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Find video protocols related to scientific articles indexed in Pubmed.
Clinical Accuracy of a Continuous Glucose Monitoring System With an Advanced Algorithm.
J Diabetes Sci Technol
PUBLISHED: 11-06-2014
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We assessed the performance of a modified Dexcom G4 Platinum system with an advanced algorithm, in comparison with frequent venous samples measured on a laboratory reference (YSI) during a clinic session and in comparison to self-monitored blood glucose (SMBG) during home use. Fifty-one subjects with diabetes were enrolled in a prospective multicenter study. Subjects wore 1 sensor for 7-day use and participated in one 12-hour in-clinic session on day 1, 4, or 7 to collect YSI reference venous glucose every 15 minutes and capillary SMBG test every 30 minutes. Carbohydrate consumption and insulin dosing and timing were manipulated to obtain data in low and high glucose ranges. In comparison with the laboratory reference method (n = 2,263) the system provided a mean and median absolute relative differences (ARD) of 9.0% and 7.0%, respectively. The mean absolute difference for CGM was 6.4 mg/dL when the YSIs were within hypoglycemia ranges (? 70 mg/dL). The percentage in the clinically accurate Clarke error grid A zone was 92.4% and in the benign error B zone was 7.1%. Majority of the sensors (73%) had an aggregated MARD in reference to YSI ? 10%. The MARD of CGM-SMBG for home use was 11.3%. The study showed that the point and rate accuracy, clinical accuracy, reliability, and consistency over the duration of wear and across glycemic ranges were superior to current commercial real-time CGM systems. The performance of this CGM is reaching that of a self-monitoring blood glucose meter in real use environment.
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NFIX Regulates Proliferation and Migration Within the Murine SVZ Neurogenic Niche.
Cereb. Cortex
PUBLISHED: 10-22-2014
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Transcription factors of the nuclear factor one (NFI) family play a pivotal role in the development of the nervous system. One member, NFIX, regulates the development of the neocortex, hippocampus, and cerebellum. Postnatal Nfix(-/-) mice also display abnormalities within the subventricular zone (SVZ) lining the lateral ventricles, a region of the brain comprising a neurogenic niche that provides ongoing neurogenesis throughout life. Specifically, Nfix(-/-) mice exhibit more PAX6-expressing progenitor cells within the SVZ. However, the mechanism underlying the development of this phenotype remains undefined. Here, we reveal that NFIX contributes to multiple facets of SVZ development. Postnatal Nfix(-/-) mice exhibit increased levels of proliferation within the SVZ, both in vivo and in vitro as assessed by a neurosphere assay. Furthermore, we show that the migration of SVZ-derived neuroblasts to the olfactory bulb is impaired, and that the olfactory bulbs of postnatal Nfix(-/-) mice are smaller. We also demonstrate that gliogenesis within the rostral migratory stream is delayed in the absence of Nfix, and reveal that Gdnf (glial-derived neurotrophic factor), a known attractant for SVZ-derived neuroblasts, is a target for transcriptional activation by NFIX. Collectively, these findings suggest that NFIX regulates both proliferation and migration during the development of the SVZ neurogenic niche.
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Usability and Training Differences Between Two Personal Insulin Pumps.
J Diabetes Sci Technol
PUBLISHED: 10-16-2014
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The purpose of this study was to determine if there were usability and training differences between the Medtronic MiniMed Paradigm Revel™ Insulin Pump and the Tandem Diabetes Care t:slim® Insulin Pump during use by representative users, performing representative tasks, in a simulated use environment. This study utilized a between-subjects experimental design with a total of 72 participants from 5 sites across the United States. Study participants were randomized to either the Revel pump group or the t:slim Pump group. Participants were 18 years of age or older and managed their diabetes using multiple daily insulin injections. Dependent variables included training time, training satisfaction, time on task, task failures, System Usability Scale (SUS) ratings, perceived task difficulty, and a pump survey that measured different aspects of the pumps and training sessions. There was a statistically significant difference in training times and error rates between the t:slim and Revel groups. The training time difference represented a 27% reduction in time to train on the t:slim versus the Revel pump. There was a 65% reduction in participants' use error rates between the t:slim and the Revel group. The t:slim Pump had statistically significant training and usability advantages over the Revel pump. The reduction in training time may have been a result of an optimized information architecture, an intuitive navigational layout, and an easy-to-read screen. The reduction in use errors with the t:slim may have been a result of dynamic error handling and active confirmation screens, which may have prevented programming errors.
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Creating and validating cis-regulatory maps of tissue-specific gene expression regulation.
Nucleic Acids Res.
PUBLISHED: 09-08-2014
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Predicting which genomic regions control the transcription of a given gene is a challenge. We present a novel computational approach for creating and validating maps that associate genomic regions (cis-regulatory modules-CRMs) with genes. The method infers regulatory relationships that explain gene expression observed in a test tissue using widely available genomic data for 'other' tissues. To predict the regulatory targets of a CRM, we use cross-tissue correlation between histone modifications present at the CRM and expression at genes within 1 Mbp of it. To validate cis-regulatory maps, we show that they yield more accurate models of gene expression than carefully constructed control maps. These gene expression models predict observed gene expression from transcription factor binding in the CRMs linked to that gene. We show that our maps are able to identify long-range regulatory interactions and improve substantially over maps linking genes and CRMs based on either the control maps or a 'nearest neighbor' heuristic. Our results also show that it is essential to include CRMs predicted in multiple tissues during map-building, that H3K27ac is the most informative histone modification, and that CAGE is the most informative measure of gene expression for creating cis-regulatory maps.
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Differential motif enrichment analysis of paired ChIP-seq experiments.
BMC Genomics
PUBLISHED: 09-02-2014
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Motif enrichment analysis of transcription factor ChIP-seq data can help identify transcription factors that cooperate or compete. Previously, little attention has been given to comparative motif enrichment analysis of pairs of ChIP-seq experiments, where the binding of the same transcription factor is assayed under different conditions. Such comparative analysis could potentially identify the distinct regulatory partners/competitors of the assayed transcription factor under different conditions or at different stages of development.
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Assessment for ease of use and preference of a new prefilled insulin pen (FlexTouch Degludec U100/U200) versus the SoloSTAR insulin pen by patients with diabetes and healthcare professionals.
Expert Opin Drug Deliv
PUBLISHED: 06-12-2014
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FlexTouch® (FT) is a new prefilled insulin pen with no push-button extension and a low injection force used to deliver several basal insulins, including insulin degludec across a wide dose range (1 - 80 units with FT 100 IU/ml [FT100] and 2 - 160 units with 200 IU/ml [FT200]). This study was carried out to evaluate whether the novel features of FT affect the preferences of the device among patients with diabetes and healthcare professionals compared with the widely used SoloSTAR® pen.
