bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-resolved 3D rotational angiography: display of detailed neurovascular anatomy in patients with intracranial vascular malformations
Authors: Lescher Stephanie , Gehrisch Sonja , Klein Sigrun , Berkefeld Joachim 
Published: August 2016

PurposeThe purpose of this pilot study was to demonstrate the applicability of time-resolved three-dimensional (3D) reconstructions from 3D digital subtraction angiography (DSA) rotational angiography (RA) datasets (four-dimensional (4D) DSA) to provide a more detailed display of the architecture of intracranial vascular malformations.MethodsThe experimental reconstruction software was applied to the existing 3D DSA datasets obtained with Siemens Artis zee biplane neuroangiography equipment. We included 27 patients with clinical indications for 3DRA for preinterventional or preoperative evaluation of intracranial dural arteriovenous fistulas (dAVFs, n=8) or arteriovenous malformations (AVMs, n=19). A modified DSA acquisition protocol covering an extended rotation angle of the C-arm of 260° during a scan time of 12 s was used. 4D volumes were displayed with up to 30 frames/s in a transparent volume rendering (VRT) mode and time-resolved multiplanar reconstructions (MPRs). Arterial feeders, fistulous points, or the shunt zone within the AVM nidus and venous drainage patterns as well as associated aneurysms were assessed after definition of a standardized evaluation procedure by consensus of two reviewers in comparison with 2D DSA and conventional 3D reconstructions.ResultsIn all cases calculation of 4D reconstructions were technically feasible and evaluable. In two cases image quality was slightly compromised by movement artifacts. Compared with standard DSA projection images and 3D reconstructions, 4D VRTs and MPRs were rated significantly superior to define a proper projection and display of the shunt zone. In 12 out of 27 cases 4D reconstructions showed details of the angioarchitecture at the fistulous point or the nidus better than the other modalities and came close to the quality of superselective angiography. The efficacy of 3D and 4D applications was equal in the detection of pre- and intranidal aneurysms. The course of long arterial feeders and draining veins was difficult to assess on VRTs and MPRs. Especially for dAVFs, 2D DSA was clearly superior in identifying meningeal feeders. For detecting smaller vessels and for distinction between angiographic phases, 2D DSA is still considered to be superior to 4D imaging. Venous drainage was slightly better displayed in 4D reconstructions.ConclusionsTime-resolved 3DRA with 4D VRTs and MPRs is technically feasible and provides a detailed display of the angioarchitecture at the fistulous point or the nidus. Visualization of all angiographic features demands additional post-processing. Further standardization of evaluation tools and studies with blinded independent reviewers are necessary before the new technique can replace conventional neuroangiographic approaches.
Anthelmintic Niclosamide Disrupts the Interplay of p65 and FOXM1/β-catenin and Eradicates Leukemia Stem Cells in Chronic Myelogenous Leukemia
Authors: Jin Bei , Wang Chengyan , Li Juan , Du Xin , Ding Ke , Pan Jingxuan 
Published: August 2016

