bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationale and Preclinical Efficacy of a Novel Anti-EMP2 Antibody for the Treatment of Invasive Breast Cancer
Authors: Fu Maoyong , Maresh Erin L. , Helguera Gustavo F. , Kiyohara Meagan , Qin Yu , Ashki Negin , Daniels-Wells Tracy R. , Aziz Najib , Gordon Lynn K. , Braun Jonathan , Elshimali Yahya , Soslow Robert A. , Penichet Manuel L. , Goodglick Lee , Wadehra Madhuri 
Published: January 2014

Abstract
Despite significant advances in biology and medicine, the incidence and mortality due to breast cancer worldwide is still unacceptably high. Thus, there is an urgent need to discover new molecular targets. In this article, we show evidence for a novel target in human breast cancer, the tetraspan protein epithelial membrane protein-2 (EMP2). Using tissue tumor arrays, protein expression of EMP2 was measured and found to be minimal in normal mammary tissue, but it was upregulated in 63% of invasive breast cancer tumors and in 73% of triple-negative tumors tested. To test the hypothesis that EMP2 may be a suitable target for therapy, we constructed a fully human immunoglobulin G1 (IgG1) antibody specific for a conserved domain of human and murine EMP2. Treatment of breast cancer cells with the anti-EMP2 IgG1 significantly inhibited EMP2-mediated signaling, blocked FAK/Src signaling, inhibited invasion, and promoted apoptosis in vitro. In both human xenograft and syngeneic metastatic tumor monotherapy models, anti-EMP2 IgG1 retarded tumor growth without detectable systemic toxicity. This antitumor effect was, in part, attributable to a potent antibody-dependent cell-mediated cytotoxicity response as well as direct cytotoxicity induced by the monoclonal antibody. Together, these results identify EMP2 as a novel therapeutic target for invasive breast cancer. Mol Cancer Ther; 13(4); 902–15. ©2014 AACR.
Decreased miR-340 Expression in Bone Marrow Is Associated with Liver Metastasis of Colorectal Cancer
Authors: Takeyama Hiroshi , Yamamoto Hirofumi , Yamashita Shinya , Wu Xin , Takahashi Hidekazu , Nishimura Junichi , Haraguchi Naotsugu , Miyake Yasuhiro , Suzuki Rei , Murata Kohei , Ohue Masayuki , Kato Takeshi , Takemasa Ichiro , Mizushima Tsunekazu , Ishii Hideshi , Mimori Koshi , Doki Yuichiro , Mori Masaki 
Published: January 2014

Abstract
Studies have shown the prognostic significance of disseminated tumor cells (DTC) in bone marrow of patients with colorectal cancer. However, the molecular characteristics of DTCs, including their miRNA expression profiles, remain mostly unknown. In this study, we analyzed the miRNA expression of DTCs in bone marrow. EpCAM+ bone marrow cells were collected using immunomagnetic beads after exclusion of CD14+ and CD45+ cells, then subjected to miRNA microarray analysis. Cluster analysis (7 colorectal cancer patients with liver metastasis and 12 colorectal cancer patients without liver metastasis) indicated that miR-340 and miR-542-3p expressions were significantly decreased in EpCAM+ bone marrow cells of patients with liver metastasis (P = 0.019 and 0.037, respectively). We demonstrated that pre-miR-340 administration inhibited growth of colon cancer cells and suppressed c-Met expression in vitro. In clinical samples of colorectal cancer, miR-340 was expressed at significantly lower levels in tumor tissues compared with normal mucosa. Survival analysis in 136 patients with colorectal cancer indicated that low miR-340 expression was correlated with shorter 5-year disease-free survival (P = 0.023) and poor 5-year overall survival (P = 0.046). It was of note that the colorectal cancer group with low miR-340 and high c-Met expression had the worst prognosis. We further demonstrated that systemic pre-miR-340 administration suppressed growth of pre-established HCT116 tumors in animal therapeutic models. These findings indicate that miR-340 may be useful as a novel prognostic factor and as a therapeutic tool against colorectal cancer. Our data suggest that miR-340 in bone marrow may play an important role in regulating the metastasis cascade of colorectal cancer. Mol Cancer Ther; 13(4); 976–85. ©2014 AACR.
Utilization of Liquid Chromatography Mass Spectrometry Analyses to Identify LKB1–APC Interaction in Modulating Wnt/β-Catenin Pathway of Lung Cancer Cells
Authors: Jian Shu-Fang , Hsiao Chang-Chun , Chen Shin-Yi , Weng Ching-Chieh , Kuo Tzu-Lei , Wu Deng-Chyang , Hung Wen-Chun , Cheng Kuang-Hung 
Published: January 2014

