bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fault Monitoring with Sequential Matrix Factorization
Authors: Feng Dawei , Germain Cecile 
Published: October 2015

For real-world distributed systems, the knowledge component at the core of the MAPE-K loop has to be inferred, as it cannot be realistically assumed to be defined a priori. Accordingly, this paper considers fault monitoring as a latent factors discovery problem. In the context of end-to-end probing, the goal is to devise an efficient sampling policy that makes the best use of a constrained sampling budget.
Previous work addresses fault monitoring in a collaborative prediction framework, where the information is a snapshot of the probes outcomes. Here, we take into account the fact that the system dynamically evolves at various time scales. We propose and evaluate Sequential Matrix Factorization (SMF) that exploits both the recent advances in matrix factorization for the instantaneous information and a new sampling heuristics based on historical information. The effectiveness of the SMF approach is exemplified on datasets of increasing difficulty and compared with state of the art history-based or snapshot-based methods. In all cases, strong adaptivity under the specific flavor of active learning is required to unleash the full potential of coupling the most confident and the most uncertain sampling heuristics, which is the cornerstone of SMF.
The CUL4B/AKT/β-Catenin Axis Restricts the Accumulation of Myeloid-Derived Suppressor Cells to Prohibit the Establishment of a Tumor-Permissive Microenvironment
Authors: Qian Yanyan , Yuan Jupeng , Hu Huili , Yang Qifeng , Li Jisheng , Zhang Shuqian , Jiang Baichun , Shao Changshun , Gong Yaoqin 
Published: October 2015

AbstractCancer progression requires a permissive microenvironment that shields cancer from the host immunosurveillance. The presence of myeloid-derived suppressor cells (MDSC) is a key feature of a tumor-permissive microenvironment. Cullin 4B (CUL4B), a scaffold protein in the Cullin 4B-RING E3 ligase complex (CRL4B), represses tumor suppressors through diverse epigenetic mechanisms and is overexpressed in many malignancies. We report here that CUL4B unexpectedly functions as a negative regulator of MDSC functions in multiple tumor settings. Conditional ablation of CUL4B in the hematopoietic system, driven by Tek-Cre, resulted in significantly enhanced accumulation and activity of MDSCs. Mechanistically, we demonstrate that the aberrant abundance of MDSCs in the absence of CUL4B was mediated by the downregulation of the AKT/β-catenin pathway. Moreover, CUL4B repressed the phosphatases PP2A and PHLPP1/2 that dephosphorylate and inactivate AKT to sustain pathway activation. Importantly, the CUL4B/AKT/β-catenin axis was downregulated in MDSCs of healthy individuals and was further suppressed in tumor-bearing mice and cancer patients. Thus, our findings point to a pro- and antitumorigenic role for CUL4B in malignancy, in which its ability to impede the formation of a tumor-supportive microenvironment may be context-specific. Cancer Res; 75(23); 5070–83. ©2015 AACR.
Pigment Epithelium–Derived Factor Alleviates Tamoxifen-Induced Endometrial Hyperplasia
Authors: Goldberg Keren , Bar-Joseph Hadas , Grossman Hadas , Hasky Noa , Uri-Belapolsky Shiri , Stemmer Salomon M. , Chuderland Dana , Shalgi Ruth , Ben-Aharon Irit 
Published: October 2015

Abstract
Tamoxifen is a cornerstone component of adjuvant endocrine therapy for patients with hormone-receptor–positive breast cancer. Its significant adverse effects include uterine hyperplasia, polyps, and increased risk of endometrial cancer. However, the underlying molecular mechanism remains unclear. Excessive angiogenesis, a hallmark of tumorigenesis, is a result of disrupted balance between pro- and anti-angiogenic factors. VEGF is a pro-angiogenic factor shown to be elevated by tamoxifen in the uterus. Pigment epithelium–derived factor (PEDF) is a potent anti-angiogenic factor that suppresses strong pro-angiogenic factors, such as VEGF. Our aim was to investigate whether angiogenic balance plays a role in tamoxifen-induced uterine pathologies, elucidate the molecular impairment in that network, and explore potential intervention to offset the proposed imbalance elicited by tamoxifen. Using in vivo mouse models, we demonstrated that tamoxifen induced a dose-dependent shift in endogenous uterine angiogenic balance favoring VEGF over PEDF. Treatment with recombinant PEDF (rPEDF) abrogated tamoxifen-induced uterine hyperplasia and VEGF elevation, resulting in reduction of blood vessels density. Exploring the molecular mechanism revealed that tamoxifen promoted survival and malignant transformation pathways, whereas rPEDF treatment prevents these changes. Activation of survival pathways was decreased, demonstrated by reduction in AKT phosphorylation concomitant with elevation in JNK phosphorylation. Estrogen receptor-α and c-Myc oncoprotein levels were reduced. Our findings provide novel insight into the molecular mechanisms tamoxifen induces in the uterus, which may become the precursor events of subsequent endometrial hyperplasia and cancer. We demonstrate that rPEDF may serve as a useful intervention to alleviate the risk of tamoxifen-induced endometrial pathologies. Mol Cancer Ther; 14(12); 2840–9. ©2015 AACR.
Deletion of Methionine Sulfoxide Reductase A Does Not Affect Atherothrombosis but Promotes Neointimal Hyperplasia and Extracellular Signal-Regulated Kinase 1/2 Signaling
Authors: Klutho Paula J. , Pennington Steven M. , Scott Jason A. , Wilson Katina M. , Gu Sean X. , Doddapattar Prakash , Xie Litao , Venema Ashlee N. , Zhu Linda J. , Chauhan Anil K. , Lentz Steven R. , Grumbach Isabella M. 
Published: October 2015

