bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Anorectal Manometry Testing in Left Lateral and Lithotomy Positions
Authors: Kadam-Halani Priyanka K. , Pahwa Avita K. , Koelper Nathanael C. , Arya Lily A. , Sammel Mary D. , Andy Uduak U.
Published: October 2018

Objectives

Anorectal manometry (ARM) is typically performed in left lateral position, but many practitioners are more familiar with the lithotomy position. We aimed to evaluate agreement between ARM performed in left lateral and lithotomy positions and patient preference for testing position.

Methods

We performed a prospective comparison study of left lateral versus lithotomy position for women undergoing ARM for the evaluation of fecal incontinence. Women were randomly assigned to undergo testing in either left lateral position first followed by lithotomy position, or vice versa. Women then completed a survey assessing preference of position. We performed Bland-Altman analysis to measure the level of agreement between anorectal measurements obtained in the 2 positions.

Results

Twenty-one women were enrolled (mean age, 65 ± 2.2 years). We noted an acceptable level of agreement between anal pressure values obtained in left lateral versus lithotomy positions: anal resting pressure (mean difference, 0.9 mm Hg; 95% limits of agreement, 30.2 and −28.5) and anal squeeze pressure (mean difference, 1.8 mm Hg; 95% limits of agreement, 54.3 and −50.7). The level of agreement for sensory values was outside the predetermined clinical acceptability range. Most women (17/21 [81%]) reported a “good” or “very good” experience in both positions.

Conclusions

Anorectal manometry testing in the 2 positions can be used interchangeably for anal resting and squeeze pressures, but not for anorectal sensation. This modification can be introduced into clinical practice to accommodate the preference of women and practitioners who favor lithotomy position.
Genome sequence of the corn leaf aphid (Rhopalosiphum maidis Fitch)
Authors: Chen Wenbo , Shakir Sara , Bigham Mahdiyeh , Fei Zhangjun , Jander Georg
Published: October 2018

Background

The corn leaf aphid (Rhopalosiphum maidis Fitch) is the most economically damaging aphid pest on maize (Zea mays), one of the world’s most important grain crops. In addition to causing direct damage due to the removal of photoassimilates, R. maidis transmits several destructive maize viruses, including Maize yellow dwarf virus, Barley yellow dwarf virus, Sugarcane mosaic virus, and Cucumber mosaic virus.

Findings

A 326-Mb genome assembly of BTI-1, a parthenogenetically reproducing R. maidis clone, was generated with a combination of PacBio (208-fold coverage) and Illumina sequencing (80-fold coverage), which contains a total of 689 contigs with an N50 size of 9.0 Mb. The contigs were further clustered into four scaffolds using the Phase Genomics Hi-C interaction maps, consistent with the commonly observed 2n = 8 karyotype of R. maidis. Most of the assembled contigs (473 spanning 321 Mb) were successfully orientated in the four scaffolds. The R. maidis genome assembly captured the full length of 95.8% of the core eukaryotic genes, suggesting that it is highly complete. Repetitive sequences accounted for 21.2% of the assembly, and a total of 17,647 protein-coding genes were predicted in the R. maidis genome with integrated evidence from ab initio and homology-based gene predictions and transcriptome sequences generated with both PacBio and Illumina. An analysis of likely horizontally transferred genes identified two from bacteria, seven from fungi, two from protozoa, and nine from algae.

Conclusions

A high-quality R. maidis genome was assembled at the chromosome level. This genome sequence will enable further research related to ecological interactions, virus transmission, pesticide resistance, and other aspects of R. maidis biology. It also serves as a valuable resource for comparative investigation of other aphid species.
Comparative validation of breast cancer risk prediction models and projections for future risk stratification
Authors: Pal Choudhury Parichoy , Wilcox Amber N. , Brook Mark N. , Zhang Yan , Ahearn Thomas , Orr Nick , Coulson Penny , Schoemaker Minouk J. , Jones Michael E. , Gail Mitchell H. , Swerdlow Anthony J. , Chatterjee Nilanjan , Garcia-Closas Montserrat
Published: October 2018

Background

Well-validated risk models are critical for risk stratified breast cancer prevention. We used the Individualized Coherent Absolute Risk Estimation (iCARE) tool for comparative model validation of five-year risk of invasive breast cancer in a prospective cohort, and to make projections for population risk stratification.

Methods

Performance of two recently developed models, iCARE-BPC3 and iCARE-Lit, were compared with two established models (BCRAT, IBIS) based on classical risk factors in a UK-based cohort of 64,874 women (863 cases) aged 35-74 years. Risk projections in US White non-Hispanic women aged 50-70 years were made to assess potential improvements in risk stratification by adding mammographic breast density (MD) and polygenic risk score (PRS).

Results

The best calibrated models were iCARE-Lit (expected to observed number of cases (E/O)=0.98 (95% confidence interval [CI]=0.87 to 1.11)) for women younger than 50 years; and iCARE-BPC3 (E/O=1.00 (0.93 to 1.09)) for women 50 years or older. Risk projections using iCARE-BPC3 indicated classical risk factors can identify ~500,000 women at moderate to high risk (>3% five-year risk). Additional information on MD and a PRS based on 172 variants is expected to increase this to ~3.6 million, and among them, ~155,000 invasive breast cancer cases are expected within five years.

