bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychological models in sport psychology: A preliminary investigation
Authors: Collins Dave , Winter Stacy
Published: November 2019

Applied psychology is characterised by a variety of theoretical models, informing distinct approaches to classification, explanation, and intervention in service‐delivery. Such theoretical or psychological models include behavioural, biological, cognitive, humanistic, psychodynamic, and social paradigms, with exposure to these models and attitude formation occurring within the structured university‐based stage of sport psychology development. It is, therefore, important for the sport psychological domain to investigate developing attitudes, given these models inform subsequent professional practice and decision making. Accordingly, the present study explored the attitudes of Stage‐1 sport psychology students through a modified form of the Maudsley Attitude Questionnaire (34 males, M age = 24.71 years, SD = 7.23 and 42 females, M age = 24.76 years, SD = 6.20). The questionnaire was designed to assess attitudes across eight psychological models (e.g. biological, cognitive) and four sport psychology issues (pre‐performance anxiety, a lack of confidence, depression, and eating disorders). Analyses of variance demonstrated significant main, model, and interaction effects. No one psychological model was endorsed by all respondents, with model endorsement varying signiﬁcantly as a function of the issue presented. Principal Axis Factoring revealed a large contribution attributable to cognitive–behavioural and ‘eclectic’ (mixed elements of social constructionism, biological, and psychodynamic) models. In contrast, the spiritual model represented low levels of participant endorsement and application. Investigation of Stage‐1 students can promote an evidence‐based understanding on currently developing attitudes and inform the development of sport psychology education, supervision of training routes, and subsequent professional delivery.
Improving the space-bandwidth product of structured illumination microscopy using a transillumination configuration
Authors: Joseph Joby , Faiz Kandankulangara P , Lahrberg Marcel , Tinguely Jean-Claude , Ahluwalia Balpreet Singh
Published: November 2019

Applying structured instead of plane illumination in widefield optical fluorescence microscopy can improve the spatial resolution beyond what is known as the Abbe limit. In general it is not only the resolution of an imaging system that is of interest but also its field of view (FOV). These two parameters are expressed in the space-bandwidth product (SBP). Here we introduce a modified structured illumination microscopy (SIM) approach that offers a larger SBP than any other available implementation. This is achieved through a transillumination geometry instead of the typical epifluorescent configuration. Compared to conventional SIM, the illumination path is decoupled from the objective lens by using a multi-mirror setup to generate the sinusoidal interference pattern for structured illumination in transmission mode. The spatial frequency of the illumination pattern can be controlled by changing the angle of the mirrors, achieving comparably fine patterns over a large FOV. In this work simulation results demonstrate the potential resolution improvement to be expected by the suggested implementation. Preliminary experimental results demonstrate phase-shifting ability and the stability of fringe frequencies over a large FOV of (

16 mm2) at different numerical apertures, fulfilling the prerequisites for SIM acquisition.
High-speed x-ray tomography of silo discharge
Authors: Stannarius Ralf , Martinez Diego Sancho , Börzsönyi Tamás , Bieberle Martina , Barthel Frank , Hampel Uwe
Published: November 2019

The outflow of granular materials from storage containers with narrow outlets is studied by means of ultrafast x-ray computed tomography (UFXCT). The used acquisition speed of this tomograph is high enough to allow high-speed recording of two horizontal cross sections (each of them at a rate of 1000 images per second) of the container during the discharge of material. Analyzing space-time plots that were generated from the tomograms, we retrieve velocity profiles and packing structures in the container. We compare hard spherical grains with soft, low-friction hydrogel spheres. Their flow profiles are qualitatively different. While the hard spheres form stagnant zones at the container side walls, the hydrogel spheres with extremely low friction coefficient flow in all regions of the container. Moreover, a shell-like positional arrangement of the soft spheres induced by the container walls is revealed. The results obtained for the flow field structure confirm earlier conclusions drawn from sequences of x-ray tomograms of clogged states.
Quantum limits of localisation microscopy
Authors: Bisketzi Evangelia , Branford Dominic , Datta Animesh
Published: November 2019

Localisation microscopy of multiple weak, incoherent point sources with possibly different intensities in one spatial dimension is equivalent to estimating the amplitudes of a classical mixture of coherent states of a simple harmonic oscillator. This enables us to bound the multi-parameter covariance matrix for an unbiased estimator for the locations in terms of the quantum Fisher information matrix, which we obtained analytically. In the regime of arbitrarily small separations we find it to be no more than rank two—implying that no more than two independent parameters can be estimated irrespective of the number of point sources. We use the eigenvalues of the classical and quantum Fisher information matrices to compare the performance of spatial-mode demultiplexing and direct imaging in localisation microscopy with respect to the quantum limits.
Identification of Genes That Result in High Mortality of Oryctes rhinoceros (Scarabaeidae: Coleoptera) When Targeted Using an RNA Interference Approach: Implications for Large Invasive Insects
Authors: Watanabe Shizu , Adams Brandi-Leigh , Kong Alexandra , Masang Nelson , Vowell Tomie , Melzer Michael
Published: November 2019

