bluuebunny/crossref_metadata_2025_split huggingface dataset:
Snail1-Expressing Fibroblasts in the Tumor Microenvironment Display Mechanical Properties That Support Metastasis
Authors: Stanisavljevic Jelena , Loubat-Casanovas Jordina , Herrera Mercedes , Luque Tomás , Peña Raúl , Lluch Ana , Albanell Joan , Bonilla Félix , Rovira Ana , Peña Cristina , Navajas Daniel , Rojo Federico , García de Herreros Antonio , Baulida Josep 
Published: December 2014

Abstract
Crosstalk between tumor and stromal cells in the tumor microenvironment alter its properties in ways that facilitate the invasive behavior of tumor cells. Here, we demonstrate that cancer-associated fibroblasts (CAF) increase the stiffness of the extracellular matrix (ECM) and promote anisotropic fiber orientation, two mechanical signals generated through a Snail1/RhoA/αSMA–dependent mechanism that sustains oriented tumor cell migration and invasiveness. Snail1-depleted CAF failed to acquire myofibroblastic traits in response to TGFβ, including RhoA activation, αSMA-positive stress fibers, increased fibronectin fibrillogenesis, and production of a stiff ECM with oriented fibers. Snail1 expression in human tumor–derived CAF was associated with an ability to organize the ECM. In coculture, a relatively smaller number of Snail1-expressing CAF were capable of imposing an anisotropic ECM architecture, compared with nonactivated fibroblasts. Pathologically, human breast cancers with Snail1+ CAF tended to exhibit desmoplastic areas with anisotropic fibers, lymph node involvement, and poorer outcomes. Snail1 involvement in driving an ordered ECM was further confirmed in wound-healing experiments in mice, with Snail1 depletion preventing the anisotropic organization of granulation tissue and delaying wound healing. Overall, our results showed that inhibiting Snail1 function in CAF could prevent tumor-driven ECM reorganization and cancer invasion. Cancer Res; 75(2); 284–95. ©2014 AACR.
miR30a Inhibits LOX Expression and Anaplastic Thyroid Cancer Progression
Authors: Boufraqech Myriem , Nilubol Naris , Zhang Lisa , Gara Sudheer Kumar , Sadowski Samira M. , Mehta Amit , He Mei , Davis Sean , Dreiling Jennifer , Copland John A. , Smallridge Robert C. , Quezado Martha M. , Kebebew Electron 
Published: December 2014

Abstract
Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies, but its genetic drivers remain little understood. In this study, we report losses in expression of the miRNA miR30a, which is downregulated in ATC compared with differentiated thyroid cancer and normal tissue. miR30a downregulation was associated with advanced differentiated thyroid cancer and higher mortality. Mechanistically, we found miR30a decreased cellular invasion and migration, epithelial–mesenchymal transition marker levels, lysyl oxidase (LOX) expression, and metastatic capacity. LOX was identified as a direct target of miR30a that was overexpressed in ATC and associated with advanced differentiated thyroid cancer and higher mortality rate. Consistent with its role in other cancers, we found that LOX inhibited cell proliferation, cellular invasion, and migration and metastasis in vitro and in vivo. Together, our findings establish a critical functional role for miR30a downregulation in mediating LOX upregulation and thyroid cancer progression, with implications for LOX targeting as a rational therapeutic strategy in ATC. Cancer Res; 75(2); 367–77. ©2014 AACR.
Preclinical Characterization of RSM-932A, a Novel Anticancer Drug Targeting the Human Choline Kinase Alpha, an Enzyme Involved in Increased Lipid Metabolism of Cancer Cells
Authors: Lacal Juan Carlos , Campos Joaquín M. 
Published: December 2014

Abstract
Choline kinase α (CHKA; here designated as ChoKα) is the first enzyme in the CDP-choline pathway, implicated in phospholipids metabolism. It is overexpressed in several human tumors such as breast, lung, bladder, colorectal, prostate, ovary, and liver. The overexpression of ChoKα has oncogenic potential and synergizes with other known oncogenes. It has been proposed as a novel cancer drug target with a distinct mechanism of action. We have generated a set of ChoKα inhibitors with potent in vitro antiproliferative and in vivo antitumoral activity against human xenografts in mice, showing high efficacy with low toxicity profiles. Among these inhibitors, RSM-932A has been chosen for further clinical development due to its potent antiproliferative activity in vitro against a large variety of tumor-derived cell lines, a potent in vivo anticancer activity, and lack of toxicity at the effective doses. Here, we provide the preclinical evidence to support the use of RSM-932A as a good candidate to be tested in clinical trials as the “first in humans” drug targeting ChoKα. Mol Cancer Ther; 14(1); 31–39. ©2014 AACR.
The Effect of Hurricane Sandy on Cardiovascular Events in New Jersey
Authors: Swerdel Joel N. , Janevic Teresa M. , Cosgrove Nora M. , Kostis John B. ,   the Myocardial Infarction Data Acquisition System (MIDAS 24) Study Group
Published: December 2014

