bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endovascular treatment of intracranial aneurysms with the LVIS device: a systematic review
Authors: Zhang Xiaoguang , Zhong Junjie , Gao Heng , Xu Feng , Bambakidis Nicholas C 
Published: May 2016

ObjectiveDespite promising initial results, current knowledge regarding the use of the Low-profile Visualized Intraluminal Support (LVIS) device to treat wide-necked intracranial aneurysms is still limited. Our aim is to evaluate the feasibility, efficacy, and safety of the LVIS device in stent-assisted coiling of intracranial aneurysms.MethodsWe conducted a systematic review by searching PubMed, EMBASE, and Cochrane Library for all published studies on the treatment of intracranial aneurysms with the LVIS device up to March 2016. Feasibility was evaluated by the technical success rate during the procedure, efficacy was evaluated by the rate of complete aneurysm occlusion at follow-up angiography, and safety was assessed by procedure-related morbidity and mortality.ResultsA total of nine studies were included in the analysis, including 384 patients with 390 aneurysms. The overall technical success rate was 96.8% (95% CI 94.4% to 99.1%). The aneurysmal complete occlusion rate was 54.6% (95% CI 31.8% to 77.4%) on immediate control and 84.3% (95% CI 78.9% to 89.7%) at follow-up angiography. Procedural-related morbidity and mortality were 1.4% (95% CI 0.2% to 2.6%) and 0% (95% CI 0%), respectively. The thromboembolic event rate was 4.9% (95% CI 1.9% to 7.9%) and the hemorrhagic event rate was 2.1% (95% CI 0.7% to 3.5%), with 0.9% (95% CI 0% to 1.8%) experiencing neurologic hemorrhagic complications and 1.9% (95% CI 0.5% to 3.2%) experiencing non-neurologic hemorrhagic complications.ConclusionsOur systematic review suggests that endovascular treatment of intracranial aneurysms with the LVIS device is feasible, safe, and effective in the short term. However, the rate of thromboembolic complications is not negligible. Further prospective studies are needed to evaluate the long-term efficacy and safety of the LVIS device.
Solutions of evolution equations associated to infinite-dimensional Laplacian
Authors: Ouerdiane Habib 
Published: May 2016

We study an evolution equation associated with the integer power of the Gross Laplacian [Formula: see text] and a potential function V on an infinite-dimensional space. The initial condition is a generalized function. The main technique we use is the representation of the Gross Laplacian as a convolution operator. This representation enables us to apply the convolution calculus on a suitable distribution space to obtain the explicit solution of the perturbed evolution equation. Our results generalize those previously obtained by Hochberg [K. J. Hochberg, Ann. Probab. 6 (1978) 433.] in the one-dimensional case with [Formula: see text], as well as by Barhoumi–Kuo–Ouerdiane for the case [Formula: see text] (See Ref. [A. Barhoumi, H. H. Kuo and H. Ouerdiane, Soochow J. Math. 32 (2006) 113.]).
BRAF Mutation Testing in Cell-Free DNA from the Plasma of Patients with Advanced Cancers Using a Rapid, Automated Molecular Diagnostics System
Authors: Janku Filip , Huang Helen J. , Claes Bart , Falchook Gerald S. , Fu Siqing , Hong David , Ramzanali Nishma M. , Nitti Giovanni , Cabrilo Goran , Tsimberidou Apostolia M. , Naing Aung , Piha-Paul Sarina A. , Wheler Jennifer J. , Karp Daniel D. , Holley Veronica R. , Zinner Ralph G. , Subbiah Vivek , Luthra Rajyalakshmi , Kopetz Scott , Overman Michael J. , Kee Bryan K. , Patel Sapna , Devogelaere Benoit , Sablon Erwin , Maertens Geert , Mills Gordon B. , Kurzrock Razelle , Meric-Bernstam Funda 
Published: May 2016