Abstract
Purpose: Leukemia stem cells (LSC), which are insensitive to tyrosine kinase inhibitors (TKI), are an important source of TKI resistance and disease relapse in chronic myelogenous leukemia (CML). Obstacles to eradicating LSCs include limited understanding of the regulation network of LSCs. The current study aimed to examine the interplay between NF-κB and FOXM1/β-catenin, and the effect of its chemical intervention on CML LSCs.
Experimental Design: The interplay between NF-κB and FOXM1/β-catenin was analyzed by reciprocal coimmunoprecipitation (co-IP) and chromatin immunoprecipitation (ChIP) assay in CML cells. The effect of disturbing NF-κB and FOXM1/β-catenin by niclosamide on the self-renewal capacity and survival of LSCs was evaluated in vitro in human primary CML CD34+ cells and in vivo in CML mice.
Results: Reciprocal co-IP experiments showed physical interaction of p65 and FOXM1. p65 promoted transcription of FOXM1 gene. ChIP assay revealed recruitment of p65 on the promoter of FOXM1 gene. Conversely, FOXM1 and β-catenin positively regulated the nuclear translocation and transcriptional activity of NF-κB in CML cells. Niclosamide disrupted the positive feedback loop between NF-κB and FOXM1/β-catenin, thereby impairing the self-renewal capacity and survival of CML LSCs. Niclosamide decreased the long-term engraftment of human CML LSCs in NOD-SCID IL2Rγ chain-deficient (NOG) mice, and prolonged the survival of CML mice.
Conclusions: Interaction of p65 with FOXM1/β-catenin is critical in CML and its disruption by niclosamide eradicates LSCs. These findings may improve the understanding of a self-renewal regulatory mechanism of LSCs and offer a rationale-based approach to eliminate LSCs in CML. Clin Cancer Res; 23(3); 789–803. ©2016 AACR.
Loss of SMAD4 Promotes Lung Metastasis of Colorectal Cancer by Accumulation of CCR1+ Tumor-Associated Neutrophils through CCL15-CCR1 Axis
Authors: Yamamoto Takamasa , Kawada Kenji , Itatani Yoshiro , Inamoto Susumu , Okamura Ryosuke , Iwamoto Masayoshi , Miyamoto Ei , Chen-Yoshikawa Toyofumi F. , Hirai Hideyo , Hasegawa Suguru , Date Hiroshi , Taketo Makoto M. , Sakai Yoshiharu 
Published: August 2016

Abstract
Purpose: We have reported loss of SMAD4 promotes expression of CCL15 from colorectal cancer to recruit CCR1+ myeloid cells through the CCL15-CCR1 axis, which contributes to invasion and liver metastasis. However, the molecular mechanism of lung metastasis is yet to be elucidated. Our purpose is to determine whether similar mechanism is involved in the lung metastasis of colorectal cancer.
Experimental Design: In a mouse model, we examined whether SMAD4 could affect the metastatic activity of colorectal cancer cells to the lung through the CCL15-CCR1 axis. We immunohistochemically analyzed expression of SMAD4, CCL15, and CCR1 with 107 clinical specimens of colorectal cancer lung metastases. We also characterized the CCR1+ myeloid cells using several cell-type–specific markers.
Results: In a mouse model, CCL15 secreted from SMAD4-deficient colorectal cancer cells recruited CCR1+ cells, promoting their metastatic activities to the lung. Immunohistochemical analysis of lung metastases from colorectal cancer patients revealed that CCL15 expression was significantly correlated with loss of SMAD4, and that CCL15-positive metastases recruited approximately 1.9 times more numbers of CCR1+ cells than CCL15-negative metastases. Importantly, patients with CCL15-positive metastases showed a significantly shorter relapse-free survival (RFS) than those with CCL15-negative metastases, and multivariate analysis indicated that CCL15 expression was an independent predictor of shorter RFS. Immunofluorescent staining showed that most CCR1+ cells around lung metastases were tumor-associated neutrophil, although a minor fraction was granulocytic myeloid-derived suppressor cell.
Conclusions: CCL15-CCR1 axis may be a therapeutic target to prevent colorectal cancer lung metastasis. CCL15 can be a biomarker indicating poor prognosis of colorectal cancer patients with lung metastases. Clin Cancer Res; 23(3); 833–44. ©2016 AACR.
Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin–Angiotensin System Blockade
Authors: Jin Sang-Man , Han Kyung Ah , Yu Jae Myung , Sohn Tae Seo , Choi Sung Hee , Chung Choon Hee , Park Ie Byung , Rhee Eun Jung , Baik Sei Hyun , Park Tae Sun , Lee In-Kyu , Ko Seung-Hyun , Hwang You-Cheol , Cha Bong Soo , Lee Hyoung Woo , Nam Moon-Suk , Lee Moon-Kyu 
Published: August 2016

Objective—
To determine the effect of probucol on urine albumin excretion in type 2 diabetes mellitus patients with albuminuria using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

