bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Patient-Independent System for Detection of Electrical Onset of Seizures
Authors: Sridevi Veerasingam , Ramasubba Reddy Machireddy , Srinivasan Kannan , Radhakrishnan Kurupath , Rathore Chaturbhuj , Nayak Dinesh S. 
Published: October 2018

Purpose:
To design a non–patient-specific system to detect the electrical onset of seizures in patients with temporal lobe epilepsy.

Methods:
We used EEG data from 29 seizures of 18 temporal lobe epilepsy patients who underwent multiday video-scalp EEG monitoring as part of their presurgical evaluations. We segmented each data set into preictal and ictal phases, and identified spectral entropy, spectral energy, and signal energy as useful features for discriminating normal and seizure conditions. The performance of five different classifiers was analyzed using these features to design an automated detection system.

Results:
Among the five classifiers, decision tree, k-nearest neighbor, and support vector machine performed with sensitivity (specificity) of 79% (81%), 75% (85%), and 80% (86%), respectively. The other two, linear discriminant algorithm and Naive Bayes classifiers, performed with sensitivity (specificity) of 54% (94%), 47% (96%), respectively.

Conclusions:
The support vector machine–based seizure detection system showed better detection capability in terms of sensitivity and specificity measures as compared to linear discriminant algorithm, Naive Bayes, decision tree, and k-nearest neighbor classifiers.

Conclusions:
Our study shows that a generalized system to detect the electrical onset of seizures in temporal lobe epilepsy using scalp-recorded EEG is possible. If confirmed on a larger data set, our findings may have significant implications for the management of seizures, especially in patients with drug-resistant epilepsy.
Interrater and Intrarater Agreement in Neonatal Electroencephalogram Background Scoring
Authors: Massey Shavonne L. , Shou Haochang , Clancy Robert , DiGiovine Marissa , Fitzgerald Mark P. , Fung France W. , Farrar John , Abend Nicholas S. 
Published: October 2018

Purpose:
Many neonates undergo electroencephalogram (EEG) monitoring to identify and manage acute symptomatic seizures. Information about brain function contained in the EEG background data may also help predict neurobehavioral outcomes. For EEG background features to be useful as prognostic indicators, the interpretation of these features must be standardized across electroencephalographers. We aimed at determining the interrater and intrarater agreement among electroencephalographers interpreting neonatal EEG background patterns.

Methods:
Five neonatal electroencephalographers reviewed 5-to-7.5-minute epochs of EEG from full-term neonates who underwent continuous conventional EEG monitoring. The EEG assessment tool used to classify background patterns was based on the American Clinical Neurophysiology Society's guideline for neonatal EEG terminology. Interrater and intrarater agreement were measured using Kappa coefficients.

Results:
Interrater agreement was consistently highest for voltage (binary: substantial, kappa = 0.783; categorical: moderate, kappa = 0.562), seizure presence (fair–substantial; kappa = 0.375–0.697), continuity (moderate; kappa = 0.481), burst voltage (moderate; kappa = 0.574), suppressed background presence (moderate–substantial; kappa = 0.493–0.643), delta activity presence (fair–moderate; kappa = 0.369–0.432), theta activity presence (fair–moderate; kappa = 0.347–0.600), presence of graphoelements (fair; kappa = 0.381), and overall impression (binary: moderate, kappa = 0.495; categorical: fair–moderate, kappa = 0.347, 0.465). Agreement was poor or inconsistent for all other patterns. Intrarater agreement was variable, with highest average agreement for voltage (binary: substantial, kappa = 0.75; categorical: substantial, kappa = 0.714) and highest consistent agreement for continuity (moderate–substantial; kappa = 0.43–0.67) and overall impression (moderate–substantial; kappa = 0.42–0.68).