Abstract
Cell-free (cf) DNA from plasma offers an easily obtainable material for BRAF mutation analysis for diagnostics and response monitoring. In this study, plasma-derived cfDNA samples from patients with progressing advanced cancers or malignant histiocytosis with known BRAFV600 status from formalin-fixed paraffin-embedded (FFPE) tumors were tested using a prototype version of the Idylla BRAF Mutation Test, a fully integrated real-time PCR-based test with turnaround time about 90 minutes. Of 160 patients, BRAFV600 mutations were detected in 62 (39%) archival FFPE tumor samples and 47 (29%) plasma cfDNA samples. The two methods had overall agreement in 141 patients [88%; κ, 0.74; SE, 0.06; 95% confidence interval (CI), 0.63–0.85]. Idylla had a sensitivity of 73% (95% CI, 0.60–0.83) and specificity of 98% (95% CI, 0.93–1.00). A higher percentage, but not concentration, of BRAFV600 cfDNA in the wild-type background (&gt;2% vs. ≤ 2%) was associated with shorter overall survival (OS; P = 0.005) and in patients with BRAF mutations in the tissue, who were receiving BRAF/MEK inhibitors, shorter time to treatment failure (TTF; P = 0.001). Longitudinal monitoring demonstrated that decreasing levels of BRAFV600 cfDNA were associated with longer TTF (P = 0.045). In conclusion, testing for BRAFV600 mutations in plasma cfDNA using the Idylla BRAF Mutation Test has acceptable concordance with standard testing of tumor tissue. A higher percentage of mutant BRAFV600 in cfDNA corresponded with shorter OS and in patients receiving BRAF/MEK inhibitors also with shorter TTF. Mol Cancer Ther; 15(6); 1397–404. ©2016 AACR.
LGR5-Targeted Antibody–Drug Conjugate Eradicates Gastrointestinal Tumors and Prevents Recurrence
Authors: Gong Xing , Azhdarinia Ali , Ghosh Sukhen C. , Xiong Wei , An Zhiqiang , Liu Qingyun , Carmon Kendra S. 
Published: May 2016

Abstract
Gastrointestinal cancer is one of the leading causes of cancer-related mortality in men and women worldwide. The adult stem cell marker LGR5 (leucine-rich repeat-containing, G protein–coupled receptor 5) is highly expressed in a significant fraction of gastrointestinal tumors of the colon, liver, pancreas, and stomach, relative to normal tissues. LGR5 is located on the cell surface and undergoes rapid, constitutive internalization independent of ligand. Furthermore, LGR5-high cancer cells have been shown to exhibit the properties of tumor-initiating cells or cancer stem cells (CSC). On the basis of these attributes, we generated two LGR5-targeting antibody–drug conjugates (ADC) by tethering the tubulin-inhibiting cytotoxic drug monomethyl auristatin E to a highly specific anti-LGR5 mAb via a protease cleavable or noncleavable chemical linker and compared them in receptor binding, cell internalization, and cytotoxic efficacy in cancer cells. Here, we show that both ADCs bind LGR5 with high specificity and equivalent nanomolar affinity and rapidly internalize to the lysosomes of LGR5-expressing gastrointestinal cancer cells. The anti-LGR5 ADCs effectively induced cytotoxicity in LGR5-high gastrointestinal cancer cells, but not in LGR5-negative or -knockdown cancer cell lines. Overall, we demonstrate that the cleavable ADC exhibited higher potency in vitro and was able to eradicate tumors and prevent recurrence in a xenograft model of colon cancer. These findings provide preclinical evidence for the potential of LGR5-targeting ADCs as effective new therapeutics for the treatment and eradication of gastrointestinal tumors and CSCs with high LGR5 expression. Mol Cancer Ther; 15(7); 1580–90. ©2016 AACR.
Aristotle and the Scope of Justice
Authors: Riesbeck David J 
Published: May 2016

It is often thought that Aristotle restricts the scope of justice to existing communities. Against prominent treatments of this problem, this paper argues that while Aristotle does indeed restrict the scope of justice, he recognizes eudaimonic reasons to cultivate co-operative and benevolent relations and to eschew manipulative and exploitative ones. His limitation of justice to existing communities thereby avoids the unsavory implications often attributed to it.
Carotid Intima‐Media Thickness and Arterial Stiffness and the Risk of Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study, Multi‐Ethnic Study of Atherosclerosis (MESA), and the Rotterdam Study
Authors: Chen Lin Y. , Leening Maarten J. G. , Norby Faye L. , Roetker Nicholas S. , Hofman Albert , Franco Oscar H. , Pan Wei , Polak Joseph F. , Witteman Jacqueline C.M. , Kronmal Richard A. , Folsom Aaron R. , Nazarian Saman , Stricker Bruno H. , Heckbert Susan R. , Alonso Alvaro 
Published: May 2016

Background
We evaluated the association of carotid intima‐media thickness (cIMT), carotid plaque, carotid distensibility coefficient (DC), and aortic pulse wave velocity (PWV) with incident atrial fibrillation (AF) and their role in improving AF risk prediction beyond the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)‐AF risk score.

