bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-Folate Receptor-α IgE but not IgG Recruits Macrophages to Attack Tumors via TNFα/MCP-1 Signaling
Authors: Josephs Debra H. , Bax Heather J. , Dodev Tihomir , Georgouli Mirella , Nakamura Mano , Pellizzari Giulia , Saul Louise , Karagiannis Panagiotis , Cheung Anthony , Herraiz Cecilia , Ilieva Kristina M. , Correa Isabel , Fittall Matthew , Crescioli Silvia , Gazinska Patrycja , Woodman Natalie , Mele Silvia , Chiaruttini Giulia , Gilbert Amy E. , Koers Alexander , Bracher Marguerite , Selkirk Christopher , Lentfer Heike , Barton Claire , Lever Elliott , Muirhead Gareth , Tsoka Sophia , Canevari Silvana , Figini Mariangela , Montes Ana , Downes Noel , Dombrowicz David , Corrigan Christopher J. , Beavil Andrew J. , Nestle Frank O. , Jones Paul S. , Gould Hannah J. , Sanz-Moreno Victoria , Blower Philip J. , Spicer James F. , Karagiannis Sophia N. 
Published: January 2017

Abstract
IgE antibodies are key mediators of antiparasitic immune responses, but their potential for cancer treatment via antibody-dependent cell-mediated cytotoxicity (ADCC) has been little studied. Recently, tumor antigen–specific IgEs were reported to restrict cancer cell growth by engaging high-affinity Fc receptors on monocytes and macrophages; however, the underlying therapeutic mechanisms were undefined and in vivo proof of concept was limited. Here, an immunocompetent rat model was designed to recapitulate the human IgE-Fcϵ receptor system for cancer studies. We also generated rat IgE and IgG mAbs specific for the folate receptor (FRα), which is expressed widely on human ovarian tumors, along with a syngeneic rat tumor model expressing human FRα. Compared with IgG, anti-FRα IgE reduced lung metastases. This effect was associated with increased intratumoral infiltration by TNFα+ and CD80+ macrophages plus elevated TNFα and the macrophage chemoattractant MCP-1 in lung bronchoalveolar lavage fluid. Increased levels of TNFα and MCP-1 correlated with IgE-mediated tumor cytotoxicity by human monocytes and with longer patient survival in clinical specimens of ovarian cancer. Monocytes responded to IgE but not IgG exposure by upregulating TNFα, which in turn induced MCP-1 production by monocytes and tumor cells to promote a monocyte chemotactic response. Conversely, blocking TNFα receptor signaling abrogated induction of MCP-1, implicating it in the antitumor effects of IgE. Overall, these findings show how antitumor IgE reprograms monocytes and macrophages in the tumor microenvironment, encouraging the clinical use of IgE antibody technology to attack cancer beyond the present exclusive reliance on IgG. Cancer Res; 77(5); 1127–41. ©2017 AACR.
Comparison of Triage Strategies for HPV-Positive Women: Canadian Cervical Cancer Screening Trial Results
Authors: Isidean Sandra D. , Mayrand Marie-Hélène , Ramanakumar Agnihotram V. , Rodrigues Isabel , Ferenczy Alex , Ratnam Sam , Coutlée François , Franco Eduardo L. 
Published: January 2017