Conclusions

iCARE models based on classical risk factors perform similarly or better than BCRAT or IBIS. Addition of MD and PRS can lead to substantial improvements in risk stratification. Independent prospective validation of integrated models is needed prior to clinical evaluation risk stratified breast cancer screening and prevention.
Evaluation of the NCCN guidelines using the RIGHT Statement and AGREE II instrument: a cross-sectional review
Authors: Wayant Cole , Cooper Craig , Turner D’Arcy , Vassar Matt
Published: October 2018

Introduction

Robust, clearly reported clinical practice guidelines (CPGs) are essential for evidence-based clinical practice. The Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument were published to improve the methodological and reporting quality in healthcare CPGs.

Methods

We applied the RIGHT statement checklist and AGREE II instrument to 48 National Comprehensive Cancer Network (NCCN) guidelines. Our primary objective was to assess the adherence to RIGHT and AGREE II items. Since neither RIGHT nor AGREE-II can judge the clinical usefulness of a guideline, our study is designed to only focus on the methodological and reporting quality of each guideline.

Results

The NCCN guidelines demonstrated notable strengths and weaknesses. For example, RIGHT statement items 19 (conflicts of interest), 7b (description of subgroups), and 13a (clear, precise recommendations) were fully reported in all guidelines. However, the guidelines inconsistently incorporated patient values and preferences and cost, nor did they consistently describe the method for assessing the quality and certainty of evidence. Regarding the AGREE II instrument, the NCCN guidelines scored highly on the domains 4 (clear, precise recommendations) and 6 (handling of conflicts of interest), but lowest on domain 2 (inclusion of all relevant stakeholders).

Conclusions

In this investigation we found that NCCN CPGs demonstrate key strengths and weaknesses with respect to the reporting of key items essential to CPGs. We recommend the continued use of NCCN guidelines and adherence to the RIGHT and AGREE II items. Doing so serves to improve the evidence delivered to healthcare providers, thus potentially improving patient care.
A fast and general method to empirically estimate the complexity of brain responses to transcranial and intracranial stimulations
Authors: Comolatti Renzo , Pigorini Andrea , Casarotto Silvia , Fecchio Matteo , Faria Guilherme , Sarasso Simone , Rosanova Mario , Gosseries Olivia , Boly Mélanie , Bodart Olivier , Ledoux Didier , Brichant Jean-François , Nobili Lino , Laureys Steven , Tononi Giulio , Massimini Marcello , Casali Adenauer G.
Published: October 2018

Background

The Perturbational Complexity Index (PCI) was recently introduced to assess the capacity of thalamocortical circuits to engage in complex patterns of causal interactions. While showing high accuracy in detecting consciousness in brain injured patients, PCI depends on elaborate experimental setups and offline processing and has restricted applicability to other types of brain signals beyond transcranial magnetic stimulation and high-density EEG (TMS/hd-EEG) recordings.

Objective

We aim to address these limitations by introducing PCIST, a fast method for estimating perturbational complexity of any given brain response signal.

Methods

PCISTis based on dimensionality reduction and state transitions (ST) quantification of evoked potentials. The index was validated on a large dataset of TMS/hd-EEG recordings obtained from 108 healthy subjects and 108 brain injured patients, and tested on sparse intracranial recordings (SEEG) of 9 patients undergoing intra-cerebral single-pulse electrical stimulation (SPES).

Results

When calculated on TMS/hd-EEG potentials, PCISTperformed with the same accuracy as the original PCI, while improving on the previous method by being computed in less than a second and requiring a simpler set-up. In SPES/SEEG signals, the index was able to quantify a systematic reduction of intracerebral complexity during sleep, confirming the occurrence of state-dependent changes in the effective connectivity of thalamocortical circuits, as originally assessed through TMS/hd-EEG.

Conclusions

PCISTrepresents a fundamental advancement towards the implementation of a reliable and fast clinical tool for the bedside assessment of consciousness as well as a general measure to explore the neuronal mechanisms of loss/recovery of brain complexity across scales and models.
MicroED data collection with SerialEM
Authors: Jason de la Cruz M. , Martynowycz Michael W. , Hattne Johan , Gonen Tamir
Published: October 2018

We developed a procedure for the cryoEM method MicroED using SerialEM. With this approach, SerialEM coordinates stage rotation, microscope operation, and camera functions for automated continuous-rotation MicroED data collection. More than 300 datasets can be collected overnight in this way, facilitating high-throughput MicroED data collection for large-scale data analyses.
Causal Association between Birth Weight and Adult Diseases: Evidence from a Mendelian Randomisation Analysis
Authors: Zeng Ping , Zhou Xiang
Published: October 2018

Background

It has long been hypothesized that birth weight has a profound long-term impact on individual predisposition to various diseases at adulthood: a hypothesis commonly referred to as the fetal origins of adult diseases. However, it is not fully clear to what extent the fetal origins of adult diseases hypothesis holds and it is also not completely known what types of adult diseases are causally affected by birth weight. Determining the causal impact of birth weight on various adult diseases through traditional randomised intervention studies is a challenging task.