Objective—
Emerging evidence suggests that methionine oxidation can directly affect protein function and may be linked to cardiovascular disease. The objective of this study was to define the role of the methionine sulfoxide reductase A (MsrA) in models of vascular disease and identify its signaling pathways.

Approach and Results—

MsrA was readily identified in all layers of the vascular wall in human and murine arteries. Deletion of the
MsrA
gene did not affect atherosclerotic lesion area in apolipoprotein E–deficient mice and had no significant effect on susceptibility to experimental thrombosis after photochemical injury. In contrast, the neointimal area after vascular injury caused by complete ligation of the common carotid artery was significantly greater in MsrA-deficient than in control mice. In aortic vascular smooth muscle cells lacking MsrA, cell proliferation was significantly increased because of accelerated G
1
/S transition. In parallel, cyclin D1 protein and cdk4/cyclin D1 complex formation and activity were increased in MsrA-deficient vascular smooth muscle cell, leading to enhanced retinoblastoma protein phosphorylation and transcription of E2F. Finally, MsrA-deficient vascular smooth muscle cell exhibited greater activation of extracellular signal-regulated kinase 1/2 that was caused by increased activity of the Ras/Raf/mitogen-activated protein kinase signaling pathway.

Conclusions—
Our findings implicate MsrA as a negative regulator of vascular smooth muscle cell proliferation and neointimal hyperplasia after vascular injury through control of the Ras/Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 signaling pathway.
Protein-Bound Plasma N
ε
-(Carboxymethyl)lysine Is Inversely Associated With Central Obesity and Inflammation and Significantly Explain a Part of the Central Obesity–Related Increase in Inflammation
Authors: Gaens Katrien H.J. , Ferreira Isabel , van de Waarenburg Marjo P.H. , van Greevenbroek Marleen M. , van der Kallen Carla J.H. , Dekker Jacqueline M. , Nijpels Giel , Rensen Sander S. , Stehouwer Coen D.A. , Schalkwijk Casper G. 
Published: October 2015

Objective—

Adipose tissue inflammation contributes to the development of complications, such as insulin resistance and type 2 diabetes mellitus. We previously reported that plasma levels of N
ε
-(carboxymethyl)lysine (CML) were decreased in obese subjects resulting from CML accumulation in adipose tissue and that this CML accumulation plays an important role in adipose tissue inflammation. The objective of this study is to investigate associations between obesity (body mass index, waist circumference, and trunk fat mass), plasma CML (as an inversely correlated marker of CML accumulation in adipose tissue), and low-grade inflammation (LGI) in a large sample of individuals whose weight status ranged from normal to morbid obesity.

Approach and Results—
We studied 1270 individuals of the Cohort on Diabetes and Atherosclerosis Maastricht Study and Hoorn Study, in whom protein-bound CML levels were measured by UPLC-Tandem MS (ultra performance liquid chromatography-tandem mass spectrometry), and 6 inflammatory markers were measured with multiarrays. These inflammatory markers were compiled into an LGI score. Multiple linear regression, adjusted for covariates, showed that (1) waist circumference was inversely associated with protein-bound CML plasma levels (standardized regression coefficient [β]=−0.357 [95% confidence interval: −0.414; −0.301]); (2) protein-bound CML was inversely associated with LGI score (β=−0.073 [−0.130;-0.015]); and (3) the association between waist circumference and LGI (β=0.262 [0.203;0.321]) was attenuated after adjustment for protein-bound CML plasma levels and other potential mediators (to β=0.202 [0.138;0.266]), with CML explaining the greatest portion of the attenuation (≈12%). Further analysis with dual-energy X-ray absorptiometry measures of body composition confirmed a strong inverse association of fat mass preferentially accumulated in the trunk with protein-bound CML plasma levels, significantly explaining ≈21% of the trunk fat–LGI association.