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Switching on sex: transcriptional regulation of the testis-determining gene Sry.
Development
PUBLISHED: 05-29-2014
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Mammalian sex determination hinges on the development of ovaries or testes, with testis fate being triggered by the expression of the transcription factor sex-determining region Y (Sry). Reduced or delayed Sry expression impairs testis development, highlighting the importance of its accurate spatiotemporal regulation and implying a potential role for SRY dysregulation in human intersex disorders. Several epigenetic modifiers, transcription factors and kinases are implicated in regulating Sry transcription, but it remains unclear whether or how this farrago of factors acts co-ordinately. Here we review our current understanding of Sry regulation and provide a model that assembles all known regulators into three modules, each converging on a single transcription factor that binds to the Sry promoter. We also discuss potential future avenues for discovering the cis-elements and trans-factors required for Sry regulation.
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GT-Scan: identifying unique genomic targets.
Bioinformatics
PUBLISHED: 05-23-2014
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A number of technologies, including CRISPR/Cas, transcription activator-like effector nucleases and zinc-finger nucleases, allow the user to target a chosen locus for genome editing or regulatory interference. Specificity, however, is a major problem, and the targeted locus must be chosen with care to avoid inadvertently affecting other loci ('off-targets') in the genome. To address this we have created 'Genome Target Scan' (GT-Scan), a flexible web-based tool that ranks all potential targets in a user-selected region of a genome in terms of how many off-targets they have. GT-Scan gives the user flexibility to define the desired characteristics of targets and off-targets via a simple 'target rule', and its interactive output allows detailed inspection of each of the most promising candidate targets. GT-Scan can be used to identify optimal targets for CRISPR/Cas systems, but its flexibility gives it potential to be adapted to other genome-targeting technologies as well.
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Motif-based analysis of large nucleotide data sets using MEME-ChIP.
Nat Protoc
PUBLISHED: 05-22-2014
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MEME-ChIP is a web-based tool for analyzing motifs in large DNA or RNA data sets. It can analyze peak regions identified by ChIP-seq, cross-linking sites identified by CLIP-seq and related assays, as well as sets of genomic regions selected using other criteria. MEME-ChIP performs de novo motif discovery, motif enrichment analysis, motif location analysis and motif clustering, providing a comprehensive picture of the DNA or RNA motifs that are enriched in the input sequences. MEME-ChIP performs two complementary types of de novo motif discovery: weight matrix-based discovery for high accuracy; and word-based discovery for high sensitivity. Motif enrichment analysis using DNA or RNA motifs from human, mouse, worm, fly and other model organisms provides even greater sensitivity. MEME-ChIP's interactive HTML output groups and aligns significant motifs to ease interpretation. This protocol takes less than 3 h, and it provides motif discovery approaches that are distinct and complementary to other online methods.
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Accuracy and acceptability of the 6-day Enlite continuous subcutaneous glucose sensor.
Diabetes Technol. Ther.
PUBLISHED: 04-07-2014
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This study evaluated the performance and acceptability of the Enlite(®) glucose sensor (Medtronic MiniMed, Inc., Northridge, CA).
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Improving MEME via a two-tiered significance analysis.
Bioinformatics
PUBLISHED: 03-24-2014
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With over 9000 unique users recorded in the first half of 2013, MEME is one of the most popular motif-finding tools available. Reliable estimates of the statistical significance of motifs can greatly increase the usefulness of any motif finder. By analogy, it is difficult to imagine evaluating a BLAST result without its accompanying E-value. Currently MEME evaluates its EM-generated candidate motifs using an extension of BLAST's E-value to the motif-finding context. Although we previously indicated the drawbacks of MEME's current significance evaluation, we did not offer a practical substitute suited for its needs, especially because MEME also relies on the E-value internally to rank competing candidate motifs.
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An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation.
BMC Genomics
PUBLISHED: 03-11-2014
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Lung maturation is a late fetal developmental event in both mice and humans. Because of this, lung immaturity is a serious problem in premature infants. Disruption of genes for either the glucocorticoid receptor (Nr3c1) or the NFIB transcription factors results in perinatal lethality due to lung immaturity. In both knockouts, the phenotype includes excess cell proliferation, failure of saccularization and reduced expression of markers of epithelial differentiation. This similarity suggests that the two genes may co-regulate a specific set of genes essential for lung maturation.
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NFIB-mediated repression of the epigenetic factor Ezh2 regulates cortical development.
J. Neurosci.
PUBLISHED: 02-21-2014
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Epigenetic mechanisms are essential in regulating neural progenitor cell self-renewal, with the chromatin-modifying protein Enhancer of zeste homolog 2 (EZH2) emerging as a central player in promoting progenitor cell self-renewal during cortical development. Despite this, how Ezh2 is itself regulated remains unclear. Here, we demonstrate that the transcription factor nuclear factor IB (NFIB) plays a key role in this process. Nfib(-/-) mice exhibit an increased number of proliferative ventricular zone cells that express progenitor cell markers and upregulation of EZH2 expression within the neocortex and hippocampus. NFIB binds to the Ezh2 promoter and overexpression of NFIB represses Ezh2 transcription. Finally, key downstream targets of EZH2-mediated epigenetic repression are misregulated in Nfib(-/-) mice. Collectively, these results suggest that the downregulation of Ezh2 transcription by NFIB is an important component of the process of neural progenitor cell differentiation during cortical development.
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Predicting the dynamics of protein abundance.
Mol. Cell Proteomics
PUBLISHED: 02-16-2014
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Protein synthesis is finely regulated across all organisms, from bacteria to humans, and its integrity underpins many important processes. Emerging evidence suggests that the dynamic range of protein abundance is greater than that observed at the transcript level. Technological breakthroughs now mean that sequencing-based measurement of mRNA levels is routine, but protocols for measuring protein abundance remain both complex and expensive. This paper introduces a Bayesian network that integrates transcriptomic and proteomic data to predict protein abundance and to model the effects of its determinants. We aim to use this model to follow a molecular response over time, from condition-specific data, in order to understand adaptation during processes such as the cell cycle. With microarray data now available for many conditions, the general utility of a protein abundance predictor is broad. Whereas most quantitative proteomics studies have focused on higher organisms, we developed a predictive model of protein abundance for both Saccharomyces cerevisiae and Schizosaccharomyces pombe to explore the latitude at the protein level. Our predictor primarily relies on mRNA level, mRNA-protein interaction, mRNA folding energy and half-life, and tRNA adaptation. The combination of key features, allowing for the low certainty and uneven coverage of experimental observations, gives comparatively minor but robust prediction accuracy. The model substantially improved the analysis of protein regulation during the cell cycle: predicted protein abundance identified twice as many cell-cycle-associated proteins as experimental mRNA levels. Predicted protein abundance was more dynamic than observed mRNA expression, agreeing with experimental protein abundance from a human cell line. We illustrate how the same model can be used to predict the folding energy of mRNA when protein abundance is available, lending credence to the emerging view that mRNA folding affects translation efficiency. The software and data used in this research are available at http://bioinf.scmb.uq.edu.au/proteinabundance/.
