Miracle-dz/UniFAR-FTUs huggingface dataset:
H2O2-Induced Dilation in Human Coronary Arterioles: Role of Protein Kinase G Dimerization and Large-Conductance Ca2+-Activated K+ Channel Activation

Rationale: Hydrogen peroxide (H2O2) serves as a key endothelium-derived hyperpolarizing factor mediating flow-induced dilation in human coronary arterioles (HCAs). The precise mechanisms by which H2O2 elicits smooth muscle hyperpolarization are not well understood. An important mode of action of H2O2 involves the oxidation of cysteine residues in its target proteins, including protein kinase G (PKG)-I&agr;, thereby modulating their activities. Objective: Here we hypothesize that H2O2 dilates HCAs through direct oxidation and activation of PKG-I&agr; leading to the opening of the large-conductance Ca2+-activated K+ (BKCa) channel and subsequent smooth muscle hyperpolarization. Methods and Results: Flow and H2O2 induced pressure gradient/concentration-dependent vasodilation in isolated endothelium-intact and -denuded HCAs, respectively. The dilation was largely abolished by iberiotoxin, a BKCa channel blocker. The PKG inhibitor Rp-8-Br-PET-cGMP also markedly inhibited flow- and H2O2-induced dilation, whereas the soluble guanylate cyclase inhibitor ODQ had no effect. Treatment of coronary smooth muscle cells (SMCs) with H2O2 elicited dose-dependent, reversible dimerization of PKG-I&agr;, and induced its translocation to the plasma membrane. Patch-clamp analysis identified a paxilline-sensitive single-channel K+ current with a unitary conductance of 246-pS in freshly isolated coronary SMCs. Addition of H2O2 into the bath solution significantly increased the probability of BKCa single-channel openings recorded from cell-attached patches, an effect that was blocked by the PKG-I&agr; inhibitor DT-2. H2O2 exhibited an attenuated stimulatory effect on BKCa channel open probability in inside-out membrane patches. Conclusions: H2O2 dilates HCAs through a novel mechanism involving protein dimerization and activation of PKG-I&agr; and subsequent opening of smooth muscle BKCa channels.
Global health and domestic policy – What motivated the development of the German Global Health Strategy?

ABSTRACT In 2013, the German government published its national Global Health Strategy, outlining principles and focal topics for German engagement in global health. We asked the question of why Germany has decided to establish a national policy framework for global health at this point in time, and how the development process has taken place. The ultimate goal of this study was to achieve better insights into the respective health and foreign policy processes at the national level. This article reports on the results of semi-structured interviews with those actors that were responsible for initiating and drafting the German Global Health Strategy (GGHS). Our study shows that a series of external developments, stakeholders, and advocacy efforts created an environment conducive to the creation of the strategic document. In addition, a number of internal considerations, struggles, and capacities played a decisive role during the development phase of the GGHS. Understanding these factors better can not only provide substantial insights into global health related policy processes in Germany, but also contribute to the general discourse on the role of the nation state in global health governance.
A Longitudinal Investigation of the Home Literacy Environment and Shared Book Reading in Young Children With Hearing Loss