Coconut rhinoceros beetle, Oryctes rhinoceros (L., 1758), is a large scarab beetle native to Southeast Asia and a major pest of coconut (Cocos nucifera) and oil (Elaeis guineensis) palms in its invaded range. Few tools are available for coconut rhinoceros beetle management, particularly for an emerging haplotype with resistance to known strains of Oryctes rhinoceros nudivirus, the traditional biological control agent used in coconut rhinoceros beetle management programs. RNA interference (RNAi) represents an emerging tool for insect pest control that exploits an existing pathway for gene regulation in the target organism. In this study, we evaluated RNAi as a potential tool for coconut rhinoceros beetle management. Using transcriptome data generated from gut tissue of early instar larvae, we identified 24 RNAi target sequences that were either highly expressed or had demonstrated efficacy in other insect systems. Double-stranded (ds)RNAs ranging from 249 to 297 bp in length were generated for 23 of these target sequences and 150 ng were microinjected into coconut rhinoceros beetle 1st, 2nd, and 3rd instar larvae and adults. Five of these dsRNAs that targeted genes putatively encoding V-type ATPase, polyadenylate binding protein, and three forms of actin induced 30.8–100% mortality within 14 days post injection (dpi). Microinjection of 2nd instars with 10 and 100 ng of these same five dsRNAs induced 20–100% and 80–100% mortality at 7 and 14 dpi, respectively. These results indicate RNAi should be explored as a possible management option for coconut rhinoceros beetle. Coconut rhinoceros beetle may also represent a model species for using RNAi in the management of large invasive insect species.
Long-Term Trajectories of Body Weight, Diet, and Physical Activity From Midlife Through Late Life and Subsequent Cognitive Decline in Women
Authors: Wagner Maude , Grodstein Francine , Proust-Lima Cécile , Samieri Cécilia
Published: November 2019

Healthy lifestyles are promising targets for prevention of cognitive aging, yet the optimal time windows for interventions remain unclear. We selected a case-control sample nested within the Nurses’ Health Study (starting year 1976, mean age = 51 years), including 14,956 women aged ≥70 years who were free of both stroke and cognitive impairment at enrollment in a cognitive substudy (1995–2001). Cases (n = 1,496) were women with the 10% worst slopes of cognitive decline, and controls (n = 7,478) were those with slopes better than the median. We compared the trajectories of body mass index (weight (kg)/height (m)2), alternate Mediterranean diet (A-MeDi) score, and physical activity between groups, from midlife through 1 year preceding the cognitive substudy. In midlife, cases had higher body mass index than controls (mean difference (MD) = 0.59 units, 95% confidence interval (CI): 0.39, 0.80), lower physical activity (MD = –1.41 metabolic equivalent of task–hours/week, 95% CI: –2.07, –0.71), and worse A-MeDi scores (MD = –0.16 points, 95% CI: –0.26, –0.06). From midlife through later life, compared with controls, cases had consistently lower A-MeDi scores but a deceleration of weight gain and a faster decrease in physical activity. In conclusion, maintaining a healthy lifestyle since midlife may help reduce cognitive decline in aging. At older ages, both deceleration of weight gain and a decrease in physical activity may reflect early signs of cognitive impairment.
Evolutionary history of a relict conifer, Pseudotaxus chienii (Taxaceae), in south-east China during the late Neogene: old lineage, young populations
Authors: Kou Yixuan , Zhang Li , Fan Dengmei , Cheng Shanmei , Li Dezhu , Hodel Richard G J , Zhang Zhiyong
Published: November 2019

Background and Aims

Many monotypic gymnosperm lineages in south-east China paradoxically remain in relict status despite long evolutionary histories and ample opportunities for allopatric speciation, but this paradox has received little attention and has yet to be resolved. Here, we address this issue by investigating the evolutionary history of a relict conifer, Pseudotaxus chienii (Taxaceae).

Methods

DNA sequences from two chloroplast regions and 14 nuclear loci were obtained for 134 samples. The demographic history was inferred and the contribution of isolation by environment (IBE) in patterning genetic divergence was compared with that of isolation by distance (IBD).

Key Results

Three genetic clusters were identified. Approximate Bayesian computation analyses showed that the three clusters diverged in the late Pliocene (~3.68 Ma) and two admixture events were detected. Asymmetric gene flow and similar population divergence times (~ 3.74 Ma) were characterized using the isolation with migration model. Neither IBD nor IBE contributed significantly to genetic divergence, and the contribution of IBE was much smaller than that of IBD.

Conclusions

These results suggest that several monotypic relict gymnosperm lineages like P. chienii in south-east China did not remain in situ and undiversified for millions of years. On the contrary, they have been evolving and the extant populations have become established more recently, having insufficient time to speciate. Our findings provide a new perspective for understanding the formation and evolution of the relict gymnosperm flora of China as well as of the Sino-Japanese Flora.
Deep learning for mining protein data
Authors: Shi Qiang , Chen Weiya , Huang Siqi , Wang Yan , Xue Zhidong
Published: November 2019

The recent emergence of deep learning to characterize complex patterns of protein big data reveals its potential to address the classic challenges in the field of protein data mining. Much research has revealed the promise of deep learning as a powerful tool to transform protein big data into valuable knowledge, leading to scientific discoveries and practical solutions. In this review, we summarize recent publications on deep learning predictive approaches in the field of mining protein data. The application architectures of these methods include multilayer perceptrons, stacked autoencoders, deep belief networks, two- or three-dimensional convolutional neural networks, recurrent neural networks, graph neural networks, and complex neural networks and are described from five perspectives: residue-level prediction, sequence-level prediction, three-dimensional structural analysis, interaction prediction, and mass spectrometry data mining. The advantages and deficiencies of these architectures are presented in relation to various tasks in protein data mining. Additionally, some practical issues and their future directions are discussed, such as robust deep learning for protein noisy data, architecture optimization for specific tasks, efficient deep learning for limited protein data, multimodal deep learning for heterogeneous protein data, and interpretable deep learning for protein understanding. This review provides comprehensive perspectives on general deep learning techniques for protein data analysis.
HypercubeME: two hundred million combinatorially complete datasets from a single experiment
Authors: Esteban Laura A , Lonishin Lyubov R , Bobrovskiy Daniil M , Leleytner Gregory , Bogatyreva Natalya S , Kondrashov Fyodor A , Ivankov Dmitry N
Published: November 2019

