bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipodystrophy among patients with HIV infection on antiretroviral therapy: a systematic review protocol
Authors: Lana Lorena Gomes Cunha , Junqueira Daniela Rezende Garcia , Perini Edson , Menezes de Pádua Cristiane 
Published: March 2014

IntroductionLipodystrophy is a frequent and disfiguring adverse effect of antiretroviral therapy (ART) in patients with HIV. It affects the quality of life of the patient and adherence to treatment, and generates new needs for comprehensive healthcare services. The aim of this study will be to conduct a systematic review of the literature from observational studies and describe lipodystrophy among patients with HIV infection during current or previous use of ART.Methods and analysisA systematic review of observational studies published in MEDLINE, CINAHL, LILACS, EMBASE and International Pharmaceutical Abstracts will be carried out. Citations of included studies will be checked to identify additional studies not identified in the electronic searches. It will include any observational study that considered lipodystrophy as the primary or secondary outcome and that had enrolled adolescent and adult patients with HIV infection who were on current or previous ART for at least 6 months. Data extraction and analysis will be performed independently by two reviewers. The extracted data will be discussed, decisions documented and, where necessary, the authors of the studies will be contacted for clarification. Measures of frequency, prevalence and incidence of lipodystrophy will be stratified according to definition, method of diagnosis and risk factors of the outcome.Ethics and disseminationEthics is not required given this is a protocol for a systematic review. The findings of this study will be widely disseminated through peer-reviewed publications and conference presentations. Updates of the review will be conducted to inform and guide healthcare practice.Protocol registrationPROSPERO—42013005450.
Mapping patient safety: a large-scale literature review using bibliometric visualisation techniques
Authors: Rodrigues S P , van Eck N J , Waltman L , Jansen F W 
Published: March 2014

BackgroundThe amount of scientific literature available is often overwhelming, making it difficult for researchers to have a good overview of the literature and to see relations between different developments. Visualisation techniques based on bibliometric data are helpful in obtaining an overview of the literature on complex research topics, and have been applied here to the topic of patient safety (PS).MethodsOn the basis of title words and citation relations, publications in the period 2000–2010 related to PS were identified in the Scopus bibliographic database. A visualisation of the most frequently cited PS publications was produced based on direct and indirect citation relations between publications. Terms were extracted from titles and abstracts of the publications, and a visualisation of the most important terms was created. The main PS-related topics studied in the literature were identified using a technique for clustering publications and terms.ResultsA total of 8480 publications were identified, of which the 1462 most frequently cited ones were included in the visualisation. The publications were clustered into 19 clusters, which were grouped into three categories: (1) magnitude of PS problems (42% of all included publications); (2) PS risk factors (31%) and (3) implementation of solutions (19%). In the visualisation of PS-related terms, five clusters were identified: (1) medication; (2) measuring harm; (3) PS culture; (4) physician; (5) training, education and communication. Both analysis at publication and term level indicate an increasing focus on risk factors.ConclusionsA bibliometric visualisation approach makes it possible to analyse large amounts of literature. This approach is very useful for improving one's understanding of a complex research topic such as PS and for suggesting new research directions or alternative research priorities. For PS research, the approach suggests that more research on implementing PS improvement initiatives might be needed.
Maintaining Glycogen Synthase Kinase-3 Activity Is Critical for mTOR Kinase Inhibitors to Inhibit Cancer Cell Growth
Authors: Koo Junghui , Yue Ping , Gal Anthony A. , Khuri Fadlo R. , Sun Shi-Yong 
Published: March 2014