Abstract
STK11/LKB1, a serine/threonine protein kinase and tumor suppressor, is a key upstream kinase of adenine monophosphate-activated protein kinase, which is a kinase involved in controlling cell polarity and maintaining cellular energy homeostasis. LKB1 is mutated in a significant number of Peutz–Jeghers syndrome (PJS) cases and sporadic cancers, and is most frequently mutated in lung adenocarcinomas; however, little is known about how LKB1 is involved in lung cancer progression. In this study, immunoprecipitation-HPLC tandem mass spectrometry (IP-LC-MS/MS) was performed to identify novel proteins interacting with LKB1 in lung cancer. Interestingly, many LKB1-interacting proteins acquired from the LC-MS/MS approach were mapped, using MetaCore pathway analysis, to the cystic fibrosis transmembrane conductance regulator activation pathway. Moreover, it was determined that LKB1 directly interacts with APC, and this LKB1–APC interaction was further confirmed by reverse immunoprecipitation assays, but GSK3β was dispensable for the association of LKB1 and APC. Importantly, LKB1 binds to APC to suppress the Wnt/β-catenin signaling pathway, which is known to be involved in cell proliferation and migration. Subsequent analysis of the downstream targets of the Wnt/TCF pathway led to the identification of several Wnt-regulated genes, such as CD44, COX-2, survivin, and c-Myc, whose expression levels are downregulated by LKB1. In summary, these results demonstrate that LKB1 regulates the Wnt pathway through a direct interaction with APC to suppress the tumorigenic/metastatic potential of lung tumors.
Implications: LKB1 status influences the molecular circuitry (Wnt/β-catenin pathway), cellular biology, and may serve as a potential therapeutic node in genetically defined subsets of lung cancer. Mol Cancer Res; 12(4); 622–35. ©2014 AACR.
PI3K-AKT Signaling Is a Downstream Effector of Retinoid Prevention of Murine Basal Cell Carcinogenesis
Authors: So Po-Lin , Wang Grace Y. , Wang Kevin , Chuang Mindy , Chiueh Venice Calinisan , Kenny Paraic A. , Epstein Ervin H. 
Published: January 2014

Abstract
Basal cell carcinoma (BCC) is the most common human cancer. We have demonstrated previously that topical application of the retinoid prodrug tazarotene profoundly inhibits murine BCC carcinogenesis via retinoic acid receptor γ–mediated regulation of tumor cell transcription. Because topical retinoids can cause adverse cutaneous effects and because tumors can develop resistance to retinoids, we have investigated mechanisms downstream of tazarotene's antitumor effect in this model. Specifically we have used (i) global expression profiling to identify and (ii) functional cell-based assays to validate the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway as a downstream target pathway of tazarotene's action. Crucially, we have demonstrated that pharmacologic inhibition of this downstream pathway profoundly reduces murine BCC cell proliferation and tumorigenesis both in vitro and in vivo. These data identify PI3K/AKT/mTOR signaling as a highly attractive target for BCC chemoprevention and indicate more generally that this pathway may be, in some contexts, an important mediator of retinoid anticancer effects. Cancer Prev Res; 7(4); 407–17. ©2014 AACR.
Piper Betel Leaf: A Reservoir of Potential Xenohormetic Nutraceuticals with Cancer-Fighting Properties
Authors: Gundala Sushma R. , Aneja Ritu 
Published: January 2014