Motivation

Epistasis, the context-dependence of the contribution of an amino acid substitution to fitness, is common in evolution. To detect epistasis, fitness must be measured for at least four genotypes: the reference genotype, two different single mutants and a double mutant with both of the single mutations. For higher-order epistasis of the order n, fitness has to be measured for all 2n genotypes of an n-dimensional hypercube in genotype space forming a ‘combinatorially complete dataset’. So far, only a handful of such datasets have been produced by manual curation. Concurrently, random mutagenesis experiments have produced measurements of fitness and other phenotypes in a high-throughput manner, potentially containing a number of combinatorially complete datasets.

Results

We present an effective recursive algorithm for finding all hypercube structures in random mutagenesis experimental data. To test the algorithm, we applied it to the data from a recent HIS3 protein dataset and found all 199 847 053 unique combinatorially complete genotype combinations of dimensionality ranging from 2 to 12. The algorithm may be useful for researchers looking for higher-order epistasis in their high-throughput experimental data.

Availability and implementation

https://github.com/ivankovlab/HypercubeME.git.

Supplementary information

Supplementary data are available at Bioinformatics online.
An integrative approach for fine-mapping chromatin interactions
Authors: Jaroszewicz Artur , Ernst Jason
Published: November 2019

Motivation

Chromatin interactions play an important role in genome architecture and gene regulation. The Hi-C assay generates such interactions maps genome-wide, but at relatively low resolutions (e.g. 5-25 kb), which is substantially coarser than the resolution of transcription factor binding sites or open chromatin sites that are potential sources of such interactions.

Results

To predict the sources of Hi-C-identified interactions at a high resolution (e.g. 100 bp), we developed a computational method that integrates data from DNase-seq and ChIP-seq of TFs and histone marks. Our method, χ-CNN, uses this data to first train a convolutional neural network (CNN) to discriminate between called Hi-C interactions and non-interactions. χ-CNN then predicts the high-resolution source of each Hi-C interaction using a feature attribution method. We show these predictions recover original Hi-C peaks after extending them to be coarser. We also show χ-CNN predictions enrich for evolutionarily conserved bases, eQTLs and CTCF motifs, supporting their biological significance. χ-CNN provides an approach for analyzing important aspects of genome architecture and gene regulation at a higher resolution than previously possible.

Availability and implementation

χ-CNN software is available on GitHub (https://github.com/ernstlab/X-CNN).

Supplementary information

Supplementary data are available at Bioinformatics online.
Improved linking of motifs to their TFs using domain information
Authors: Baumgarten Nina , Schmidt Florian , Schulz Marcel H
Published: November 2019

Motivation

A central aim of molecular biology is to identify mechanisms of transcriptional regulation. Transcription factors (TFs), which are DNA-binding proteins, are highly involved in these processes, thus a crucial information is to know where TFs interact with DNA and to be aware of the TFs’ DNA-binding motifs. For that reason, computational tools exist that link DNA-binding motifs to TFs either without sequence information or based on TF-associated sequences, e.g. identified via a chromatin immunoprecipitation followed by sequencing (ChIP-seq) experiment.

In this paper, we present MASSIF, a novel method to improve the performance of existing tools that link motifs to TFs relying on TF-associated sequences. MASSIF is based on the idea that a DNA-binding motif, which is correctly linked to a TF, should be assigned to a DNA-binding domain (DBD) similar to that of the mapped TF. Because DNA-binding motifs are in general not linked to DBDs, it is not possible to compare the DBD of a TF and the motif directly. Instead we created a DBD collection, which consist of TFs with a known DBD and an associated motif. This collection enables us to evaluate how likely it is that a linked motif and a TF of interest are associated to the same DBD. We named this similarity measure domain score, and represent it as a P-value. We developed two different ways to improve the performance of existing tools that link motifs to TFs based on TF-associated sequences: (i) using meta-analysis to combine P-values from one or several of these tools with the P-value of the domain score and (ii) filter unlikely motifs based on the domain score.

Results

We demonstrate the functionality of MASSIF on several human ChIP-seq datasets, using either motifs from the HOCOMOCO database or de novo identified ones as input motifs. In addition, we show that both variants of our method improve the performance of tools that link motifs to TFs based on TF-associated sequences significantly independent of the considered DBD type.

Availability and implementation

MASSIF is freely available online at https://github.com/SchulzLab/MASSIF.

Supplementary information

Supplementary data are available at Bioinformatics online.
BRM: a statistical method for QTL mapping based on bulked segregant analysis by deep sequencing
Authors: Huang Likun , Tang Weiqi , Bu Suhong , Wu Weiren
Published: November 2019

Motivation

Bulked segregant analysis by deep sequencing (BSA-seq) has been widely used for quantitative trait locus (QTL) mapping in recent years. A number of different statistical methods for BSA-seq have been proposed. However, determination of significance threshold, the key point for QTL identification, remains to be a problem that has not been well solved due to the difficulty of multiple testing correction. In addition, estimation of the confidence interval is also a problem to be solved.

