Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinase-dependent pathways and the development of insulin resistance in hepatocytes

Hepatic insulin resistance is considered to be a dominant component in the pathogenesis of fasting hyperglycemia in Type 2 diabetes. The role of nutrients, free fatty acids and secretory inflammatory factors released by visceral fat in the pathogenesis of liver insulin resistance requires clarification, but a number of signaling pathways and serine kinases have been implicated. These include the discovery of c-Jun N-terminal kinase, I κβ kinase, protein kinase C θ, δ and ε, and ribosomal protein S6 kinase 1 as critical regulators of insulin action and steatosis in liver. In this article, the causes and mechanisms involved in the development of hepatic insulin resistance, and the signaling pathways and kinases involved, will be discussed. Elucidation of the molecular mechanisms underlying regulation and specificity may prompt novel approaches to the pharmacological modulation of protein kinase activities involved in hepatic insulin resistance. This review will detail recent discoveries and highlight emerging kinase targets that hold potential to reduce hepatic insulin resistance and normalize blood glucose.
The effectiveness of dietary workplace interventions: a systematic review of systematic reviews

Abstract Objective To summarise findings of systematic reviews that distinctively report dietary intervention components and their effects on diet-, health- and economic-related outcomes in the workplace setting. Design MEDLINE, Embase, CINAHL, Web of Science, Cochrane Library and Google Scholar were searched in December 2014 and the search was updated in August 2017. Results The search identified 1137 titles, of which nineteen systematic reviews from the initial search and two systematic reviews from the updated search met the inclusion criteria (twenty-one systematic reviews, published in twenty-two papers). Most systematic reviews were of moderate quality and focused on dietary behaviour change outcomes and some health-related biomarkers. Evidence was strongest for interventions to increase fruit and vegetable intake, reduce fat intake, aid weight loss and reduce cholesterol. Few reported workplace-related and evaluation outcomes. Conclusions These findings suggest that workplace dietary interventions can positively influence diet and health outcomes. Suggestions for effective interventions components have been made.
Intracoronary administration of nicorandil-induced cardiac arrest during primary percutaneous coronary intervention

Rationale: Primary percutaneous coronary intervention (PPCI) is the most effective therapy for patients with an acute ST-segment elevation myocardial infarction (STEMI). However, up to half of STEMI patients suffer from coronary microvascular dysfunction, presenting as the slow flow or no-reflow phenomenon. Patients concerns: A 78-year-old man was admitted to the chest pain center with sudden chest pain and tightness for about an hour. Diagnoses: Electrocardiography demonstrated ST-segment elevation in leads II, III, aVF, and third-degree atrioventricular block. Coronary angiography showed acute total occlusion in the distal right coronary artery (RCA). Interventions: PPCI was performed on the patient. After thrombus aspiration, a stent was placed in the distal RCA. As coronary angiography showed TIMI grade 2 flow in RCA, 6 mg nicorandil was intracoronary administrated in twice. Immediately, cardiac arrest occurred and cardiopulmonary resuscitation (CPR) was performed. Outcomes: The patient survived and had a good outcome during follow-up for >6 months. Lessons: Up to now, there has been no case report of cardiac arrest caused by nicorandil. Although intracoronary nicorandil is one of the most commonly used methods to improve coronary flow, much more attention should be paid to side effects of nicorandil.
Characterization and engineering of photoactivated adenylyl cyclases

Cyclic nucleoside monophosphates (cNMP) serve as universal second messengers in signal transduction across prokaryotes and eukaryotes. As signaling often relies on transiently formed microdomains of elevated second messenger concentration, means to precisely perturb the spatiotemporal dynamics of cNMPs are uniquely poised for the interrogation of the underlying physiological processes. Optogenetics appears particularly suited as it affords light-dependent, accurate control in time and space of diverse cellular processes. Several sensory photoreceptors function as photoactivated adenylyl cyclases (PAC) and hence serve as light-regulated actuators for the control of intracellular levels of 3′, 5′-cyclic adenosine monophosphate. To characterize PACs and to refine their properties, we devised a test bed for the facile analysis of these photoreceptors. Cyclase activity is monitored in bacterial cells via expression of a fluorescent reporter, and programmable illumination allows the rapid exploration of multiple lighting regimes. We thus probed two PACs responding to blue and red light, respectively, and observed significant dark activity for both. We next engineered derivatives of the red-light-sensitive PAC with altered responses to light, with one variant, denoted DdPAC, showing enhanced response to light. These PAC variants stand to enrich the optogenetic toolkit and thus facilitate the detailed analysis of cNMP metabolism and signaling.
Two-Tier Mapper, an unbiased topology-based clustering method for enhanced global gene expression analysis