Abstract
Plants contain a much greater diversity of bioactive compounds than any man-made chemical library. Heart-shaped Piper betel leaves are magnificent reservoirs of phenolic compounds with antiproliferative, antimutagenic, antibacterial, and antioxidant properties. Widely consumed in South Asian countries, the glossy leaf contains a multitude of biophenolics such as hydroxychavicol, eugenol, chavibetol, and piperols. Convincing data underscore the remarkable chemotherapeutic and chemopreventive potential of betel leaves against a variety of cancer types. The leaf constituents modulate an extensive array of signaling molecules such as transcription factors as well as reactive oxygen species (ROS) to control multiple nodes of various cellular proliferation and death pathways. Herein, we provide an overall perspective on the cancer-fighting benefits of the phenolic phytochemicals in betel leaves and a comprehensive overview of the mechanisms responsive to dose-driven ROS-mediated signaling cascades conscripted by bioactive phenolics to confer chemotherapeutic and chemopreventive advantages. Intriguingly, these ROS-triggered responses are contextual and may either elicit a protective xenohormetic antioxidant response to premalignant cells to constitute a chemopreventive effect or generate a curative chemotherapeutic response by pro-oxidatively augmenting the constitutively elevated ROS levels in cancer cells to tip the balance in favor of selective apoptosis induction in cancer cells while sparing normal ones. In conclusion, this review provides an update on how distinct ROS levels exist in normal versus cancer cells and how these levels can be strategically modulated and exploited for therapeutic gains. We emphasize the yet untapped potential of the evergreen vine, betel leaf, for chemopreventive and chemotherapeutic management of cancer. Cancer Prev Res; 7(5); 477–86. ©2014 AACR.
Comparison of the Serum Lipidome in Patients With Abdominal Aortic Aneurysm and Peripheral Artery Disease
Authors: Moxon Joseph V. , Liu Dawei , Wong Gerard , Weir Jacquelyn M. , Behl-Gilhotra Ratnesh , Bradshaw Barbara , Kingwell Bronwyn A. , Meikle Peter J. , Golledge Jonathan 
Published: January 2014

Background—
Currently, the relationship between circulating lipids and abdominal aortic aneurysm (AAA) is unclear. We conducted a lipidomic analysis to identify serum lipids associated with AAA presence. Secondary analyses assessed the ability of models incorporating lipidomic features to improve stratification of patient groups with and without AAA beyond traditional risk factors.

Methods and Results—

Serum lipids were profiled via liquid chromatography tandem mass spectrometry analysis of serum from 161 patients with AAA and 168 controls with peripheral artery disease. Binary logistic regression was used to identify AAA-associated lipids. Classification models were created based on a combination of (1) traditional risk factors only or (2) lipidomic features and traditional risk factors. Model performance was assessed using receiver operator characteristic curves. Three diacylglycerols and 7 triacylglycerols were associated with AAA. Combining lipidomic features with traditional risk factors significantly improved stratification of AAA and peripheral artery disease groups when compared with traditional risk factors alone (mean area under the receiver operator characteristic curve [95% confidence interval], 0.760 [0.756–0.763] and 0.719 [0.716–0.723], respectively;
P
<0.05).

Conclusions—
A group of linoleic acid containing triacylglycerols and diacylglycerols were significantly associated with AAA presence. Inclusion of lipidomic features in multivariate analyses significantly improved prediction of AAA presence when compared with traditional risk factors alone.
A Flexible Parameterization for Shortwave Optical Properties of Ice Crystals*
Authors: van Diedenhoven Bastiaan , Ackerman Andrew S. , Cairns Brian , Fridlind Ann M. 
Published: January 2014

AbstractA parameterization is presented that provides extinction cross section σe, single-scattering albedo ω, and asymmetry parameter g of ice crystals for any combination of volume, projected area, aspect ratio, and crystal distortion at any wavelength in the shortwave. Similar to previous parameterizations, the scheme makes use of geometric optics approximations and the observation that optical properties of complex, aggregated ice crystals can be well approximated by those of single hexagonal crystals with varying size, aspect ratio, and distortion levels. In the standard geometric optics implementation used here, σe is always twice the particle projected area. It is shown that ω is largely determined by the newly defined absorption size parameter and the particle aspect ratio. These dependences are parameterized using a combination of exponential, lognormal, and polynomial functions. The variation of g with aspect ratio and crystal distortion is parameterized for one reference wavelength using a combination of several polynomials. The dependences of g on refractive index and ω are investigated and factors are determined to scale the parameterized g to provide values appropriate for other wavelengths. The parameterization scheme consists of only 88 coefficients. The scheme is tested for a large variety of hexagonal crystals in several wavelength bands from 0.2 to 4 μm, revealing absolute differences with reference calculations of ω and g that are both generally below 0.015. Over a large variety of cloud conditions, the resulting root-mean-squared differences with reference calculations of cloud reflectance, transmittance, and absorptance are 1.4%, 1.1%, and 3.4%, respectively. Some practical applications of the parameterization in atmospheric models are highlighted.
Assessing the Risk of Persistent Drought Using Climate Model Simulations and Paleoclimate Data
Authors: Ault Toby R. , Cole Julia E. , Overpeck Jonathan T. , Pederson Gregory T. , Meko David M. 
Published: January 2014