Objectives: The principle goal of this longitudinal study was to examine parent perceptions of home literacy environment (e.g., frequency of book reading, ease of book reading with child) and observed behaviors during shared book reading (SBR) interactions between parents and their children with hearing loss (HL) as compared with parents and their children with normal hearing (NH) across 3 time points (12, 24, and 36 months old). Relationships were also explored among home literacy environment factors and SBR behaviors and later language outcomes, across all three time points for parents of children with and without HL. Design: Participants were a group of parents and their children with HL (N = 17) and typically developing children with NH (N = 34). Parent perceptions about the home literacy environment were captured through a questionnaire. Observed parent behaviors and their use of facilitative language techniques were coded during videotaped SBR interactions. Children’s oral language skills were assessed using a standardized language measure at each time point. Results: No significant differences emerged between groups of parents (HL and NH) in terms of perceived home literacy environment at 12 and 36 months. However, significant group differences were evident for parent perceived ease of reading to their child at 24 months. Group differences also emerged for parental SBR behaviors for literacy strategies and interactive reading at 12 months and for engagement and interactive reading at 36 months, with parents of children with HL scoring lower in all factors. No significant relationships emerged between early home literacy factors and SBR behaviors at 12 months and oral language skills at 36 months for parents of children with NH. However, significant positive relationships were evident between early home literacy environment factors at 12 months and oral language skills at 36 months for parents and their children with HL. Conclusions: Although both groups of parents increased their frequency of SBR behaviors over time, parents of children with HL may need additional support to optimize SBR experiences to better guide their toddlers’ and preschoolers’ language skills. Early intervention efforts that focus on SBR interactions that are mutually enjoyed and incorporate specific ways to encourage parent–child conversations will be essential as children with HL acquire language.
The Lower Lid Diamond: A Simple Entropion Repair to Correct Both Horizontal and Lower-Lid Retractor Laxity

Purpose: To describe a simple technique for involutional entropion correction and to present the findings of a pilot study. Methods: Consecutive case series of 42 procedures. Patients presenting with involutional entropion in the absence of lateral canthal tendon laxity (lateral canthus could be distracted 1 cm or more medially) underwent a modified full-thickness eyelid shortening combined with retractor plication. Main outcome measures were correction of entropion and cosmesis of the surgical site at final follow up. Results: At final follow up, 92% of patients had a satisfactory eyelid position with no recurrence of entropion and a cosmetically satisfactory scar. Conclusions: This is a useful technique with a higher success rate than everting sutures and is particularly suitable for patients for whom rapid surgery is needed or a lateral canthotomy is best avoided.
Allogeneic platelet‐rich plasma affects monocyte differentiation to dendritic cells causing an anti‐inflammatory microenvironment, putatively fostering wound healing

Autologous platelet‐rich plasma (PRP) is used clinically to induce repair of different tissues through the release of bioactive molecules. In some patients, the production of efficient autologous PRP is unfeasible due to their compromised health. Allogeneic PRP mismatched for AB0 and Rh antigens was developed. The effect of allogeneic PRP on immune response should be defined to use it in clinical practice avoiding side effects. Thus, whether PRP affects the differentiation of peripheral blood monocytes to dendritic cells upon stimulation with granulocyte monocyte colony stimulating factor and interleukin‐4 was investigated. Indeed, these cells are the main players of immune response and tissue repair. PRP inhibited the differentiation of monocytes to CD1a+ dendritic cells and favoured the expansion of phagocytic CD163+CD206+ fibrocyte‐like cells. These cells produced interleukin‐10 and prostaglandin‐E2, but not interferon‐γ, upon stimulation with lipopolysaccharides. Moreover, they promoted the expansion of regulatory CD4+CD25+FoxP3+ T cells upon allostimulation or antigen specific priming. Finally, the conditioned medium harvested from monocytes differentiated with PRP triggered a strong chemotactic effect on mesenchymal cells in both scratch and transwell migration assays. These results strongly suggest that allogeneic PRP can foster the differentiation of monocytes to a regulatory anti‐inflammatory population, possibly favouring wound healing. Copyright © 2016 John Wiley & Sons, Ltd.
Enhanced Charge Collection in MOF‐525–PEDOT Nanotube Composites Enable Highly Sensitive Biosensing