Abstract
Background: High-risk human papillomavirus (HR-HPV) testing has become a preferred cervical cancer screening strategy in some countries due to its superior sensitivity over cytology-based methods for identifying cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). Improved sensitivity has been accompanied by reductions in specificity and concerns regarding overscreening and overtreatment of women with transient or nonprogressing HR-HPV infections. Triage of HR-HPV+ women to colposcopy is, thus, warranted for appropriate management and treatment.
Methods: Using data from the Canadian Cervical Cancer Screening Trial (CCCaST), we compared the performance of cytology and HR-HPV strategies to detect CIN2+ among HR-HPV+ women (age, 30–69 years). Colposcopy referral rates and performance gains from adding other HR-HPV genotypes to HPV16/18+ triage were also evaluated.
Results: A strategy referring all women HPV16/18+ and HPV16/18−, but with atypical squamous cells of undetermined significance or worse cytology (ASC-US+) had the highest sensitivity [82.5%; 95% confidence interval (CI), 70.9%–91.0%] but yielded the highest colposcopy referral rate. HPV16/18+ triage was the next most sensitive strategy (64.1%; 95% CI, 51.1%–75.7%). Low-grade squamous intraepithelial lesion or worse cytology (LSIL+) triage yielded a low sensitivity (32.8%; 95% CI, 21.9%–45.4%) but had the most favorable specificity (93.6%; 95% CI, 91.0%–95.6%), positive predictive value (41.5%; 95% CI, 28.1%–55.9%), and colposcopy referral rate of strategies examined. HPV viral load triage strategies did not perform optimally overall. Inclusion of HR-HPV genotypes 31 and 52 to HPV16/18+ triage provided the highest sensitivities.
Conclusion: Concerns surrounding HPV-based screening can be effectively mitigated via triage.
Impact: Balancing the benefits of HPV-based primary cervical screening with informed management recommendations for HR-HPV+ women may decide the success of its widening utilization. Cancer Epidemiol Biomarkers Prev; 26(6); 923–9. ©2017 AACR.
In Hepatocellular Carcinoma miR-221 Modulates Sorafenib Resistance through Inhibition of Caspase-3–Mediated Apoptosis
Authors: Fornari Francesca , Pollutri Daniela , Patrizi Clarissa , La Bella Tiziana , Marinelli Sara , Casadei Gardini Andrea , Marisi Giorgia , Baron Toaldo Marco , Baglioni Michele , Salvatore Veronica , Callegari Elisa , Baldassarre Maurizio , Galassi Marzia , Giovannini Catia , Cescon Matteo , Ravaioli Matteo , Negrini Massimo , Bolondi Luigi , Gramantieri Laura 
Published: January 2017

Abstract
Purpose: The aberrant expression of miR-221 is a hallmark of human cancers, including hepatocellular carcinoma (HCC), and its involvement in drug resistance, together with a proved in vivo efficacy of anti-miR-221 molecules, strengthen its role as an attractive target candidate in the oncologic field. The discovery of biomarkers predicting the response to treatments represents a clinical challenge in the personalized treatment era. This study aimed to investigate the possible role of miR-221 as a circulating biomarker in HCC patients undergoing sorafenib treatment as well as to evaluate its contribution to sorafenib resistance in advanced HCC.
Experimental Design: A chemically induced HCC rat model and a xenograft mouse model, together with HCC-derived cell lines were employed to analyze miR-221 modulation by Sorafenib treatment. Data from the functional analysis were validated in tissue samples from surgically resected HCCs. The variation of circulating miR-221 levels in relation to Sorafenib treatment were assayed in the animal models and in two independent cohorts of patients with advanced HCC.
Results: MiR-221 over-expression was associated with Sorafenib resistance in two HCC animal models and caspase-3 was identified as its target gene, driving miR-221 anti-apoptotic activity following Sorafenib administration. Lower pre-treatment miR-221 serum levels were found in patients subsequently experiencing response to Sorafenib and an increase of circulating miR-221 at the two months assessment was observed in responder patients.
Conclusions: MiR-221 might represent a candidate biomarker of likelihood of response to Sorafenib in HCC patients to be tested in future studies. Caspase-3 modulation by miR-221 participates to Sorafenib resistance. Clin Cancer Res; 23(14); 3953–65. ©2017 AACR.
Activation of TRPA1 Channel by Antibacterial Agent Triclosan Induces VEGF Secretion in Human Prostate Cancer Stromal Cells
Authors: Derouiche Sandra , Mariot Pascal , Warnier Marine , Vancauwenberghe Eric , Bidaux Gabriel , Gosset Pierre , Mauroy Brigitte , Bonnal Jean-Louis , Slomianny Christian , Delcourt Philippe , Dewailly Etienne , Prevarskaya Natalia , Roudbaraki Morad 
Published: January 2017