Conclusions—
Obesity, in particular central obesity, is characterized by greater levels of LGI but by lower levels of circulating CML; the latter significantly explaining a portion of the positive association between central obesity and inflammation.
Three-Dimensional Vascular Network Assembly From Diabetic Patient-Derived Induced Pluripotent Stem Cells
Authors: Chan Xin Yi , Black Rebecca , Dickerman Kayla , Federico Joseph , Lévesque Mathieu , Mumm Jeff , Gerecht Sharon 
Published: October 2015

Objective—
In diabetics, hyperglycemia results in deficient endothelial progenitors and cells, leading to cardiovascular complications. We aim to engineer 3-dimensional (3D) vascular networks in synthetic hydrogels from type 1 diabetes mellitus (T1D) patient–derived human-induced pluripotent stem cells (hiPSCs), to serve as a transformative autologous vascular therapy for diabetic patients.

Approach and Results—
We validated and optimized an adherent, feeder-free differentiation procedure to derive early vascular cells (EVCs) with high portions of vascular endothelial cadherin-positive cells from hiPSCs. We demonstrate similar differentiation efficiency from hiPSCs derived from healthy donor and patients with T1D. T1D-hiPSC–derived vascular endothelial cadherin-positive cells can mature to functional endothelial cells–expressing mature markers: von Willebrand factor and endothelial nitric oxide synthase are capable of lectin binding and acetylated low-density lipoprotein uptake, form cords in Matrigel and respond to tumor necrosis factor-α. When embedded in engineered hyaluronic acid hydrogels, T1D-EVCs undergo morphogenesis and assemble into 3D networks. When encapsulated in a novel hypoxia-inducible hydrogel, T1D-EVCs respond to low oxygen and form 3D networks. As xenografts, T1D-EVCs incorporate into developing zebrafish vasculature.

Conclusions—
Using our robust protocol, we can direct efficient differentiation of T1D-hiPSC to EVCs. Early endothelial cells derived from T1D-hiPSC are functional when mature. T1D-EVCs self-assembled into 3D networks when embedded in hyaluronic acid and hypoxia-inducible hydrogels. The capability of T1D-EVCs to assemble into 3D networks in engineered matrices and to respond to a hypoxic microenvironment is a significant advancement for autologous vascular therapy in diabetic patients and has broad importance for tissue engineering.
Severity of Psoriasis Associates With Aortic Vascular Inflammation Detected by FDG PET/CT and Neutrophil Activation in a Prospective Observational Study
Authors: Naik Haley B. , Natarajan Balaji , Stansky Elena , Ahlman Mark A. , Teague Heather , Salahuddin Taufiq , Ng Qimin , Joshi Aditya A. , Krishnamoorthy Parasuram , Dave Jenny , Rose Shawn M. , Doveikis Julia , Playford Martin P. , Prussick Ronald B. , Ehrlich Alison , Kaplan Mariana J. , Lockshin Benjamin N. , Gelfand Joel M. , Mehta Nehal N. 
Published: October 2015

Objective—

To understand whether directly measured psoriasis severity is associated with vascular inflammation assessed by
18
F-fluorodeoxyglucose positron emission tomography computed tomography.

Approach—

In-depth cardiovascular and metabolic phenotyping was performed in adult psoriasis patients (n=60) and controls (n=20). Psoriasis severity was measured using psoriasis area severity index. Vascular inflammation was measured using average aortic target-to-background ratio using
18
F-fluorodeoxyglucose positron emission tomography computed tomography.

Results—

Both the psoriasis patients (28 men and 32 women, mean age 47 years) and controls (13 men and 7 women, mean age 41 years) were young with low cardiovascular risk. Psoriasis area severity index scores (median 5.4; interquartile range 2.8–8.3) were consistent with mild-to-moderate skin disease severity. Increasing psoriasis area severity index score was associated with an increase in aortic target-to-background ratio (β=0.41,
P
=0.001), an association that changed little after adjustment for age, sex, and Framingham risk score. We observed evidence of increased neutrophil frequency (mean psoriasis, 3.7±1.2 versus 2.9±1.2;
P
=0.02) and activation by lower neutrophil surface CD16 and CD62L in blood. Serum levels of S100A8/A9 (745.1±53.3 versus 195.4±157.8 ng/mL;
P
<0.01) and neutrophil elastase-1 (43.0±2.4 versus 30.8±6.7 ng/mL;
P
<0.001) were elevated in psoriasis. Finally, S100A8/A9 protein was related to both psoriasis skin disease severity (β=0.53;
P
=0.02) and vascular inflammation (β=0.48;
P
=0.02).