Conclusions:
This study demonstrates substantial variability in neonatal EEG background interpretation across electroencephalographers, indicating a need for educational and technological strategies aimed at improving performance.
Stability analysis of Beck's column over a fractional-order hereditary foundation
Authors: Bologna E. , Zingales M. 
Published: October 2018

This paper considers the case of Beck's column resting on a hereditary bed of independent springpots. The springpot possesses an intermediate rheological behaviour among linear spring and linear dashpot. It is defined by means of couple (
C

β

,
β
) that characterize the material of the element and is ruled by a Caputo's fractional derivative. In this paper, we investigate the critical load of the column under the action of a follower load by means of a novel complex transform that allows to use the Routh–Hurwitz theorem in the complex half-plane for the stability analysis.
DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
Authors: Wiklund Petri , Karhunen Ville , Richmond Rebecca C , Rodriguez Alina , De Silva Maneka , Wielscher Matthias , Rezwan Faisal I , Richardson Tom G , Veijola Juha , Heinz-Herzig Karl , Holloway John W , Relton Caroline L , Sebert Sylvain , Järvelin Marjo-Riitta 
Published: October 2018

AbstractMaternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. To test this, we examined the association of prenatal maternal smoking with DNA methylation in 2,821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess, whether methylation markers have causal effects on disease outcomes in the offspring. We identify 69 differentially methylated CpGs in 36 genomic regions (P < 1×10−7), and show that DNA methylation may represent a biological mechanism through which maternal smoking is associated with increased risk of psychiatric morbidity in the exposed offspring.
Clean lighting leads to decreased indoor air pollution and improved respiratory health in rural Uganda
Authors: Nyakato Viola N. , Mwine Nicholas , Aiden Erez Lieberman , Aiden Aviva P. 
Published: October 2018

AbstractExposure to smoke is a major cause of respiratory illness in the developing world. To date, cookstoves have been the most widely studied source of smoke exposure in developing countries. We hypothesized that exposure to kerosene lighting, utilized by 86% of rural off-the-grid communities in sub-Saharan Africa may also be a significant source of smoke exposure and may be responsible for respiratory pathology. We performed an interventional field trial including 230 people in rural Uganda to assess the impact of clean lighting on indoor air pollution and respiratory health. Each member of the study households were asked about their exposure to smoke, the types of lighting they used, and their recent history of respiratory symptoms. Next, we provided solar-powered lamps to households in the intervention group, and compared to households in the control group who continued to use kerosene lamps. We monitored indoor air quality in a subset of intervention and control households over a three-month period, and performed an exit survey to assess symptoms of respiratory illness in both groups. All of the households we surveyed were found to use kerosene lamps as their primary lighting source. We found that the average person was exposed to 3.3 hours of smoke from kerosene lamps, as compared to 44 minutes of exposure from cookstoves. Next, we found that average soot levels (elemental carbon) in intervention homes were 19-fold lower than soot levels in control homes. After three months, we observed reduced rates of all symptoms assessed, and significantly reduced risk of cough, sore throat, and overall illness in the intervention homes. Our findings demonstrate that kerosene lighting is a significant source of smoke exposure in the developing world, and that the introduction of clean lighting in homes reliant on kerosene lighting can have a rapid and significant impact on overall health.
A curated list of genes that control elemental accumulation in plants
Authors: Whitt Lauren , Ricachenevsky Felipe Klein , Ziegler Greg , Clemens Stephan , Walker Elsbeth , Maathuis Frans JM , Kear Philip , Baxter Ivan 
Published: October 2018

AbstractUnderstanding the mechanisms underlying plants’ adaptation to their environment will require knowledge of the genes and alleles underlying elemental composition. Modern genetics is capable of quickly, and cheaply indicating which regions of DNA are associated with particular phenotypes in question, but most genes remain poorly annotated, hindering the identification of candidate genes. To help identify candidate genes underlying elemental accumulations, we have created the known ionome gene (KIG) list: a curated collection of genes experimentally shown to change uptake, accumulation, and distribution of elements. We have also created an automated computational pipeline to generate lists of KIG orthologs in other plant species using the PhytoMine database. The current version of KIG consists of 176 known genes covering 5 species, 23 elements and their 1588 orthologs in 10 species. Analysis of the known genes demonstrated that most were identified in the model plant Arabidopsis thaliana, and that transporter coding genes and genes altering the accumulation of iron and zinc are overrepresented in the current list.
Learning mechanism of chromatin domain formation with big data
Authors: Xie Wen Jun , Zhang Bin 
Published: October 2018