Approach and Results—

This was a 16-week, phase II, randomized, placebo-controlled, parallel-group study in type 2 diabetes mellitus patients with a urinary albumin/creatinine ratio of ≥300 mg/g using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, conducted in 17 tertiary referral hospitals. Eligible patients were randomized to probucol 250 mg/d (n=44), probucol 500 mg/d (n=41), and placebo (n=41) groups in a ratio of 1:1:1 after block randomization procedures, keeping the treatment assignment blinded to the investigators, patients, and study assistants. The primary end point was change in the geometric mean of urinary albumin/creatinine ratio from baseline to week 16 (
ClinicalTrials.gov
identifier NCT01726816). The study was started on November 8, 2012, and completed on March 24, 2014. The least squares mean change±SE from baseline in urinary albumin/creatinine ratio at week 16 was −7.2±639.5 mg/g in the probucol 250 mg/d group (n=43;
P
=0.2077 versus placebo group), 9.3±587.4 mg/g in the probucol 500 mg/d group (n=40;
P
=0.1975 versus placebo group), and 259.0±969.1 mg/g in the placebo group (n=41). Although the majority of subjects were on statins, probucol treatment significantly lowered total cholesterol and low-density lipoprotein cholesterol levels. QT prolongation occurred in one and two subjects in control and probucol 250 mg/d groups, respectively.

Conclusions—
Four months of probucol up to 500 mg/d failed to reduce urinary albumin excretion.
Sex and Race/Ethnicity Differences in Implantable Cardioverter-Defibrillator Counseling and Use Among Patients Hospitalized With Heart Failure
Authors: Hess Paul L. , Hernandez Adrian F. , Bhatt Deepak L. , Hellkamp Anne S. , Yancy Clyde W. , Schwamm Lee H. , Peterson Eric D. , Schulte Phillip J. , Fonarow Gregg C. , Al-Khatib Sana M. 
Published: August 2016

Background:
Previous studies have found that women and black patients eligible for a primary prevention implantable cardioverter-defibrillator (ICD) are less likely than men or white patients to receive one.

Methods:
We performed an observational analysis of the Get With The Guidelines-Heart Failure Program from January 1, 2011, to March 21, 2014. Patients admitted with heart failure and an ejection fraction ≤35% without an ICD were included. Rates of ICD counseling among eligible patients and ICD receipt among counseled patients were examined by sex and race/ethnicity.

Results:

Among 21 059 patients from 236 sites, 4755 (22.6%) received predischarge ICD counseling. Women were counseled less frequently than men (19.3% versus 24.6%,
P
<0.001, adjusted odds ratio [OR], 0.84; 95% confidence interval [CI], 0.78–0.91). Racial and ethnic minorities were less likely to receive counseling than white patients (black 22.6%, Hispanic 18.6%, other race/ethnic group 14.4% versus white 24.3%,
P
<0.001 for each): adjusted OR versus white, 0.69; 95% CI, 0.63 to 0.76 for black patients; adjusted OR, 0.62; 95% CI, 0.55 to 0.70 for Hispanic patients; adjusted OR, 0.53; 95% CI, 0.43 to 0.65 for other patients. Among the 4755 counseled patients, 2977 (62.6%) received an ICD or had one planned for placement after hospital stay. Among those counseled, women and men were similarly likely to receive an ICD (adjusted OR, 1.13; 95% CI, 0.99–1.29). However, black (adjusted OR, 0.70; 95% CI, 0.56–0.88) and Hispanic patients (adjusted OR, 0.68; 95% CI, 0.46–1.01) were less likely to receive an ICD.