Background

Hurricane Sandy made landfall in New Jersey (
NJ
) on October 29, 2012. We studied the impact of this extreme weather event on the incidence of, and 30‐day mortality from, cardiovascular (CV) events (
CVEs
), including myocardial infarctions (
MI
) and strokes, in
NJ
.

Methods and Results

Data were obtained from the MI data acquisition system (
MIDAS
), a database of all inpatient hospital discharges with CV diagnoses in
NJ,
including death certificates. Patients were grouped by their county of residence, and each county was categorized as either high‐ (41.5% of the
NJ
population) or low‐impact area based on data from the Federal Emergency Management Agency and other sources. We utilized Poisson regression comparing the 2 weeks following Sandy landfall with the same weeks from the 5 previous years. In addition, we used
CVE
data from the 2 weeks previous in each year as to adjust for yearly changes. In the high‐impact area,
MI
incidence increased by 22%, compared to previous years (attributable rate ratio [
ARR]
, 1.22; 95% confidence interval [
CI],
1.16, 1.28), with a 31% increase in 30‐day mortality (
ARR,
1.31; 95%
CI,
1.22, 1.41). The incidence of stroke increased by 7% (
ARR,
1.07; 95%
CI,
1.03, 1.11), with no significant change in 30‐day stroke mortality. There were no changes in incidence or 30‐day mortality of
MI
or stroke in the low‐impact area.

Conclusion

In the 2 weeks following Hurricane Sandy, there were increases in the incidence of, and 30‐day mortality from,
MI
and in the incidence of stroke.
Removing Diurnal Cycle Contamination in Satellite-Derived Tropospheric Temperatures: Understanding Tropical Tropospheric Trend Discrepancies
Authors: Po-Chedley Stephen , Thorsen Tyler J. , Fu Qiang 
Published: December 2014

Abstract
Independent research teams have constructed long-term tropical time series of the temperature of the middle troposphere (TMT) using satellite Microwave Sounding Unit (MSU) and Advanced MSU (AMSU) measurements. Despite careful efforts to homogenize the MSU/AMSU measurements, tropical TMT trends beginning in 1979 disagree by more than a factor of 3. Previous studies suggest that the discrepancy in tropical TMT trends is caused by differences in both the NOAA-9 warm target factor and diurnal drift corrections. This work introduces a new observationally based method for removing biases related to satellite diurnal drift. Over land, the derived diurnal correction is similar to a general circulation model (GCM) diurnal cycle. Over ocean, the diurnal corrections have a negligible effect on TMT trends, indicating that oceanic biases are small. It is demonstrated that this method is effective at removing biases between coorbiting satellites and biases between nodes of individual satellites. Using a homogenized TMT dataset, the ratio of tropical tropospheric temperature trends relative to surface temperature trends is in accord with the ratio from GCMs. It is shown that bias corrections for diurnal drift based on a GCM produce tropical trends very similar to those from the observationally based correction, with a trend difference smaller than 0.02 K decade−1. Differences between various TMT datasets are explored further. Large differences in tropical TMT trends between this work and that of the University of Alabama in Huntsville (UAH) are attributed to differences in the treatment of the NOAA-9 target factor and the diurnal cycle correction.
North American Pancontinental Droughts in Model Simulations of the Last Millennium*
Authors: Coats Sloan , Cook Benjamin I. , Smerdon Jason E. , Seager Richard 
Published: December 2014