Conclusions—
Psoriasis severity is associated with vascular inflammation beyond cardiovascular risk factors. Psoriasis increased neutrophil activation and neutrophil markers, and S100A8/A9 was related to both skin disease severity and vascular inflammation.
Systematic Review of Guidelines for the Management of Asymptomatic and Symptomatic Carotid Stenosis
Authors: Abbott Anne L. , Paraskevas Kosmas I. , Kakkos Stavros K. , Golledge Jonathan , Eckstein Hans-Henning , Diaz-Sandoval Larry J. , Cao Longxing , Fu Qiang , Wijeratne Tissa , Leung Thomas W. , Montero-Baker Miguel , Lee Byung-Chul , Pircher Sabine , Bosch Marije , Dennekamp Martine , Ringleb Peter 
Published: October 2015

Background and Purpose—
We systematically compared and appraised contemporary guidelines on management of asymptomatic and symptomatic carotid artery stenosis.

Methods—
We systematically searched for guideline recommendations on carotid endarterectomy (CEA) or carotid angioplasty/stenting (CAS) published in any language between January 1, 2008, and January 28, 2015. Only the latest guideline per writing group was selected. Each guideline was analyzed independently by 2 to 6 authors to determine clinical scenarios covered, recommendations given, and scientific evidence used.

Results—
Thirty-four eligible guidelines were identified from 23 different regions/countries in 6 languages. Of 28 guidelines with asymptomatic carotid artery stenosis procedural recommendations, 24 (86%) endorsed CEA (recommended it should or may be provided) for ≈50% to 99% average-surgical-risk asymptomatic carotid artery stenosis, 17 (61%) endorsed CAS, 8 (29%) opposed CAS, and 1 (4%) endorsed medical treatment alone. For asymptomatic carotid artery stenosis patients considered high-CEA-risk because of comorbidities, vascular anatomy, or undefined reasons, CAS was endorsed in 13 guidelines (46%). Thirty-one of 33 guidelines (94%) with symptomatic carotid artery stenosis procedural recommendations endorsed CEA for patients with ≈50% to 99% average-CEA-risk symptomatic carotid artery stenosis, 19 (58%) endorsed CAS and 9 (27%) opposed CAS. For high-CEA-risk symptomatic carotid artery stenosis because of comorbidities, vascular anatomy, or undefined reasons, CAS was endorsed in 27 guidelines (82%). Guideline procedural recommendations were based only on results of trials in which patients were randomized 12 to 34 years ago, rarely reflected medical treatment improvements and often understated potential CAS hazards. Qualifying terminology summarizing recommendations or evidence lacked standardization, impeding guideline interpretation, and comparison.

Conclusions—
This systematic review has identified many opportunities to modernize and otherwise improve carotid stenosis management guidelines.
Quantitative Intracerebral Hemorrhage Localization
Authors: Muschelli John , Ullman Natalie L. , Sweeney Elizabeth M. , Eloyan Ani , Martin Neil , Vespa Paul , Hanley Daniel F. , Crainiceanu Ciprian M. 
Published: October 2015

Background and Purpose—
The location of intracerebral hemorrhage (ICH) is currently described in a qualitative way; we provide a quantitative framework for estimating ICH engagement and its relevance to stroke outcomes.

Methods—
We analyzed 111 patients with ICH from the Minimally Invasive Surgery Plus Recombinant-Tissue Plasminogen Activator for Intracerebral Evacuation (MISTIE) II clinical trial. We estimated ICH engagement at a population level using image registration of computed tomographic scans to a template and a previously labeled atlas. Predictive regions of National Institutes of Health Stroke Scale and Glasgow Coma Scale stroke severity scores, collected at enrollment, were estimated.

Results—

The percent coverage of the ICH by these regions strongly outperformed the reader-labeled locations. The adjusted
R
2
almost doubled from 0.129 (reader-labeled model) to 0.254 (quantitative location model) for National Institutes of Health Stroke Scale and more than tripled from 0.069 (reader-labeled model) to 0.214 (quantitative location model). A permutation test confirmed that the new predictive regions are more predictive than chance:
P<
0.001 for National Institutes of Health Stroke Scale and
P<
0.01 for Glasgow Coma Scale.