Methods

Mendelian randomisation was employed and multiple genetic variants associated with birth weight were used as instruments to explore the relationship between 21 adult diseases and 38 other complex traits from 37 large-scale genome-wide association studies up to 340,000 individuals of European ancestry. Causal effects of birth weight were estimated using inverse-variance weighted methods. The identified causal relationships between birth weight and adult diseases were further validated through extensive sensitivity analyses and simulations.

Results

Among the 21 adult diseases, three were identified to be inversely causally affected by birth weight with a statistical significance level passing the Bonferroni corrected significance threshold. The measurement unit of birth weight was defined as its standard deviation (i.e. 488 grams), and one unit lower birth weight was causally related to an increased risk of coronary artery disease (CAD), myocardial infarction (MI), type 2 diabetes (T2D) and BMI-adjusted T2D, with the estimated odds ratios of 1.34 [95% confidence interval (CI) 1.17 - 1.53,p= 1.54E-5], 1.30 (95% CI 1.13 - 1.51,p= 3.31E-4), 1.41 (95% CI 1.15 - 1.73,p= 1.11E-3) and 1.54 (95% CI 1.25 - 1.89,p= 6.07E-5), respectively. All these identified causal associations were robust across various sensitivity analyses that guard against various confounding due to pleiotropy or maternal effects as well as inverse causation. In addition, analysis on 38 additional complex traits found that the inverse causal association between birth weight and CAD/MI/T2D was not likely to be mediated by other risk factors such as blood-pressure related traits and adult weight.

Conclusions

The results suggest that lower birth weight is causally associated with an increased risk of CAD, MI and T2D in later life, supporting the fetal origins of adult diseases hypothesis.
Genomic and transcriptomic determinants of therapy resistance and immune landscape evolution during anti-EGFR treatment in colorectal cancer
Authors: Woolston Andrew , Khan Khurum , Spain Georgia , Barber Louise J , Griffiths Beatrice , Exposito Reyes Gonzalez , Patil Yatish , Mansukhani Sonia , Davies Matthew N , Furness Andrew , Sclafani Francesco , Peckitt Clare , Kouvelakis Kyriakos , Ranftl Romana , Begum Ruwaida , Rana Isma , Thomas Janet , Bryant Annette , Quezada Sergio , Wotherspoon Andrew , Khan Nasir , Fotiadis Nikolaos , Marafioti Teresa , Powles Thomas , Calvo Fernando , Guettler Sebastian , von Loga Katharina , Rao Sheela , Watkins David , Starling Naureen , Chau Ian , Sadanandam Anguraj , Cunningham David , Gerlinger Marco
Published: October 2018

Anti-epidermal growth factor receptor (EGFR) antibodies (anti-EGFR-Ab) are effective in a subgroup of patients with metastatic colorectal cancer (CRC). We applied genomic and transcriptomic analyses to biopsies from 35 RAS wild-type CRCs treated with the anti-EGFR-Ab cetuximab in a prospective trial to interrogate the molecular resistance landscape. This validated transcriptomic CRC-subtypes as predictors of cetuximab benefit; identified novel associations of NF1-inactivation and non-canonical RAS/RAF-aberrations with primary progression; and of FGF10- and non-canonical BRAF-aberrations with AR. No genetic resistance drivers were detected in 64% of AR biopsies. The majority of these had switched from the cetuximab-sensitive CMS2-subtype pretreatment to the fibroblast- and growth factor-rich CMS4-subtype at progression. Fibroblast supernatant conferred cetuximab resistance in vitro, together supporting subtype-switching as a novel mechanism of AR. Cytotoxic immune infiltrates and immune-checkpoint expression increased following cetuximab responses, potentially providing opportunities to treat CRCs with molecularly heterogeneous AR with immunotherapy.
The First Implication of Image Processing Techniques on Influenza A Virus Sub-Typing Based on HA/NA Protein Sequences, using Convolutional Deep Neural Network
Authors: Ahsan Reza , Ebrahimi Mansour
Published: October 2018

Increase in influenza A virus host range throughout its evolution has given rise to major concerns worldwide. Although the increasing host range mechanism of the virus is largely unknown; persistent genetic mutations have been blamed as a key factor in the re-organization of the host response and the host range. To uncover the underlying core bases of the two important antigenic proteins of influenza virus (HA and NA), functional data mining and image processing analysis of over 8000 protein sequences of different HA and NA subtypes were performed. Each amino acid sequence in HA or NA proteins sat as a feature or variable and two polynomial datasets were created and subjected into conventional prediction models. The average accuracies of these predictive models for HA subtype classifications ranged from 38.9% for SVM to 87.2% for Decision Tree models. NA subtype classification with conventional prediction models varied from 81.3% to 99.87% for SVM and KNN models, respectively. Then amino acid sequence datasets were converted to binary images; subtypes feature sat as target variable, and target label determined by image processing convolution neural network. The performances of Image processing models (convolutional neural network) on binary images for both HA and NA datasets reached to 100%; and the application of Gabor2 filter decreased the time for the predicting model to reach the best performance for HA subtype; while it increased the epochs time for NA subtype classification.