Conclusions:
Up to 4 of 5 hospitalized patients with heart failure eligible for ICD counseling did not receive it, particularly women and minority patients. Among counseled patients, ICD use differences by race and ethnicity persisted.
Dynamic Predictive Scores for Cardiac Surgery–Associated Acute Kidney Injury
Authors: Jiang Wuhua , Teng Jie , Xu Jiarui , Shen Bo , Wang Yimei , Fang Yi , Zou Zhouping , Jin Jifu , Zhuang Yamin , Liu Lan , Luo Zhe , Wang Chunsheng , Ding Xiaoqiang 
Published: August 2016

Background

Cardiac surgery–associated acute kidney injury (
CSA
‐
AKI
) is a common complication with a poor prognosis. In order to identify modifiable perioperative risk factors for
AKI
, which existing risk scores are insufficient to predict, a dynamic clinical risk score to allow clinicians to estimate the risk of
CSA
‐
AKI
from preoperative to early postoperative periods is needed.

Methods and Results

A total of 7233 cardiac surgery patients in our institution from January 2010 to April 2013 were enrolled prospectively and distributed into 2 cohorts. Among the derivation cohort, logistic regression was used to analyze
CSA
‐
AKI
risk factors preoperatively, on the day of
ICU
admittance and 24 hours after
ICU
admittance. Sex, age, valve surgery combined with coronary artery bypass grafting, preoperative
NYHA
score >2, previous cardiac surgery, preoperative kidney (without renal replacement therapy) disease, intraoperative cardiopulmonary bypass application, intraoperative erythrocyte transfusions, and postoperative low cardiac output syndrome were identified to be associated with
CSA
‐
AKI
. Among the other 1152 patients who served as a validation cohort, the point scoring of risk factor combinations led to area under receiver operator characteristics curves (
AUROC
) values for
CSA
‐
AKI
prediction of 0.74 (preoperative), 0.75 (on the day of
ICU
admission), and 0.82 (postoperative), and Hosmer–Lemeshow goodness‐of‐fit tests revealed a good agreement of expected and observed
CSA
‐
AKI
rates.

Conclusions

The first dynamic predictive score system, with Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition, was developed and predictive efficiency for
CSA
‐
AKI
was validated in cardiac surgery patients.
The Capillary Index Score as a Marker of Viable Cerebral Tissue
Authors: Al-Ali Firas , Berkhemer Olvert A. , Yousman Wina P. , Elias John J. , Bender Evin N. , Lingsma Hester F. , van der Lugt Aad , Dippel Diederik W.J. , Roos Yvo B.W.E.M. , van Oostenbrugge Robert J. , van Zwam Wim H. , Dillon William P. , Majoie Charles B.L.M. 
Published: August 2016

Background and Purpose—
The capillary index score (CIS) is based on the hypothesis that areas lacking capillary blush on pretreatment cerebral digital subtraction angiograms correspond to nonviable cerebral tissue.

Methods—
Pretreatment digital subtraction angiograms and post-treatment noncontrast enhanced computed tomographic scans from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) trial were evaluated for areas lacking capillary blush and with tissue hypodensity, respectively. Because the superior and middle zones of the CIS correspond to the 7 cerebral cortex regions of the Alberta Stroke Program Early CT (ASPECT) score, capillary blush was scored in these 2 zones (0–2), called sub-CIS, and compared with the ASPECT score in these 7 regions (0–7), called hypodensity score. The presence and extent of hypodensity were compared between sub-CIS zones with contingency tables and nonparametric comparisons between groups, respectively.

Results—

On the basis of a sample size of 50 subjects, 100% with sub-CIS <2 had the presence of hypodensity (hypodensity score ≥1) versus 57% for sub-CIS=2 (
P
=0.004). The extent of hypodensity (numeric hypodensity score) was significantly lower for sub-CIS=2 than 0 or 1 (
P
=0.02). For 42 subjects with revascularization data, the presence and extent of hypodensity were significantly lower for sub-CIS=2 plus good revascularization than for other combinations of sub-CIS and revascularization (
P
=0.02 and 0.01, respectively).

Conclusions—
The absence of capillary blush on pretreatment digital subtraction angiogram seems to correspond to nonviable cerebral tissue. Successful revascularization reduces the chance of tissue hypodensity (infarction), when capillary blush is present.