Results

In this paper, we propose a new statistical method for BSA-seq, named Block Regression Mapping (BRM). BRM is robust to sequencing noise and is applicable to the case of low sequencing depth. Significance threshold can be reasonably determined by taking multiple testing correction into account. Meanwhile, the confidence interval of QTL position can also be estimated.

Availability and implementation

The R scripts of our method are open source under GPLv3 license at https://github.com/huanglikun/BRM.

Supplementary information

Supplementary data are available at Bioinformatics online.
Doubly functional graphical models in high dimensions
Authors: Qiao Xinghao , Qian Cheng , James Gareth M , Guo Shaojun
Published: November 2019

We consider estimating a functional graphical model from multivariate functional observations. In functional data analysis, the classical assumption is that each function has been measured over a densely sampled grid. However, in practice the functions have often been observed, with measurement error, at a relatively small number of points. We propose a class of doubly functional graphical models to capture the evolving conditional dependence relationship among a large number of sparsely or densely sampled functions. Our approach first implements a nonparametric smoother to perform functional principal components analysis for each curve, then estimates a functional covariance matrix and finally computes sparse precision matrices, which in turn provide the doubly functional graphical model. We derive some novel concentration bounds, uniform convergence rates and model selection properties of our estimator for both sparsely and densely sampled functional data in the high-dimensional large-$p$, small-$n$ regime. We demonstrate via simulations that the proposed method significantly outperforms possible competitors. Our proposed method is applied to a brain imaging dataset.
Expertise, Emotion and Specialization in the Development of Persistent Burglary
Authors: Meenaghan Amy , Nee Claire , Van Gelder Jean-Louis , Vernham Zarah , Otte Marco
Published: November 2019

This article describes a qualitative analysis of interviews conducted among 70 experienced residential burglars regarding the reasons for getting involved in and maintaining criminal behaviour. Themes emerging reflected an interaction between skill-development and affect, which played a key role in the initiation and continuation of burglary-related behaviour. Early participation in burglary seemed to be strongly influenced by the desire for excitement. Over time this diminished and was replaced by habitual engagement in burglary. With respect to the actual commission of offences, automatic decision-making appeared to be characteristic of the entire decision-chain, from initial thoughts to the commission of the burglary. Implications of the interaction between affect, cognition and expertise on diversification, specialization and desistance from crime are discussed.
Examining the how of Plural Policing: Moving from Normative Debate to Empirical Enquiry
Authors: Nøkleberg Martin
Published: November 2019

The networked and plural nature of policing suggests that agencies are often involved in extensive exchanges of expertise, resources and knowledge. However, the network structure and distribution of power between various policing actors can vary considerably. This highlights the importance of developing sound analytical perspectives that can help unpack the complexities behind the linkages. Applying the network perspective, this article underlines the value of utilizing analytical tools and approaches drawn from social network analysis, such as brokerage and homophily, to empirically assess the roles of agencies and their contribution to plural policing. This, in turn, shows how, in the mixed economy of policing, as well as being understood in terms of the normative debates that often figure in the current literature, relational phenomena also require more sophisticated empirical approaches.
The ‘Collective Voice that Could Change the World’: A Qualitative Interpretive Meta-Synthesis of Arts-Based Programming for Adults Experiencing Homelessness
Authors: Murphy Erin R , Alexander Amanda S
Published: November 2019

Homelessness is a global phenomenon that contributes to and exacerbates social exclusion and marginalisation. The objective of this study is to generate a rich description of the experience of participating in arts-based programming as told by adults experiencing homelessness using a qualitative interpretive meta-synthesis. The synthesis includes eight studies, using direct quotes provided by fifty-three individuals in Canada, the USA and Australia. Synthesis of the eight studies results in three themes that describe the experience of participating in arts-based programming across geographic locations and art mediums: ‘arts as healing’, ‘arts as advocacy’ and ‘arts as self-empowerment’. While social workers, homelessness service providers, arts-based educators and researchers may be intuitively aware of the power of the arts, the synergistic findings of these eight articles indicate its influence among marginally housed populations. Implications and opportunities for future research are discussed.
Dexterous Object Manipulation Requires Context-Dependent Sensorimotor Cortical Interactions in Humans
Authors: Parikh Pranav J , Fine Justin M , Santello Marco
Published: November 2019

Dexterous object manipulation is a hallmark of human evolution and a critical skill for everyday activities. A previous work has used a grasping context that predominantly elicits memory-based control of digit forces by constraining where the object should be grasped. For this “constrained” grasping context, the primary motor cortex (M1) is involved in storage and retrieval of digit forces used in previous manipulations. In contrast, when choice of digit contact points is allowed (“unconstrained” grasping), behavioral studies revealed that forces are adjusted, on a trial-to-trial basis, as a function of digit position. This suggests a role of online feedback of digit position for force control. However, despite the ubiquitous nature of unconstrained hand–object interactions in activities of daily living, the underlying neural mechanisms are unknown. Using noninvasive brain stimulation, we found the role of primary motor cortex (M1) and somatosensory cortex (S1) to be sensitive to grasping context. In constrained grasping, M1 but not S1 is involved in storing and retrieving learned digit forces and position. In contrast, in unconstrained grasping, M1 and S1 are involved in modulating digit forces to position. Our findings suggest that the relative contribution of memory and online feedback modulates sensorimotor cortical interactions for dexterous manipulation.
Relationship between soluble urokinase-type plasminogen activator receptor and serum biomarkers of endothelial activation in patients with idiopathic nephrotic syndrome
Authors: Roca Neus , Jatem Elias , Martín María Luisa , Muñoz Marina , Molina Maria , Martínez Cristina , Segarra Alfons
Published: November 2019