Methods and Results
We analyzed data from 3 population‐based cohort studies: Atherosclerosis Risk in Communities (ARIC) Study (n=13 907); Multi‐Ethnic Study of Atherosclerosis (MESA; n=6640), and the Rotterdam Study (RS; n=5220). We evaluated the association of arterial indices with incident AF and computed the C‐statistic, category‐based net reclassification improvement (NRI), and relative integrated discrimination improvement (IDI) of incorporating arterial indices into the CHARGE‐AF risk score (age, race, height weight, systolic and diastolic blood pressure, antihypertensive medication use, smoking, diabetes, previous myocardial infarction, and previous heart failure). Higher cIMT (meta‐analyzed hazard ratio [95% CI] per 1‐SD increment, 1.12 [1.08–1.16]) and presence of carotid plaque (1.30 [1.19–1.42]) were associated with higher AF incidence after adjustment for CHARGE‐AF risk‐score variables. Lower DC and higher PWV were associated with higher AF incidence only after adjustment for the CHARGE‐AF risk‐score variables excepting height, weight, and systolic and diastolic blood pressure. Addition of cIMT or carotid plaque marginally improved CHARGE‐AF score prediction as assessed by the relative IDI (estimates, 0.025–0.051), but not when assessed with the C‐statistic and NRI.

Conclusions
Higher cIMT, presence of carotid plaque, and greater arterial stiffness are associated with higher AF incidence, indicating that atherosclerosis and arterial stiffness play a role in AF etiopathogenesis. However, arterial indices only modestly improve AF risk prediction.
Hospital Readmissions Following Endovascular Therapy for Critical Limb Ischemia: Associations With Wound Healing, Major Adverse Limb Events, and Mortality
Authors: Reed Grant W. , Raeisi‐Giglou Pejman , Kafa Rami , Malik Umair , Salehi Negar , Shishehbor Mehdi H. 
Published: May 2016

Background

The significance of hospital readmission after endovascular therapy for critical limb ischemia (
CLI
) is not well established. We sought to investigate the incidence, timing, and causes of readmissions after endovascular therapy for
CLI
and whether readmission is associated with major adverse limb events (
MALE
) or mortality.

Methods and Results

This was a retrospective study of 252 patients treated with endovascular therapy for
CLI
. During median follow‐up of 381 days (interquartile range [
IQR
], 115–718), 140 (56%) were readmitted, with median time to readmission of 83 days (
IQR,
33–190). Readmission within 30 days occurred in 14% of patients (n=35; 25% of readmissions). Most readmissions occurred between 30 and 180 days (n=67; 48% of readmissions). The most frequent reason for readmission was unhealed wounds (n=63; 45% of readmissions). Independent predictors of readmission by Cox proportional hazards analysis were unhealed wounds, presence of multiple wounds, age ≥70, female sex, hemodialysis, and history of heart failure (
P
<0.05 for each). By Kaplan–Meier analysis, readmission was greatest in patients with unhealed wounds, followed by patients who never had a wound, and lowest in patients whose wounds completely healed (
P
<0.0001 overall, and
P
<0.01 between groups). After multivariable adjustment, readmission remained an independent predictor of composite
MALE
(major amputation, bypass, or endarterectomy) or mortality (adjusted hazard ratio, 3.1; 95%
CI
, 1.5–6.5;
P
=0.002).

Conclusions

Most readmissions occur 30 and 180 days after endovascular therapy for nonprocedural reasons. Unhealed wounds are an independent risk factor for readmission. Readmission is associated with increased
MALE
and mortality after endovascular therapy for
CLI
.
Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Receiving Antiplatelet Therapy: A Systematic Review and Meta‐analysis of 19 Studies
Authors: Luo Shengyuan , Zhuang Mei , Zeng Wutao , Tao Jun 
Published: May 2016

Background
The safety and long‐term outcome of systemic thrombolysis in patients receiving antiplatelet medications remain subjects of great clinical significance. The objective of this meta‐analysis was to determine how prestroke antiplatelet therapy affects the risks and benefits of intravenous thrombolysis in patients with acute ischemic stroke.