AbstractChromatin modifications play critical roles in gene regulation and encoding cell phenotypic diversity. The molecular mechanism for their establishment and maintenance is not fully understood due to the complexity of chromatin regulatory pathways. Here we took a data-driven approach and parameterized an information-theoretic model to infer mechanism of chromatin domain formation from genome-wide epigenetic modification profiles. The energy landscape of this model reveals many important chromatin domains that span multiple nucleosomes and exhibit distinct combinatorial patterns of histone modifications, including super (stretch) enhancers, broad H3K4me3 promoter domains, heterochromatin, etc. Transition path analysis further demonstrates that enhancer and promoter domains undergo a sequential maturation process along which the regulatory elements grow from short but stable nucleosome segments to long and potent ones that are modified with many activation marks. On the other hand, the formation of heterochromatin domains is a highly cooperative process, and no intermediate states were found along the transition path. Interaction energies of the information-theoretic model further suggest that heterochromatin domains adopt collapsed, globular three-dimensional conformations that can be stabilized by phase-separated liquid droplets.Our results demonstrate the usefulness of statistical mechanical models and molecular biophysical approaches in interpreting the rich information encoded in epigenomics data.
Infectious Entry of Merkel Cell Polyomavirus
Authors: Becker Miriam , Dominguez Melissa , Greune Lilo , Soria-Martinez Laura , Pfleiderer Moritz M. , Schowalter Rachel , Buck Christopher B. , Blaum Bärbel S. , Alexander Schmidt M. , Schelhaas Mario 
Published: October 2018

AbstractMerkel Cell Polyomavirus (MCPyV) is a small, non-enveloped tumor virus associated with an aggressive form of skin cancer, the Merkel cell carcinoma (MCC). MCPyV infections are highly prevalent in the human population with MCPyV virions being continuously shed from human skin. However, the precise host cell tropism(s) of MCPyV remains unclear: MCPyV is able to replicate within a subset of dermal fibroblasts, but MCPyV DNA has also been detected in a variety of other tissues. However, MCPyV appears different from other polyomaviruses as it requires sulfated polysaccharides such as heparan sulfates and/or chondroitin sulfates for initial attachment. Like other polyomaviruses, MCPyV engages sialic acid as a (co-receptor). To explore the infectious entry process of MCPyV, we analyzed the cell biological determinants of MCPyV entry into A549 cells, a highly transducible lung carcinoma cell line, in comparison to well-studied simian virus 40 and a number of other viruses. Our results indicate that MCPyV enters cells via caveolar/lipid raft-mediated endocytosis but not macropinocytosis, clathrin-mediated endocytosis or glycosphingolipid-enriched carriers. The viruses internalized in small endocytic pits that led the virus to endosomes and from there to the endoplasmic reticulum (ER). Similar to other polyomaviruses, trafficking required microtubular transport, acidification of endosomes, and a functional redox environment. To our surprise, the virus was found to acquire a membrane envelope within endosomes, a phenomenon not reported for other viruses. Only minor amounts of viruses reached the ER, while the majority was retained in endosomal compartments suggesting that endosome-to-ER trafficking is a bottleneck during infectious entry.ImportanceMCPyV is the first polyomavirus directly implicated in the development of an aggressive human cancer, the Merkel Cell Carcinoma (MCC). Although MCPyV is constantly shed from healthy skin, MCC incidence increases among aging and immunocompromised individuals. To date, the events connecting initial MCPyV infection and subsequent transformation still remain elusive. MCPyV differs from other known polyomaviruses concerning its cell tropism, entry receptor requirements, and infection kinetics. In this study, we examined the cellular requirements for endocytic entry as well as the subcellular localization of incoming virus particles. A thorough understanding of the determinants of the infectious entry pathway and the specific biological niche will benefit prevention of virus-derived cancers such as MCC.
PRODIGY: personalized prioritization of driver genes
Authors: Dinstag Gal , Shamir Ron 
Published: October 2018