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Statistical confidence estimation for Hi-C data reveals regulatory chromatin contacts.
Genome Res.
PUBLISHED: 02-05-2014
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Our current understanding of how DNA is packed in the nucleus is most accurate at the fine scale of individual nucleosomes and at the large scale of chromosome territories. However, accurate modeling of DNA architecture at the intermediate scale of ?50 kb-10 Mb is crucial for identifying functional interactions among regulatory elements and their target promoters. We describe a method, Fit-Hi-C, that assigns statistical confidence estimates to mid-range intra-chromosomal contacts by jointly modeling the random polymer looping effect and previously observed technical biases in Hi-C data sets. We demonstrate that our proposed approach computes accurate empirical null models of contact probability without any distribution assumption, corrects for binning artifacts, and provides improved statistical power relative to a previously described method. High-confidence contacts identified by Fit-Hi-C preferentially link expressed gene promoters to active enhancers identified by chromatin signatures in human embryonic stem cells (ESCs), capture 77% of RNA polymerase II-mediated enhancer-promoter interactions identified using ChIA-PET in mouse ESCs, and confirm previously validated, cell line-specific interactions in mouse cortex cells. We observe that insulators and heterochromatin regions are hubs for high-confidence contacts, while promoters and strong enhancers are involved in fewer contacts. We also observe that binding peaks of master pluripotency factors such as NANOG and POU5F1 are highly enriched in high-confidence contacts for human ESCs. Furthermore, we show that pairs of loci linked by high-confidence contacts exhibit similar replication timing in human and mouse ESCs and preferentially lie within the boundaries of topological domains for human and mouse cell lines.
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Hypoglycemia begets hypoglycemia: The order effect in the ASPIRE in-clinic study.
Diabetes Technol. Ther.
PUBLISHED: 01-09-2014
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The ASPIRE in-clinic study established that automatic suspension of insulin with the threshold suspend (TS) feature reduces the duration of induced hypoglycemia. The study's crossover design allowed the effects of antecedent hypoglycemia to be studied.
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Accuracy of a first-generation intravenous blood glucose monitoring system in subjects with diabetes mellitus: a multicenter study.
J Diabetes Sci Technol
PUBLISHED: 12-20-2013
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Hyperglycemia and hypoglycemia in hospitalized patients have been associated with increased morbidity and mortality. Improvements in glucose monitoring technology may be helpful in the clinical management of critically ill patients with abnormal glucose levels. A first-generation intravenous blood glucose monitoring (IVBG) system was developed to facilitate glycemic control therapy in hospitalized patients. A nonrandomized, single-arm, multicenter study was performed to evaluate the safety and accuracy of the IVBG system in insulin-treated subjects with diabetes mellitus.
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Practical guidelines for the comprehensive analysis of ChIP-seq data.
PLoS Comput. Biol.
PUBLISHED: 11-01-2013
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Mapping the chromosomal locations of transcription factors, nucleosomes, histone modifications, chromatin remodeling enzymes, chaperones, and polymerases is one of the key tasks of modern biology, as evidenced by the Encyclopedia of DNA Elements (ENCODE) Project. To this end, chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is the standard methodology. Mapping such protein-DNA interactions in vivo using ChIP-seq presents multiple challenges not only in sample preparation and sequencing but also for computational analysis. Here, we present step-by-step guidelines for the computational analysis of ChIP-seq data. We address all the major steps in the analysis of ChIP-seq data: sequencing depth selection, quality checking, mapping, data normalization, assessment of reproducibility, peak calling, differential binding analysis, controlling the false discovery rate, peak annotation, visualization, and motif analysis. At each step in our guidelines we discuss some of the software tools most frequently used. We also highlight the challenges and problems associated with each step in ChIP-seq data analysis. We present a concise workflow for the analysis of ChIP-seq data in Figure 1 that complements and expands on the recommendations of the ENCODE and modENCODE projects. Each step in the workflow is described in detail in the following sections.
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Pharmacologic inhibition of the renal outer medullary potassium channel causes diuresis and natriuresis in the absence of kaliuresis.
J. Pharmacol. Exp. Ther.
PUBLISHED: 10-18-2013
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The renal outer medullary potassium (ROMK) channel, which is located at the apical membrane of epithelial cells lining the thick ascending loop of Henle and cortical collecting duct, plays an important role in kidney physiology by regulating salt reabsorption. Loss-of-function mutations in the human ROMK channel are associated with antenatal type II Bartters syndrome, an autosomal recessive life-threatening salt-wasting disorder with mild hypokalemia. Similar observations have been reported from studies with ROMK knockout mice and rats. It is noteworthy that heterozygous carriers of Kir1.1 mutations associated with antenatal Bartters syndrome have reduced blood pressure and a decreased risk of developing hypertension by age 60. Although selective ROMK inhibitors would be expected to represent a new class of diuretics, this hypothesis has not been pharmacologically tested. Compound A [5-(2-(4-(2-(4-(1H-tetrazol-1-yl)phenyl)acetyl)piperazin-1-yl)ethyl)isobenzofuran-1(3H)-one)], a potent ROMK inhibitor with appropriate selectivity and characteristics for in vivo testing, has been identified. Compound A accesses the channel through the cytoplasmic side and binds to residues lining the pore within the transmembrane region below the selectivity filter. In normotensive rats and dogs, short-term oral administration of compound A caused concentration-dependent diuresis and natriuresis that were comparable to hydrochlorothiazide. Unlike hydrochlorothiazide, however, compound A did not cause any significant urinary potassium losses or changes in plasma electrolyte levels. These data indicate that pharmacologic inhibition of ROMK has the potential for affording diuretic/natriuretic efficacy similar to that of clinically used diuretics but without the dose-limiting hypokalemia associated with the use of loop and thiazide-like diuretics.
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A new test strip technology platform for self-monitoring of blood glucose.
