bluuebunny/crossref_metadata_2025_split huggingface dataset:
The PSTD Method with the 4th-Order Time Integration for 3D TAT Reconstruction of a Breast Model
Authors: Ye Gang , Deng Chunhua , Liu Qing Huo 
Published: June 2014

The thermoacoustic tomography (TAT) is a novel noninvasive and nonionizing medical imaging modality for breast cancer detection. In the TAT, a short pulse of microwave is irradiated to the breast tissue. The tissue absorbs the microwave energy and is heated up momentarily, thus it generates acoustic waves due to the thermoelastic expansion. If the pulse width of the microwave radiation is around one microsecond, the generated acoustic waves are ultrasonic and are in the MHz range. Wide-band ultrasonic transducers are employed to acquire the time-resolved ultrasound signals, which carry information about the microwave absorption properties (mainly related to conductivities) of different tissues. An image showing such properties can then be reconstructed from the time-resolved ultrasound signals. Most existing TAT reconstruction methods are based on the assumption that the tissue under study is acoustically homogeneous. In practice, however, most biological tissues are inhomogeneous. For example, the speed of sound has about 10% variation in breast tissue. The acoustic heterogeneity will cause phase distortion of the pressure field, which will in turn cause blurring in the reconstructed image, thus limiting the ability to resolve small objects. In this work, a 3D inhomogeneous reconstruction method based on pseudo-spectral time-domain (PSTD) is presented to overcome this problem. The method includes two steps. The first step is a homogeneous reconstruction process, from which an initial image is obtained. Since the inhomogeneity itself is usually an acoustic source, the shape and location of the inhomogeneity can be estimated. Then, the acoustic properties of the inhomogeneities (available from the literatures for known tissue types) are assigned to the classified regions, and the other reconstruction based on the updated acoustic property map is conducted. With this process, the phase distortion can be effectively corrected. So it can improve the ability to image small objects. A 3D breast phantom is used to study the proposed method. The breast phantom was generated based on the data set of the Visible Human Project. Regions of different tissue types have been classified and acoustic and electric properties are assigned to such regions. Small phantom tumors placed in the breast phantom have been reconstructed successfully with the inhomogeneous reconstruction method. Improved resolution has been achieved compared to that obtained by homogeneous method.
A note on the elliptic Kirchhoff equation in ℝNperturbed by a local nonlinearity
Authors: Azzollini A. 
Published: June 2014

In this note, we complete the study made in [The elliptic Kirchhoff equation in ℝNperturbed by a local nonlinearity, Differential Integral Equations 25 (2012) 543–554] on a Kirchhoff type equation with a Berestycki–Lions nonlinearity. We also correct Theorem 0.6 inside.
TRIM29 Suppresses TWIST1 and Invasive Breast Cancer Behavior
Authors: Ai Lingbao , Kim Wan-Ju , Alpay Merve , Tang Ming , Pardo Carolina E. , Hatakeyama Shigetsugu , May W. Stratford , Kladde Michael P. , Heldermon Coy D. , Siegel Erin M. , Brown Kevin D. 
Published: June 2014

Abstract
TRIM29 (ATDC) exhibits a contextual function in cancer, but seems to exert a tumor-suppressor role in breast cancer. Here, we show that TRIM29 is often silenced in primary breast tumors and cultured tumor cells as a result of aberrant gene hypermethylation. RNAi-mediated silencing of TRIM29 in breast tumor cells increased their motility, invasiveness, and proliferation in a manner associated with increased expression of mesenchymal markers (N-cadherin and vimentin), decreased expression of epithelial markers (E-cadherin and EpCAM), and increased expression and activity of the oncogenic transcription factor TWIST1, an important driver of the epithelial–mesenchymal transition (EMT). Functional investigations revealed an inverse relationship in the expression of TRIM29 and TWIST1, suggesting the existence of a negative regulatory feedback loop. In support of this relationship, we found that TWIST1 inhibited TRIM29 promoter activity through direct binding to a region containing a cluster of consensus E-box elements, arguing that TWIST1 transcriptionally represses TRIM29 expression. Analysis of a public breast cancer gene-expression database indicated that reduced TRIM29 expression was associated with reduced relapse-free survival, increased tumor size, grade, and metastatic characteristics. Taken together, our results suggest that TRIM29 acts as a tumor suppressor in breast cancer through its ability to inhibit TWIST1 and suppress EMT. Cancer Res; 74(17); 4875–87. ©2014 AACR.
Neuronal Pentraxin 2 Supports Clear Cell Renal Cell Carcinoma by Activating the AMPA-Selective Glutamate Receptor-4
Authors: von Roemeling Christina A. , Radisky Derek C. , Marlow Laura A. , Cooper Simon J. , Grebe Stefan K. , Anastasiadis Panagiotis Z. , Tun Han W. , Copland John A. 
Published: June 2014

Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and has the highest propensity to manifest as metastatic disease. Recent characterizations of the genetic signature of ccRCC have revealed several factors correlated with tumor cell migration and invasion; however, the specific events driving malignancy are not well defined. Furthermore, there remains a lack of targeted therapies that result in long-term, sustainable response in patients with metastatic disease. We show here that neuronal pentraxin 2 (NPTX2) is overexpressed specifically in ccRCC primary tumors and metastases, and that it contributes to tumor cell viability and promotes cell migration through its interaction with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR4. We propose NPTX2 as a novel molecular target for therapy for patients with ccRCC diagnosed with or at risk of developing metastatic disease. Cancer Res; 74(17); 4796–810. ©2014 AACR.
Pentraxin 3: A Novel Biomarker for Predicting Progression from Prostatic Inflammation to Prostate Cancer
Authors: Stallone Giovanni , Cormio Luigi , Netti Giuseppe Stefano , Infante Barbara , Selvaggio Oscar , Fino Giuseppe Di , Ranieri Elena , Bruno Francesca , Prattichizzo Clelia , Sanguedolce Francesca , Tortorella Simona , Bufo Pantaleo , Grandaliano Giuseppe , Carrieri Giuseppe 
Published: June 2014

Abstract
Pentraxin-3 (PTX3) is a member of the pentraxin family of innate immune regulators, which includes C-reactive protein (CRP). PTX3 has been implicated in angiogenesis, proliferation, and immune escape in cancer. In the present study, we evaluated PTX3 tissue expression and serum concentration as a biomarker to discriminate prostatic inflammation and benign prostatic hyperplasia (BPH) from prostate cancer, and to determine whether PTX3 status may predict progression from BPH to prostate cancer. We analyzed 40 patients with biopsy-proven BPH who underwent a second prostate biopsy 12 to 36 months later when they were diagnosed with prostate cancer or inflammation/BPH (n = 20 patients each group). Furthermore, we evaluated PTX3 serum concentrations in an independent set of patients with biopsy-proven inflammation/BPH (n = 61) and prostate cancer (n = 56). We found reduced PTX3 tissue expression in patients with prostatic inflammation/BPH compared with patients who developed prostate cancer. In the latter group, there was an increase in PTX3 tissue expression between the first and second prostate biopsy. PTX3 serum levels were also higher in patients with prostate cancer than in patients with inflammation/BPH. In contrast, there was no difference in serum PSA or CRP levels in these two groups. ROC curve analysis confirmed the reliability of PTX3 serum levels in predicting prostate cancer development, identifying a cutoff value of 3.25 ng/mL with a sensitivity and a specificity of 89.3% and 88.5%, respectively. In summary, our results encourage further evaluation of PTX3 as a tissue biopsy and blood-borne biomarker to discriminate BPH from prostate cancer. Cancer Res; 74(16); 4230–8. ©2014 AACR.
Association of Insulin-Related Serum Factors with Colorectal Polyp Number and Type in Adult Males
Authors: Comstock Sarah S. , Xu Diana , Hortos Kari , Kovan Bruce , McCaskey Sarah , Pathak Dorothy R. , Fenton Jenifer I. 
Published: June 2014