AbstractBackgroundEvolution of cancer is driven by few somatic mutations that disrupt cellular processes, causing abnormal proliferation and tumor development, while most somatic mutations have no impact on progression. Distinguishing those mutated genes that drive tumorigenesis in a patient is a primary goal in cancer therapy: Knowledge of these genes and the pathways on which they operate can illuminate disease mechanisms and indicate potential therapies and drug targets. Current research focuses mainly on cohort-level driver gene identification, but patient-specific driver gene identification remains a challenge.MethodsWe developed a new algorithm for patient-specific ranking of driver genes. The algorithm, called PRODIGY, analyzes the expression and mutation profiles of the patient along with data on known pathways and protein-protein interactions. Prodigy quantifies the impact of each mutated gene on every deregulated pathway using the prize collecting Steiner tree model. Mutated genes are ranked by their aggregated impact on all deregulated pathways.ResultsIn testing on five TCGA cancer cohorts spanning >2500 patients and comparison to validated driver genes, Prodigy outperformed extant methods and ranking based on network centrality measures. Our results pinpoint the pleiotropic effect of driver genes and show that Prodigy is capable of identifying even very rare drivers. Hence, Prodigy takes a step further towards personalized medicine and treatment.AvailabilityThe Prodigy R package is available at: https://github.com/Shamir-Lab/PRODIGY.
Is physiological stress state reflected in acoustic structure of vocalizations? An experimental test in wild North American red squirrels
Authors: Sehrsweeney Matt , Wilson David R. , Bain Maggie , Boutin Stan , Lane Jeffrey E. , McAdam Andrew G. , Dantzer Ben 
Published: October 2018

AbstractAcoustic signaling is an important means by which animals communicate both stable and labile characteristics. Although it is widely appreciated that vocalizations can convey information on labile state, such as fear and aggression, very few studies have experimentally examined the acoustic expression of short-term stress state. The transmission of such information about physiological state could have broad implications, potentially allowing other individuals to modify their behavior or life history traits in response to this public information. North American red squirrels (Tamiasciurus hudsonicus) produce vocalizations known as rattles that advertise territorial ownership. We examined the influence of changes in physiological stress state on rattle acoustic structure through the application of a stressor (trapping and handling the squirrels) and by provisioning squirrels with exogenous glucocorticoids (GCs). We characterized the acoustic structure of rattles emitted by these squirrels by measuring rattle duration, mean frequency, and entropy. Our results provide mixed evidence that rattles show a “stress signature”. When squirrels were trapped and handled, they produced rattles that were longer in duration with a higher frequency and increased entropy. However, squirrels that were administered exogenous GCs had similar rattle duration, frequency, and entropy as squirrels that received control treatments and unmanipulated (unfed) squirrels. Our results indicate that short-term stress does affect the acoustic structure of vocalizations, but elevated circulating GC levels are not solely responsible for such changes.
Personalized and graph genomes reveal missing signal in epigenomic data
Authors: Groza Cristian , Kwan Tony , Soranzo Nicole , Pastinen Tomi , Bourque Guillaume 
Published: October 2018