Background

Serum levels of soluble urokinase-type plasminogen activator receptor (suPAR) are high in some patients with idiopathic nephrotic syndrome (INS). Given that suPAR constitutes a predictor of vascular disease and has been associated with endothelial dysfunction, we hypothesized that suPAR levels are related to endothelial activation or dysfunction in INS patients. The aims of this study were to evaluate the relationship between serum concentrations of endothelial biomarkers and suPAR in patients with different histological patterns of INS and healthy controls, and to determine the demographic, clinical and biochemical characteristics of INS patients that influence suPAR serum levels.

Methods

This observational, cross-sectional study included patients with INS, diagnosed with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) or membranous nephropathy (MN) by renal biopsy. Patient demographic, clinical and biochemical characteristics were recorded and blood samples were obtained at the time of diagnosis. Measurements of suPAR and endothelial molecules via serum levels were performed using Enzyme-Linked ImmunoSorbent Assay kits.

Results

Patients with nephrotic syndrome (n = 152) caused by FSGS, MCD or MN had increased circulating levels of endothelial markers. suPAR levels positively correlated with age and the serum levels of almost all endothelial markers. Generally, endothelial cell molecules positively correlated with each other. suPAR levels were not associated with the histopathological pattern of INS.

Conclusions

In patients with INS secondary to FSGS, MCD and NM, circulating levels of suPAR are independent of the primary renal disease, and significantly associated with age, glomerular filtration rate and the levels of various endothelial markers.
Imbalanced turnover of collagen type III is associated with disease progression and mortality in high-risk chronic kidney disease patients
Authors: Genovese Federica , Rasmussen Daniel Guldager Kring , Karsdal Morten A , Jesky Mark , Ferro Charles , Fenton Anthony , Cockwell Paul
Published: November 2019

Background

Tubulointerstitial fibrosis is a major pathological feature in chronic kidney disease (CKD) and collagen type III (COL3) is a major component of the renal fibrotic scar. We hypothesized that a dysregulated turnover of COL3 is an important determinant of CKD progression. We assessed the relationship between fragments reflecting active formation (PRO-C3) and degradation (C3M) of COL3 and CKD disease progression and mortality in a prospective cohort of CKD patients.

Methods

We measured PRO-C3 and C3M in urine (uPRO-C3 and uC3M) and serum (sPRO-C3 and sC3M) of 500 patients from the Renal Impairment in Secondary Care study. Disease progression was defined as a decline in estimated glomerular filtration rate >30% or the start of renal replacement therapy within 12 and 30 months.

Results

Levels of uC3M/creatinine decreased, whereas levels of uPRO-C3/creatinine and sPRO-C3 increased with increasing CKD stage. uC3M/creatinine was inversely and independently associated with disease progression by 12 months {odds ratio [OR] 0.39 [95% confidence interval (CI) 0.18–0.83]; P = 0.01 per doubling of uC3M/creatinine} with development of end-stage renal disease [hazard ratio (HR) 0.70 (95% CI 0.50–0.97); P = 0.03 per doubling of uC3M/creatinine]. sPRO-C3 at baseline was independently associated with increased mortality [HR 1.93 (95% CI 1.21–3.1); P = 0.006 per doubling of sPRO-C3] and disease progression by 30 months [OR 2.16 (95% CI 1.21–3.84); P = 0.009 per doubling of sPRO-C3].

Conclusions

Dynamic products of COL3 formation and degradation were independently associated with CKD progression and mortality and may represent an opportunity to link pathological processes with targeted treatments against fibrosis.
Nitric oxide modulates cardiomyocyte pH control through a biphasic effect on sodium/hydrogen exchanger-1
Authors: Richards Mark A , Simon Jillian N , Ma Ruichong , Loonat Aminah A , Crabtree Mark J , Paterson David J , Fahlman Richard P , Casadei Barbara , Fliegel Larry , Swietach Pawel
Published: November 2019

Aims

When activated, Na+/H+ exchanger-1 (NHE1) produces some of the largest ionic fluxes in the heart. NHE1-dependent H+ extrusion and Na+ entry strongly modulate cardiac physiology through the direct effects of pH on proteins and by influencing intracellular Ca2+ handling. To attain an appropriate level of activation, cardiac NHE1 must respond to myocyte-derived cues. Among physiologically important cues is nitric oxide (NO), which regulates a myriad of cardiac functions, but its actions on NHE1 are unclear.

Methods and results

NHE1 activity was measured using pH-sensitive cSNARF1 fluorescence after acid-loading adult ventricular myocytes by an ammonium prepulse solution manoeuvre. NO signalling was manipulated by knockout of its major constitutive synthase nNOS, adenoviral nNOS gene delivery, nNOS inhibition, and application of NO-donors. NHE1 flux was found to be activated by low [NO], but inhibited at high [NO]. These responses involved cGMP-dependent signalling, rather than S-nitros(yl)ation. Stronger cGMP signals, that can inhibit phosphodiesterase enzymes, allowed [cAMP] to rise, as demonstrated by a FRET-based sensor. Inferring from the actions of membrane-permeant analogues, cGMP was determined to activate NHE1, whereas cAMP was inhibitory, which explains the biphasic regulation by NO. Activation of NHE1-dependent Na+ influx by low [NO] also increased the frequency of spontaneous Ca2+ waves, whereas high [NO] suppressed these aberrant forms of Ca2+ signalling.