Abstract
Accruing evidence indicates that exposure to environmental compounds may adversely affect human health and promote carcinogenesis. Triclosan (TCS), an antimicrobial agent widely used as a preservative in personal care products, has been shown to act as an endocrine disruptor in hormone-dependent tissues. Here, we demonstrate a new molecular mechanism by which TCS stimulates the secretion by human prostate cancer stromal cells of vascular endothelial growth factor (VEGF), a factor known to promote tumor growth. This mechanism involves an increase in intracellular calcium levels due to the direct activation of a membrane ion channel. Using calcium imaging and electrophysiology techniques, we show for the first time that environmentally relevant concentrations of TCS activate a cation channel of the TRP family, TRPA1 (Transient Receptor Potential Ankirin 1), in primary cultured human prostate cancer stromal cells. The TCS-induced TRPA1 activation increased basal calcium in stromal cells and stimulated the secretion of VEGF and epithelial cells proliferation. Interestingly, immunofluorescence labeling performed on formalin-fixed paraffin-embedded prostate tissues showed an exclusive expression of the TRPA1 channel in prostate cancer stromal cells. Our data demonstrate an impact of the environmental factor TCS on the tumor microenvironment interactions, by activating a tumor stroma-specific TRPA1 ion channel. Cancer Prev Res; 10(3); 177–87. ©2017 AACR.
Hospital Variation in Functional Recovery After Stroke
Authors: Bettger Janet Prvu , Thomas Laine , Liang Li , Xian Ying , Bushnell Cheryl D. , Saver Jeffrey L. , Fonarow Gregg C. , Peterson Eric D. 
Published: January 2017

Background—
Functional status is a key patient-centric outcome, but there are little data on whether functional recovery post-stroke varies among hospitals. This study examined the distribution of functional status 3 months after stroke, determined whether these outcomes vary among hospitals, and identified hospital characteristics associated with better (or worse) functional outcomes.

Methods and Results—
Observational analysis of the AVAIL study (Adherence Evaluation After Ischemic Stroke-Longitudinal) included 2083 ischemic stroke patients enrolled from 82 US hospitals participating in Get With The Guidelines-Stroke and AVAIL. The primary outcome was dependence or death at 3 months (modified Rankin Scale [mRS] score of 3–6). Secondary outcomes included functional dependence (mRS score of 3–5), disabled (mRS score of 2–5), and mRS evaluated as a continuous score. By 3 months post-discharge, 36.5% of patients were functionally dependent or dead. Rates of dependence or death varied widely by discharging hospitals (range: 0%–67%). After risk adjustment, patients had lower rates of 3-month dependence or death when treated at teaching hospitals (odds ratio, 0.72; 95% confidence interval, 0.54–0.96) and certified primary stroke centers (odds ratio, 0.69; 95% confidence interval, 0.53–0.91). In contrast, a composite measure of hospital-level adherence to acute stroke care performance metrics, stroke volume, and bed size was not associated with downstream patient functional status. Findings were robust across mRS end points and sensitivity analyses.

Conclusions—
One third of acute ischemic stroke patients were functionally dependent or dead 3 months postacute stroke; functional recovery rates varied considerably among hospitals, supporting the need to better determine which care processes can maximize functional outcomes.
Atrial Fibrillation Diagnosis Timing, Ambulatory ECG Monitoring Utilization, and Risk of Recurrent Stroke
Authors: Lip Gregory Y. H. , Hunter Tina D. , Quiroz Maria E. , Ziegler Paul D. , Turakhia Mintu P. 
Published: January 2017

Background—
The risk of recurrence after an initial ischemic stroke or transient ischemic attack (TIA) may be impacted by undiagnosed atrial fibrillation (AF). We therefore assessed the impact of AF diagnosis and timing on stroke/TIA recurrence rates in a large real-world sample of patients.

