bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Disparate Twins: A Comparative Study of CXCR4 and CXCR7 in SDF-1α–Induced Gene Expression, Invasion and Chemosensitivity of Colon Cancer
Authors: Heckmann Doreen , Maier Patrick , Laufs Stephanie , Li Li , Sleeman Jonathan P. , Trunk Marcus J. , Leupold Jörg H. , Wenz Frederik , Zeller W. Jens , Fruehauf Stefan , Allgayer Heike 
Published: November 2013

Abstract
Purpose: In colorectal cancer, increased expression of the CXC chemokine receptor 4 (CXCR4) has been shown to provoke metastatic disease due to the interaction with its ligand stromal cell-derived factor-1 (SDF-1). Recently, a second SDF-1 receptor, CXCR7, was found to enhance tumor growth in solid tumors. Albeit signaling cascades via SDF-1/CXCR4 have been intensively studied, the significance of the SDF-1/CXCR7–induced intracellular communication triggering malignancy is still only marginally understood.
Experimental Design: In tumor tissue of 52 patients with colorectal cancer, we observed that expression of CXCR7 and CXCR4 increased with tumor stage and tumor size. Asking whether activation of CXCR4 or CXCR7 might result in a similar expression pattern, we performed microarray expression analyses using lentivirally CXCR4- and/or CXCR7-overexpressing SW480 colon cancer cell lines with and without stimulation by SDF-1α.
Results: Gene regulation via SDF-1α/CXCR4 and SDF-1α/CXCR7 was completely different and partly antidromic. Differentially regulated genes were assigned by gene ontology to migration, proliferation, and lipid metabolic processes. Expressions of AKR1C3, AXL, C5, IGFBP7, IL24, RRAS, and TNNC1 were confirmed by quantitative real-time PCR. Using the in silico gene set enrichment analysis, we showed that expressions of miR-217 and miR-218 were increased in CXCR4 and reduced in CXCR7 cells after stimulation with SDF-1α. Functionally, exposure to SDF-1α increased invasiveness of CXCR4 and CXCR7 cells, AXL knockdown hampered invasion. Compared with controls, CXCR4 cells showed increased sensitivity against 5-FU, whereas CXCR7 cells were more chemoresistant.
Conclusions: These opposing results for CXCR4- or CXCR7-overexpressing colon carcinoma cells demand an unexpected attention in the clinical application of chemokine receptor antagonists such as plerixafor. Clin Cancer Res; 20(3); 604–16. ©2013 AACR.
The Natural Inhibitor of DNA Topoisomerase I, Camptothecin, Modulates HIF-1α Activity by Changing miR Expression Patterns in Human Cancer Cells
Authors: Bertozzi Davide , Marinello Jessica , Manzo Stefano G. , Fornari Francesca , Gramantieri Laura , Capranico Giovanni 
Published: November 2013

Abstract
DNA topoisomerase I (Top1) inhibition by camptothecin derivatives can impair the hypoxia-induced cell transcriptional response. In the present work, we determined molecular aspects of the mechanism of camptothecin's effects on hypoxia-inducible factor-1α (HIF-1α) activity in human cancer cells. In particular, we provide evidence that low concentrations of camptothecin, without interfering with HIF-1α mRNA levels, can reduce HIF-1α protein expression and activity. As luciferase assays demonstrated the involvement of the HIF-1α mRNA 3′ untranslated region in camptothecin-induced impairment of HIF-1α protein regulation, we performed microarray analysis to identify camptothecin-induced modification of microRNAs (miRNA) targeting HIF-1α mRNA under hypoxic-mimetic conditions. The selected miRNAs were then further analyzed, demonstrating a role for miR-17-5p and miR-155 in HIF-1α protein expression after camptothecin treatments. The present findings establish miRNAs as key factors in a molecular pathway connecting Top1 inhibition and human HIF-1α protein regulation and activity, widening the biologic and molecular activity of camptothecin derivatives and the perspective for novel clinical interventions. Mol Cancer Ther; 13(1); 239–48. ©2013 AACR.
Licochalcone A, a Natural Inhibitor of c-Jun N-Terminal Kinase 1
Authors: Yao Ke , Chen Hanyong , Lee Mee-Hyun , Li Haitao , Ma Weiya , Peng Cong , Song Nu Ry , Lee Ki Won , Bode Ann M. , Dong Ziming , Dong Zigang 
Published: November 2013