Abstract
Pancontinental droughts in North America, or droughts that simultaneously affect a large percentage of the geographically and climatically distinct regions of the continent, present significant on-the-ground management challenges and, as such, are an important target for scientific research. The methodology of paleoclimate-model data comparisons is used herein to provide a more comprehensive understanding of pancontinental drought dynamics. Models are found to simulate pancontinental drought with the frequency and spatial patterns exhibited by the paleoclimate record. They do not, however, agree on the modes of atmosphere–ocean variability that produce pancontinental droughts because simulated El Niño–Southern Oscillation (ENSO), Pacific decadal oscillation (PDO), and Atlantic multidecadal oscillation (AMO) dynamics, and their teleconnections to North America, are different between models and observations. Despite these dynamical differences, models are able to reproduce large-magnitude centennial-scale variability in the frequency of pancontinental drought occurrence—an important feature of the paleoclimate record. These changes do not appear to be tied to exogenous forcing, suggesting that simulated internal hydroclimate variability on these time scales is large in magnitude. Results clarify our understanding of the dynamics that produce real-world pancontinental droughts while assessing the ability of models to accurately characterize future drought risks.
Interannual and Interdecadal Variability of the Number of Cold Days in Hong Kong and Their Relationship with Large-Scale Circulation
Authors: Cheung Hoffman H. N. , Zhou Wen , Lee Sai-ming , Tong Hang-wai 
Published: December 2014

Abstract
During the past decade (2004/05–2013/14), the number of cold days in Hong Kong (NCD), as a proxy of the temperature of southern China, appeared to have increased from the historical minimum, in contrast to a remarkable decline in the entire postwar period. This is related to the recent apparent changes in the large-scale circulation upstream and downstream of the East Asian winter monsoon (EAWM) region: the increase in Ural blocking (UB) that enhances cold advection from the polar region and reinforces the Siberian high and the decrease in a western Pacific (WP)-like index that corresponds to increasing meridional gradient of geopotential height over the EAWM region. Overall, UB and WP account for 26.4% of the interannual (≤8 yr) variance and 83.7% of the decadal (&gt;8 yr) variance of NCD for the period 1948/49–2013/14, indicating that further study could lead to improvement in the prediction of NCD.
A normal polymorphism site of TLR2 3′ untranslated region is related to rheumatic heart disease by up-regulating TLR2 expression
Authors: Li Yanhua , Zhang Shu , Xu Wenhuan , Guo Xinhong , Xu Qiang , Chen Yundai 
Published: December 2014

Background The worldwide incidence of rheumatic heart disease is at least 15.6 million cases and is responsible for around 233,000 deaths per year. The pathogenesis of rheumatic heart disease is complex and involves genetic factors that predispose a person to the development of autoimmune reactions. Although Arg753Gln polymorphism of the TLR2 gene was considered to be related to acute rheumatic fever susceptibility in child, two groups have identified that there were no relations between this Arg753Gln polymorphism and rheumatic heart disease susceptibility. Methods In this study, we scanned the full length 826 bp of 3′ untranslated region of TLR2 in a Chinese-Han population and found that the rare allele G of rs35514500 was highly related to rheumatic heart disease. Results Results of dual-luciferase assay indicated that this T->G variation weakens the interaction between miR-340 and TLR2 3′ untranslated region and up-regulated firefly luciferase expression. Further results about the patients’ serum cytokines concentration detection constructed a relationship between G allele of rs35514550 and up-regulated serum IL-6 and TNFα. Conclusions These findings may give insight into understanding of rheumatic heart disease development and create an opportunity to approach the diagnosis and treatment of rheumatic heart disease.
Serum protein electrophoresis patterns in human immunodeficiency virus-infected individuals not on antiretroviral treatment
Authors: Zemlin Annalise E , Ipp Hayley , Maleka Sechaba , Erasmus Rajiv T 
Published: December 2014