Conclusions—
Objective measures of ICH location and engagement using advanced computed tomographic imaging processing provide finer, objective, and more quantitative anatomic information than that provided by human readers.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00224770.
Intracerebral Hematoma Morphologic Appearance on Noncontrast Computed Tomography Predicts Significant Hematoma Expansion
Authors: Blacquiere Dylan , Demchuk Andrew M. , Al-Hazzaa Mohammed , Deshpande Anirudda , Petrcich William , Aviv Richard I. , Rodriguez-Luna David , Molina Carlos A. , Silva Blas Yolanda , Dzialowski Imanuel , Czlonkowska Anna , Boulanger Jean-Martin , Lum Cheemun , Gubitz Gord , Padma Vasantha , Roy Jayanta , Kase Carlos S. , Bhatia Rohit , Hill Michael D. , Dowlatshahi Dar 
Published: October 2015

Background and Purpose—
Hematoma expansion in intracerebral hemorrhage is associated with higher morbidity and mortality. The computed tomography (CT) angiographic spot sign is highly predictive of expansion, but other morphological features of intracerebral hemorrhage such as fluid levels, density heterogeneity, and margin irregularity may also predict expansion, particularly in centres where CT angiography is not readily available.

Methods—
Baseline noncontrast CT scans from patients enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study were assessed for the presence of fluid levels and degree of density heterogeneity and margin irregularity using previously validated scales. Presence and grade of these metrics were correlated with the presence of hematoma expansion as defined by the PREDICT study on 24-hour follow-up scan.

Results—

Three hundred eleven patients were included in the analysis. The presence of fluid levels and increasing heterogeneity and irregularity were associated with 24-hour hematoma expansion (
P
=0.021, 0.003 and 0.049, respectively) as well as increases in absolute hematoma size. Fluid levels had the highest positive predictive value (50%; 28%–71%), whereas margin irregularity had the highest negative predictive value (78%; 71%–85). Noncontrast metrics had comparable predictive values as spot sign for expansion when controlled for vitamin K, antiplatelet use, and baseline National Institutes of Health Stroke Scale, although in a combined area under the receiver-operating characteristic curve model, spot sign remained the most predictive.

Conclusions—
Fluid levels, density heterogeneity, and margin irregularity on noncontrast CT are associated with hematoma expansion at 24 hours. These markers may assist in prediction of outcomes in scenarios where CT angiography is not readily available and may be of future help in refining the predictive value of the CT angiography spot sign.
Acute Loss of miR-221 and miR-222 in the Atherosclerotic Plaque Shoulder Accompanies Plaque Rupture
Authors: Bazan Hernan A. , Hatfield Samuel A. , O’Malley Chasity B. , Brooks Ashton J. , Lightell Daniel , Woods T. Cooper 
Published: October 2015

Background and Purpose—
Atherosclerotic plaque vulnerability is accompanied by changes in the molecular and cellular function in the plaque shoulder, including a decrease in vascular smooth muscle cell proliferation. We aimed to determine whether the expression of 3 miRNAs that regulate vascular smooth muscle cell proliferation (miR-145, miR-221, and miR-222) is altered with plaque rupture, suggesting a role in regulating plaque stability.

Methods—
miRNAs were measured in the plaque shoulder of carotid plaques obtained from patients undergoing carotid endarterectomy (CEA) for 3 distinct clinical scenarios: (1) patients without previous neurological events but high-grade carotid stenosis (asymptomatic), (2) patients with an acute neurological event within 5 days of the CEA (urgent), and (3) patients undergoing CEA>5 days after a neurological event (symptomatic).

Results—

Mean time from plaque rupture event to CEA was 2.4 days in the urgent group. The urgent group exhibited a significant decrease in miR-221 and miR-222 expression in the plaque shoulder, whereas no significant differences were seen in miR-145 across the 3 groups. Regression analysis demonstrated a significant correlation between time from the neurological event to CEA and increasing miR-221 and miR-222, but not miR-145. mRNA encoding p27
Kip1
, a target of miR-221 and miR-222 that inhibits vascular smooth muscle cell proliferation, was increased in the urgent group.

Conclusions—

Atherosclerotic plaque rupture is accompanied by a loss of miR-221 and miR-222 and an increase in p27
Kip1
mRNA expression in the plaque shoulder, suggesting an association between these miRNAs and atherosclerotic plaque stability.