Abstract
The c-Jun N-terminal kinases (JNK) play an important role in many physiologic processes induced by numerous stress signals. Each JNK protein appears to have a distinct function in cancer, diabetes, or Parkinson's disease. Herein, we found that licochalcone A, a major phenolic constituent isolated from licorice root, suppressed JNK1 activity but had little effect on JNK2 in vitro activity. Although licochalcone A binds with JIP1 competitively with either JNK1 or JNK2, a computer simulation model showed that after licochalcone A binding, the ATP-binding cleft of JNK1 was distorted more substantially than that of JNK2. This could reduce the affinity of JNK1 more than JNK2 for ATP binding. Furthermore, licochalcone A inhibited JNK1-mediated, but not JNK2-mediated, c-Jun phosphorylation in both ex vivo and in vitro systems. We also observed that in colon and pancreatic cancer cell lines, JNK1 is highly expressed compared with normal cell lines. In cancer cell lines, treatment with licochalcone A or knocking down JNK1 expression suppressed colon and pancreatic cancer cell proliferation and colony formation. The inhibition resulted in G1 phase arrest and apoptosis. Moreover, an in vivo xenograft mouse study showed that licochalcone A treatment effectively suppressed the growth of HCT116 xenografts, without affecting the body weight of mice. These results show that licochalcone A is a selective JNK1 inhibitor. Therefore, we suggest that because of the critical role of JNK1 in colon cancer and pancreatic carcinogenesis, licochalcone A might have preventive or therapeutic potential against these devastating diseases. Cancer Prev Res; 7(1); 139–49. ©2013 AACR.
The Effect of an EDTA-based Chelation Regimen on Patients With Diabetes Mellitus and Prior Myocardial Infarction in the Trial to Assess Chelation Therapy (TACT)
Authors: Escolar Esteban , Lamas Gervasio A. , Mark Daniel B. , Boineau Robin , Goertz Christine , Rosenberg Yves , Nahin Richard L. , Ouyang Pamela , Rozema Theodore , Magaziner Allan , Nahas Richard , Lewis Eldrin F. , Lindblad Lauren , Lee Kerry L. 
Published: November 2013

Background—
The Trial to Assess Chelation Therapy (TACT) showed clinical benefit of an EDTA-based infusion regimen in patients aged ≥50 years with prior myocardial infarction. Diabetes mellitus before enrollment was a prespecified subgroup.

Methods and Results—

Patients received 40 infusions of EDTA chelation or placebo. A total of 633 (37%) patients had diabetes mellitus (322 EDTA and 311 placebo). EDTA reduced the primary end point (death, reinfarction, stroke, coronary revascularization, or hospitalization for angina; 25% versus 38%; hazard ratio, 0.59; 95% confidence interval [CI], 0.44–0.79;
P
<0.001) over 5 years. The result remained significant after Bonferroni adjustment for multiple subgroups (99.4% CI, 0.39–0.88; adjusted
P
=0.002). All-cause mortality was reduced by EDTA chelation (10% versus 16%; hazard ratio, 0.57; 95% CI, 0.36–0.88;
P
=0.011), as was the secondary end point (cardiovascular death, reinfarction, or stroke; 11% versus 17%; hazard ratio, 0.60; 95% CI, 0.39–0.91;
P
=0.017). However, after adjusting for multiple subgroups, those results were no longer significant. The number needed to treat to reduce 1 primary end point over 5 years was 6.5 (95% CI, 4.4–12.7). There was no reduction in events in non–diabetes mellitus (n=1075;
P
=0.877), resulting in a treatment by diabetes mellitus interaction (
P
=0.004).

Conclusions—
Post–myocardial infarction patients with diabetes mellitus aged ≥50 demonstrated a marked reduction in cardiovascular events with EDTA chelation. These findings support efforts to replicate these findings and define the mechanisms of benefit. However, they do not constitute sufficient evidence to indicate the routine use of chelation therapy for all post–myocardial infarction patients with diabetes mellitus.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00044213.
Impact of Partner Bereavement on Quality of Cardiovascular Disease Management
Authors: Shah Sunil M. , Carey Iain M. , Harris Tess , DeWilde Stephen , Victor Christina R. , Cook Derek G. 
Published: November 2013

Background—
Bereavement is a period of increased risk of cardiovascular death. There is limited understanding of the potential contribution of quality of cardiovascular disease management to this increased risk.

