a peak of viremia, which resulted in a 90% survival rate. However, the antiviral effect of 7-deaza-2′-C- methyladenosine was absent or negligible when the treatment was started 8 days post-infection (i.e., at the time of extensive brain infection). The 4′-azido moiety appears to be another important determinant for highly efficient inhibition of WNV replication in vitro. However, the strong anti-WNV effect of 4′-azidocytidine and 4′-azido-aracytidine was cell type-dependent and observed predominantly in PS cells. The effect was much less pronounced in Vero cells. Our results indicate that 2′-C- methylated or 4′-azidated nucleosides merit further investigation as potential therapeutic agents for treating WNV infections, as well as infections caused by other medically important flaviviruses.
Identification of C. elegans strains using a fully convolutional neural network on behavioural dynamics
Authors: Javer Avelino , Brown André E.X. , Kokkinos Iasonas , Rittscher Jens 
Published: October 2018

AbstractThe nematode C. elegans is a promising model organism to understand the genetic basis of behaviour due to its anatomical simplicity. In this work, we present a deep learning model capable of discerning genetically diverse strains based only on their recorded spontaneous activity, and explore how its performance changes as different embeddings are used as input. The model outperforms hand-crafted features on strain classification when trained directly on time series of worm postures.
PCAGO: An interactive web service to analyze RNA-Seq data with principal component analysis
Authors: Gerst Ruman , Hölzer Martin 
Published: October 2018

ABSTRACTThe initial characterization and clustering of biological samples is a critical step in the analysis of any transcriptomic study. In many studies, principal component analysis (PCA) is the clustering algorithm of choice to predict the relationship of samples or cells based solely on differential gene expression. In addition to the pure quality evaluation of the data, a PCA can also provide initial insights into the biological background of an experiment and help researchers to interpret the data and design the subsequent computational steps accordingly. However, to avoid misleading clusterings and interpretations, an appropriate selection of the underlying gene sets to build the PCA and the choice of the most fitting principal components for the visualization are crucial parts. Here, we present PCAGO, an easy-to-use and interactive web service to analyze gene quantification data derived from RNA sequencing (RNA-Seq) experiments with PCA. The tool includes features such as read-count normalization, filtering of read counts by gene annotation, and various visualization options. Additionally, PCAGO helps to select appropriate parameters such as the number of genes and principal components to create meaningful visualizations.Availability and implementationThe web service is implemented in R and freely available at pcago.bioinf.uni-jena.de.Contactmartin.hoelzer@uni-jena.de
When sinks become sources: adaptive colonization in asexuals
Authors: Lavigne Florian , Martin Guillaume , Anciaux Yoann , Papaϯx Julien , Roques Lionel 
Published: October 2018

AbstractThe successful establishment of a population into a new empty habitat outside of its initial niche is a phenomenon akin to evolutionary rescue in the presence of immigration. It underlies a wide range of processes, such as biological invasions by alien organisms, host shifts in pathogens or the emergence of resistance to pesticides or antibiotics from untreated areas.In this study, we derive an analytically tractable framework to describe the coupled evolutionary and demographic dynamics of asexual populations in a source-sink system. In particular, we analyze the influence of several factors — immigration rate, mutational parameters, and harshness of the stress induced by the change of environment — on the establishment success in the sink (i.e. the formation of a self-sufficient population in the sink), and on the time until establishment. To this aim, we use a classic phenotype-fitness landscape (Fisher’s geometrical model inndimensions) where source and sink habitats determine distinct phenotypic optima. The harshness of stress, in the sink, is determined by the distance between the fitness optimum in the sink and that of the source. The dynamics of the full distribution of fitness and of population size in the sink are analytically predicted under a strong mutation strong immigration limit where the population is always polymorphic.The resulting eco-evolutionary dynamics depend on mutation and immigration rates in a non straightforward way. Below some mutation rate threshold, establishment always occurs in the sink, following a typical four-phases trajectory of the mean fitness. The waiting time to this establishment is independent of the immigration rate and decreases with the mutation rate. Beyond the mutation rate threshold, lethal mutagenesis impedes establishment and the sink population remains so, albeit with an equilibrium state that depends on the details of the fitness landscape. We use these results to get some insight into possible effects of several management strategies.