Motivation Unbiased clustering methods are needed to analyze growing numbers of complex data sets. Currently available clustering methods often depend on parameters that are set by the user, they lack stability, and are not applicable to small data sets. To overcome these shortcomings we used topological data analysis, an emerging field of mathematics that can discerns additional feature and discover hidden insights on data sets and has a wide application range. Results We have developed a topology-based clustering method called Two-Tier Mapper (TTMap) for enhanced analysis of global gene expression datasets. First, TTMap discerns divergent features in the control group, adjusts for them, and identifies outliers. Second, the deviation of each test sample from the control group in a high-dimensional space is computed, and the test samples are clustered using a new Mapper-based topological algorithm at two levels: a global tier and local tiers. All parameters are either carefully chosen or data-driven, avoiding any user-induced bias. The method is stable, different datasets can be combined for analysis, and significant subgroups can be identified. It outperforms current clustering methods in sensitivity and stability on synthetic and biological datasets, in particular when sample sizes are small; outcome is not affected by removal of control samples, by choice of normalization, or by subselection of data. TTMap is readily applicable to complex, highly variable biological samples and holds promise for personalized medicine. Availability TTMap is supplied as an R package in Bioconductor. Supplementary information Supplementary data are available at Bioinformatics online.
Therapist adherence/competence and treatment outcome: A meta-analytic review.

OBJECTIVE The authors conducted a meta-analytic review of adherence-outcome and competence-outcome findings, and examined plausible moderators of these relations. METHOD A computerized search of the PsycINFO database was conducted. In addition, the reference sections of all obtained studies were examined for any additional relevant articles or review chapters. The literature search identified 36 studies that met the inclusion criteria. RESULTS R-type effect size estimates were derived from 32 adherence-outcome and 17 competence-outcome findings. Neither the mean weighted adherence-outcome (r = .02) nor competence-outcome (r = .07) effect size estimates were found to be significantly different from zero. Significant heterogeneity was observed across both the adherence-outcome and competence-outcome effect size estimates, suggesting that the individual studies were not all drawn from the same population. Moderator analyses revealed that larger competence-outcome effect size estimates were associated with studies that either targeted depression or did not control for the influence of the therapeutic alliance. CONCLUSIONS One explanation for these results is that, among the treatment modalities represented in this review, therapist adherence and competence play little role in determining symptom change. However, given the significant heterogeneity observed across findings, mean effect sizes must be interpreted with caution. Factors that may account for the nonsignificant adherence-outcome and competence-outcome findings reported within many of the studies reviewed are addressed. Finally, the implication of these results and directions for future process research are discussed.
Cariprazine for the treatment of bipolar depression: a review

ABSTRACT Introduction: Depressive symptoms and episodes dominate the course of bipolar disorder. The morbidity of bipolar disorder is disproportionately mediated by depressive symptoms; economic costs of bipolar disorder are also disproportionately due to unremitting depressive symptoms. Relatively few treatment options have established unequivocal efficacy in the treatment of bipolar depression. Herein we review evidence regarding the efficacy of the D3 preferring D2/D3 partial agonist cariprazine in the treatment of adults with bipolar depression. Areas covered: Randomized controlled trials that sought to determine the efficacy, tolerability, and safety of cariprazine in adults with bipolar I depression. Expert opinion: The available evidence from clinical trials indicates that cariprazine is effective at treating bipolar depression wherein treatment for bipolar depression remains an unmet need in bipolar disorder. Cariprazine has demonstrated good tolerability and safety profiles in bipolar disorder. Furthermore, cariprazine may be effective in improving both anhedonia and cognitive dysfunction. Long term prevention studies in bipolar depression, as well as separate studies evaluating efficacy in adults with bipolar II depression, are needed.
Epigenetic activation of POTE genes in ovarian cancer

ABSTRACT The POTE gene family consists of 14 homologous genes localized to autosomal pericentromeres, and a sub-set of POTEs are cancer-testis antigen (CTA) genes. POTEs are over-expressed in epithelial ovarian cancer (EOC), including the high-grade serous subtype (HGSC), and expression of individual POTEs correlates with chemoresistance and reduced survival in HGSC. The mechanisms driving POTE overexpression in EOC and other cancers is unknown. Here, we investigated the role of epigenetics in regulating POTE expression, with a focus on DNA hypomethylation. Consistent with their pericentromeric localization, Pan-POTE expression in EOC correlated with expression of the pericentromeric repeat NBL2, which was not the case for non-pericentromeric CTAs. POTE genomic regions contain LINE-1 (L1) sequences, and Pan-POTE expression correlated with both global and POTE-specific L1 hypomethylation in EOC. Analysis of individual POTEs using RNA-seq and DNA methylome data from fallopian tube epithelia (FTE) and HGSC revealed that POTEs C, E, and F have increased expression in HGSC in conjunction with DNA hypomethylation at 5’ promoter or enhancer regions. Moreover, POTEs C/E/F showed additional increased expression in recurrent HGSC in conjunction with 5’ hypomethylation, using patient-matched samples. Experiments using decitabine treatment and DNMT knockout cell lines verified a functional contribution of DNA methylation to POTE repression, and epigenetic drug combinations targeting histone deacetylases (HDACs) and histone methyltransferases (HMTs) in combination with decitabine further increased POTE expression. In summary, several alterations of the cancer epigenome, including pericentromeric activation, global and locus-specific L1 hypomethylation, and locus-specific 5’ CpG hypomethylation, converge to promote POTE expression in ovarian cancer.
Translating Research Into Practice for Healthcare Providers: The American Heart Association's Strategy for Building Healthier Lives, Free of Cardiovascular Diseases and Stroke