Abstract
Background: Dysregulated insulin signaling is thought to contribute to cancer risk.
Methods: To determine if insulin-related serum factors are associated with colon polyps, 126 asymptomatic men (48–65 years) were recruited at colonoscopy. Blood was collected. Odds ratios were determined using polytomous logistic regression for polyp number and type.
Results: Males with serum C-peptide concentration &gt;3.3 ng/mL were 3.8 times more likely to have an adenoma relative to no polyp than those with C-peptide ≤1.8 ng/mL. As C-peptide tertile increased, an individual was 2 times more likely to have an adenoma (P = 0.01) than no polyp. There were no associations between insulin-like growth factor or its binding proteins with polyp number or type. Males with soluble receptor for advanced glycation end products (sRAGE) concentration &gt;120.4 pg/mL were 0.25 times less likely to have ≥3 polyps relative to no polyps compared with males with sRAGE ≤94.5 pg/mL. For each increase in sRAGE tertile, a man was 0.5 times less likely to have ≥3 polyps than no polyps (P = 0.03). Compared with males with a serum vascular endothelial growth factor (VEGF) concentration ≤104.7 pg/mL, males with a serum VEGF concentration &gt;184.2 pg/mL were 3.4 times more likely to have ≥3 polyps relative to no polyps. As the VEGF tertile increased, a man was 1.9 times more likely to have ≥3 polyps than no polyps (P = 0.049).
Conclusions: Serum concentrations of C-peptide, sRAGE, and VEGF may indicate which men could benefit most from colonoscopy.
Impact: Identification of biomarkers could reduce medical costs through the elimination of colonoscopies on low-risk individuals. Cancer Epidemiol Biomarkers Prev; 23(9); 1843–51. ©2014 AACR.
Reversible LSD1 Inhibition Interferes with Global EWS/ETS Transcriptional Activity and Impedes Ewing Sarcoma Tumor Growth
Authors: Sankar Savita , Theisen Emily R. , Bearss Jared , Mulvihill Timothy , Hoffman Laura M. , Sorna Venkataswamy , Beckerle Mary C. , Sharma Sunil , Lessnick Stephen L. 
Published: June 2014

Abstract
Purpose: Ewing sarcoma is a pediatric bone tumor that absolutely relies on the transcriptional activity of the EWS/ETS family of fusion oncoproteins. While the most common fusion, EWS/FLI, utilizes lysine-specific demethylase 1 (LSD1) to repress critical tumor suppressors, small-molecule blockade of LSD1 has not yet been thoroughly explored as a therapeutic approach for Ewing sarcoma. We therefore evaluated the translational potential of potent and specific LSD1 inhibition with HCI2509 on the transcriptional program of both EWS/FLI and EWS/ERG as well as the downstream oncogenic phenotypes driven by EWS/ETS fusions in both in vitro and in vivo models of Ewing sarcoma.
Experimental Design: RNA-seq was used to compare the transcriptional profiles of EWS/FLI, EWS/ERG, and treatment with HCI2509 in both EWS/FLI- and EWS/ERG-containing cell lines. We then evaluated morphologic phenotypes of treated cells with immunofluorescence. The induction of apoptosis was evaluated using caspase-3/7 activation and TUNEL staining. Colony forming assays were used to test oncogenic transformation and xenograft studies with patient-derived cell lines were used to evaluate the effects of HCI2509 on tumorigenesis.
Results: HCI2509 caused a dramatic reversal of both the up- and downregulated transcriptional profiles of EWS/FLI and EWS/ERG accompanied by the induction of apoptosis and disruption of morphologic and oncogenic phenotypes modulated by EWS/FLI. Importantly, HCI2509 displayed single-agent efficacy in multiple xenograft models.
Conclusions: These data support epigenetic modulation with HCI2509 as a therapeutic strategy for Ewing sarcoma, and highlight a critical dual role for LSD1 in the oncogenic transcriptional activity of EWS/ETS proteins. Clin Cancer Res; 20(17); 4584–97. ©2014 AACR.
Carcinogen-Induced Skin Tumor Development Requires Leukocytic Expression of the Transcription Factor Runx3
Authors: Bauer Omri , Hantisteanu Shay , Lotem Joseph , Groner Yoram 
Published: June 2014

Abstract
Carcinogen-induced skin tumorigenesis depends heavily on proinflammatory tumor-promoting processes. Here, we show that leukocytic Runx3 expression is central to the two-stage DMBA/TPA-induced skin tumorigenesis. Runx3-null mice were highly resistant to this process and concomitant ablation of Runx3 in dendritic and T cells fully recapitulated this resistance. Mechanistically, this resistance was associated with a shift in the skin cytokine milieu toward a tumor nonpermissive microenvironment. Specifically, leukocytic Runx3 loss substantially increased the antitumorigenic cytokine thymic stromal lymphopoietin (TSLP) and profoundly decreased two protumorigenic cytokines, interleukin-17a and osteopontin. Therefore, inflammation-mediated tumor promotion requires leukocytic Runx3 expression, as its loss creates a unique cytokine composition that polarizes the tumor microenvironment to a potent antitumorigenic state. Cancer Prev Res; 7(9); 913–26. ©2014 AACR.
Fibrosis-Related Biomarkers and Incident Cardiovascular Disease in Older Adults
Authors: Agarwal Isha , Glazer Nicole L. , Barasch Eddy , Biggs Mary L. , Djousse Luc , Fitzpatrick Annette L. , Gottdiener John S. , Ix Joachim H. , Kizer Jorge R. , Rimm Eric B. , Sicovick David S. , Tracy Russell P. , Mukamal Kenneth J. 
Published: June 2014

Background—
Fibrotic changes in the heart and arteries have been implicated in a diverse range of cardiovascular diseases (CVD), but whether circulating biomarkers that reflect fibrosis are associated with CVD is unknown.