For the first time ever, converting influenza virus’ HA and NA amino acid sequences into the binary image datasets and their classifications by convolution neural network increased the prediction accuracies and performances to the highest possible point. The finding of this paper paves new avenues for virus classification based on antigenic HA and NA amino acid profiles, and easily classifying and predicting the possible future emerging strains of pandemic influenza.
Antibiotic resistance is lower in Staphylococcus aureus isolated from antibiotic-free raw meat as compared to conventional raw meat
Authors: Kyler J. Haskell , Samuel R. Schriever , Kenisi D. Fonoimoana , Benjamin Haws , Bryan B. Hair , Trevor M. Wienclaw , Joseph G. Holmstead , Andrew B. Barboza , Erik T. Berges , Matthew J. Heaton , Berges Bradford K.
Published: October 2018

The frequent use of antibiotics contributes to antibiotic resistance in bacteria, resulting in an increase in infections that are difficult to treat. Livestock are commonly administered antibiotics in their feed, but there is current interest in raising animals that are only administered antibiotics during active infections. Staphylococcus aureus (SA) is a common pathogen of both humans and livestock raised for human consumption. SA has achieved high levels of antibiotic resistance, but the origins and locations of resistance selection are poorly understood. We determined the prevalence of SA and MRSA in conventional and antibiotic-free (AF) meat products, and also measured rates of antibiotic resistance in these isolates. We isolated SA from raw conventional turkey, chicken, beef, and pork samples and also from AF chicken and turkey samples. We found that SA contamination was common, with an overall prevalence of 22.64% (range of 2.78-30.77%) in conventional meats and 13.0% (range of 12.5-13.2%) in AF poultry meats. MRSA was isolated from 15.72% of conventional raw meats (range of 2.78-20.41%) but not from AF-free meats. The degree of antibiotic resistance in conventional poultry products was significantly higher vs AF poultry products for a number of different antibiotics, and while multi-drug resistant strains were relatively common in conventional meats none were detected in AF meats. The use of antibiotics in livestock contributes to high levels of antibiotic resistance in SA found in meat products. Our results support the use of AF conditions for livestock in order to prevent antibiotic resistance development in SA.
The outer membrane proteins OmpA, FhuA, OmpF, EstA, BtuB and OmpX have unique lipopolysaccharide fingerprints
Authors: Shearer Jonathan , Jefferies Damien , Khalid Syma
Published: October 2018

The outer membrane of Gram-negative bacteria has a highly complex asymmetrical architecture, containing a mixture of phospholipids in the inner leaflet and in the outer leaflet they contain almost exclusively lipopolysaccharide (LPS) molecules. In E. coli, the outer membrane contains a wide range proteins with a beta barrel architecture, that vary in size from the smallest having eight strands to larger barrels composed of twenty-two strands. Here we report coarse-grain molecular dynamics simulations of six proteins from the E. coli outer membrane OmpA, OmpX, BtuB, FhuA, OmpF and EstA in a range of membrane environments, which are representative of the in vivo for different strains of E. coli. We show that each protein has a unique pattern of interaction with the surrounding membrane, which is influenced by the composition of the protein, the level of LPS in the outer leaflet and the differing mobilities of the lipids in the two leaflets of the membrane. Overall we present analyses from over 200 microseconds of simulation for each protein.

Author summary

We present data from over 200 microseconds of coarse-grain simulations that show the complexities of protein-lipid interactions within the outer membranes of Gram-negative bacteria. We show that the slow movement of lipolysaccharide molecules necessitate simulations of over 30 microsecond duration to achieve converged properties such as protein tilt angle. Each of the six proteins studied here shows a unique pattern of interactions with the outer membrane and thus constitute a ‘fingerprint’ or ‘signature’.
Interplay between consensus and divergent RNA polymerase II C-terminal domain repeats in viability and targeting
Authors: Lu Feiyue , Portz Bede , Gilmour David S.
Published: October 2018

The carboxy-terminal domain (CTD) of RNA polymerase II (Pol II) is composed of repeats of the consensus YSPTSPS, and is an essential binding scaffold for transcription-associated factors. Metazoan CTDs have well-conserved lengths and sequence compositions arising from the evolution of divergent motifs, features thought to be essential for development. To the contrary, we show that a truncated CTD composed solely of YSPTSPS repeats fully supportsDrosophilaviability, but a CTD with enough YSPTSPS repeats to match the length of the wild-typeDrosophilaCTD is defective. Furthermore, a fluorescently-tagged CTD lacking the rest of Pol II dynamically enters transcription compartments, indicating that the CTD functions as a signal sequence. However, CTDs with too many YSPTSPS repeats are more prone to localize to static nuclear foci independent of the chromosomes. We propose that the sequence complexity of the CTD offsets aberrant behavior caused by excessive repetitive sequences without compromising its targeting function.
Mutational meltdown in asexual populations doomed to extinction
Authors: Olofsson Peter , Chipkin Logan , Daileda Ryan C. , Azevedo Ricardo B. R.
Published: October 2018

Asexual populations are expected to accumulate deleterious mutations through a process known as Muller’s ratchet. Lynch and colleagues proposed that the ratchet eventually results in a vicious cycle of mutation accumulation and population decline that drives populations to extinction. They called this phenomenon mutational meltdown. Here, we analyze mutational meltdown using a multi-type branching process model where, in the presence of mutation, populations are doomed to extinction. We analyse the change in size and composition of the population and the time of extinction under this model.
Rhopalocnemis phalloides has one of the most reduced and mutated plastid genomes known
Authors: Schelkunov Mikhail I. , Nuraliev Maxim S. , Logacheva Maria D.
Published: October 2018