Conclusions

Physiological levels of NO stimulation increase NHE1 activity, which boosts pH control during acid-disturbances and results in Na+-driven cellular Ca2+ loading. These responses are positively inotropic but also increase the likelihood of aberrant Ca2+ signals, and hence arrhythmia. Stronger NO signals inhibit NHE1, leading to a reversal of the aforementioned effects, ostensibly as a potential cardioprotective intervention to curtail NHE1 overdrive.
The independent and incremental value of ultrasound carotid plaque length to predict the presence and severity of coronary artery disease: analysis from the carotid plaque length prospective registry
Authors: Tang Wendong , Shen Xiaxian , Li Hailing , Bai Yuan , Zhang Bili , Guo Zhifu , Wu Hong , Li Pan , Zhao Xianxian
Published: November 2019

Aims 

Data regarding the relationship between carotid plaque length (CPL) and coronary artery disease (CAD) are lacking. This study aimed to assess the predictive value of CPL for the severity of CAD.

Methods and results

We prospectively enrolled 2149 consecutive patients who underwent both first coronary angiography and carotid ultrasonography with measurements of intima-media thickness (IMT), plaque score (PS), and CPL. In total, 1408 (65.5%) patients had CAD (defined as stenosis ≥50%), and 741 (34.5%) patients had no CAD. Patients with CAD had longer maximal CPL than those without CAD (P < 0.001). The severity of CAD, measured by the Gensini score (GS), was closely correlated with max-CPL (rs = 0.560), followed by PS (rs = 0.486) and mean-IMT (rs = 0.292). Multivariate analysis revealed that max-CPL remained independently associated with CAD and high-GS after adjustment for traditional risk factors (TRF). Max-CPL, compared with PS or mean-IMT, had significantly higher discrimination value for predicting high-GS [area under the curve (AUC) 0.819 vs. 0.769 vs. 0.634, P < 0.001]. At a cut-off value for the max-CPL of 6.3 mm, the sensitivity and negative predictive value for high-GS were 84.6% and 89.1%, respectively. Furthermore, the addition of max-CPL significantly improved the discrimination (AUC 0.832 vs. 0.720, P < 0.001) and reclassification (net reclassification improvement = 0.431, P < 0.001) over TRF for high-GS.

Conclusion 

Ultrasound max-CPL provides independent and incremental predictive value for the clinical severity of CAD over TRF and seems a simple useful marker in CAD risk stratification.
Risk of gastrointestinal bleeding associated with oral anticoagulation and non-steroidal anti-inflammatory drugs in patients with atrial fibrillation: a nationwide study
Authors: Olsen Anne-Marie Schjerning , McGettigan Patricia , Gerds Thomas Alexander , Fosbøl Emil Loldrup , Olesen Jonas Bjerring , Sindet-Pedersen Caroline , Staerk Laila , Lock Hansen Morten , Pallisgaard Jannik Langtved , Køber Lars , Torp-Pedersen Christian , Gislason Gunnar Hilmar , Lamberts Morten
Published: November 2019

Aims

Non-vitamin K antagonist oral anticoagulants (NOACs) are displacing vitamin K antagonists (VKAs) for stroke prophylaxis in patients with atrial fibrillation (AF). Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) could increase gastrointestinal bleeding (GIB) risks among these patients. The aim of this study was to examine the risk of GIB among Danish AF patients taking oral anticoagulants (OACs) and NSAIDs.

Methods and results

Using nationwide administrative registries, we determined concomitant NSAID use among anticoagulant-naïve patients with AF initiating OACs between August 2011 and June 2017. We calculated short-term absolute risks differences and hazard ratios (HRs) for GIB based on multiple adjusted cause-specific Cox regressions with time-dependent NSAID treatment. Among 41 183 patients [median age 70 years (interquartile range 64–78); 55% men], 21% of patients on NOACs and 18% on VKA were co-prescribed NSAIDs. The differences in absolute risk [95% confidence interval (CI)] of GIB within 14 days of commencing concomitant NSAID therapy (vs. no concomitant NSAID therapy) were 0.10% (0.04–0.18%) for NOACs and 0.13% (0.03–0.24%) for VKA. NOACs overall were associated with less GIB than VKA [HR 0.77 (95% CI 0.69–0.85)]. Compared with OACs alone, concomitant NSAIDs doubled the GIB risk associated with NOACs overall [HR 2.01 (95% CI 1.40–2.61)] and with VKA [HR 1.95 (95% CI 1.21–2.69)].