Abstract
mTOR kinase inhibitors that target both mTORC1 and mTORC2 are being evaluated in cancer clinical trials. Here, we report that glycogen synthase kinase-3 (GSK3) is a critical determinant for the therapeutic response to this class of experimental drugs. Pharmacologic inhibition of GSK3 antagonized their suppressive effects on the growth of cancer cells similarly to genetic attenuation of GSK3. Conversely, expression of a constitutively activated form of GSK3β sensitized cancer cells to mTOR inhibition. Consistent with these findings, higher basal levels of GSK3 activity in a panel of human lung cancer cell lines correlated with more efficacious responses. Mechanistic investigations showed that mTOR kinase inhibitors reduced cyclin D1 levels in a GSK3β-dependent manner, independent of their effects on suppressing mTORC1 signaling and cap binding. Notably, selective inhibition of mTORC2 triggered proteasome-mediated cyclin D1 degradation, suggesting that mTORC2 blockade is responsible for GSK3-dependent reduction of cyclin D1. Silencing expression of the ubiquitin E3 ligase FBX4 rescued this reduction, implicating FBX4 in mediating this effect of mTOR inhibition. Together, our findings define a novel mechanism by which mTORC2 promotes cell growth, with potential implications for understanding the clinical action of mTOR kinase inhibitors. Cancer Res; 74(9); 2555–68. ©2014 AACR.
Curcumin Promotes Autophagic Survival of a Subset of Colon Cancer Stem Cells, Which Are Ablated by DCLK1-siRNA
Authors: Kantara Carla , O'Connell Malaney , Sarkar Shubhashish , Moya Stephanie , Ullrich Robert , Singh Pomila 
Published: March 2014

Abstract
Curcumin is known to induce apoptosis of cancer cells by different mechanisms, but its effects on cancer stem cells (CSC) have been less investigated. Here, we report that curcumin promotes the survival of DCLK1-positive colon CSCs, potentially confounding application of its anticancer properties. At optimal concentrations, curcumin greatly reduced expression levels of stem cell markers (DCLK1/CD44/ALDHA1/Lgr5/Nanog) in three-dimensional spheroid cultures and tumor xenografts derived from colon cancer cells. However, curcumin unexpectedly induced proliferation and autophagic survival of a subset of DCLK1-positive CSCs. Spheroid cultures were disintegrated by curcumin in vitro but regrew within 30 to 40 days of treatment, suggesting a survival benefit from autophagy, permitting long-term persistence of colorectal cancer. Notably, RNA interference–mediated silencing of DCLK1 triggered apoptotic cell death of colon cancer cells in vitro and in vivo, and abolished colorectal cancer survival in response to curcumin; combination of DCLK1-siRNA and curcumin dramatically reversed CSC phenotype, contributing to attenuation of the growth of spheroid cultures and tumor xenografts. Taken together, our findings confirm a role of DCLK1 in colon CSCs and highlight DCLK1 as a target to enhance antitumor properties of curcumin. Cancer Res; 74(9); 2487–98. ©2014 AACR.
Differential Association of Plasma Angiopoietin-Like Proteins 3 and 4 With Lipid and Metabolic Traits
Authors: Mehta Nidhi , Qamar Arman , Qu Liming , Qasim Atif N. , Mehta Nehal N. , Reilly Muredach P. , Rader Daniel J. 
Published: March 2014

Objective—

Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) are secreted proteins that inhibit lipoprotein lipase in vitro. Genetic variants at the
ANGPTL3
and
ANGPTL4
gene loci are significantly associated with plasma lipid traits. The aim of this study was to evaluate the association of plasma ANGPTL3 and ANGPTL4 concentrations with lipid and metabolic traits in a large community-based sample.

Approach and Results—

Plasma ANGPTL3 and ANGPTL4 levels were measured in 1770 subjects using a validated ELISA assay. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, sex, and race were performed. ANGPTL3 levels were significantly positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels (both
P
<2×10
−5
) but not triglycerides. In contrast, ANGPTL4 levels were significantly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (both
P
<2×10
−5
) and positively associated with triglycerides (
P
=0.003). In addition, ANGPTL4, but not ANGPTL3, levels were significantly positively associated with fasting blood glucose and metabolic syndrome.

Conclusions—
Despite having similar biochemical effects in vitro, plasma ANGPTL3 and ANGPTL4 concentrations have nearly opposite relationships with plasma lipids. ANGPTL4 is strongly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and positively with multiple features of the metabolic syndrome including triglycerides, whereas ANGPTL3 is positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and not with metabolic syndrome traits including triglycerides. Although ANGPTL3 and ANGPTL4 both inhibit lipoprotein lipase in vitro and influence lipoprotein metabolism in vivo, the physiology of these related proteins and their effects on lipoproteins is clearly divergent and complex.
Is a Diabetes Mellitus–Linked Amino Acid Signature Associated With β-Blocker–Induced Impaired Fasting Glucose?
Authors: Cooper-DeHoff Rhonda M. , Hou Wei , Weng Liming , Baillie Rebecca A. , Beitelshees Amber L. , Gong Yan , Shahin Mohamed H.A. , Turner Stephen T. , Chapman Arlene , Gums John G. , Boyle Stephen H. , Zhu Hongjie , Wikoff William R. , Boerwinkle Eric , Fiehn Oliver , Frye Reginald F. , Kaddurah-Daouk Rima , Johnson Julie A. 
Published: March 2014