Methods and Results—

Using commercial claims data (Truven Health Analytics MarketScan), we performed a retrospective cohort study of patients with an index stroke or TIA event recorded in years 2008 through 2011. Patients were characterized by baseline oral anticoagulation, CHADS
2
and CHA
2
DS
2
-VASc scores, AF diagnosis and timing with respect to the index stroke, and presence or absence of post-index ambulatory cardiac monitoring. The primary outcome was the recurrence of an ischemic stroke or TIA. Of 179 160 patients (age 67±16.2 years; 53.7% female), the Kaplan-Meier estimate for stroke/TIA recurrence within 1 year was 10.6%. Not having oral anticoagulation prescribed at baseline and having AF first diagnosed >7 days post-stroke (late AF) was highly associated with recurrent stroke/TIA (hazard ratio, 2.0; 95% confidence interval, 1.9–2.1). Among patients with at least 1 year of follow-up, only 2.6% and 9.7% had ambulatory ECG monitoring in the 7 days and 12 months post-stroke, respectively.

Conclusions—
AF diagnosed after stroke is an important hallmark of recurrent stroke risk. Increasing the low utilization of cardiac monitoring after stroke could identify undiagnosed AF earlier, leading to appropriate oral anticoagulation treatment and a reduction in stroke/TIA recurrence.
Racial and Ethnic Differences in Antihypertensive Medication Use and Blood Pressure Control Among US Adults With Hypertension
Authors: Gu Anna , Yue Yu , Desai Raj P. , Argulian Edgar 
Published: January 2017

Background—
A key to reduce and eradicate racial disparities in hypertension outcomes is to understand their causes. We aimed at evaluating racial differences in antihypertensive drug utilization patterns and blood pressure control by insurance status, age, sex, and presence of comorbidities.

Methods and Results—
A total of 8796 hypertensive individuals ≥18 years of age were identified from the National Health and Nutrition Examination Survey (2003–2012) in a repeated cross-sectional study. During the study period, all 3 racial groups (whites, blacks, and Hispanics) experienced substantial increase in hypertension treatment and control. The overall treatment rates were 73.9% (95% confidence interval [CI], 71.6%–76.2%), 70.8% (95% CI, 68.6%–73.0%), and 60.7% (95% CI, 57.0%–64.3%) and hypertension control rates were 42.9% (95% CI, 40.5%–45.2%), 36.9% (95% CI, 34.7%–39.2%), and 31.2% (95% CI, 28.6%–33.9%) for whites, blacks, and Hispanics, respectively. When stratified by insurance status, blacks (odds ratio, 0.74 [95% CI, 0.64–0.86] for insured and 0.59 [95% CI, 0.36–0.94] for uninsured) and Hispanics (odds ratio, 0.74 [95% CI, 0.60–0.91] for insured and 0.58 [95% CI, 0.36–0.94] for uninsured) persistently had lower rates of hypertension control compared with whites. Racial disparities also persisted in subgroups stratified by age (≥60 and <60 years of age) and presence of comorbidities but worsened among patients <60 years of age.

Conclusions—
Black and Hispanic patients had poorer hypertension control compared with whites, and these differences were more pronounced in younger and uninsured patients. Although black patients received more intensive antihypertensive therapy, Hispanics were undertreated. Future studies should further explore all aspects of these disparities to improve cardiovascular outcomes.
Use of Strategies to Improve Door-to-Needle Times With Tissue-Type Plasminogen Activator in Acute Ischemic Stroke in Clinical Practice
Authors: Xian Ying , Xu Haolin , Lytle Barbara , Blevins Jason , Peterson Eric D. , Hernandez Adrian F. , Smith Eric E. , Saver Jeffrey L. , Messé Steven R. , Paulsen Mary , Suter Robert E. , Reeves Mathew J. , Jauch Edward C. , Schwamm Lee H. , Fonarow Gregg C. 
Published: January 2017

Background—
The implementation of Target: Stroke Phase I, the first stage of the American Heart Association’s national quality improvement initiative to accelerate door-to-needle (DTN) times, was associated with an average 15-minute reduction in DTN times. Target: Stroke phase II was launched in April 2014 with a goal of promoting further reduction in treatment times for tissue-type plasminogen activator (tPA) administration.