With the aim of a reliable biosensing exhibiting enhanced sensitivity and selectivity, this study demonstrates a dopamine (DA) sensor composed of conductive poly(3,4‐ethylenedioxythiophene) nanotubes (PEDOT NTs) conformally coated with porphyrin‐based metal–organic framework nanocrystals (MOF‐525). The MOF‐525 serves as an electrocatalytic surface, while the PEDOT NTs act as a charge collector to rapidly transport the electron from MOF nanocrystals. Bundles of these particles form a conductive interpenetrating network film that together: (i) improves charge transport pathways between the MOF‐525 regions and (ii) increases the electrochemical active sites of the film. The electrocatalytic response is measured by cyclic voltammetry and differential pulse voltammetry techniques, where the linear concentration range of DA detection is estimated to be 2 × 10−6–270 × 10−6m and the detection limit is estimated to be 0.04 × 10−6m with high selectivity toward DA. Additionally, a real‐time determination of DA released from living rat pheochromocytoma cells is realized. The combination of MOF5‐25 and PEDOT NTs creates a new generation of porous electrodes for highly efficient electrochemical biosensing.
Decoding visemes: Improving machine lip-reading

To undertake machine lip-reading, we try to recognise speech from a visual signal. Current work often uses viseme classification supported by language models with varying degrees of success. A few recent works suggest phoneme classification, in the right circumstances, can outperform viseme classification. In this work we present a novel two-pass method of training phoneme classifiers which uses previously trained visemes in the first pass. With our new training algorithm, we show classification performance which significantly improves on previous lip-reading results.
The Impact of Perceived Supervisor Support on Employees' Work-related Attitudes and Silence Behavior

The paper tried to examine the effects of perceived supervisor support on employees' work-related attitudes and silence behavior,and investigate the mediating influence of trust in supervisor and psychological safety in Chinese organizational context.Data were collected from four hundred and eighty-five full-time employees from enterprises located in the Pearl River Delta region.In line with predictions,the authors found that perceived supervisor support had significant positive effects on subordinates' organizational commitment and job involvement,but a negative impact on silence behavior.The results also indicated that trust in supervisor and psychological safety fully mediated the effects of perceived supervisor support on organizational commitment,job involvement and silence behavior.
Predictors of well-being in the lives of student service members and veterans

ABSTRACT Objective: The current study examined predictors of well-being, including quality of life and academic engagement, in a sample of student service members and veteran college students. Methods: Eighty-seven student service members/veterans (SSM/V) completed an online survey containing questions about post-deployment social support, emotion regulation skills, psychological distress, academic engagement, quality of life, and demographics. Participants were recruited from September 2012 through May 2014. Results: Results provided partial support for the proposed bi-directional mediational relations between post-deployment social support and emotion regulation predicting to quality of life and academic engagement. Path models indicated that both post-deployment social support and emotion regulation skills partially mediated the relation with quality of life while accounting for the effect of psychological distress, and that emotion regulation skills fully mediated the relation between social support and academic engagement. Conclusions: These findings suggest that both social support and emotion regulation skills may be useful targets for health promotion and intervention efforts for this population. Limitations and clinical implications for the development of on-campus SSM/V focused health promotion services are discussed.
Practitioner Training for Use of Evidence-Based Practice in Occupational Therapy

ABSTRACT The purpose of this integrative review was to examine the evidence-based practice (EBP) training literature for occupational therapy practitioners in order to describe the relationships between EBP use in practice and practitioner training for EBP. A systematic search of literature related to EBP training in occupational therapy was followed by a research evaluation, review of case examples, and qualitative content analysis. Findings suggest that comprehensive, contextually-relevant, and collaborative training approaches are necessary for practitioners to address implementation of EBP. Research investigating the mechanisms of practitioner training and ways to measure the relationships between training, changes in how practitioners use evidence-based practices, and client outcomes and other quality indicators is recommended.
Treatment of unruptured intracranial aneurysms: a review

ABSTRACT Introduction: Unruptured brain aneurysms (UIAs) present a challenge due to the lack of definitive understanding of their natural history and treatment outcomes. As the treatment of UIAs is aimed at preventing the possibility of rupture, the immediate risk of treatment must be weighed against the risk of rupture in the future. As such, treatment for a large proportion of UIAs is currently individualized. Areas covered: In this article, we discuss the important natural history studies of UIAs and discuss the existing scientific evidence and recent advances that help identify the rupture risk guide management of UIAs. We also address the recent advances in pharmacological therapy of UIAs. Expert commentary: In the recent years, there have been great advances in understanding the pathophysiology of UIAs and determining the rupture risk going beyond the traditional parameter of aneurysm size. Aneurysm morphology and hemodynamics play a pivotal role in growth and rupture. A true randomized trial for the management of UIAs is the need of the hour.
Pain in chemotherapy‐induced peripheral neurotoxicity