Background—
The 5-amino acid (AA) signature, including isoleucine, leucine, valine, tyrosine, and phenylalanine, has been associated with incident diabetes mellitus and insulin resistance. We investigated whether this same AA signature, single-nucleotide polymorphisms in genes in their catabolic pathway, was associated with development of impaired fasting glucose (IFG) after atenolol treatment.

Methods and Results—

Among 234 European American participants enrolled in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study and treated with atenolol for 9 weeks, we prospectively followed a nested cohort that had both metabolomics profiling and genotype data available for the development of IFG. We assessed the association between baseline circulating levels of isoleucine, leucine, valine, tyrosine, and phenylalanine, as well as single-nucleotide polymorphisms in
branched-chain amino-acid transaminase 1 (BCAT1) and phenylalanine hydroxylase (PAH
) with development of IFG. All baseline AA levels were strongly associated with IFG development. Each increment in standard deviation of the 5 AAs was associated with the following odds ratio and 95% confidence interval for IFG based on a fully adjusted model: isoleucine 2.29 (1.31–4.01), leucine 1.80 (1.10–2.96), valine 1.77 (1.07–2.92), tyrosine 2.13 (1.20–3.78), and phenylalanine 2.04 (1.16–3.59). The composite
P
value was 2×10
−5
. Those with
PAH
(rs2245360) AA genotype had the highest incidence of IFG (
P
for trend=0.0003).

Conclusions—
Our data provide important insight into the metabolic and genetic mechanisms underlying atenolol-associated adverse metabolic effects.

Clinical Trial Registration—

http://www.clinicaltrials.gov
; Unique Identifier: NCT00246519
Changes in Mipomersen Dosing Regimen Provide Similar Exposure With Improved Tolerability in Randomized Placebo‐Controlled Study of Healthy Volunteers
Authors: Flaim JoAnn D. , Grundy John S. , Baker Brenda F. , McGowan Mary P. , Kastelein John J. P. 
Published: March 2014

Background

Mipomersen, an apolipoprotein B synthesis inhibitor, demonstrated significant reductions in low‐density lipoprotein (LDL) cholesterol, non‐high density lipoprotein cholesterol, and apolipoprotein B in 4 phase 3 studies at the
FDA
‐approved subcutaneous dose of 200 mg once weekly.

Methods and Results

A short‐term phase 1 study in healthy volunteers was conducted to evaluate the relative bioavailability, safety, and tolerability of mipomersen in 2 test dose regimens in reference to the 200 mg weekly dose regimen. Eighty‐four adults were randomized to 1 of 3 cohorts (30 mg once daily, 70 mg 3 times weekly, or 200 mg once weekly) and then mipomersen or placebo (3:1 ratio) for 3 weeks of treatment. Comparable mipomersen post‐distribution phase plasma concentrations were observed across the 3 dose regimens suggesting similar tissue exposure. Injection site reactions were reported, but did not lead to treatment discontinuation. The median incidence of these responses per injection was decreased by lowering the dose. Signals from a diverse panel of systemic inflammation markers were essentially indistinguishable between dose regimens and placebo treatment. The one exception was a modest transient post‐dose elevation of C‐reactive protein (
CRP
) in the mipomersen 200 mg weekly group. This elevation was not associated with an increase in other proinflammatory markers.