Methods and Results—

We determined the associations of 2 biomarkers of fibrosis, transforming growth factor- β (TGF-β), and procollagen type III N-terminal propeptide (PIIINP), with incident heart failure, myocardial infarction, and stroke among community-living older adults in the Cardiovascular Health Study. We measured circulating TGF-β (n=1371) and PIIINP (n=2568) from plasma samples collected in 1996 and ascertained events through 2010. Given TGF-β’s pleiotropic effects on inflammation and fibrogenesis, we investigated potential effect modification by C-reactive protein in secondary analyses. After adjustment for sociodemographic, clinical, and biochemical risk factors, PIIINP was associated with total CVD (hazard ratio [HR] per SD=1.07; 95% confidence interval [CI], 1.01–1.14) and heart failure (HR per SD=1.08; CI, 1.01–1.16) but not myocardial infarction or stroke. TGF-β was not associated with any CVD outcomes in the full cohort but was associated with total CVD (HR per SD=1.16; CI, 1.02–1.31), heart failure (HR per SD=1.16; CI, 1.01–1.34), and stroke (HR per SD=1.20; CI, 1.01–1.42) among individuals with C-reactive protein above the median, 2.3 mg/L (
P
interaction <0.05).

Conclusions—
Our findings provide large-scale, prospective evidence that circulating biomarkers of fibrosis, measured in community-living individuals late in life, are associated with CVD. Further research on whether TGF-β has a stronger fibrogenic effect in the setting of inflammation is warranted.
Radial Versus Femoral Access Is Associated With Reduced Complications and Mortality in Patients With Non–ST-Segment–Elevation Myocardial Infarction
Authors: Iqbal M. Bilal , Arujuna Aruna , Ilsley Charles , Archbold Andrew , Crake Tom , Firoozi Sam , Kalra Sundeep , Knight Charles , Lim Pitt , Malik Iqbal S. , Mathur Anthony , Meier Pascal , Rakhit Roby D. , Redwood Simon , Whitbread Mark , Bromage Dan , Rathod Krishna , Wragg Andrew , MacCarthy Philip , Dalby Miles 
Published: June 2014

Background—
Compared with transfemoral access, transradial access (TRA) for percutaneous coronary intervention is associated with reduced risk of bleeding and vascular complications. Studies suggest that TRA may reduce mortality in patients with ST-segment–elevation myocardial infarction. However, there are few data on the effect of TRA on mortality, specifically, in patients with non–ST-segment–elevation myocardial infarction.

Methods and Results—

We analyzed 10 095 consecutive patients with non–ST-segment–elevation myocardial infarction treated with percutaneous coronary intervention between 2005 and 2011 in all 8 tertiary cardiac centers in London, United Kingdom. TRA was a predictor for reduced bleeding (odds ratio=0.21; 95% confidence interval [CI]: 0.08–0.57;
P
=0.002), access-site complications (odds ratio=0.47; 95% CI: 0.23–0.95;
P
=0.034), and 1-year mortality (hazard ratio [HR]=0.72; 95% CI: 0.54–0.94;
P
=0.017). Between 2005 and 2007, TRA did not appear to reduce mortality at 1 year (HR=0.81; 95% CI: 0.51–1.28;
P
=0.376), whereas between 2008 and 2011, TRA conferred survival benefit at 1 year (HR=0.65; 95% CI: 0.46–0.92;
P
=0.015). The mortality benefit with TRA at 1 year was not seen at the low-volume centers (HR=0.80; 95% CI: 0.47–1.38;
P
=0.428) but specifically seen in the high volume radial centers (HR=0.70; 95% CI: 0.51–0.97;
P
=0.031). In propensity-matched analyses, TRA remained a predictor for survival at 1 year (HR=0.60; 95% CI: 0.42–0.85;
P
=0.005). Instrumental variable analysis demonstrated that TRA conferred mortality benefit at 1-year with an absolute mortality reduction of 5.8% (
P
=0.039).