J Diabetes Sci Technol
PUBLISHED: 10-16-2013
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In the management of diabetes, accuracy of devices used for self-monitoring of blood glucose (SMBG) is critical because SMBG results can affect patient diabetes-related health outcomes. A new blood glucose monitoring system (BGMS) platform has been developed that is based on the new CONTOUR® NEXT (CN) test strip. This BGMS platform uses a proprietary electron mediator and algorithm to minimize errors at different steps in the testing process, thus minimizing outliers and significantly improving accuracy from prior-generation blood glucose meter systems. As demonstrated by questionnaire results from clinical studies with the new BGMS platform, accuracy and ease of use are important considerations for people with diabetes and their health care professionals when selecting an SMBG device. This article provides an overview of laboratory studies and clinical trials in the hands of lay users involving the performance of the portfolio of blood glucose meters that uses the new test strip. Each BGMS in the platform, which includes the CONTOUR XT (CONTOUR NEXT EZ in the United States), CONTOUR NEXT LINK, CONTOUR NEXT USB, and CN systems, demonstrated advanced accuracy both in the laboratory and in the hands of subjects (people with diabetes) and trained health care professionals. All systems met and exceeded International Organization for Standardization accuracy criteria (both ISO 15197:2003 and ISO 15197:2013). Each system in the new BGMS platform delivers advanced accuracy, which is essential to people who utilize SMBG for improved management.
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Options for combination therapy in type 2 diabetes: comparison of the ADA/EASD position statement and AACE/ACE algorithm.
Am. J. Med.
PUBLISHED: 08-20-2013
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Treating patients with diabetes is one of the most challenging and important activities a physician (primary care physician or specialist) can undertake. A key to successful therapy for type 2 diabetes is the insight that this condition is progressive and that the need for additional agents over time is normative. The ability to individualize therapy by patient and medication characteristics comes from experience and knowledge of pertinent clinical studies. However, guidelines from expert bodies such as the American Diabetes Association/European Association for the Study of Diabetes and American Association of Clinical Endocrinologists/American College of Endocrinology can help clinicians of all levels of expertise to approach therapy choices more rationally. There is unity across these guidelines about the role and benefits of metformin as first-line pharmacological treatment, probability of good efficacy, low risk of hypoglycemia, modest weight loss, and overall long-term data. Unfortunately, this unity does not extend to recommendations for subsequent pharmacological agents and their use in combination to intensify treatment when insulin is not (yet) appropriate. Across both statements, some drug classes seem more prominent, and looking at their benefit-risk profile, it is clear why this is the case. The most profound recent change in diabetes therapy has been the introduction of incretin therapies. Incretin therapies minimize 2 important adverse effects seen with many other therapies: hypoglycemia and weight gain. These agents have increased the range of options available for early intensification of treatment of type 2 diabetes. In combination with more established therapies, there are more opportunities than ever to accommodate patient preferences while improving glycemic control and harnessing extraglycemic benefits of a second (or third) agent.
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Discovery of a novel sub-class of ROMK channel inhibitors typified by 5-(2-(4-(2-(4-(1H-Tetrazol-1-yl)phenyl)acetyl)piperazin-1-yl)ethyl)isobenzofuran-1(3H)-one.
Bioorg. Med. Chem. Lett.
PUBLISHED: 07-30-2013
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A sub-class of distinct small molecule ROMK inhibitors were developed from the original lead 1. Medicinal chemistry endeavors led to novel ROMK inhibitors with good ROMK functional potency and improved hERG selectivity. Two of the described ROMK inhibitors were characterized for the first in vivo proof-of-concept biology studies, and results from an acute rat diuresis model confirmed the hypothesis that ROMK inhibitors represent new mechanism diuretic and natriuretic agents.
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A new-generation continuous glucose monitoring system: improved accuracy and reliability compared with a previous-generation system.
Diabetes Technol. Ther.
PUBLISHED: 06-18-2013
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Use of continuous glucose monitoring (CGM) systems can improve glycemic control, but widespread adoption of CGM utilization has been limited, in part because of real and perceived problems with accuracy and reliability. This study compared accuracy and performance metrics for a new-generation CGM system with those of a previous-generation device.
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Defining the RGG/RG motif.
Mol. Cell
PUBLISHED: 06-11-2013
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Motifs rich in arginines and glycines were recognized several decades ago to play functional roles and were termed glycine-arginine-rich (GAR) domains and/or RGG boxes. We review here the evolving functions of the RGG box along with several sequence variations that we collectively term the RGG/RG motif. Greater than 1,000 human proteins harbor the RGG/RG motif, and these proteins influence numerous physiological processes such as transcription, pre-mRNA splicing, DNA damage signaling, mRNA translation, and the regulation of apoptosis. In particular, we discuss the role of the RGG/RG motif in mediating nucleic acid and protein interactions, a function that is often regulated by arginine methylation and partner-binding proteins. The physiological relevance of the RGG/RG motif is highlighted by its association with several diseases including neurological and neuromuscular diseases and cancer. Herein, we discuss the evidence for the emerging diverse functionality of this important motif.
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Triplex-Inspector: an analysis tool for triplex-mediated targeting of genomic loci.
Bioinformatics
PUBLISHED: 06-05-2013
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At the heart of many modern biotechnological and therapeutic applications lies the need to target specific genomic loci with pinpoint accuracy. Although landmark experiments demonstrate technological maturity in manufacturing and delivering genetic material, the genomic sequence analysis to find suitable targets lags behind. We provide a computational aid for the sophisticated design of sequence-specific ligands and selection of appropriate targets, taking gene location and genomic architecture into account.
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A long-acting human growth hormone with delayed clearance (VRS-317): results of a double-blind, placebo-controlled, single ascending dose study in growth hormone-deficient adults.
J. Clin. Endocrinol. Metab.
PUBLISHED: 04-12-2013
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Administration of daily recombinant human GH (rhGH) poses a considerable challenge to patient compliance. Reduced dosing frequency may improve treatment adherence and potentially overall treatment outcomes.
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Recommendations for standardizing glucose reporting and analysis to optimize clinical decision making in diabetes: the ambulatory glucose profile.
J Diabetes Sci Technol
PUBLISHED: 04-10-2013
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Underutilization of glucose data and lack of easy and standardized glucose data collection, analysis, visualization, and guided clinical decision making are key contributors to poor glycemic control among individuals with type 1 diabetes mellitus. An expert panel of diabetes specialists, facilitated by the International Diabetes Center and sponsored by the Helmsley Charitable Trust, met in 2012 to discuss recommendations for standardizing the analysis and presentation of glucose monitoring data, with the initial focus on data derived from continuous glucose monitoring systems. The panel members were introduced to a universal software report, the Ambulatory Glucose Profile, and asked to provide feedback on its content and functionality, both as a research tool and in clinical settings. This article provides a summary of the topics and issues discussed during the meeting and presents recommendations from the expert panel regarding the need to standardize glucose profile summary metrics and the value of a uniform glucose report to aid clinicians, researchers, and patients.