Methods and Results—
We conducted a second survey of Get With The Guidelines-Stroke hospitals regarding strategies used to reduce delays after Target: Stroke and quantify their association with DTN times. A total of 16 901 ischemic stroke patients were treated with intravenous tPA within 4.5 hours of symptom onset from 888 surveyed hospitals between June 2014 and April 2015. The patient-level median DTN time was 56 minutes (interquartile range, 42–75), with 59.3% of patients receiving intravenous tPA within 60 minutes and 30.4% within 45 minutes after hospital arrival. Most hospitals reported routinely using a majority of Target: Stroke key practice strategies, although direct transport of patients to computed tomographic/magenetic resonance imaging scanner, premix of tPA ahead of time, initiation of tPA in brain imaging suite, and prompt data feedback to emergency medical services providers were used less frequently. Overall, we identified 16 strategies associated with significant reductions in DTN times. Combined, a total of 20 minutes (95% confidence intervals 15–25 minutes) could be saved if all strategies were implemented.

Conclusions—
Get With The Guidelines-Stroke hospitals have initiated a majority of Target: Stroke–recommended strategies to reduce DTN times in acute ischemic stroke. Nevertheless, certain strategies were infrequently practiced and represent a potential immediate target for further improvements.
High‐Saturated‐Fat Diet Increases Circulating Angiotensin‐Converting Enzyme, Which Is Enhanced by the rs4343 Polymorphism Defining Persons at Risk of Nutrient‐Dependent Increases of Blood Pressure
Authors: Schüler Rita , Osterhoff Martin A. , Frahnow Turid , Seltmann Anne‐Cathrin , Busjahn Andreas , Kabisch Stefan , Xu Li , Mosig Alexander S. , Spranger Joachim , Möhlig Matthias , Hornemann Silke , Kruse Michael , Pfeiffer Andreas F. H. 
Published: January 2017

Background

Angiotensin‐converting enzyme (
ACE
) plays a major role in blood pressure regulation and cardiovascular homeostasis. Contrary to the assumption that
ACE
levels are stable, circulating
ACE
has been shown to be altered in obesity and weight loss. We sought to examine effects of a high‐saturated‐fat (
HF
) diet on
ACE
within the
NU
triGenomic Analysis in Twins (
NUGAT
) study.

Methods and Results

Forty‐six healthy and nonobese twin pairs initially consumed a carbohydrate‐rich, low‐fat diet over a period of 6 weeks to standardize for nutritional behavior prior to the study, followed by 6 weeks of
HF
diet under isocaloric conditions. After 6 weeks of
HF
diet, circulating
ACE
concentrations increased by 15% (
P
=1.6×10
−30
), accompanied by an increased
ACE
gene expression in adipose tissue (
P
=3.8×10
−6
). Stratification by
ACE
rs4343, a proxy for the
ACE
insertion/deletion polymorphism (I/D), revealed that homozygous carriers (
GG
) of the variant had higher baseline
ACE
concentrations (
P
=7.5×10
−8
) and additionally showed a 2‐fold increase in
ACE
concentrations in response to the
HF
diet as compared to non‐ or heterozygous carriers (
AA
/
AG
,
P
=2×10
−6
).
GG
carriers also responded with higher systolic blood pressure as compared to
AA
/
AG
carriers (
P=
0.008). The strong gene‐diet interaction was confirmed in a second independent, cross‐sectional cohort, the Metabolic Syndrome Berlin Potsdam (MeSyBePo) study.