Methods and Results

A dual‐reviewer search was conducted in PubMed and
EMBASE
databases through November 2015, from which 19 studies involving a total of 108 588 patients with acute ischemic stroke were identified based on preset inclusion criteria. Information on study designs, patient characteristics, exposures, outcomes, and adjusting confounders was extracted, and estimates were combined by using random‐effects models. The pooled crude estimates suggested that taking long‐term antiplatelet medications was associated with higher odds of symptomatic intracranial hemorrhage (odds ratio [OR] 1.70, 95%
CI
1.47–1.97) and death (
OR
1.46, 95%
CI
1.22–1.75) and lower odds of favorable functional outcomes (
OR
0.86, 95%
CI
0.80–0.93). However, the combined confounder‐adjusted results only confirmed a relatively weak positive association between prior antiplatelet therapy and symptomatic intracranial hemorrhage (
OR
1.21, 95%
CI
1.02–1.44) and demonstrated no significant relationship between antiplatelet therapy and the other 2 outcomes (favorable outcome
OR
1.09, 95%
CI
0.96–1.24; death
OR
1.02, 95%
CI
0.98–1.07). Subgroup analyses revealed that the associations between prestroke antiplatelet therapy and outcomes were dependent on time and antiplatelet agents.

Conclusions
Patients with acute ischemic stroke receiving long‐term antiplatelet medications were associated with greater risks of developing symptomatic intracranial hemorrhage after systemic thrombolysis. However, the overall independent association between prestroke antiplatelet therapy and unfavorable outcomes or mortality was insignificant.
Stroke Ready Intervention: Community Engagement to Decrease Prehospital Delay
Authors: Skolarus Lesli E. , Zimmerman Marc A. , Bailey Sarah , Dome Mackenzie , Murphy Jillian B. , Kobrossi Christina , Dombrowski Stephan U. , Burke James F. , Morgenstern Lewis B. 
Published: May 2016

Background
Time‐limited acute stroke treatments are underused, primarily due to prehospital delay. One approach to decreasing prehospital delay is to increase stroke preparedness, the ability to recognize stroke, and the intention to immediately call emergency medical services, through community engagement with high‐risk communities.

Methods and Results

Our community–academic partnership developed and tested “Stroke Ready,” a peer‐led, workshop‐based, health behavior intervention to increase stroke preparedness among African American youth and adults in Flint, Michigan. Outcomes were measured with a series of 9 stroke and nonstroke 1‐minute video vignettes; after each video, participants selected their intended response (primary outcome) and symptom recognition (secondary outcome), receiving 1 point for each appropriate stroke response and recognition. We assessed differences between baseline and posttest appropriate stroke response, which was defined as intent to call 911 for stroke vignettes and not calling 911 for nonstroke, nonemergent vignettes and recognition of stroke. Outcomes assessments were performed before workshop 1 (baseline), at the conclusion of workshop 2 (immediate post‐test), and 1 month later (delayed post‐test). A total of 101 participants completed the baseline assessment (73 adults and 28 youths), 64 completed the immediate post‐test, and 68 the delayed post‐test. All participants were African American. The median age of adults was 56 (interquartile range 35–65) and of youth was 14 (interquartile range 11–16), 65% of adults were women, and 50% of youths were women. Compared to baseline, appropriate stroke response was improved in the immediate post‐test (4.4 versus 5.2,
P
<0.01) and was sustained in the delayed post‐test (4.4 versus 5.2,
P
<0.01). Stroke recognition did not change in the immediate post‐test (5.9 versus 6.0,
P
=0.34), but increased in the delayed post‐test (5.9 versus 6.2,
P
=0.04).

Conclusions
Stroke Ready increased stroke preparedness, a necessary step toward increasing acute stroke treatment rates.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov/
. Unique identifier:
NCT
01499173.
Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Elevated in Patients With Peripheral Artery Disease and Associated With Metabolic Disorders and Dysfunction in Circulating Progenitor Cells
Authors: Chao Ting‐Hsing , Chen I‐Chih , Li Yi‐Heng , Lee Po‐Tseng , Tseng Shih‐Ya 
Published: May 2016

Background

Proprotein convertase subtilisin/kexin type 9 (
PCSK
9) is involved in cholesterol homeostasis, inflammation, and oxidative stress. This study investigated the association of plasma
PCSK
9 levels with the presence and severity of peripheral artery disease (
PAD
) and with parameters of endothelial homeostasis.