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Accuracy and preference assessment of prefilled insulin pen versus vial and syringe with diabetes patients, caregivers, and healthcare professionals.
Curr Med Res Opin
PUBLISHED: 03-19-2013
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The primary objective of this study was to investigate the dosing accuracy of the new prefilled FlexTouch insulin pen (FT) in comparison to conventional vial and syringe (V&S) when used by patients (Pts), caregivers (CG) and healthcare professionals (HCPs).
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Recommendations for standardizing glucose reporting and analysis to optimize clinical decision making in diabetes: the Ambulatory Glucose Profile (AGP).
Diabetes Technol. Ther.
PUBLISHED: 02-28-2013
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Abstract Underutilization of glucose data and lack of easy and standardized glucose data collection, analysis, visualization, and guided clinical decision making are key contributors to poor glycemic control among individuals with type 1 diabetes. An expert panel of diabetes specialists, facilitated by the International Diabetes Center and sponsored by the Helmsley Charitable Trust, met in 2012 to discuss recommendations for standardization of analysis and presentation of glucose monitoring data, with the initial focus on data derived from CGM systems. The panel members were introduced to a universal software report, the Ambulatory Glucose Profile (AGP), and asked to provide feedback on its content and functionality, both as a research tool and in clinical settings. This paper provides a summary of the topics and issues discussed during the meeting and presents recommendations from the expert panel regarding the need to standardize glucose profile summary metrics and the value of a uniform glucose report to aid clinicians, researchers, and patients.
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Nuclear factor one X regulates Bobby sox during development of the mouse forebrain.
Cell. Mol. Neurobiol.
PUBLISHED: 01-20-2013
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The transcription factor nuclear factor one X (NFIX) plays a central role during the development of the neocortex and hippocampus, through the activation of astrocyte-specific gene expression and the repression of progenitor-specific pathways. However, our understanding of transcriptional targets of NFIX during cortical development remains limited. Here, we identify the transcription factor Bobby sox (Bbx) as a target for NFI-mediated transcriptional control. BBX is expressed within ventricular zone progenitor cells within the developing neocortex and hippocampus, and its expression is upregulated in Nfix (-/-) mice. Moreover, we reveal that NFIX can repress Bbx promoter-driven expression. Collectively, these data suggest that Bbx is a downstream target of NFIX during development of the forebrain.
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SVM-based prediction of propeptide cleavage sites in spider toxins identifies toxin innovation in an Australian tarantula.
PLoS ONE
PUBLISHED: 01-01-2013
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Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree) and developed an algorithm (SpiderP) for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM) framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor) from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP) is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html), a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from the SpiderP website.
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Healthcare professional and patient assessment of a new prefilled insulin pen versus two widely available prefilled insulin pens for ease of use, teaching and learning.
Curr Med Res Opin
PUBLISHED: 12-20-2011
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FlexTouch * (FT) is a new prefilled insulin pen with no push-button extension at any set dose and a low activation force that is designed to improve ease of use and insulin administration. This paper reports the results of two usability studies assessing perceptions of FT compared with KwikPen † (KP)and SoloStar ‡ (SS) among healthcare professionals (HCPs; both physicians and nurses) and people with diabetes (both insulin pen-experienced and insulin pen-naïve).
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Accuracy of the Enlite 6-day glucose sensor with guardian and Veo calibration algorithms.
Diabetes Technol. Ther.
PUBLISHED: 12-06-2011
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This study investigates the accuracy of a newly developed, next-generation subcutaneous glucose sensor, evaluated for 6-day use.
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Epigenetic priors for identifying active transcription factor binding sites.
Bioinformatics
PUBLISHED: 11-08-2011
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Accurate knowledge of the genome-wide binding of transcription factors in a particular cell type or under a particular condition is necessary for understanding transcriptional regulation. Using epigenetic data such as histone modification and DNase I, accessibility data has been shown to improve motif-based in silico methods for predicting such binding, but this approach has not yet been fully explored.
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Analysis and perspective: A randomized, open-label, comparative crossover handling trial between two durable pens in patients with type 1 or 2 diabetes mellitus.
J Diabetes Sci Technol
PUBLISHED: 10-27-2011
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Insulin pen therapy is superior to vial and syringe with regard to more accurate insulin delivery, patient preference, adherence, and favorable health economics. In this issue of Journal of Diabetes Science and Technology, Sommavilla and Pietranera compare two generations of NovoPen, showing significant improvements in selecting and injecting the insulin dose as well as superior overall satisfaction with the newer versus older generation insulin pen among both experienced pen users and insulin-naïve patients. There are other potentially useful features that might be implemented and better-studied in future pen devices. These include insulin dose tracking, insulin error mitigation, and insulin dosing advice. Caring more effectively for the multitude of people impacted by the diabetes epidemic requires a new approach that will require "smarter," more "connected" devices.
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Performance of the DIDGET blood glucose monitoring system in children, teens, and young adults.
J Diabetes Sci Technol
PUBLISHED: 10-27-2011
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This study evaluated the performance of the DIDGET® blood glucose monitoring system (BGMS) in the hands of its intended users: children, teens, and young adults with diabetes.
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A 16-week open-label, multicenter pilot study assessing insulin pump therapy in patients with type 2 diabetes suboptimally controlled with multiple daily injections.
J Diabetes Sci Technol
PUBLISHED: 09-02-2011
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We assessed the efficacy, safety, and patient-reported outcomes (PROs) of insulin pump therapy in patients with type 2 diabetes mellitus (T2DM) who were suboptimally controlled with a multiple daily injection (MDI) regimen.
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Tissue-specific prediction of directly regulated genes.
Bioinformatics
PUBLISHED: 06-30-2011
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Direct binding by a transcription factor (TF) to the proximal promoter of a gene is a strong evidence that the TF regulates the gene. Assaying the genome-wide binding of every TF in every cell type and condition is currently impractical. Histone modifications correlate with tissue/cell/condition-specific (tissue specific) TF binding, so histone ChIP-seq data can be combined with traditional position weight matrix (PWM) methods to make tissue-specific predictions of TF-promoter interactions.
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Evaluation of a combined blood glucose monitoring and gaming system (Didget®) for motivation in children, adolescents, and young adults with type 1 diabetes.