Methods and Results—
In a UK primary-care database, 12 722 older individuals with preexisting cardiovascular disease (coronary heart disease, hypertension, diabetes mellitus, stroke) and a partner bereavement were matched with a non-bereaved control group (n=33 911). We examined key routine annual process measures of care in the year before and after bereavement and cardiovascular medication prescribing (lipid-lowering, antiplatelet, renin–angiotensin system drugs). Odds ratios for change after bereavement compared with the change in non-bereaved matched controls are presented. In the bereaved, uptake of all annual measures was lower in the year before bereavement, with improvement in the year after, whereas in the controls, uptake was relatively stable. The odds ratio for change was 1.30 (95% confidence interval, 1.15–1.46) for cholesterol measurement and 1.40 (95% confidence interval, 1.22–1.61) for blood pressure measurement. For all medication, there was a transient fall in prescribing in the peri-bereavement period lasting until about 3 months after bereavement. The odds ratio for at least 80% prescription coverage in the 30 days after bereavement was 0.80 (95% confidence interval, 0.73–0.88) for lipid-lowering medication and 0.82 (95% confidence interval, 0.74–0.91) for antiplatelet medication compared with the change in non-bereaved individuals.

Conclusions—
Lower uptake of key cardiovascular care measures in the year before bereavement and reduced medication coverage after bereavement may contribute to increased cardiovascular risk. Clinicians need to ensure that quality of cardiovascular care is maintained in the pre- and post-bereavement periods.
Efficacy and Safety of Longer-Term Administration of Evolocumab (AMG 145) in Patients With Hypercholesterolemia
Authors: Koren Michael J. , Giugliano Robert P. , Raal Frederick J. , Sullivan David , Bolognese Michael , Langslet Gisle , Civeira Fernando , Somaratne Ransi , Nelson Patric , Liu Thomas , Scott Rob , Wasserman Scott M. , Sabatine Marc S. 
Published: November 2013

Background—
Evolocumab (AMG 145), a monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein cholesterol (LDL-C) in phase 2 studies of 12 weeks’ duration. The longer-term efficacy and safety of PCSK9 inhibition remain undefined.

Methods and Results—

Of 1359 randomized and dosed patients in the 4 evolocumab phase 2 parent studies, 1104 (81%) elected to enroll into the Open-Label Study of Long-term Evaluation Against LDL-C (OSLER) study. Regardless of their treatment assignment in the parent study, patients were randomized 2:1 to receive either open-label subcutaneous evolocumab 420 mg every 4 weeks with standard of care (SOC) (evolocumab+SOC, n=736) or SOC alone (n=368). Ninety-two percent of patients in the evolocumab+SOC group and 89% of patients in the SOC group completed 52 weeks of follow-up. Patients who first received evolocumab in OSLER experienced a mean 52.3% [SE, 1.8%] reduction in LDL-C at week 52 (
P
<0.0001). Patients who received 1 of 6 dosing regimens of evolocumab in the parent studies and received evolocumab+SOC in OSLER had persistent LDL-C reductions (mean reduction, 50.4% [SE, 0.8%] at the end of the parent study versus 52.1% [SE, 1.0%] at 52 weeks;
P
=0.31). In patients who discontinued evolocumab on entry into OSLER, LDL-C levels returned to near baseline levels. Adverse events and serious adverse events occurred in 81.4% and 7.1% of the evolocumab+SOC group patients and 73.1% and 6.3% of the SOC group patients, respectively.