Although most plant species are photosynthetic, several hundred species have lost the ability to photosynthesize and instead obtain nutrients via various types of heterotrophic feeding. Their genomes, especially plastid genomes, markedly differ from the genomes of photosynthetic plants. In this work, we describe the sequenced plastid genome of the heterotrophic plant Rhopalocnemis phalloides, which belongs to the family Balanophoraceae and feeds by parasitizing on other plants. The genome is highly reduced (18 622 base pairs versus approximately 150 kilobase pairs in autotrophic plants) and possesses an outstanding AT content, 86.8%, the highest of all sequenced plant plastid genomes. The gene content of this genome is quite typical of heterotrophic plants, with all of the genes related to photosynthesis having been lost. The remaining genes are notably distorted by a high mutation rate and the aforementioned AT content. The high AT content has led to sequence convergence between some of the remaining genes and their homologues from AT-rich plastid genomes of protists. Overall, the plastid genome of R. phalloides is one of the most unusual plastid genomes known.
A relative comparison between Hidden Markov- and Log-Linear-based models for differential expression analysis in a real time course RNA sequencing data
Authors: Gholizadeh Fatemeh , Salehi Zahra , banaei-Moghaddam Ali Mohammad , Rahimi Foroushani Abbas , kavousi Kaveh
Published: October 2018

With the advent of the Next Generation Sequencing technologies, RNA-seq has become known as an optimal approach for studying gene expression profiling. Particularly, time course RNA-seq differential expression analysis has been used in many studies to identify candidate genes. However, applying a statistical method to efficiently identify differentially expressed genes (DEGs) in time course studies is challenging due to inherent characteristics of such data including correlation and dependencies over time. Here we aim to relatively compare EBSeq-HMM, a Hidden Markov-based model, with multiDE, a Log-Linear-based model, in a real time course RNA sequencing data. In order to conduct the comparison, common DEGs detected by edgeR, DESeq2 and Voom (referred to as Benchmark DEGs) were utilized as a measure. Each of the two models were compared using different normalization methods. The findings revealed that multiDE identified more Benchmark DEGs and showed a higher agreement with them than EBSeq-HMM. Furthermore, multiDE and EBSeq-HMM displayed their best performance using TMM and Upper-Quartile normalization methods, respectively.
The jellyfish genome sheds light on the early evolution of active predation
Authors: Kim Hak-Min , Weber Jessica A. , Lee Nayoung , Park Seung Gu , Sung Cho Yun , Bhak Youngjune , Lee Nayun , Jeon Yeonsu , Jeon Sungwon , Luria Victor , Karger Amir , Kirschner Marc W. , Jo Ye Jin , Woo Seonock , Shin Kyoungsoon , Chung Oksung , Ryu Jae-Chun , Yim Hyung-Soon , Lee Jung-Hyun , Edwards Jeremy S. , Manica Andrea , Bhak Jong , Yum Seungshic
Published: October 2018

Background

Unique among cnidarians, jellyfish have remarkable morphological and biochemical innovations that allow them to actively hunt in the water column. One of the first animals to become free-swimming, jellyfish employ pulsed jet propulsion and venomous tentacles to capture prey.

Results

To understand these key innovations, we sequenced the genome of the giant Nomura’s jellyfish (Nemopilema nomurai), the transcriptomes of its bell and tentacles, and transcriptomes across tissues and developmental stages of the Sanderia malayensis jellyfish. Analyses of Nemopilema and other cnidarian genomes revealed adaptations associated with swimming, marked by codon bias in muscle contraction and expansion of neurotransmitter genes, along with expanded Myosin type II family and venom domains; possibly contributing to jellyfish mobility and active predation. We also identified gene family expansions of Wnt and posterior Hox genes, and discovered the important role of retinoic acid signaling in this ancient lineage of metazoans, which together may be related to the unique jellyfish body plan (medusa formation).

Conclusions

Taken together, the jellyfish genome and transcriptomes genetically confirm their unique morphological and physiological traits that have combined to make these animals one of the world’s earliest and most successful multi-cellular predators.
Heart Rate n-Variability (HRnV): A Novel Representation of Beat-to-Beat Variation in Electrocardiogram
Authors: Liu Nan , Guo Dagang , Koh Zhi Xiong , Wah Ho Andrew Fu , Hock Ong Marcus Eng
Published: October 2018

Heart rate variability (HRV) is a widely adopted tool for evaluating changes in cardiac autonomic regulation. The majority of efforts have focused on developing methods to assess HRV by deriving sophisticated parameters with linear and nonlinear techniques and adopting advanced signal processing tools for efficient noise removal and accurate QRS detection. In this paper, we propose a novel representation of beat-to-beat variation in an electrocardiogram (ECG), called heart rate n-variability (HRnV), as an alternative to conventional HRV measures. We derived two novel HRnV measures based on non-overlapped and overlapped RR intervals. We also conducted a simulation study by using an ECG record from the MIT-BIH Normal Sinus Rhythm Database to demonstrate the feasibility of calculating HRnV parameters. Among the time domain parameters, we observed that the values were generally incremental with the increase in n. We observed the same trend of changes for the frequency domain parameters. In the nonlinear analysis, the differences between HRV and HRnV from Poincare plot measures were obvious, while those from entropy and detrended fluctuation analysis metrics were not. HRnV measures enable us to augment conventional HRV measures with additional parameters. Although issues remain to be addressed regarding HRnV, we hope to stimulate a new stream of research on this new representation of HRV. HRnV is an important addition to HRV and will contribute to extending the landscape of current studies on HRV.
DNA-mediated self-assembly of gold nanoparticles on protein superhelix
Authors: Zhang Tao , André Ingemar
Published: October 2018