Background B lymphocyte stimulation is described in human immunodeficiency virus (HIV) infection and results in ongoing immunoglobulin production with abnormal serum protein electrophoresis patterns. We hypothesized that serum protein electrophoresis patterns would be abnormal in untreated HIV subjects and correlate with markers of disease severity. Methods Serum protein electrophoresis was performed on 70 HIV-positive, clinically well treatment-naïve subjects and 42 HIV-negative controls and correlated with markers of disease severity, namely CD4+ counts, viral loads, IgG and albumin. Results The mean age for both groups was 33 years, and female-to-male ratios were 4:1. All were of Black ethnicity. Mean CD4 counts ± SD for HIV group and controls were 419.5 ± 218.6 and 960.4 ± 378.5 cells/mm3, respectively. Of the HIV-infected group, 44% showed polyclonal hypergammaglobulinaemia versus 10% of controls ( P < 0.01). The HIV group had 27% with an abnormal pattern requiring immunofixation which revealed nine (12.5% of total) had oligoclonal bands, seven (10.3% of total) had polyclonal hypergammaglobulinaemia and three (4% of total) had monoclonal bands. CD4+ counts were lower in those with polyclonal hypergammaglobulinaemia or abnormal serum protein electrophoresis. Interestingly, viral load results showed no statistically significant differences. Conclusion We found a remarkably high level (53%) of polyclonal hypergammaglobulinaemia in our untreated population compared with uninfected controls (10%). Only 4% of the HIV-positive group had a monoclonal band. Polyclonal hypergammaglobulinaemia correlated significantly with lower CD4+ counts. These results highlight the generalized B cell stimulation in untreated HIV infection. Future longitudinal studies will be important to determine the prognostic value of these findings.
A Randomized Controlled Trial to Provide Adherence Information and Motivational Interviewing to Improve Diabetes and Lipid Control
Authors: Pladevall Manel , Divine George , Wells Karen E. , Resnicow Ken , Williams L. Keoki 
Published: December 2014

Purpose The purpose of this study was to assess whether providing medication adherence information with or without motivational interviewing improves diabetes and lipid control. Methods Study participants were adult members of a health system in southeast Michigan, were using both oral diabetes and lipid-lowering medications, and had glycated hemoglobin (A1C) or low-density lipoprotein cholesterol (LDL-C) levels not at goal. Participants were randomly assigned to receive usual care (UC), n = 567; have medication adherence information (AI) provided to their physician, n = 569; or have AI and receive motivational interviewing (MI) though trained staff (AI + MI), n = 556. Primary outcomes were A1C and LDL-C levels at 18 months post randomization. Results Primary outcomes were not significantly different between patients in the AI or AI + MI study arms when compared with UC. Similarly, neither oral diabetes nor lipid-lowering medication adherence was significantly different between groups. Patient participation in the AI + MI arm was low and limit the interpretation of the study results, but post hoc analysis of the AI + MI study arm showed that the number of MI sessions received was positively associated with only oral diabetes medication adherence. Conclusion Neither AI nor MI significantly improved diabetes and lipid control when compared with UC. Moreover, patient participation appeared to be a particular barrier for MI.
A survey of clinician attitudes and self-reported practices regarding end-of-life care in heart failure
Authors: Dunlay Shannon M , Foxen Jilian L , Cole Terese , Feely Molly A , Loth Ann R , Strand Jacob J , Wagner Jean A , Swetz Keith M , Redfield Margaret M 
Published: December 2014

Background: As heart failure often follows an unpredictable clinical trajectory, there has been an impetus to promote iterative patient-provider discussions regarding prognosis and preferences for end-of-life care. Aim: To examine clinicians’ practices, expectations, and personal level of confidence in discussing goals of care and providing end-of-life care to their patients with heart failure. Design: Multi-site clinician survey. Setting and Participants: Physicians, nurse practitioners, and physician assistants at Mayo Clinic (Rochester, Minnesota, USA) and its surrounding health system were asked to participate in an electronic survey in October 2013. Tertiary Care Cardiology, Community Cardiology, and Primary Care clinicians were surveyed. Results: A total of 95 clinicians participated (52.5% response rate). Only 12% of clinicians reported having annual end-of-life discussions as advocated by the American Heart Association. In total, 52% of clinicians hesitated to discuss end-of-life care citing provider discomfort (11%), perception of patient (21%) or family (12%) unreadiness, fear of destroying hope (9%), or lack of time (8%). Tertiary and Community Cardiology clinicians (66%) attributed responsibility for end-of-life discussions to the heart failure cardiologist, while 66% of Primary Care clinicians felt it was their responsibility. Overall, 30% of clinicians reported a low or very low level of confidence in one or more of the following: initiating prognosis or end-of-life discussions, enrolling patients in hospice, or providing end-of-life care. Most clinicians expressed interest in further skills acquisition. Conclusion: Clinicians vary in their views and approaches to end-of-life discussions and care. Some lack confidence and most are interested in further skills acquisition.
Role of low dose CT angiography in the follow-up after endovascular aneurysm repair of abdominal aorta
Authors: Macchi Monica , Floridi Chiara , Strocchi Sabina , Fontana Federico , Mangini Monica , Piacentino Filippo , Duka Ejona , Donati Alberto V , Fugazzola Carlo 
Published: December 2014