Conclusion

Among this nationwide AF population taking OACs, concomitant NSAID therapy increased the short-term absolute risk of GIB. Non-vitamin K antagonist oral anticoagulants alone were associated with lower GIB risks than VKA but concomitant NSAIDs abolished this advantage. The findings align with post hoc analyses from randomized studies. Physicians should exercise appropriate caution when prescribing NSAIDs for patients with AF taking NOACs or VKA.
Cabins, castles, and constant hearts: rhythm control therapy in patients with atrial fibrillation
Authors: Willems Stephan , Meyer Christian , de Bono Joseph , Brandes Axel , Eckardt Lars , Elvan Arif , van Gelder Isabelle , Goette Andreas , Gulizia Michele , Haegeli Laurent , Heidbuchel Hein , Haeusler Karl Georg , Kautzner Josef , Mont Lluis , Ng G Andre , Szumowski Lukasz , Themistoclakis Sakis , Wegscheider Karl , Kirchhof Paulus
Published: November 2019

Recent innovations have the potential to improve rhythm control therapy in patients with atrial fibrillation (AF). Controlled trials provide new evidence on the effectiveness and safety of rhythm control therapy, particularly in patients with AF and heart failure. This review summarizes evidence supporting the use of rhythm control therapy in patients with AF for different outcomes, discusses implications for indications, and highlights remaining clinical gaps in evidence. Rhythm control therapy improves symptoms and quality of life in patients with symptomatic AF and can be safely delivered in elderly patients with comorbidities (mean age 70 years, 3–7% complications at 1 year). Atrial fibrillation ablation maintains sinus rhythm more effectively than antiarrhythmic drug therapy, but recurrent AF remains common, highlighting the need for better patient selection (precision medicine). Antiarrhythmic drugs remain effective after AF ablation, underpinning the synergistic mechanisms of action of AF ablation and antiarrhythmic drugs. Atrial fibrillation ablation appears to improve left ventricular function in a subset of patients with AF and heart failure. Data on the prognostic effect of rhythm control therapy are heterogeneous without a clear signal for either benefit or harm. Rhythm control therapy has acceptable safety and improves quality of life in patients with symptomatic AF, including in elderly populations with stroke risk factors. There is a clinical need to better stratify patients for rhythm control therapy. Further studies are needed to determine whether rhythm control therapy, and particularly AF ablation, improves left ventricular function and reduces AF-related complications.
The impact of mechanical oesophageal deviation on posterior wall pulmonary vein reconnection
Authors: Iwasawa Jin , Koruth Jacob S , Mittnacht Alexander J , Tran Van N , Palaniswamy Chandrasekar , Sharma Dinesh , Bhardwaj Rahul , Naniwadekar Aditi , Joshi Kamal , Sofi Aamir , Syros Georgios , Choudry Subbarao , Miller Marc A , Dukkipati Srinivas R , Reddy Vivek Y
Published: November 2019

Aims

During atrial fibrillation ablation, oesophageal heating typically prompts reduction or termination of radiofrequency energy delivery. We previously demonstrated oesophageal temperature rises are associated with posterior left atrial pulmonary vein reconnection (PVR) during redo procedures. In this study, we assessed whether mechanical oesophageal deviation (MED) during an index procedure minimizes posterior wall PVRs during redo procedures.

Methods and results

Patients in whom we performed a first-ever procedure followed by a clinically driven redo procedure were divided based on both the use of MED for oesophageal protection and the ablation catheter employed (force or non-force sensing) in the first procedure. The PVR sites were compared between MED using a force-sensing catheter (MEDForce), or no MED with a non-force (ControlNoForce) or force (ControlForce) sensing catheter. Despite similar clinical characteristics, the MEDForce redo procedure rate (9.2%, 26/282 patients) was significantly less than the ControlNoForce (17.2%, 126/734 patients; P = 0.002) and ControlForce (17.5%, 20/114 patients; P = 0.024) groups. During the redo procedure, the posterior PVR rate with MEDForce (2%, 1/50 PV pairs) was significantly less than with either ControlNoForce (17.7%, 44/249 PV pairs; P = 0.004) or ControlForce (22.5%, 9/40 PV pairs; P = 0.003), or aggregate Controls (18.3%, 53/289 PV pairs; P = 0.006). However, the anterior PVR rate with MEDForce (8%, 4/50 PV pairs) was not significantly different than Controls (aggregate Controls—3.5%, 10/289 PV pairs, P = 0.136; ControlNoForce—2.4%, 6/249 PV pairs, P = 0.067; ControlForce—10%, 4/40 PV pairs, P = 1.0).

Conclusion

Oesophageal deviation improves the durability of the posterior wall ablation lesion set during AF ablation.
Desmoglein-2 mutations in propeptide cleavage-site causes arrhythmogenic right ventricular cardiomyopathy/dysplasia by impairing extracellular 1-dependent desmosomal interactions upon cellular stress
Authors: Vite Alexia , Gandjbakhch Estelle , Hery Tiphaine , Fressart Veronique , Gary Francoise , Simon Francoise , Varnous Shaida , Hidden Lucet Francoise , Charron Philippe , Villard Eric
Published: November 2019

Aims

Desmoglein-2 (DSG2) mutations, which encode a heart-specific cadherin crucial for desmosomal adhesion, are frequent in arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). DSG2 mutations have been associated with higher risk of biventricular involvement. Among DSG2 mutations, mutations of the inhibitory propeptide consensus cleavage-site (Arg-X-Arg/Lys-Arg), are particularly frequent. In the present work, we explored the functional consequences of DSG2 propeptide cleavage site mutations p.Arg49His, p.Arg46Trp, and p.Arg46Gln on localization, adhesive properties, and desmosome incorporation of DSG2.