Conclusions
This study demonstrated a similar drug exposure and overall safety profile between the 3 dosing regimens. Exploratory assessment of a diverse panel of biomarkers found no indication of a systemic inflammatory response to mipomersen treatment. These results support assessment of alternative dose regimens in longer‐term studies.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01061814.
Extravascular Optical Coherence Tomography
Authors: Wicks Robert T. , Huang Yong , Zhang Kang , Zhao Mingtao , Tyler Betty M. , Suk Ian , Hwang Lee , Ruzevick Jacob , Jallo George , Brem Henry , Pradilla Gustavo , Kang Jin U. 
Published: March 2014

Background and Purpose—
Extravascular optical coherence tomography (OCT), as a noninvasive imaging methodology with micrometer resolution, was evaluated in a murine model of carotid atherosclerosis by way of assessing the efficacy of pravastatin therapy.

Methods—

An OCT device was engineered for extravascular plaque imaging. Wild-type mice and apolipoprotein E–deficient (ApoE
−/−
) mice were randomized to 3 treatment groups: (1) wild-type on a diet of standard rodent chow (n=13); (2) ApoE
−/−
on a high-fat, atherosclerotic diet (HFD; n=13); and (3) ApoE
−/−
on a HFD given daily pravastatin (n=13). Mice were anesthetized and the left common carotid was surgically exposed. Three-dimensional (3D; 2 spatial dimensions+time) and 4D (3 spatial dimensions+time) OCT images of the vessel lumen patency were evaluated. After perfusion, in situ OCT imaging was performed for statistical comparison with the in vivo results and final histology.

Results—

Intraoperative OCT imaging positively identified carotid plaque in 100% of ApoE
−/−
mice on HFD. ApoE
−/−
mice on HFD had a significantly decreased lumen patency when compared with that in wild-type mice (
P
<0.001). Pravastatin therapy was found to increase lumen patency significantly in ApoE
−/−
mice on HFD (
P
<0.01; compared with ApoE
−/−
on HFD). The findings were confirmed with OCT imaging after perfusion and histology.

Conclusions—

OCT imaging offers the potential for real-time, detailed vessel lumen evaluation, potentially improving surgical accuracy and outcomes during cerebrovascular neurosurgical procedures. Pravastatin significantly increases vessel lumen patency in the ApoE
−/−
mouse on HFD.
Climate Change Impacts on the Water Balance of the Colorado Headwaters: High-Resolution Regional Climate Model Simulations
Authors: Rasmussen Roy , Ikeda Kyoko , Liu Changhai , Gochis David , Clark Martyn , Dai Aiguo , Gutmann Ethan , Dudhia Jimy , Chen Fei , Barlage Mike , Yates David , Zhang Guo 
Published: March 2014

Abstract
A high-resolution climate model (4-km horizontal grid spacing) is used to examine the following question: How will long-term changes in climate impact the partitioning of annual precipitation between evapotranspiration and runoff in the Colorado Headwaters?
This question is examined using a climate sensitivity approach in which eight years of current climate is compared to a future climate created by modifying the current climate signal with perturbation from the NCAR Community Climate System Model, version 3 (CCSM3), model forced by the A1B scenario for greenhouse gases out to 2050. The current climate period is shown to agree well with Snowpack Telemetry (SNOTEL) surface observations of precipitation (P) and snowpack, as well as streamflow and AmeriFlux evapotranspiration (ET) observations. The results show that the annual evaporative fraction (ET/P) for the Colorado Headwaters is 0.81 for the current climate and 0.83 for the future climate, indicating increasing aridity in the future despite a positive increase of precipitation. Runoff decreased by an average of 6%, reflecting the increased aridity.
Precipitation increased in the future winter by 12%, but decreased in the summer as a result of increased low-level inhibition to convection. The fraction of precipitation that fell as snow decreased from 0.83 in the current climate to 0.74 in the future. Future snowpack did not change significantly until January. From January to March the snowpack increased above ~3000 m MSL and decreased below that level. Snowpack decreased at all elevations in the future from April to July. The peak snowpack and runoff over the headwaters occurred 2–3 weeks earlier in the future simulation, in agreement with previous studies.
Vessel wall BAMBI contributes to hemostasis and thrombus stability
Authors: Salles-Crawley Isabelle I. , Monkman James H. , Ahnström Josefin , Lane David A. , Crawley James T. B. 
Published: March 2014