Clinical Trial Registration—

URL:
http://www.trialregister.nl
. Unique identifier: NTR number 1804. URL:
http://www.isrctn.com
. Unique identifier: ISRCTN10888758.
FABS
Authors: Goyal Nitin , Tsivgoulis Georgios , Male Shailesh , Metter E. Jeffrey , Iftikhar Sulaiman , Kerro Ali , Chang Jason J. , Frey James L. , Triantafyllou Sokratis , Papadimitropoulos Georgios , Abedi Vida , Alexandrov Anne W. , Alexandrov Andrei V. , Zand Ramin 
Published: August 2016

Background and Purpose—
A large number of patients with symptoms of acute cerebral ischemia are stroke mimics (SMs). In this study, we sought to develop a scoring system (FABS) for screening and stratifying SM from acute cerebral ischemia and to identify patients who may require magnetic resonance imaging to confirm or refute a diagnosis of stroke in the emergency setting.

Methods—
We designed a scoring system: FABS (6 variables with 1 point for each variable present): absence of Facial droop, negative history of Atrial fibrillation, Age <50 years, systolic Blood pressure <150 mm Hg at presentation, history of Seizures, and isolated Sensory symptoms without weakness at presentation. We evaluated consecutive patients with symptoms of acute cerebral ischemia and a negative head computed tomography for any acute finding within 4.5 hours after symptom onset in 2 tertiary care stroke centers for validation of FABS.

Results—
A total of 784 patients (41% SMs) were evaluated. Receiver operating characteristic curve (C statistic, 0.95; 95% confidence interval [CI], 0.93–0.98) indicated that FABS≥3 could identify patients with SM with 90% sensitivity (95% CI, 86%–93%) and 91% specificity (95% CI, 88%–93%). The negative predictive value and positive predictive value were 93% (95% CI, 90%–95%) and 87% (95% CI, 83%–91%), respectively.

Conclusions—
FABS seems to be reliable in stratifying SM from acute cerebral ischemia cases among patients in whom the head computed tomography was negative for any acute findings. It can help clinicians consider advanced imaging for further diagnosis.
Protective Effects and Magnetic Resonance Imaging Temperature Mapping of Systemic and Focal Hypothermia in Cerebral Ischemia
Authors: Vieites-Prado Alba , Iglesias-Rey Ramón , Fernández-Susavila Héctor , da Silva-Candal Andrés , Rodríguez-Castro Emilio , Gröhn Olli H.J. , Wellmann Sven , Sobrino Tomás , Castillo José , Campos Francisco 
Published: August 2016

Background and Purpose—
Hypothermia is potentially the most effective protective therapy for brain ischemia; however, its use is limited because of serious side effects. Although focal hypothermia (FH) has a significantly lower stress profile than systemic hypothermia (SH), its efficacy in ischemia has been poorly studied. We aimed to compare the therapeutic effects of each treatment on various short- and long-term clinically relevant end points.

Methods—
Sprague–Dawley rats were subjected to transient (45 minutes) occlusion of the middle cerebral artery. One hour after arterial reperfusion, animals were randomly assigned to groups for treatment with SH or FH (target temperature: 32°C) for 4 or 24 hours. Lesion volume, edema, functional recovery, and histological markers of cellular injury were evaluated for 1 month after ischemic injury. Effects of SH and FH on cerebral temperature were also analyzed for the first time by magnetic resonance thermometry, an approach that combines spectroscopy with gradient-echo–based phase mapping.

Results—

Both therapeutic approaches reduced ischemic lesion volume (
P
<0.001), although a longer FH treatment (24 hours) was required to achieve similar protective effects to those induced by 4 hours of SH. In addition, magnetic resonance thermometry demonstrated that systemic hypothermia reduced whole-brain temperature, whereas FH primarily reduced the temperature of the ischemic region.