The American Heart Association's (AHA's) mission is “to build healthier lives, free of cardiovascular diseases and stroke. ” This first article in a 2-part series will serve to present an overview of the work the AHA has undertaken to translate evidence into practice for healthcare professionals. It describes the extensive work of the AHA to support and further the delivery of evidence-based medicine, which includes the following: (1) supporting scientific discovery and the next generation of healthcare professionals and researchers; (2) disseminating scientific information; (3) developing evidence-based guidelines and statements; (4) creating and advocating for the implementation of performance indicators/measures; (5) developing clinical decision support and quality improvement tools; and (6) developing directed-cause campaigns, all of which can lead to improved patient care. This article also discusses the need for novel approaches and some of the AHA's evolving strategies to help address gaps in care. The second article, which will be published shortly after this one, will examine the AHA's efforts to engage and empower healthcare consumers to become more involved with their own health and health care.
An Improved Index of Image Quality for Task-based Performance of CT Iterative Reconstruction across Three Commercial Implementations.

PURPOSE To develop and validate a metric of computed tomographic (CT) image quality that incorporates the noise texture and resolution properties of an image. MATERIALS AND METHODS Images of the American College of Radiology CT quality assurance phantom were acquired by using three commercial CT systems at seven dose levels with filtered back projection (FBP) and iterative reconstruction (IR). Image quality was characterized by the contrast-to-noise ratio (CNR) and a detectability index (d') that incorporated noise texture and spatial resolution. The measured CNR and d' were compared with a corresponding observer study by using the Spearman rank correlation coefficient to determine how well each metric reflects the ability of an observer to detect subtle lesions. Statistical significance of the correlation between each metric and observer performance was determined by using a Student t distribution; P values less than . 05 indicated a significant correlation. Additionally, each metric was used to estimate the dose reduction potential of IR algorithms while maintaining image quality. RESULTS Across all dose levels, scanner models, and reconstruction algorithms, the d' correlated strongly with observer performance in the corresponding observer study (ρ = 0.95; P < .001), whereas the CNR correlated weakly with observer performance (ρ = 0.31; P = .21). Furthermore, the d' showed that the dose-reduction capabilities differed between clinical implementations (range, 12%-35%) and were less than those predicted from the CNR (range, 50%-54%). CONCLUSION The strong correlation between the observer performance and the d' indicates that the d' is superior to the CNR for the evaluation of CT image quality. Moreover, the results of this study indicate that the d' improves less than the CNR with the use of IR, which indicates less potential for IR dose reduction than previously thought.
Solvolysis Artifacts: Leucettazoles as Cryptic Macrocyclic Alkaloid Dimers from a Southern Australian Marine Sponge, Leucetta sp.

Chemical analysis of a southern Australian sponge, Leucetta sp. , led to the discovery of a pair of solvolysis adducts, leucettazoles A1 (1a) and B1 (2a), as artifacts of an unprecedented family of 15-membered macrocyclic alkaloid dimers featuring a pair of imino bridged 2-aminoimidazoles, together with a putative monomeric precursor, leucettazine A (3). The dimeric alkaloids 1a and 2a, and monomer 3, were identified by detailed spectroscopic analysis, supported by chemical transformations, analytical mass spectrometry, and biosynthetic considerations. Global natural product social networking (GNPS) molecular analysis of crude sponge extracts and solvent partitions, supported by single ion extraction (SIE) and diagnostic MS/MS fragmentations, revealed the associated natural products, leucettazoles A (1) and B (2). This study highlights that the study of natural product artifacts can be useful, and can on occasion serve as a pathway to discover cryptic new classes of natural products.
Development of a deep neural network for automated electromyographic pattern classification