Conclusions—
In this analysis of patients with non–ST-segment–elevation myocardial infarction, TRA appears to be a predictor for survival. Furthermore, the evolving learning curve, experience, and expertise may be important factors contributing to the prognostic benefit conferred with TRA.
Dual-Contrast Molecular Imaging Allows Noninvasive Characterization of Myocardial Ischemia/Reperfusion Injury After Coronary Vessel Occlusion in Mice by Magnetic Resonance Imaging
Authors: von Elverfeldt Dominik , Maier Alexander , Duerschmied Daniel , Braig Moritz , Witsch Thilo , Wang Xiaowei , Mauler Maximilian , Neudorfer Irene , Menza Marius , Idzko Marco , Zirlik Andreas , Heidt Timo , Bronsert Peter , Bode Christoph , Peter Karlheinz , von zur Muhlen Constantin 
Published: June 2014

Background—
Inflammation and myocardial necrosis play important roles in ischemia/reperfusion injury after coronary artery occlusion and recanalization. The detection of inflammatory activity and the extent of myocardial necrosis itself are of great clinical and prognostic interest. We developed a dual, noninvasive imaging approach using molecular magnetic resonance imaging in an in vivo mouse model of myocardial ischemia and reperfusion.

Methods and Results—

Ischemia/reperfusion injury was induced in 10-week-old C57BL/6N mice by temporary ligation of the left anterior descending coronary artery. Activated platelets were targeted with a contrast agent consisting of microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody directed against a ligand-induced binding site (LIBS) on activated glycoprotein IIb/IIIa (LIBS-MPIOs). After injection and imaging of LIBS-MPIOs, late gadolinium enhancement was used to depict myocardial necrosis; these imaging experiments were also performed in P2Y
12
−/−
mice. All imaging results were correlated to immunohistochemistry findings. Activated platelets were detectable by magnetic resonance imaging via a significant signal effect caused by LIBS-MPIOs in the area of left anterior descending coronary artery occlusion 2 hours after reperfusion. In parallel, late gadolinium enhancement identified the extent of myocardial necrosis. Immunohistochemistry confirmed that LIBS-MPIOs bound significantly to microthrombi in reperfused myocardium. Only background binding was found in P2Y
12
−/−
mice.

Conclusions—
Dual molecular imaging of myocardial ischemia/reperfusion injury allows characterization of platelet-driven inflammation by LIBS-MPIOs and myocardial necrosis by late gadolinium enhancement. This noninvasive imaging strategy is of clinical interest for both diagnostic and prognostic purposes and highlights the potential of molecular magnetic resonance imaging for characterizing ischemia/reperfusion injury.
Race/Ethnic Differences in the Risk of Hemorrhagic Complications Among Patients With Ischemic Stroke Receiving Thrombolytic Therapy
Authors: Mehta Rajendra H. , Cox Margueritte , Smith Eric E. , Xian Ying , Bhatt Deepak L. , Fonarow Gregg C. , Peterson Eric D. 
Published: June 2014

Background and Purpose—
Race/ethnic-related differences in safety of intravenous thrombolytic therapy have been shown in patients with myocardial infarction, but not studied in ischemic stroke.

Methods—
Using data from the Get With The Guidelines (GWTG)-Stroke program (n=54 334), we evaluated differences in risk-adjusted bleeding rates (any, symptomatic intracerebral hemorrhage [sICH], serious life-threatening [excluding sICH], or other) and mortality in white (n=40 411), black (n=8243), Hispanic (n=4257), and Asian (n=1523) patients receiving intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke.

Results—
Compared with white patients, overall adjusted hemorrhagic complications after tPA were higher in black (odds ratio, 1.14, 95% confidence interval, 1.04–1.28) and Asian (odds ratio, 1.36, 95% confidence interval, 1.14–1.61) patients. Overall adjusted bleeding complications in Hispanics were similar to those of whites. Increased risk of overall bleeding in Asians was related to higher risk of adjusted sICH (odds ratio, 1.47, 95% confidence interval, 1.19–1.82), whereas in blacks, it was related to higher risk of other bleeding. No significant race-related difference was noted in risk of serious or life-threatening bleeding or in overall mortality or death in patients with sICH or any hemorrhagic complications.

Conclusions—
In patients with stroke receiving tPA, hemorrhagic complications were slightly higher in blacks and Asians, but not in Hispanics compared with whites. Asians also faced significantly higher risk for sICH relative to other race/ethnic groups. Future studies are needed to evaluate whether reduction in tPA dose similar to that used in many Asian countries could improve the safety of tPA therapy in Asians in the United States with acute ischemic strokes while maintaining efficacy.