AbstractBackgroundEpigenomic studies that use next generation sequencing experiments typically rely on the alignment of reads to a reference sequence. However, because of genetic diversity and the diploid nature of the human genome, we hypothesized that using a generic reference could lead to incorrectly mapped reads and bias downstream results.ResultsWe show that accounting for genetic variation using a modified reference genome (MPG) or a denovo assembled genome (DPG) can alter histone H3K4me1 and H3K27ac ChIP-seq peak calls by either creating new personal peaks or by the loss of reference peaks. MPGs are found to alter approximately 1% of peak calls while DPGs alter up to 5% of peaks. We also show statistically significant differences in the amount of reads observed in regions associated with the new, altered and unchanged peaks. We report that short insertions and deletions (indels), followed by single nucleotide variants (SNVs), have the highest probability of modifying peak calls. A counter-balancing factor is peak width, with wider calls being less likely to be altered. Next, because high-quality DPGs remain hard to obtain, we show that using a graph personalized genome (GPG), represents a reasonable compromise between MPGs and DPGs and alters about 2.5% of peak calls. Finally, we demonstrate that altered peaks have a genomic distribution typical of other peaks. For instance, for H3K4me1, 518 personal-only peaks were replicated using at least two of three approaches, 394 of which were inside or within 10Kb of a gene.ConclusionsAnalysing epigenomic datasets with personalized and graph genomes allows the recovery of new peaks enriched for indels and SNVs. These altered peaks are more likely to differ between individuals and, as such, could be relevant in the study of various human phenotypes.
Novel Mechanism for Surface Layer Shedding and Regenerating in Bacteria Exposed to Metal-Contaminated Conditions
Authors: Chandramohan Archjana , Duprat Elodie , Remusat Laurent , Zirah Severine , Lombard Carine , Adrienne Kish 
Published: October 2018

AbstractSurface layers (S-layers) are self-assembling, ordered structures composed of repeating protein subunits found as components of the cell walls throughout the Bacteria and the Archaea. S-layers act as an interface between prokaryotic cells and their surrounding environment, and provide protection for microorganisms against diverse environmental stresses including heavy metal stress. We have previously characterized the process by which S-layers serve as a nucleation site for metal mineralization in the presence of high concentration of metals. Here, we test the hypothesis originally proposed in cyanobacteria that a “shedding” mechanism exists in prokaryotes for replacing S-layers that have become mineral-encrusted. We used a metallotolerant gram-positive bacterium bearing an S-layer,Lysinibacillussp. TchIII 20n38, as a model organism. We characterize for the first time a mechanism for resistance to metals through S-layer shedding and regeneration. S-layers nucleate the formation of Fe-mineral on the cell surface, leading to the encrustation of the S-layer. Using a combination of scanning electron microscopy (SEM) and nanoSIMS, we show that mineral-encrusted S-layers are shed by the bacterial cells, and the emerging cells regenerate new S-layers as part of their cell wall structure. This novel mechanism for the survival of prokaryotes in metal-contaminated environments may also provide elements necessary for the development of renewable systems for metal bioremediation.
N6-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis
Authors: Kuppers Daniel A. , Arora Sonali , Lim Yiting , Lim Andrea , Carter Lucas , Corrin Philip , Plaisier Christopher L. , Basom Ryan , Delrow Jeffrey J. , Wang Shiyan , He Housheng Hansen , Torok-Storb Beverly , Hsieh Andrew C. , Paddison Patrick J. 
Published: October 2018

AbstractMany of the regulatory features governing erythrocyte specification, maturation, and associated disorders remain enigmatic. To identify new regulators of erythropoiesis, we performed a functional genomic screen for genes affecting expression of the erythroid marker CD235a/GYPA. Among validating hits were genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including,METTL14,METTL3, andWTAP. We found that m6A MTase activity promotes erythroid gene expression programs and lineage specification through selective translation of >200 m6A marked mRNAs, including those coding for SETD methyltransferase, ribosome, and polyA RNA binding proteins. Remarkably, loss of m6A marks resulted in dramatic loss of H3K4me3 across key erythroid-specific KLF1 transcriptional targets (e.g., Heme biosynthesis genes). Further, each m6A MTase subunit and a subset of their mRNAs targets, includingBRD7,CXXC1,PABPC1,PABPC4,STK40, andTADA2B, were required for erythroid specification. Thus, m6A mRNA marks promote the translation of a network of genes required for human erythropoiesis.