Recent advances in protein engineering have enabled methods to control the self-assembly of protein on various length-scales. One attractive application for designed proteins is to direct the spatial arrangement of nanomaterials of interest. Until now, however, a reliable conjugation method is missing to facilitate site-specific positioning. In particular, bare inorganic nanoparticles tend to aggregate in the presence of buffer conditions that are often required for the formation of stable proteins. Here, we demonstrated a DNA mediated conjugation method to link gold nanoparticles with protein structures. To achieve this, we constructed de novo designed protein fibers based on previously published uniform alpha-helical units. DNA modification rendered gold nanoparticles with increased stability against ionic solutions and the use of complementary strands hybridization guaranteed the site-specific binding to the protein. The combination of high resolution placement of anchor points in designed protein assemblies with the increased control of covalent attachment through DNA binding can enable investigations of multilevel physical coupling events of nanocomponents on protein templates and expand the application of protein structures to material sciences.
Evolution of gene regulatory networks by means of selection and random genetic drift
Authors: Kioukis Antonios , Pavlidis Pavlos
Published: October 2018

The evolution of a population by means of genetic drift and natural selection operating on a gene regulatory network (GRN) of an individual has not been scrutinized in depth. Thus, the relative importance of various evolutionary forces and processes on shaping genetic variability in GRNs is understudied. Furthermore, it is not known if existing tools that identify recent and strong positive selection from genomic sequences, in simple models of evolution, can detect recent positive selection when it operates on GRNs. Here, we propose a simulation framework, called EvoNET, that simulates forward-in-time the evolution of GRNs in a population. Since the population size is finite, random genetic drift is explicitly applied. The fitness of a mutation is not constant, but we evaluate the fitness of each individual by measuring its genetic distance from an optimal genotype. Mutations and recombination may take place from generation to generation, modifying the genotypic composition of the population. Each individual goes through a maturation period, where its GRN reaches equilibrium. At the next step, individuals compete to produce the next generation. As time progresses, the beneficial genotypes push the population higher in the fitness landscape. We examine properties of the GRN evolution such as robustness against the deleterious effect of mutations and the role of genetic drift. We confirm classical results from Andreas Wagner’s work that GRNs show robustness against mutations and we provide new results regarding the interplay between random genetic drift and natural selection.
Striking reduction in neurons and glial cells in anterior thalamic nuclei of older patients with Down’s syndrome
Authors: Perry James C. , Pakkenberg Bente , Vann Seralynne D.
Published: October 2018

The anterior thalamic nuclei are important for spatial and episodic memory; however, there is surprisingly little information about how these nuclei are affected in many conditions that present with memory impairments, including Down’s syndrome. To assess the status of the anterior thalamic nuclei in Down’s syndrome we quantified neurons and glial cells in the brains from four older patients with this condition. There was a striking reduction in the volume of the anterior thalamic nuclei and this appeared to reflect the loss of approximately 70% of neurons. The number of glial cells was also reduced but to a lesser degree than neurons. The anterior thalamic nuclei appear to be particularly sensitive to effects of aging in Down’s syndrome and the pathology in this region likely contributes to the memory impairments observed. These findings re-affirm the importance of assessing the status of the anterior thalamic nuclei in conditions where memory impairments have been principally assigned to pathology in the medial temporal lobe.
Modeling cellular response in large-scale radiogenomic databases to advance precision radiotherapy
Authors: Manem Venkata SK , Lambie Meghan , Smirnov Petr , Kofia Victor , Freeman Mark , Koritzinsky Marianne , Abazeed Mohamed E , Haibe-Kains Benjamin , Bratman Scott V
Published: October 2018

Radiotherapy is integral to the care of a majority of cancer patients. Despite differences in tumor responses to radiation (radioresponse), dose prescriptions are not currently tailored to individual patients. Recent large-scale cancer cell line databases hold the promise of unravelling the complex molecular arrangements underlying cellular response to radiation, which is critical to novel predictive biomarker discovery. Here, we present RadioGx, a computational platform for integrative analyses of radioresponse using radiogenomic databases. We first used RadioGx to investigate the robustness of radioresponse assays and indicators. We then combined radioresponse and genome-wide molecular data with established radiobiological models to predict molecular pathways that are relevant for individual tissue types and conditions. We also applied RadioGx to pharmacogenomic data to identify several classes of drugs whose effects correlate with radioresponse. RadioGx provides a unique computational toolbox to advance preclinical research for radiation oncology and precision medicine.
Adding function to the genome of AfricanSalmonellaST313
Authors: Canals Rocío , Hammarlöf Disa L. , Kröger Carsten , Owen Siân V. , Fong Wai Yee , Lacharme-Lora Lizeth , Zhu Xiaojun , Wenner Nicolas , Carden Sarah E. , Honeycutt Jared , Monack Denise M. , Kingsley Robert A. , Brownridge Philip , Chaudhuri Roy R. , Rowe Will P. M. , Predeus Alexander V. , Hokamp Karsten , Gordon Melita A. , Hinton Jay C. D.
Published: October 2018