Key PointsThis is the first report to describe the influence of BAMBI on both hemostasis and thrombus stability. BAMBI present in the blood vessel wall (most likely the endothelium) rather than platelet BAMBI is required for thrombus stability.
Reconstruction of large-size abdominal wall defect using biodegradable poly-p-dioxanone mesh: an experimental canine study
Authors: Huang Kenan , Ding Xinyu , Lv Benbo , Wei Linyun , Sun Juxian , Xu Zhifei , Qin Xiong , Tang Hua 
Published: March 2014

AbstractBackgroundReconstruction of large-size abdominal wall defect (AWDs) is a huge challenge faced in current surgical practice. In this study, we aimed to evaluate the effectiveness and safety of biodegradable poly-p-dioxanone (PDO) mesh for reconstructing large-size AWDs in an experimental canine model.MethodsEighteen experimental canines were randomly and equally divided into three groups, namely, a PDO group, a Marlex group and a control group (n= 6 each). Following the creation of a 6 cm × 5.5 cm AWD, PDO mesh and Marlex mesh were used to reconstruct the defect in the PDO and Marlex groups, respectively. The defect was closed using relaxation sutures alone in the control group. Animals were killed 24 weeks after surgery, and reconstruction outcomes were evaluated using radiography, histology and biomechanical testing.ResultsAll animals except those in the control group survived the experiment. The PDO group showed no wound dehiscence, herniation or infection, whereas the animals in the Marlex group exhibited marked foreign body reactions. The PDO group had less intraabdominal adhesion than the Marlex group. As shown by radiography, histology and biomechanical testing, PDO mesh exhibited complete degradation and favorable biochemical strength at 24 weeks postsurgery.ConclusionsPDO mesh implantation is an effective, safe treatment modality for reconstructing large-size AWDs.
The thrombospondin-1 receptor CD36 is an important mediator of ovarian angiogenesis and folliculogenesis
Authors: Osz Kata , Ross Michelle , Petrik Jim 
Published: March 2014

Abstract
Background
Ovarian angiogenesis is a complex process that is regulated by a balance between pro- and anti-angiogenic factors. Physiological processes within the ovary, such as folliculogenesis, ovulation, and luteal formation are dependent upon adequate vascularization and anything that disrupts normal angiogenic processes may result in ovarian dysfunction, and possibly infertility. The objective of this study was to evaluate the role of the thrombospondin-1 (TSP-1) receptor CD36 in mediating ovarian angiogenesis and regulating ovarian function.

Methods
The role of CD36 was evaluated in granulosa cells in vitro and ovarian morphology and protein expression were determined in wild type and CD36 null mice.

Results
In vitro, CD36 inhibition increased granulosa cell proliferation and decreased apoptosis. Granulosa cells in which CD36 was knocked down also exhibited an increase in expression of survival and angiogenic proteins. Ovaries from CD36 null mice were hypervascularized, with increased expression of pro-angiogenic vascular endothelial growth factor (VEGF) and its receptor VEGFR-2. Ovaries from CD36 null mice contained an increase in the numbers of pre-ovulatory follicles and decreased numbers of corpora lutea. CD36 null mice also had fewer number of offspring compared to wild type controls.

Conclusions
The results from this study demonstrate that CD36 is integral to the regulation of ovarian angiogenesis by TSP-1 and the expression of these family members may be useful in the control of ovarian vascular disorders.
Generalized Thompson sampling for sequential decision-making and causal inference
Authors: Ortega Pedro A , Braun Daniel A 
Published: March 2014

AbstractPurposeSampling an action according to the probability that the action is believed to be the optimal one is sometimes called Thompson sampling.MethodsAlthough mostly applied to bandit problems, Thompson sampling can also be used to solve sequential adaptive control problems, when the optimal policy is known for each possible environment. The predictive distribution over actions can then be constructed by a Bayesian superposition of the policies weighted by their posterior probability of being optimal.ResultsHere we discuss two important features of this approach. First, we show in how far such generalized Thompson sampling can be regarded as an optimal strategy under limited information processing capabilities that constrain the sampling complexity of the decision-making process. Second, we show how such Thompson sampling can be extended to solve causal inference problems when interacting with an environment in a sequential fashion.ConclusionIn summary, our results suggest that Thompson sampling might not merely be a useful heuristic, but a principled method to address problems of adaptive sequential decision-making and causal inference.