Pediatr Diabetes
PUBLISHED: 06-23-2011
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The purpose of this study was to assess the performance and acceptability of a blood glucose meter coupled with a gaming system for children, adolescents, and young adults with type 1 diabetes. During an in-clinic visit, duplicate blood samples were tested by subjects (N = 147; aged 5-24 yr) and health care providers (HCPs) to evaluate the accuracy and precision of the Didget® system. Subjects meter results were compared against Yellow Springs Instruments (YSI) reference results and HCP results using least squares regression and error grid analyses. Precision was measured by average within-subject and within-HCP coefficient of variation (CV). During the home-use component of this study, subjects (n = 58) tested their blood glucose at least two to three times daily for 3-5 d to evaluate routine use of the system. Subjects meter results showed significant correlations with both YSI (r(2) = 0.94; p < 0.001 for regression slope) and HCP results (r(2) = 0.96; p < 0.001). Average within-subject and within-HCP CVs were 5.9 and 7.2%, respectively. Overall satisfaction was assessed by subjects, their parents or guardians, and HCP surveys. Subject satisfaction with the Didget® system was good to excellent; most subjects found the system easy to use, motivating, and helpful for building good blood glucose monitoring habits. Most HCPs agreed that the system fulfilled a need in diabetes management. In conclusion, the Didget® system was precise and clinically accurate in the hands of children, adolescents, and young adults with type 1 diabetes.
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Sorting the nuclear proteome.
Bioinformatics
PUBLISHED: 06-21-2011
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Quantitative experimental analyses of the nuclear interior reveal a morphologically structured yet dynamic mix of membraneless compartments. Major nuclear events depend on the functional integrity and timely assembly of these intra-nuclear compartments. Yet, unknown drivers of protein mobility ensure that they are in the right place at the time when they are needed.
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Inferring transcription factor complexes from ChIP-seq data.
Nucleic Acids Res.
PUBLISHED: 05-20-2011
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Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) allows researchers to determine the genome-wide binding locations of individual transcription factors (TFs) at high resolution. This information can be interrogated to study various aspects of TF behaviour, including the mechanisms that control TF binding. Physical interaction between TFs comprises one important aspect of TF binding in eukaryotes, mediating tissue-specific gene expression. We have developed an algorithm, spaced motif analysis (SpaMo), which is able to infer physical interactions between the given TF and TFs bound at neighbouring sites at the DNA interface. The algorithm predicts TF interactions in half of the ChIP-seq data sets we test, with the majority of these predictions supported by direct evidence from the literature or evidence of homodimerization. High resolution motif spacing information obtained by this method can facilitate an improved understanding of individual TF complex structures. SpaMo can assist researchers in extracting maximum information relating to binding mechanisms from their TF ChIP-seq data. SpaMo is available for download and interactive use as part of the MEME Suite (http://meme.nbcr.net).
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Improved similarity scores for comparing motifs.
Bioinformatics
PUBLISHED: 05-04-2011
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A question that often comes up after applying a motif finder to a set of co-regulated DNA sequences is whether the reported putative motif is similar to any known motif. While several tools have been designed for this task, Habib et al. pointed out that the scores that are commonly used for measuring similarity between motifs do not distinguish between a good alignment of two informative columns (say, all-A) and one of two uninformative columns. This observation explains why tools such as Tomtom occasionally return an alignment of uninformative columns which is clearly spurious. To address this problem, Habib et al. suggested a new score [Bayesian Likelihood 2-Component (BLiC)] which uses a Bayesian information criterion to penalize matches that are also similar to the background distribution.
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DREME: motif discovery in transcription factor ChIP-seq data.
Bioinformatics
PUBLISHED: 05-04-2011
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Transcription factor (TF) ChIP-seq datasets have particular characteristics that provide unique challenges and opportunities for motif discovery. Most existing motif discovery algorithms do not scale well to such large datasets, or fail to report many motifs associated with cofactors of the ChIP-ed TF.
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Potential in vivo roles of nucleic acid triple-helices.
RNA Biol
PUBLISHED: 05-01-2011
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The ability of double-stranded DNA to form a triple-helical structure by hydrogen bonding with a third strand is well established, but the biological functions of these structures remain largely unknown. There is considerable albeit circumstantial evidence for the existence of nucleic triplexes in vivo and their potential participation in a variety of biological processes including chromatin organization, DNA repair, transcriptional regulation, and RNA processing has been investigated in a number of studies to date. There is also a range of possible mechanisms to regulate triplex formation through differential expression of triplex-forming RNAs, alteration of chromatin accessibility, sequence unwinding and nucleotide modifications. With the advent of next generation sequencing technology combined with targeted approaches to isolate triplexes, it is now possible to survey triplex formation with respect to their genomic context, abundance and dynamical changes during differentiation and development, which may open up new vistas in understanding genome biology and gene regulation.
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Accuracy performance of the Medtronic NexSensor™ for 6 days in an inpatient setting using abdomen and buttocks insertion sites.
J Diabetes Sci Technol
PUBLISHED: 04-30-2011
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Users of continuous glucose monitoring are concerned with product accuracy and choice of insertion site. The Medtronic NexSensor™ was evaluated for accuracy during 6 days of wear when inserted in the abdomen and buttocks areas.
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MEME-ChIP: motif analysis of large DNA datasets.
Bioinformatics
PUBLISHED: 04-12-2011
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Advances in high-throughput sequencing have resulted in rapid growth in large, high-quality datasets including those arising from transcription factor (TF) ChIP-seq experiments. While there are many existing tools for discovering TF binding site motifs in such datasets, most web-based tools cannot directly process such large datasets.
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A probabilistic model of nuclear import of proteins.
Bioinformatics
PUBLISHED: 03-03-2011
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Nucleo-cytoplasmic trafficking of proteins is a core regulatory process that sustains the integrity of the nuclear space of eukaryotic cells via an interplay between numerous factors. Despite progress on experimentally characterizing a number of nuclear localization signals, their presence alone remains an unreliable indicator of actual translocation.
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FIMO: scanning for occurrences of a given motif.
Bioinformatics
PUBLISHED: 02-16-2011
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A motif is a short DNA or protein sequence that contributes to the biological function of the sequence in which it resides. Over the past several decades, many computational methods have been described for identifying, characterizing and searching with sequence motifs. Critical to nearly any motif-based sequence analysis pipeline is the ability to scan a sequence database for occurrences of a given motif described by a position-specific frequency matrix.
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The ASPIRE study: design and methods of an in-clinic crossover trial on the efficacy of automatic insulin pump suspension in exercise-induced hypoglycemia.