Conclusions—
Focal brain hypothermia requires longer cooling periods to achieve the same protective efficacy as SH. However, FH mainly affects the ischemic region, and therefore represents a promising and nonstressful alternative to SH.
Leukoaraiosis, Cerebral Hemorrhage, and Outcome After Intravenous Thrombolysis for Acute Ischemic Stroke
Authors: Charidimou Andreas , Pasi Marco , Fiorelli Marco , Shams Sara , von Kummer Rüdiger , Pantoni Leonardo , Rost Natalia 
Published: August 2016

Background and Purpose—
We performed a meta-analysis to assess whether leukoaraiosis on brain computed tomographic scans of acute ischemic stroke patients treated with intravenous thrombolysis is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) or poor functional outcome at 3 to 6 months after stroke, or both.

Methods—
We searched PubMed and pooled relevant data in meta-analyses using random effects models. Using odds ratios (OR), we quantified the strength of association between the presence and severity of leukoaraiosis and post-thrombolysis sICH or 3- to 6-month modified Rankin Score >2.

Results—

Eleven eligible studies (n=7194) were pooled in meta-analysis. The risk of sICH was higher in patients with leukoaraiosis (OR, 1.55; 95% confidence interval [CI], 1.17–2.06;
P
=0.002) and severe leukoaraiosis (OR, 2.53; 95% CI, 1.92–3.34;
P
<0.0001) compared with patients without leukoaraiosis. Leukoaraiosis was an independent predictor of sICH in 6 included studies (n=4976; adjusted OR, 1.75; 95% CI, 1.35–2.27;
P
<0.0001). OR for leukoaraiosis and poor 3- to 6-month outcome was 2.02 (95% CI, 1.54–2.65;
P
<0.0001), with significant statistical heterogeneity (
I
2
, 75.7%;
P
=0.002). In adjusted analyses, leukoaraiosis was an independent predictor of poor outcome (n=3688; adjusted OR, 1.61; 95% CI, 1.44–1.79;
P
<0.0001). In post hoc analyses, including only leukoaraiosis patients in randomized controlled trials (IST-3 [third International Stroke Trial], NINDS [National Institute of Neurological Disorders and Stroke], ECASS-1–2 [European Cooperative Acute Stroke Study]; n=2234), tissue-type plasminogen activator versus control was associated with higher sICH risk (OR, 5.50; 95% CI, 2.49–12.13), but lower poor outcome risk (OR, 0.75; 95% CI, 0.60–0.95).

Conclusions—
Leukoaraiosis might increase post-intravenous thrombolysis sICH risk and poor outcome poststroke. Despite increased sICH risk, intravenous tissue-type plasminogen activator treatment has net clinical benefit in patients with leukoaraiosis. Given the risk of bias/confounding, these results should be considered hypothesis-generating and do not justify withholding intravenous thrombolysis.
In-Transit Telemedicine Speeds Ischemic Stroke Treatment
Authors: Belt Gary H. , Felberg Robert A. , Rubin Jane , Halperin John J. 
Published: August 2016

Background and Purpose—
Time to treatment is critically important in ischemic stroke. We compared the efficacy and cost of teleneurology evaluation during patient transport with that of mobile stroke transport units.

Methods—
Using cellular-connected telemedicine devices, we assessed 89 presumptive stroke patients in ambulances in transit. Paramedics assisted remote teleneurologists in obtaining a simplified history and examination, then coordinating care with the receiving emergency department. We prospectively assessed door-to-needle and last-known-well-to-needle times for all intravenous alteplase–treated stroke patients brought to our emergency departments by emergency medical services’ transport, comparing those with and without in-transit telestroke.

Results—

From January 2015 through March 2016, 111 stroke patients received intravenous alteplase at study emergency departments. Mean door to needle was 13 minutes less with in-transit telestroke (28 versus 41;
P
=0.02). Although limitations in cellular communication degraded transmission quality, this did not prevent the completion of satisfactory patient evaluations.

Conclusions—
Improvement in time to treat seems comparable with in-transit telestroke and mobile stroke transport units. The low cost/unit makes this approach scalable, potentially providing rapid management of more patients.