Methods and results

We studied the expression of mutant-DSG2 in human heart and in epithelial and cardiac cellular models expressing wild-type or mutant (p.Arg49His, p.Arg46Trp, and p.Arg46Gln) proDSG2-GFP fusion proteins. The consequences of the p.Arg46Trp mutation on DSG2 adhesiveness were studied by surface plasmon resonance. Incorporation of mutant p.Arg46Trp DSG2 into desmosomes was studied under low-calcium culture conditions and cyclic mechanical stress. We demonstrated in human heart and cellular models that all three mutations prevented N-terminal propeptide cleavage, but did not modify intercellular junction targeting. Surface plasmon resonance experiments showed a propeptide-dependent loss of interaction between the cadherin N-terminal extracellular 1 (EC1) domains. Additionally, proDSG2 mutant proteins were abnormally incorporated into desmosomes under low-calcium culture conditions or following mechanical stress. This was accompanied by an epidermal growth factor receptor-dependent internalization of proDSG2, suggesting increased turnover of unprocessed proDSG2.

Conclusion

Our results strongly suggest weakened desmosomal adhesiveness due to abnormal incorporation of uncleaved mutant proDSG2 in cellular stress conditions. These results provide new insights into desmosomal cadherin regulation and ARVC/D pathophysiology, in particular, the potential role of mechanical stress on desmosomal dysfunction.
Does poor mental health explain socio-demographic gradients in breast cancer screening uptake? A population-based study
Authors: Ross Emma , Maguire Aideen , Donnelly Michael , Mairs Adrian , Hall Clare , O’Reilly Dermot
Published: November 2019

Background

Research from the USA indicates disparities in breast cancer screening uptake for women with poor mental health. However, no attempt has been made to examine the contribution of poor mental health to socio-demographic variations in breast screening uptake. The current study aims to examine the impact of self-reported chronic poor mental health on attendance at breast screening in the UK, and to what extent this explains socio-demographic inequalities in screening uptake.

Methods

Breast screening records were linked to 2011 Census records within the Northern Ireland Longitudinal Study. This identified a cohort of 57 328 women who were followed through one 3-year screening cycle of the National Health Service Breast Screening Programme. Information on mental health status, in addition to other individual and household-level attributes, was derived from the 2011 Census. Logistic regression was employed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of attendance at screening.

Results

10.7% of women in the cohort reported poor mental health, and in fully adjusted analyses, these individuals were 23% less likely to attend breast screening (OR 0.77; 95% CI 0.73–0.82). Although poor mental health was a strong predictor of screening uptake, it did not explain the observed inequalities in uptake by socio-economic status, marital status, or area of residence.

Conclusions

This study provides novel evidence of inequalities in breast screening uptake for women with chronic poor mental health in the UK. Targeted interventions are necessary to ensure equitable screening access and to enhance overall mortality benefit.
Age, gut location and diet impact the gut microbiome of a tropical herbivorous surgeonfish
Authors: Parata Lara , Nielsen Shaun , Xing Xing , Thomas Torsten , Egan Suhelen , Vergés Adriana
Published: November 2019

Herbivorous fishes play important ecological roles in coral reefs by consuming algae that can otherwise outcompete corals, but we know little about the gut microbiota that facilitates this process. This study focussed on the gut microbiota of an ecologically important coral reef fish, the convict surgeonfish Acanthurus triostegus. We sought to understand how the microbiome of this species varies along its gastrointestinal tract and how it varies between juvenile and adult fish. Further, we examined if the bacteria associated with the diet consumed by juveniles contributes to the gut microbiota. 16S rRNA gene amplicon sequencing showed that bacterial communities associated with the midgut and hindgut regions were distinct between adults and juveniles, however, no significant differences were seen for gut wall samples. The microbiota associated with the epilithic algal food source was similar to that of the juvenile midgut and gut wall but differed from the microbiome of the hindgut. A core bacterial community including members of taxa Epulopiscium and Brevinemataceae was observed across all gastrointestinal and diet samples, suggesting that these bacterial symbionts can be acquired by juvenile convict surgeonfish horizontally via their diet and then are retained into adulthood.
Physiological response to silver toxicity in the extremely halophilic archaeon Halomicrobium mukohataei
Authors: Buda Doriana-Mădălina , Bulzu Paul-Adrian , Barbu-Tudoran Lucian , Porfire Alina , Pătraș Laura , Sesărman Alina , Tripon Septimiu , Șenilă Marin , Ionescu Mihaela Ileana , Banciu Horia Leonard
Published: November 2019

Adaptive strategies responsible for heavy metal tolerance were explored in the extremely halophilic archaeon Halomicrobium mukohataei DSM 12286. The tested strain was seemingly able to overcome silver-induced oxidative stress (assessed by malondialdehyde quantification, catalase assay and total antioxidant capacity measurement) mainly through non-enzymatic antioxidants. Energy dispersive spectrometry analysis illustrated the presence of colloidal silver in Hmc. mukohataei cultures exposed to AgNO3. Bright-field and transmission electron microscopy images, as well as dynamic light scattering analysis, demonstrated the presence of intracellular nanoparticles, mostly spherical, within a size range of 20–100 nm. As determined by the zeta potential measurement, the biosynthesized nanoparticles were highly stable, with a negative surface charge. Our research is a first attempt in the systematic study of the oxidative stress and intracellular silver nanoparticle accumulation, generated by exposure to silver ions, in members of Halobacteria class, thus broadening our knowledge on mechanisms supporting heavy metal tolerance of microbial cells living under saline conditions.