J Diabetes Sci Technol
PUBLISHED: 02-14-2011
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The Paradigm®Veo™ System includes a low glucose suspend (LGS) feature which suspends insulin delivery when a prespecified glucose threshold setting is reached by the associated continuous glucose monitoring (CGM) sensor. The ASPIRE (Automation to Simulate Pancreatic Insulin REsponse) study is a multicenter, in-clinic, randomized, crossover study to examine the efficacy of LGS in exercise-induced hypoglycemia.
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Guidelines for optimal bolus calculator settings in adults.
J Diabetes Sci Technol
PUBLISHED: 02-10-2011
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Bolus insulin calculators (BCs) became available in insulin pumps in 2002 and are being integrated into glucose meters and portable device applets for use with multiple daily injections. A retrospective analysis of continuous subcutaneous insulin infusion data from the Actual Pump Practices (APP) study is used in this article to generate formulas for more precise BC settings. A well-designed BC determines accurate bolus doses for carbohydrate intake and for correcting elevated glucose levels. It should also provide the logic necessary to track residual bolus insulin and reduce bolus recommendations to minimize insulin stacking. To provide appropriate bolus doses, a BC requires accurate settings for the carbohydrate factor or insulin:carbohydrate ratio, glucose correction factor, duration of insulin action, and correction target. We provide guidelines to select BC settings from the users current total daily dose (TDD) of insulin and to determine more appropriate BC settings from an improved TDD based on the mean glucose level.
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Guidelines for insulin dosing in continuous subcutaneous insulin infusion using new formulas from a retrospective study of individuals with optimal glucose levels.
J Diabetes Sci Technol
PUBLISHED: 10-06-2010
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Successful insulin pump therapy depends on correct insulin doses based on an optimal total daily dose (TDD) and optimal pump settings for basal infusion, carbohydrate factor (CarbF), and glucose correction factor (CorrF) based on the TDD. There are limited data in the literature to guide providers and patients regarding methods to optimize these critical parameters for glucose control.
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Insulin pump therapy in patients with type 2 diabetes safely improved glycemic control using a simple insulin dosing regimen.
Diabetes Technol. Ther.
PUBLISHED: 07-10-2010
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This study assessed insulin dose and dosing patterns required to optimize glycemic control with an insulin pump in patients with type 2 diabetes.
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NFIA controls telencephalic progenitor cell differentiation through repression of the Notch effector Hes1.
J. Neurosci.
PUBLISHED: 07-09-2010
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The balance between self-renewal and differentiation of neural progenitor cells is an absolute requirement for the correct formation of the nervous system. Much is known about both the pathways involved in progenitor cell self-renewal, such as Notch signaling, and the expression of genes that initiate progenitor differentiation. However, whether these fundamental processes are mechanistically linked, and specifically how repression of progenitor self-renewal pathways occurs, is poorly understood. Nuclear factor I A (Nfia), a gene known to regulate spinal cord and neocortical development, has recently been implicated as acting downstream of Notch to initiate the expression of astrocyte-specific genes within the cortex. Here we demonstrate that, in addition to activating the expression of astrocyte-specific genes, Nfia also downregulates the activity of the Notch signaling pathway via repression of the key Notch effector Hes1. These data provide a significant conceptual advance in our understanding of neural progenitor differentiation, revealing that a single transcription factor can control both the activation of differentiation genes and the repression of the self-renewal genes, thereby acting as a pivotal regulator of the balance between progenitor and differentiated cell states.
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Dual-functioning transcription factors in the developmental gene network of Drosophila melanogaster.
BMC Bioinformatics
PUBLISHED: 07-02-2010
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Quantitative models for transcriptional regulation have shown great promise for advancing our understanding of the biological mechanisms underlying gene regulation. However, all of the models to date assume a transcription factor (TF) to have either activating or repressing function towards all the genes it is regulating.
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Insulin pen use for type 2 diabetes--a clinical perspective.
Diabetes Technol. Ther.
PUBLISHED: 06-03-2010
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While insulin delivery technology continues to progress, its adoption in the clinic lags behind, particularly in people with type 2 diabetes. In this article the authors present their clinical perspective regarding insulin pen therapy in this population.
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A global role for KLF1 in erythropoiesis revealed by ChIP-seq in primary erythroid cells.
Genome Res.
PUBLISHED: 05-27-2010
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KLF1 regulates a diverse suite of genes to direct erythroid cell differentiation from bipotent progenitors. To determine the local cis-regulatory contexts and transcription factor networks in which KLF1 operates, we performed KLF1 ChIP-seq in the mouse. We found at least 945 sites in the genome of E14.5 fetal liver erythroid cells which are occupied by endogenous KLF1. Many of these recovered sites reside in erythroid gene promoters such as Hbb-b1, but the majority are distant to any known gene. Our data suggests KLF1 directly regulates most aspects of terminal erythroid differentiation including production of alpha- and beta-globin protein chains, heme biosynthesis, coordination of proliferation and anti-apoptotic pathways, and construction of the red cell membrane and cytoskeleton by functioning primarily as a transcriptional activator. Additionally, we suggest new mechanisms for KLF1 cooperation with other transcription factors, in particular the erythroid transcription factor GATA1, to maintain homeostasis in the erythroid compartment.
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Comparative glycemic control, safety and patient ratings for a new 4 mm x 32G insulin pen needle in adults with diabetes.
Curr Med Res Opin
PUBLISHED: 05-01-2010
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Pen needles (PN) for subcutaneous insulin therapy have become smaller; 5 mm PNs are now the shortest in use. We evaluated the safety, efficacy and patient ratings of a new 4 mm x 32 gauge (G) PN.
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A Bayesian network model of proteins association with promyelocytic leukemia (PML) nuclear bodies.
J. Comput. Biol.
PUBLISHED: 04-30-2010
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The modularity that nuclear organization brings has the potential to explain the function of aggregates of proteins and RNA. Promyelocytic leukemia nuclear bodies are implicated in important regulatory processes. To understand the complement of proteins associated with these intra-nuclear bodies, we construct a Bayesian network model that integrates sequence and protein-protein interaction data. The model predicts association with promyelocytic leukemia nuclear bodies accurately when interaction data is available. At a false positive rate of 10%, the true positive rate is almost 50%, indicated by an independent nuclear proteome reference set. The model provides strong support for further expanding the protein complement with several important regulators and a richer functional repertoire. Using special support vector machine (SVM)-nodes (equipped with string kernels), the Bayesian network is also able to produce predictions on the basis of sequence only, with an accuracy superior to that of baseline models. Supplementary Material is available online at www.liebertonline.com.
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Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial.