Abstract
Projected changes in global rainfall patterns will likely alter water supplies and ecosystems in semiarid regions during the coming century. Instrumental and paleoclimate data indicate that natural hydroclimate fluctuations tend to be more energetic at low (multidecadal to multicentury) than at high (interannual) frequencies. State-of-the-art global climate models do not capture this characteristic of hydroclimate variability, suggesting that the models underestimate the risk of future persistent droughts. Methods are developed here for assessing the risk of such events in the coming century using climate model projections as well as observational (paleoclimate) information. Where instrumental and paleoclimate data are reliable, these methods may provide a more complete view of prolonged drought risk. In the U.S. Southwest, for instance, state-of-the-art climate model projections suggest the risk of a decade-scale megadrought in the coming century is less than 50%; the analysis herein suggests that the risk is at least 80%, and may be higher than 90% in certain areas. The likelihood of longer-lived events (&gt;35 yr) is between 20% and 50%, and the risk of an unprecedented 50-yr megadrought is nonnegligible under the most severe warming scenario (5%–10%). These findings are important to consider as adaptation and mitigation strategies are developed to cope with regional impacts of climate change, where population growth is high and multidecadal megadrought—worse than anything seen during the last 2000 years—would pose unprecedented challenges to water resources in the region.
The Potential for Mesoscale Visibility Predictions with a Multimodel Ensemble
Authors: Ryerson William R. , Hacker Joshua P. 
Published: January 2014

Abstract
This work examines the viability of producing short-range (&lt;20 h) probabilistic fog predictions in remote locations, absent an observational history, using an uncalibrated 4-km, 10-member Weather Research and Forecasting Model (WRF) ensemble configured to closely match the Air Force Weather Agency Mesoscale Ensemble Forecast Suite. Three distinct sources of error in the final predictions are considered separately to facilitate a better understanding of the total error and appropriate mitigation strategies. These include initial condition error, parameterization of subgrid-scale processes, and error in the visibility parameterization used to convert NWP model output variables to visibility. The raw WRF predictions are generally not skillful in valley and coastal regions, where they produce a shortage of light fog predictions with visibilities of 1–7 mi (1.6–11.3 km) in favor of excessive forecasts of zero cloud water, corresponding to no fog. Initial condition error and visibility parameterization error are shown to play a relatively minor role compared to error in the parameterization of subgrid-scale processes. This deficiency is caused by a negative relative humidity bias, which results from a warm overnight bias. A second-order source of error arises from an inconsistent delineation of fog and haze in the NWP model compared to the verifying observations. Results show that under most conditions it is necessary to deviate from the perfect-prog assumption, and to introduce some method of statistical postprocessing to obtain skillful visibility predictions from the ensemble.
Comparison of LDL-cholesterol estimate using the Friedewald formula and the newly proposed de Cordova formula with a directly measured LDL-cholesterol in a healthy South African population
Authors: Onyenekwu Chinelo P , Hoffmann Mariza , Smit Francois , Matsha Tandi E , Erasmus Rajiv T 
Published: January 2014

Background The accurate determination of low density lipoprotein cholesterol (LDL-c) is pertinent in clinical practice. Most laboratories employ the Friedewald formula, for convenient estimation of LDL-c, despite its shortfalls. Different formulae have been proposed for use, for more accurate but convenient estimation of LDL-c. Here, we compare a new formula recently proposed by de Cordova et al., with that of Friedewald and LDL-c determined by a homogeneous assay. We also assess its performance at very low TG levels against the modified Friedewald formula recommended by Ahmadi et al. Methods A database of 587 adults from the ‘Establishing Reference Intervals for Selected Analytes in South Africa’ study was utilized. Fasting samples were assayed for lipids. LDL-c was determined by the Daiichi method. Performance of the Friedewald and the de Cordova formulae was compared. This was exclusively repeated at very low TG levels (<1.13 mmol/L), this time, including the Ahmadi formula. Results The Friedewald formula and the de Cordova formula both had high correlations with the direct LDL-c ( r = 0.98 and r = 0.97, respectively), although the latter showed an inconsistent bias at different LDL-c levels. The two formulae had a higher correlation ( r = 0.98) than the Ahmadi formula ( r = 0.92) at very low TG levels. Conclusions The Friedewald formula showed better agreement with the direct LDL-c than the de Cordova formula, at various LDL-c levels, in our population. It also performed better than the Ahmadi formula at very low TG levels. We therefore advise that it remains the formula of choice for LDL-c estimation in South Africa.
Sizing Firefighters
Authors: Hsiao Hongwei , Whitestone Jennifer , Kau Tsui-Ying , Whisler Richard , Routley J. Gordon , Wilbur Michael 
Published: January 2014