Chemotherapy‐induced peripheral neurotoxicity (CIPN) is a potentially dose‐limiting side effect of the treatment of several cancers. CIPN is predominantly or exclusively sensory, and it is frequently associated with unpleasant symptoms, overall referred to as “pain. ” However, given the markedly different clinical presentation and course of CIPN depending on the antineoplastic drug used, the broad term “pain” in the specific context of CIPN needs to be reconsidered and refined. In fact, a precise identification of the features of CIPN has relevant implication in the design of rational‐based clinical trials and in the selection of possible active drugs.
The Quebec Respiratory Health Education Network: Integrating a model of self-management education in COPD primary care

The objective of this study is to evaluate whether a chronic obstructive pulmonary disease (COPD) self-management education program with coaching of a case manager improves patient-related outcomes and leads to practice changes in primary care. COPD patients from six family medicine clinics (FMCs) participated in a 1-year educational program offered by trained case managers who focused on treatment adherence, inhaler techniques, smoking cessation, and the use of an action plan for exacerbations. Health-care utilization, health-related quality of life (HRQL), treatment adherence, inhaler technique, and COPD knowledge were assessed at each visit with validated questionnaires. We also evaluated whether the use of spirometry and the assessment of individual patient needs led to a more COPD-targeted treatment by primary care physicians, based on changes in prescriptions for COPD (medication, immunization, and written action plan). Fifty-four patients completed the follow-up visits and were included in the analysis. The number of unscheduled physician visits went from 40 the year before intervention to 17 after 1 year of educational intervention (p = 0.033). Emergency room visits went from five to two and hospitalizations from two to three (NS). Significant improvements were observed in HRQL (p = 0.0001), treatment adherence (p = 0.025), adequate inhaler technique (p < 0.0001), and COPD knowledge (p < 0.001). Primary care physicians increased their prescriptions for long-acting bronchodilators with/without inhaled corticosteroid, flu immunizations, and COPD action plans in the event patient had an exacerbation. The COPD self-management educational intervention in FMCs reduced unscheduled visits to the clinic and improved patients’ quality of life, self-management skills, and knowledge. The program had a positive impact on COPD-related practices by primary care physicians in the FMCs.
Cross Platform Standardisation of an Experimental Pipeline for Use in the Identification of Dysregulated Human Circulating MiRNAs

Introduction Micro RNAs (miRNAs) are a class of highly conserved small non-coding RNAs that play an important part in the post-transcriptional regulation of gene expression. A substantial number of miRNAs have been proposed as biomarkers for diseases. While reverse transcriptase Real-time PCR (RT-qPCR) is considered the gold standard for the evaluation and validation of miRNA biomarkers, small RNA sequencing is now routinely being adopted for the identification of dysregulated miRNAs. However, in many cases where putative miRNA biomarkers are identified using small RNA sequencing, they are not substantiated when RT-qPCR is used for validation. To date, there is a lack of consensus regarding optimal methodologies for miRNA detection, quantification and standardisation when different platform technologies are used. Materials and Methods In this study we present an experimental pipeline that takes into consideration sample collection, processing, enrichment, and the subsequent comparative analysis of circulating small ribonucleic acids using small RNA sequencing and RT-qPCR. Results, Discussion, Conclusions Initially, a panel of miRNAs dysregulated in circulating blood from breast cancer patients compared to healthy women were identified using small RNA sequencing. MiR-320a was identified as the most dysregulated miRNA between the two female cohorts. Total RNA and enriched small RNA populations (<30 bp) isolated from peripheral blood from the same female cohort samples were then tested for using a miR-320a RT-qPCR assay. When total RNA was analysed with this miR-320a RT-qPCR assay, a 2.3-fold decrease in expression levels was observed between blood samples from healthy controls and breast cancer patients. However, upon enrichment for the small RNA population and subsequent analysis of miR-320a using RT-qPCR, its dysregulation in breast cancer patients was more pronounced with an 8.89-fold decrease in miR-320a expression. We propose that the experimental pipeline outlined could serve as a robust approach for the identification and validation of small RNA biomarkers for disease.
Metabolic Labeling and Profiling of Transfer RNAs Using Macroarrays