ABSTRACT Determining the signal quality of surface electromyography (sEMG) recordings is time consuming and requires the judgement of trained observers. An automated procedure to evaluate sEMG quality would streamline data processing and reduce time demands. This paper compares the performance of two supervised and three unsupervised artificial neural networks (ANNs) in the evaluation of sEMG quality. Manually classified sEMG recordings from various lower-limb muscles during motor tasks were used to train (n=28,000), test performance (n=12,000) and evaluate accuracy (n=47,000) of the five ANNs in classifying signals into four categories. Unsupervised ANNs demonstrated a 30–40% increase in classification accuracy (>98%) compared with supervised ANNs. AlexNet demonstrated the highest accuracy (99.55%) with negligible false classifications. The results indicate that sEMG quality evaluation can be automated via an ANN without compromising human-like classification accuracy. This classifier will be publicly available and will be a valuable tool for researchers and clinicians using electromyography. Summary: The quality of surface electromyography recordings can be automatically classified with an accuracy of 99.55% by a deep neural network (AlexNet).
Relationship Between Body Mass Index and Body Image Disturbances Among South African Mothers and Their Daughters Living in Soweto, Johannesburg

In South African families, a phenomenon of mothers' acceptance of stoutness coexists with their daughters' appreciation for thinness. A sample of N = 615 mother-and-daughter pairs was recruited to conjointly identify the relationships toward body image and body mass index between both groups by assessing body weight satisfaction, body esteem, and eating disorders risk. We observed higher prevalence of obesity in mothers and higher eating disorders risk in daughters, while mother-daughter relationships were identified for body mass index and psychometric dimensions. The high prevalence of obesity in mothers and their tolerance for stoutness could expose their daughters to eating disorders and obesity.
Cross-modal working memory binding and learning of visual-phonological associations in children with reading difficulties

ABSTRACT Reading decoding requires the association of a visual input (the printed word) with a verbal output (the spoken word), and the learning of visual-phonological associations via repeated exposure occurs both explicitly (by instruction and training) and implicitly (by exposure to written material). However, a general ability to implicitly learn visual-phonological associations (or cross-modal bindings) in children with reading difficulties (RD) has not been deeply explored. The present paper examined this issue in two studies comparing groups of children with RD with matched groups of control children in a working memory binding task involving sequences of variable combinations of nonsense shapes and nonwords (odd trials), as well as fixed combinations (even trials). Stimuli presentation was followed by a recognition test in which the nonwords were given one at a time and the children were required to mouse click on their respective shapes. In Study 1, fixed bindings were presented in random sequences across even trials, and the recognition test presented the nonwords at random. In Study 2, fixed bindings were presented in the same order across even trials, and the recognition test presented the nonwords following the same sequence order. In both studies, a consistent and strong learning effect of fixed bindings was observed for the control groups, with significantly better performance than the groups with RD. Such results suggest that poor cross-modal binding learning is associated with reading difficulties. Implications for the study and treatment of dyslexia are discussed.
Handbook of PTSD: Science and Practice.

The exponential growth of research and clinical experience regarding posttraumatic stress disorder (PTSD) since its inclusion as a diagnosis in DSM-III 27 years ago has made it increasingly difficult to keep pace with advances in knowledge about the disorder. The three highly respected editors of this book identified the need for a comprehensive textbook on PTSD and brought together a group of 60 strong contributors, predominantly from the United States (with one or two well chosen exceptions), to produce a highly readable volume that will undoubtedly be of great use to individuals specializing in traumatic stress. The chapters detailing the historical background of the disorder set the scene and the chapters concerning psychological theories, epidemiology, and neurobiological theories provide up-to-date discussions of current knowledge in these areas. One great strength of the book is the detailed consideration of memory in PTSD, trauma-induced dissociation, and gene-environment interactions. Work in these areas is increasing and our knowledge is improving, and the chapters provide readers with an opportunity to consolidate their knowledge in these important areas that are not fully covered in many other texts. The section on prevention and treatment of posttraumatic stress disorder comprehensively reviews the evidence for interventions and importantly includes a chapter on cultural issues and trauma, which are often forgotten. The final section of the book, "Uncharted Territory," provides a helpful overview of PTSD and the law. Perhaps not surprisingly, the focus is on U.S. legislation, although many of the issues can be easily translated to other countries, particularly the more developed ones. The contributing authors sensibly write, "Healthy skepticism must be tempered with an ethical obligation to deal with PTSD claimants in an honest and empathic manner. " Many texts do not consider emerging and novel treatments that have not been subjected to extensive evaluation but are in some cases already widely used. It is very important that such approaches are considered and fairly assessed. The chapter dedicated to emerging treatments for PTSD provides a useful review and helpfully recommends capitalizing on social support because of its association with recovery. Given the limited evidence for blanket early intervention, the chapter on public mental health interventions provides some excellent points, with a focus on providing for basic needs and triage. The final chapter provides a fitting end to the book with a synthesis of key questions and an agenda for future research. Overall this is a very good overview of the traumatic stress field and a volume I am very pleased to have on my bookshelf. I suspect that others will feel the same.