Conclusions

The
HF
‐diet‐induced increase of
ACE
serum concentrations reveals
ACE
to be a potential molecular link between dietary fat intake and hypertension and cardiovascular disease (
CVD
). The
GG
genotype of the
ACE
rs4343 polymorphism represents a robust nutrigenetic marker for an unfavorable response to high‐saturated‐fat diets.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01631123.
Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Peripheral Artery Disease: Insights From the ARISTOTLE Trial
Authors: Hu Peter T. , Lopes Renato D. , Stevens Susanna R. , Wallentin Lars , Thomas Laine , Alexander John H. , Hanna Michael , Lewis Basil S. , Verheugt Freek W. A. , Granger Christopher B. , Jones W. Schuyler 
Published: January 2017

Background

We studied (1) the rates of stroke or systemic embolism and bleeding in patients with atrial fibrillation and peripheral artery disease (
PAD
) and (2) the efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation with and without
PAD
.

Methods and Results

The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin for stroke/systemic embolism prevention; 884 (4.9%) patients had
PAD
at baseline. Patients with
PAD
had higher unadjusted rates of stroke and systemic embolism (hazard ratio [
HR
] 1.73, 95%
CI
1.22–2.45;
P
=0.002) and major bleeding (
HR
1.34, 95%
CI
1.00–1.81;
P
=0.05), but after adjustment, no differences existed in rates of stroke and systemic embolism (
HR
1.32, 95%
CI
0.93–1.88;
P
=0.12) and major bleeding (
HR
1.03, 95%
CI
0.76–1.40;
P
=0.83) compared with patients without
PAD
. The risk of stroke or systemic embolism was similar in patients assigned to apixaban and warfarin with
PAD
(
HR
0.63, 95%
CI
0.32–1.25) and without
PAD
(
HR
0.80, 95%
CI
0.66–0.96; interaction
P
=0.52). Patients with
PAD
did not have a statistically significant reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin (
HR
1.05, 95%
CI
0.69–1.58), whereas those without
PAD
had a statistically significant reduction (
HR
0.65, 95%
CI
0.58–0.73; interaction
P
=0.03).

Conclusions

Patients with
PAD
in
ARISTOTLE
had a higher crude risk of stroke or systemic embolism compared with patients without
PAD
that was not present after adjustment. The benefits of apixaban versus warfarin for stroke and systemic embolism were similar in patients with and without
PAD
. These findings highlight the need to optimize the treatment of patients with atrial fibrillation and
PAD
.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00412984.
Comparisons of Global Terrestrial Surface Water Datasets over 15 Years
Authors: Pham-Duc Binh , Prigent Catherine , Aires Filipe , Papa Fabrice 
Published: January 2017

Abstract
Continental surface water extents and dynamics are key information to model Earth’s hydrological and biochemical cycles. This study presents global and regional comparisons between two multisatellite surface water extent datasets, the Global Inundation Extent from Multi-Satellites (GIEMS) and the Surface Water Microwave Product Series (SWAMPS), for the 1993–2007 period, along with two widely used static inundation datasets, the Global Lakes and Wetlands Database (GLWD) and the Matthews and Fung wetland estimates. Maximum surface water extents derived from these datasets are largely different: ~13 × 106 km2 from GLWD, ~5.3 × 106 km2 from Matthews and Fung, ~6.2 × 106 km2 from GIEMS, and ~10.3 × 106 km2 from SWAMPS. SWAMPS global maximum surface extent reduces by nearly 51% (to ~5 × 106 km2) when applying a coastal filter, showing a strong contamination in this retrieval over the coastal regions. Anomalous surface waters are also detected with SWAMPS over desert areas. The seasonal amplitude of the GIEMS surface waters is much larger than the SWAMPS estimates, and GIEMS dynamics is more consistent with other hydrological variables such as the river discharge. Over the Amazon basin, GIEMS and SWAMPS show a very high time series correlation (95%), but with SWAMPS maximum extent half the size of that from GIEMS and from previous synthetic aperture radar estimates. Over the Niger basin, SWAMPS seasonal cycle is out of phase with both GIEMS and MODIS-derived water extent estimates, as well as with river discharge data.