Background Computed tomography angiography (CTA) is the most employed modality in the follow-up after endovascular aneurysm repair (EVAR) of abdominal aorta (AA); repeated standard controls expose patients to a high cumulative radiation dose (RD). Purpose To compare image quality and RD between 100 kV and 120 kV protocols in the same group of patients, previously treated with EVAR. Material and Methods Thirty patients, who had performed a previous CTA at 120 kV, underwent a low dose CTA with the same 64-detector machine. Images were evaluated qualitatively and quantitatively. The influence of body mass index (BMI), considering three groups of patients (normal weight, overweight, and obese) was also assessed. RD values (volume CT dose index and effective dose) were calculated. Results The mean qualitative score at 100 kV was worse than that at 120 kV, but the difference was not statistically significant and in all cases the image quality was satisfactory. At 100 kV the vessels mean attenuation value was significantly higher; signal-to-noise ratio significantly lower; contrast-to-noise ratio lower, but the difference was not significant. Regarding BMI, the difference in the qualitative score was significant in the obese group, but not in the other two groups; of the quantitative parameters only the signal-to-noise ratio presented a significant difference in the obese group. The average CTDIvol was reduced by 22% and the mean effective dose by 36% with the 100 kV protocol compared to the 120 kV protocol. Both differences were significant. Conclusion The 100 kV protocol allowed a consistent RD reduction, maintaining a satisfactory image quality in all patients.
Relationship between tumour angiogenesis and expression of cyclo-oxygenase-2 and vascular endothelial growth factor-A in human renal cell carcinoma
Authors: Yang Sheng , Gao Qin , Jiang Wei 
Published: December 2014

Objective *These authors contributed equally to this work. To study the relationship between tumour angiogenesis and expression of cyclo-oxygenase ( COX)-2 and vascular endothelial growth factor ( VEGF)-A in human renal cell carcinoma. Methods Archival samples of primary human renal cell carcinoma tissue and surrounding normal renal tissue (control samples) obtained from patients diagnosed with renal cell carcinoma were analysed for COX-2 and VEGF-A expression by immunohistochemistry using specific monoclonal antibodies. Tumour microvasculature was examined using factor VIII-related antigen antibody staining. Results A total of 33 renal cell carcinoma and 12 control renal tissue specimens were included. COX-2 and VEGF-A genes were overexpressed in tumour specimens compared with normal epithelia. A significant correlation was found between COX-2 and VEGF-A expression. Microvessel density was found to be increased in tumour tissues that expressed COX-2 and VEGF-A. Conclusion Microvessel density was increased in tumour tissues that expressed COX-2 and VEGF-A, suggesting that COX-2 and VEGF-A are related to tumour angiogenesis in human renal cell carcinoma.
Right or duty of information
Authors: Nunes Sofia RT , Rego Guilhermina , Nunes Rui 
Published: December 2014

Background: The theoretical framework of Jϋrgen Habermas suggests that effective communication requires competent participants with an objective attitude that complies with the rules and worlds designated as objective, social and subjective. This situation determines communicative action, which stimulates the search for mutual understanding and results in a process of interaction that promotes self-determination. Objectives: In this study, the discharge letters of patients with myocardial infarction were explored regarding the provision of information. The patient’s right to information and the duty of informing were analysed according to the perspective of Jϋrgen Habermas. Research design: This was a cross-sectional analysis (from a broader longitudinal study) of all discharge letters that were directly related to nursing interventions regarding the provision of information to 106 patients. In this major study, the difficulties faced by patients who experienced a myocardial infarction and the changes in their lifestyles were analysed based on the type of information received. Ethical considerations: The hospital Ethics Committee approved the study, which complied with ethical principles and required informed consent. Findings: In the nursing letters, interventions related to the provision of information were conducted at an average of 3.59 interventions per patient. For 8.5% of the patients, however, no interventions related to the provision of information were performed. The most common area of information during hospitalisation was related to the management of signs and symptoms and applied to 90.6% patients. Discussion: The nursing interventions did not cover patient education, transition processes or awareness of the disease. Thus, the right to information can be questioned. Conclusion: Information is a right, and communication is extremely important. Health professionals should be aware of this importance regarding both care management and the satisfaction guarantee. The sharing of information by health professionals based on their competency is essential for patients to exercise their right to self-determination and decision-making.