Objective: This article reports new anthropometric information of U.S. firefighters for fire apparatus design applications (Study 1) and presents a data method to assist in firefighter anthropometric data usage for research-to-practice propositions (Study 2). Background: Up-to-date anthropometric information of the U.S. firefighter population is needed for updating ergonomic and safety specifications for fire apparatus. Method: A stratified sampling plan of three-age by three-race/ethnicity combinations was used to collect anthropometric data of 863 male and 88 female firefighters across the U.S. regions; 71 anthropometric dimensions were measured (Study 1). Differences among original, weighted, and normality transformed data from Study 1 were compared to allowable observer errors (Study 2). Results: On average, male firefighters were 9.8 kg heavier and female firefighters were 29 mm taller than their counterparts in the general U.S. population. They also have larger upper-body builds than those of the general U.S. population. The data in weighted, unweighted, and normality transformed modes were compatible among each other with a few exceptions. Conclusion: The data obtained in this study provide the first available U.S. national firefighter anthropometric information for fire apparatus designs. The data represent the demographic characteristics of the current firefighter population and, except for a few dimensions, can be directly employed into fire apparatus design applications without major weighting or nonnormality concerns. Application: The up-to-date firefighter anthropometric data and data method will benefit the design of future fire apparatus and protective equipment, such as seats, body restraints, cabs, gloves, and bunker gear.
Radiofrequency ablation of atrial fibrillation during mitral valve surgery
Authors: Oueida Farouk , Elawady Mohamed Ahmed , Eskander Khalid 
Published: January 2014

Objectives Atrial fibrillation is the most common form of arrhythmia in mitral valve disease. Radiofrequency ablation is most commonly used for atrial fibrillation ablation during mitral valve surgery. Methods This prospective study evaluated the midterm outcomes of intraoperative radiofrequency atrial fibrillation ablation during mitral valve surgery. Results 52 patients were eligible for the study. Fifteen (28.8%) had a transseptal approach and 37 had a left atriotomy. Mitral valve replacement was performed in 16 patients, mitral valve repair in 31, and tricuspid repair in 8. Mean crossclamp time was 58.14. ± 20.08 min, and mean cardiopulmonary bypass time was 71.28 ± 20.31 min. The mean ablation time was 6.41 ± 0.21 min. There was no postoperative mortality. Sinus rhythm was documented in 44 (84.6%) patients on discharge, and 8 (15.4%) were discharged with atrial fibrillation; 2 of them returned to sinus rhythm after 3 months. After 12 months of follow-up, 46 (88.5%) patients were in sinus rhythm. Conclusion Left atrial monopolar radiofrequency ablation during mitral valve surgery is a safe procedure with a high success rate.
Long-term results of an open flexible prosthetic band for mitral insufficiency
Authors: Pragliola Claudio , Chello Massimo , Gaudino Mario , Mazza Andrea , Cellini Carlo , Spadaccio Cristiano , Covino Elvio 
Published: January 2014

Background use of a prosthetic ring is an integral part of any mitral valve repair and can influence the long-term stability of the results. We evaluated the long-term results of the AnnuloFlex ring implanted as an open flexible band in patients affected by degenerative mitral disease. Methods between 2001 and 2010, 82 patients (52 women, 30 men) with a mean age of 62 years, underwent repair of a prolapsing mitral valve with an AnnuloFlex band. One patient was reoperated on for a technical error and received a mechanical prosthesis, 3 were missing at follow-up, and the other 78 were prospectively followed up with clinical interviews and transthoracic echocardiography. Results the mean follow-up was 7.0 ± 1.8 years. Six patients died; 2 deaths were considered valve-related. The overall survival estimate at 10 years was 88.6% (95% confidence interval: 76.1%–94.8%). Freedom from endocarditis was 97.1% (95% confidence interval: 89.1%–98.5%). Freedom from thrombosis or hemorrhage was 93.7% (95% confidence interval: 81.6%–97.9%). Freedom from new or increased regurgitation was 93.1% (95% confidence interval: 87.3%–97.3%). The cumulative freedom from any valve-related event was 78.6% (95% confidence interval: 69.7%–97.1%). A single case of systolic anterior motion occurred before hospital discharge. Conclusion the long-term results of the AnnuloFlex band are excellent and stable.