Methods and Results

A post hoc analysis of 2 randomized trials (115 patients, 44 with
PAD
and 71 without atherosclerotic disease) was conducted. Patients with
PAD
had significantly higher plasma
PCSK
9 levels than those without (471.6±29.6 versus 302.4±16.1 ng/mL,
P
<0.001). Parameters for glucose homeostasis, endothelial progenitor cell functions, apoptotic circulating endothelial cell counts, and plasma levels of vascular endothelial growth factor–A165 and oxidized low‐density lipoprotein were correlated with
PCSK
9 concentration. By multivariable linear regression analysis, presence of
PAD
, plasma glucose or hemoglobin A1c levels, apoptotic
circulating endothelial cell
counts, and vascular endothelial growth factor–A165 concentration were found to be associated with
PCSK
9 levels after multivariable adjustment. Patients with extensive involvement of
PAD
or with severe
PAD
had significantly higher
PCSK
9 levels than those without PAD. Computed tomographic angiography showed that the numbers of chronic total occlusion sites and vessels involved were positively associated with
PCSK
9 levels in patients with
PAD
(
r
=0.40,
P
=0.01, and
r
=0.36,
P
=0.02, respectively).

Conclusion

PCSK
9 levels were significantly higher in patients with
PAD
, especially those with advanced
PAD
. Further large‐scale studies examining the effect of
PCSK
9‐targeting therapies or the modification of
PCSK
9 levels on cardiovascular outcomes in this clinical setting are warranted.

Clinical Trial Registration
Cohort 1: URL: ClinicalTrials.gov. Unique identifier: NCT01952756; cohort 2: URL: ClinicalTrials.gov. Unique identifier: NCT02194686.
The Effect of Cell Dose on the Early Magnetic Resonance Morphological Outcomes of Autologous Cell Implantation for Articular Cartilage Defects in the Knee
Authors: Niemeyer Philipp , Laute Volker , John Thilo , Becher Christoph , Diehl Peter , Kolombe Thomas , Fay Jakob , Siebold Rainer , Niks Milan , Fickert Stefan , Zinser Wolfgang 
Published: May 2016

Background: Although autologous chondrocyte implantation (ACI) has been established as a standard treatment for large full-thickness cartilage defects, the effect of different doses of autologous chondrocyte products on structural outcomes has never been examined. Hypothesis: In ACI, the dose level may have an influence on medium-term magnetic resonance morphological findings after treatment. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 75 patients who underwent ACI using a pure, autologous, third-generation matrix-associated ACI product were divided into 3 groups representing different doses: 3 to 7 spheroids/cm2, 10 to 30 spheroids/cm2, and 40 to 70 spheroids/cm2. Magnetic resonance imaging was performed at 1.5, 3, 6, and 12 months after ACI and was evaluated by the magnetic resonance observation of cartilage repair tissue (MOCART) score and the Knee injury and Osteoarthritis Outcome Score (KOOS). Results: MOCART scores showed improvements after 3 months, with slight dose dependence, and further improvement after 12 months, although without significant dose dependence. The mean MOCART scores after 3 months (0 = worst, 100 = best) were 59.8, 64.5, and 64.7 for the low-, medium-, and high-dose groups, respectively, and 62.9 for all patients; at 12 months, these were 74.1, 74.5, and 68.8 for the respective dose groups and 72.4 for all patients. Several MOCART items (surface of repair tissue, structure of repair tissue, signal intensity of repair tissue, subchondral bone, and synovitis) showed a more rapid response with the medium and high doses than with the low dose, suggesting a potential dose relationship. No significant correlation between the MOCART (overall and subscores) with clinical outcomes as assessed by the overall KOOS was detected at 3- and 12-month assessments. Conclusion: This study reveals a trend toward earlier recovery after treatment with higher spheroid doses in terms of better defect filling for full-thickness cartilage defects of the knee, while outcomes after 12 months were similar in all dose groups. However, a correlation with clinical outcomes or the failure rate at 1 year after ACI was not found. A longer follow-up will be required for more definite conclusions on the clinical relevance of ACI cell density to be drawn. Registration: NCT01225575 ( ClinicalTrials.gov identifier); 2009-016816-20 (EudraCT number).