Transfer RNAs (tRNA) are abundant short non-coding RNA species that are typically 76 to 90 nucleotides in length. tRNAs are directly responsible for protein synthesis by translating codons in mRNA into amino acid sequences. tRNAs were long considered as house-keeping molecules that lacked regulatory functions. However, a growing body of evidence indicates that cellular tRNA levels fluctuate in correspondence to varying conditions such as cell type, environment, and stress. The fluctuation of tRNA expression directly influences gene translation, favoring or repressing the expression of particular proteins. Ultimately comprehending the dynamic of protein synthesis requires the development of methods able to deliver high-quality tRNA profiles. The method that we present here is named SPOt, which stands for Streamlined Platform for Observing tRNA. SPOt consists of three steps starting with metabolic labeling of cell cultures with radioactive orthophosphate, followed by guanidinium thiocyanate-phenol-chloroform extraction of radioactive total RNAs and finally hybridization on in-house printed macroarrays. tRNA levels are estimated by quantifying the radioactivity intensities at each probe spot. In the protocol presented here we profile tRNAs in Mycobacterium smegmatis mc2155, a nonpathogenic bacterium often used as a model organism to study tuberculosis.
Image quality assessment method based on nonlinear feature extraction in kernel space

To match human perception, extracting perceptual features effectively plays an important role in image quality assessment. In contrast to most existing methods that use linear transformations or models to represent images, we employ a complex mathematical expression of high dimensionality to reveal the statistical characteristics of the images. Furthermore, by introducing kernel methods to transform the linear problem into a nonlinear one, a full-reference image quality assessment method is proposed based on high-dimensional nonlinear feature extraction. Experiments on the LIVE, TID2008, and CSIQ databases demonstrate that nonlinear features offer competitive performance for image inherent quality representation and the proposed method achieves a promising performance that is consistent with human subjective evaluation.
Conditioned‐fear stress increases Fos expression in monoaminergic and GABAergic neurons of the locus coeruleus and dorsal raphe nuclei

Many studies have demonstrated that physical or psychological stress can increase Fos expression in brainstem monoaminergic nuclei. Little is known, however, about the extent to which stress increases the expression of Fos in monoaminergic and nonmonoaminergic neurons in the brainstem. We examined the effects of conditioned‐fear (CF) stress following mild footshock (FS) as unconditioned stress on Fos expression in the monoaminergic and GABAergic neurons of the ventral tegmental area (VTA), locus coeruleus (LC), and dorsal raphe nucleus (DR) in rats. The CF stress significantly increased the number of Fos‐positive (Fos+) cells in both the LC and DR, whereas it did not increase the number in the VTA. Using a double‐labeling technique, we combined Fos immunostaining with that for tyrosine hydroxylase (TH), serotonin (5‐HT), or GABA for histochemical identification of the CF stress‐induced Fos+ neurons. The percentage of TH/Fos double‐labeled cells resulting from CF stress was 63% of the Fos+ cells in the LC, whereas 52% of the Fos+ cells contained 5‐HT in the DR. We also found that approximately 60% of the CF stress‐induced Fos+ cells were GABAergic neurons in these brain regions. These results indicate that CF stress induces intense Fos expression in the noradrenergic LC and serotonergic DR neurons, but not in the dopaminergic VTA neurons. They also indicate that not only monoaminergic neurons but also GABAergic neurons within the LC and DR are activated by the stress. Synapse 45:46–51, 2002. © 2002 Wiley‐Liss, Inc.