SalmonellaTyphimurium ST313 causes invasive nontyphoidalSalmonella(iNTS) disease in sub-Saharan Africa, targeting susceptible HIV+, malarial or malnourished individuals. An in-depth genomic comparison between the ST313 isolate D23580, and the well-characterized ST19 isolate 4/74 that causes gastroenteritis across the globe, revealed extensive synteny. To understand how the 856 nucleotide variations generated phenotypic differences, we devised a large-scale experimental approach that involved the global gene expression analysis of strains D23580 and 4/74 grown in sixteen infection-relevant growth conditions. Comparison of transcriptional patterns identified virulence and metabolic genes that were differentially expressed between D23580 versus 4/74, many of which were validated by proteomics. We also uncovered theS.Typhimurium D23580 and 4/74 genes that showed expression differences during infection of murine macrophages. Our comparative transcriptomic data are presented in a new enhanced version of theSalmonellaexpression compendium SalComD23580:bioinf.gen.tcd.ie/cgi-bin/salcom_v2.pl. We discovered that the ablation of melibiose utilization was caused by 3 independent SNP mutations in D23580 that are shared across ST313 lineage 2, suggesting that the ability to catabolise this carbon source has been negatively selected during ST313 evolution. The data revealed a novel plasmid maintenance system involving a plasmid-encoded CysS cysteinyl-tRNA synthetase, highlighting the power of large-scale comparative multi-condition analyses to pinpoint key phenotypic differences between bacterial pathovariants.
Parallel comparison of pre-conditioning and post-conditioning effects in human cancers and keratinocytes upon acute gamma irradiation
Authors: Cohen Jason , Vo Nguyen T. K. , Seymour Colin B. , Mothersill Carmel E.
Published: October 2018

PURPOSE

To determine and compare the effects of pre-conditioning and post-conditioning towards gamma radiation responses in human cancer cells and keratinocytes

MATERIALS AND METHODS

The clonogenic survival of glioblastoma cells (T98G), keratinocytes (HaCaT), and colorectal carcinoma cells (HCT116 p53+/+and p53-/-) was assessed following gamma ray exposure from a Cs-137 source. The priming dose preceded the challenge dose in pre-conditioning whereas the priming dose followed the challenge dose in post-conditioning. The priming dose was either 5 mGy or 0.1 Gy. The challenge dose was 0.5 – 5 Gy.

RESULTS

In both pre- and post-conditioning where the priming dose was 0.1 Gy and the challenge dose was 4 Gy, RAR developed in T98G but not in HaCaT cells. In HCT116 p53+/+, pre-conditioning had either no effect or a radiosensitizing effect and whereas post-conditioning induced either radiosensitizing or radioadaptive effect. The different observed outcomes were dependent on dose, the time interval between the priming and challenge dose, and the time before the first irradiation. Post-conditioning effects could occur with a priming dose as low as 5 mGy in HCT116 p53+/+cells. When HCT116 cells had no p53 protein expression, the radiosensitizing or radioadaptive response by the conditioning effect was abolished.

CONCLUSIONS

The results suggest that radiation conditioning responses are complex and depend on at least the following factors: the magnitude of priming/challenge dose, the time interval between priming and challenge dose, p53 status, cell seeding time prior to the first radiation treatment. This work is the first parallel comparison demonstrating the potential outcomes of pre- and post-conditioning in different human cell types using environmentally and medically relevant radiation doses.
Widespread alteration of protein autoinhibition in human cancers
Authors: Jha Ashwani , Bui Jennifer M. , Na Dokyun , Gsponer Jörg
Published: October 2018

Autoinhibition is a prevalent allosteric regulatory mechanism in signaling proteins as it prevents spurious pathway activation and primes for signal propagation only under appropriate inputs. Altered functioning of inhibitory allosteric switches underlies the tumorigenic potential of numerous cancer drivers. However, whether protein autoinhibition is altered generically in cancer cells remains elusive. Here, we reveal that cancer-associated missense mutations and fusion breakpoints are found with significant enrichment within inhibitory allosteric switches across all cancer types, which in the case of the fusion breakpoints is specific to cancer and not present in other diseases. Recurrently disrupted or mutated allosteric switches identify established and new cancer drivers. Cancer-specific mutations in allosteric switches are associated with distinct changes in signaling, and suggest molecular mechanisms for altered protein regulation, which in the case of ASK1, DAPK2 and EIF4G1 were supported by biophysical simulations. Our results demonstrate that autoinhibition-modulating genetic alterations are positively selected for by cancer cells, and that their study provides valuable insights into molecular mechanisms of cancer misregulation.
The use of open government data to citizen empowerment: an empirical validation of a proposed model
Authors: Hossain Md Nahin , Talukder Md Shamim , Hoque Md Rakibul , Bao Yukun
Published: October 2018

Purpose

The purpose of this paper is to measure the impact of open government data (OGD) on citizen empowerment.