Lancet
PUBLISHED: 04-27-2010
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Agonists of the glucagon-like peptide-1 (GLP-1) receptor provide pharmacological levels of GLP-1 activity, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors increase concentrations of endogenous GLP-1 and glucose-dependent insulinotropic polypeptide. We aimed to assess the efficacy and safety of the human GLP-1 analogue liraglutide versus the DPP-4 inhibitor sitagliptin, as adjunct treatments to metformin, in individuals with type 2 diabetes who did not achieve adequate glycaemic control with metformin alone.
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Motif Enrichment Analysis: a unified framework and an evaluation on ChIP data.
BMC Bioinformatics
PUBLISHED: 04-01-2010
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A major goal of molecular biology is determining the mechanisms that control the transcription of genes. Motif Enrichment Analysis (MEA) seeks to determine which DNA-binding transcription factors control the transcription of a set of genes by detecting enrichment of known binding motifs in the genes regulatory regions. Typically, the biologist specifies a set of genes believed to be co-regulated and a library of known DNA-binding models for transcription factors, and MEA determines which (if any) of the factors may be direct regulators of the genes. Since the number of factors with known DNA-binding models is rapidly increasing as a result of high-throughput technologies, MEA is becoming increasingly useful. In this paper, we explore ways to make MEA applicable in more settings, and evaluate the efficacy of a number of MEA approaches.
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The value of position-specific priors in motif discovery using MEME.
BMC Bioinformatics
PUBLISHED: 02-10-2010
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Position-specific priors have been shown to be a flexible and elegant way to extend the power of Gibbs sampler-based motif discovery algorithms. Information of many types-including sequence conservation, nucleosome positioning, and negative examples-can be converted into a prior over the location of motif sites, which then guides the sequence motif discovery algorithm. This approach has been shown to confer many of the benefits of conservation-based and discriminative motif discovery approaches on Gibbs sampler-based motif discovery methods, but has not previously been studied with methods based on expectation maximization (EM).
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Assigning roles to DNA regulatory motifs using comparative genomics.
Bioinformatics
PUBLISHED: 02-10-2010
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Transcription factors (TFs) are crucial during the lifetime of the cell. Their functional roles are defined by the genes they regulate. Uncovering these roles not only sheds light on the TF at hand but puts it into the context of the complete regulatory network.
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New features and performance of a next-generation SEVEN-day continuous glucose monitoring system with short lag time.
Diabetes Technol. Ther.
PUBLISHED: 12-17-2009
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The purpose of this study was to evaluate new features and performance of the SEVEN PLUS System (DexCom, Inc., San Diego, CA), a real-time continuous glucose monitoring (CGM) device. This study is the first to evaluate the SEVEN PLUS device.
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Improved quality of glycemic control and reduced glycemic variability with use of continuous glucose monitoring.
Diabetes Technol. Ther.
PUBLISHED: 11-13-2009
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We evaluated effects of unmasking of continuous display of continuous glucose monitoring (CGM) on quality of glycemic control and glycemic variability.
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Accuracy of the SEVEN continuous glucose monitoring system: comparison with frequently sampled venous glucose measurements.
J Diabetes Sci Technol
PUBLISHED: 08-05-2009
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The purpose of this study was to compare the accuracy of measurements obtained from the DexCom SEVEN system with Yellow Springs Instrument (YSI) laboratory measurements of venous blood glucose.
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Assessing phylogenetic motif models for predicting transcription factor binding sites.
Bioinformatics
PUBLISHED: 05-30-2009
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A variety of algorithms have been developed to predict transcription factor binding sites (TFBSs) within the genome by exploiting the evolutionary information implicit in multiple alignments of the genomes of related species. One such approach uses an extension of the standard position-specific motif model that incorporates phylogenetic information via a phylogenetic tree and a model of evolution. However, these phylogenetic motif models (PMMs) have never been rigorously benchmarked in order to determine whether they lead to better prediction of TFBSs than obtained using simple position weight matrix scanning.
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Continuous glucose monitoring health outcomes.
Diabetes Technol. Ther.
PUBLISHED: 05-28-2009
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Continuous glucose monitoring (CGM) is a new tool that has recently become available to people with diabetes. Properly designing and conducting trials in order to answer important questions regarding the clinical usefulness of CGM is very difficult and fraught with many confounding variables and unique challenges. Initial clinical trials using older technology using retrospective data analysis have not shown unequivocal benefit; however, more recent data using real-time CGM suggest significant improvements in important clinical outcomes such as hemoglobin A1c, time spent in the hypo- and hyperglycemic range, glucose variability, quality of life, and perceived value to physicians and patients. Additional variables such as age of the subject and duration of sensor use have important implications in defining the benefits of CGM in a heterogeneous population with diabetes. This review will present the most relevant recent literature and comment on the methodological difficulties that have made this field challenging.
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MEME SUITE: tools for motif discovery and searching.
Nucleic Acids Res.
PUBLISHED: 05-20-2009
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The MEME Suite web server provides a unified portal for online discovery and analysis of sequence motifs representing features such as DNA binding sites and protein interaction domains. The popular MEME motif discovery algorithm is now complemented by the GLAM2 algorithm which allows discovery of motifs containing gaps. Three sequence scanning algorithms--MAST, FIMO and GLAM2SCAN--allow scanning numerous DNA and protein sequence databases for motifs discovered by MEME and GLAM2. Transcription factor motifs (including those discovered using MEME) can be compared with motifs in many popular motif databases using the motif database scanning algorithm TOMTOM. Transcription factor motifs can be further analyzed for putative function by association with Gene Ontology (GO) terms using the motif-GO term association tool GOMO. MEME output now contains sequence LOGOS for each discovered motif, as well as buttons to allow motifs to be conveniently submitted to the sequence and motif database scanning algorithms (MAST, FIMO and TOMTOM), or to GOMO, for further analysis. GLAM2 output similarly contains buttons for further analysis using GLAM2SCAN and for rerunning GLAM2 with different parameters. All of the motif-based tools are now implemented as web services via Opal. Source code, binaries and a web server are freely available for noncommercial use at http://meme.nbcr.net.
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Optimizing static thermodynamic models of transcriptional regulation.
Bioinformatics
PUBLISHED: 04-27-2009
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Modeling transcriptional regulation using thermo-dynamic modeling approaches has become increasingly relevant as a way to gain a detailed understanding of transcriptional regulation. Thermodynamic models are able to model the interactions between transcription factors (TFs) and DNA that lead to a specific transcriptional output of the target gene. Such models can be trained by fitting their free parameters to data on the transcription rate of a gene and the concentrations of its regulating factors. However, the parameter fitting process is computationally very expensive and this limits the number of alternative types of model that can be explored.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.