Design/methodology/approach

This study advances the body of knowledge on OGD by proposing an integrated research model based on transparency, accountability, participation and collaboration dimensions. The research model was empirically tested using 275 responses using the on-paper survey from the university students and professionals in Bangladesh. Data were analyzed using the structured equation modeling technique.

Findings

Findings revealed that transparency and participation have a positive and significant direct and indirect influence on citizen empowerment through accountability and collaboration. Overall, the four basic pillars of OGD such as transparency, participation, accountability and collaboration interrelated with each other and have the impact on citizen empowerment.

Research limitations/implications

This study has proposed an instrument that sums the dimensions of open government, which avoids tautology and redundancy among OGD dimensions. More research should be done to validate the proposed model and the instruments used in this study.

Practical implications

For the researchers, this study provides a basis for further refinement of individual models of empowerment. For practitioners, understanding the key constructs is crucial to design, refine and implement OGD systems and applications that empower citizens, create public values and strengthen the democratic process.

Originality/value

This research is the first step that empirically investigates the impact of OGD on citizen empowerment which is the ultimate goals of any democratic government.
The effect of accounting methods on financial reporting quality
Authors: Hadiyanto Andrain , Puspitasari Evita , Ghani Erlane K.
Published: October 2018

Purpose

This study aims to examine the relationship between accounting measurement method of biological asset and financial reporting quality. Specifically, this study examines whether using fair value method or the historical cost method on biological asset provides different financial reporting quality.

Design/methodology/approach

This study uses data from 38 agricultural companies that are members of the Roundtable on Sustainable Palm Oil. The annual reports of 38 companies from the Palm Oil Growers over a five-year period starting from 2011 to 2014 are analysed.

Findings

This study shows that companies using historical cost measurement produce less reliable and less relevant information compared to the companies that are using fair value measurement.

Research limitations/implications

The results in this study imply that the use of fair value measurement improves the quality of financial information.

Practical implications

This study supports IASB’s justification of developing IAS 41 as the principle-based standard that better represents the financial information related to biological asset and subsequently lead to good accountability and harmonisation practices.

Originality/value

This study provides evidence on the best measurement to be used in agriculture activities using a larger sample size of few countries. In addition, this study contributes to the existing literature on the effect of accounting methods on financial reporting quality.
Corporate governance and the social performance: investigation on Tunisian financial institutions
Authors: Nekaa Nejia , Boudabbous Sami
Published: October 2018

Purpose

The purpose of this study is to show the specificities of the corporate governance of Tunisian financial institutions and the impact of the internal mechanisms of corporate governance of these institutions on their social performance. It is therefore interesting to establish the existing relationship between these mechanisms of corporate governance and the performance of a financial firm.

Design/methodology/approach

This study aims to study the financial sector, generally characterized by its opacity, its regulation, its evolution and its obscurity. Therefore, a study based on the questionnaire method was recommended. The questionnaire is intended for managers. Therefore, the authors interviewed 138 managers of Tunisian financial institutions dispersed between agencies and headquarters in different regions (Gabes, Tozeur, Gafsa, Sfax, Sousse and Tunisia).

Findings

As a result, an impact on performance was observed according to the empirical study. Therefore, the authors can conclude an essential role of internal mechanisms for improving the social performance of a financial institution. The empirical findings in this paper lead to important conclusions. Indeed, the variables measuring the governance mechanisms have divergent effects on the social performance of the financial institutions subject to the sample. For the variables board of directors, confidence, culture, auditing, they have a positive effect. While, the incentive remuneration effect negatively the social performance.

Originality/value

This study will be based essentially on the financial sector in Tunisia: the credit institutions (22 banks), the establishments of leasing (eight companies of leasing), two factoring companies and two banks of cases which are listed on the Stock Exchange of Tunis (BVMT).
The relationship between the concept of competitive advantage and the value of Catur Paramitha on SMEs in Sarbagita
Authors: Rahyuda I. Ketut , Rahyuda Agoes Ganesha , Rahyuda Henny , Candradewi Made Reina
Published: October 2018

Purpose

This study aimed to determine the relationship between the concept of competitive advantage and the value of Catur Paramitha on small and medium enterprises (SMEs) in Sarbagita.

Design/methodology/approach

The design of this research used a qualitative approach based on the grounded theory with explorative and phenomenological approaches.

Findings

The relationship of the concept of competitive advantage orientation and the value of Catur Paramitha on SMEs in Sarbagita forms the characters SMEs’ business actors, namely, first, fair competition without hurting or harming others can be avoided. Second, the emergence of business cooperation with various business characters can form a wise entrepreneurial spirit. Third, making the entrepreneur more professional in managing the business. Fourth, forming a happy attitude to help others, making cooperation.

Research limitations/implications

The integration of applied values of local wisdom on the concept of competitive advantage orientation in building business in SME sector in Bali as a guideline for managers and lead the business.

Originality/value

The originality of this research was conceptually, building the concept of competitive advantage with local wisdom in developed countries has done by many. However, the local wisdom in developed countries is very different from the local wisdom in Indonesia, especially in Bali. Not all the main characteristics of the basic concept of cultural values in developed countries are applicable and in accordance with local conditions and cultures in the context of country. In addition, the concept of competitive advantage in developed countries is often assumed to operate in a stable and predictable business environment.