Conclusion—
Evolocumab dosed every 4 weeks demonstrated continued efficacy and encouraging safety and tolerability over 1 year of treatment in the largest and longest evaluation of a PCSK9 inhibitor in hypercholesterolemic patients to date.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT01439880.
Convergence between DSM-5 Section II and Section III diagnostic criteria for borderline personality disorder
Authors: Sellbom Martin , Sansone Randy A , Songer Douglas A , Anderson Jaime L 
Published: November 2013

Objective: Borderline personality disorder (BPD) is a common mental health condition in psychiatric settings. The current study examined the overlap between the operationalization of BPD listed in Section II (Diagnostic Criteria and Codes) and the alternative, dimensional personality trait-based operationalization listed in Section III (Emerging Measures and Models) of the current Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Moreover, the unique contributions of specific personality traits for indexing the traditional BPD operationalization were also evaluated, including conceptually relevant traits not originally proposed for Section III BPD. Method: Participants were 145 consecutive patients from a psychiatric unit in a hospital in the USA. These individuals completed a series of questionnaires that index both traditional (DSM-IV/DSM-5 Section II) and alternative (DSM-5 Section III personality traits) diagnostic criteria for BPD. Results: Structural equation modeling results revealed that latent constructs representing the Section II and Section III operationalizations of BPD, respectively, overlapped substantially ( r = 0.86, p < 0.001). Hierarchical latent regression models indicated that at least five of the seven traits proposed to define Section III BPD uniquely accounted for variance (69%) in a latent Section II BPD variable. Finally, at least one other conceptually relevant trait (Perceptual Dysregulation) augmented the prediction of latent BPD scores. Conclusions: The proposed personality traits for Section III BPD are clearly aligned with traditional conceptualizations of this important personality disorder construct. At least five of the seven dimensional traits proposed to define Section III contributed uniquely to the characterization of Section II BPD, and these traits can be augmented by Perceptual Dysregulation. If replicated in other settings, these findings might warrant some modification to the operationalization of DSM-5 Section III BPD.
Impact of the “Like Minds, Like Mine” anti-stigma and discrimination campaign in New Zealand on anticipated and experienced discrimination
Authors: Thornicroft Calum , Wyllie Allan , Thornicroft Graham , Mehta Nisha 
Published: November 2013

Objective: The “Like Minds, Like Mine” anti-stigma and discrimination programme has been running in New Zealand since 1997. We aimed to investigate the nature and degree of anticipated and experienced discrimination reported by people with mental illness, and their views on whether the campaign was contributing to reductions in stigma and discrimination. Methods: Questionnaires were sent to randomly selected people who were representative of those who had recently used mental health services in New Zealand. The measure used was the modified Discrimination and Stigma Scale (DISC-12), adding questions on the effect of “Like Minds, Like Mine”, and also assessing overall changes in discrimination in the previous 5 years. Results: A total of 1135 participants completed the questionnaire. This included 225 Ma–ori, 196 Pacific, and 152 Asian persons. Over half of all participants reported improvement in discrimination over the previous 5 years, and 48% thought that the “Like Minds Like Mine” programme had assisted in reducing discrimination “moderately” or “a lot”. Nevertheless, a clear majority (89%) reported experiencing at least “a little” unfair treatment in the previous 12 months due to their mental health problems. The primary source of both positive and negative discrimination was the family. Many (57%) participants had concealed or hidden their mental health problems from others, and 33% had stopped themselves from applying for work because they anticipated discrimination. Conclusions: Family, friendship, and social life were the most common areas of discrimination reported by the participants; however, many believed the overall level of discrimination had reduced over the previous 5 years. Overall, these results characterize the nature of stigma and discrimination anticipated and experienced by people with mental health problems and indicate modest but clear and positive recent progress in their reduction.
Similarity maps and hierarchical clustering for annotating FT-IR spectral images
Authors: Zhong Qiaoyong , Yang Chen , Großerüschkamp Frederik , Kallenbach-Thieltges Angela , Serocka Peter , Gerwert Klaus , Mosig Axel 
Published: November 2013

Abstract

Background
Unsupervised segmentation of multi-spectral images plays an important role in annotating infrared microscopic images and is an essential step in label-free spectral histopathology. In this context, diverse clustering approaches have been utilized and evaluated in order to achieve segmentations of Fourier Transform Infrared (FT-IR) microscopic images that agree with histopathological characterization.

Results
We introduce so-called interactive similarity maps as an alternative annotation strategy for annotating infrared microscopic images. We demonstrate that segmentations obtained from interactive similarity maps lead to similarly accurate segmentations as segmentations obtained from conventionally used hierarchical clustering approaches. In order to perform this comparison on quantitative grounds, we provide a scheme that allows to identify non-horizontal cuts in dendrograms. This yields a validation scheme for hierarchical clustering approaches commonly used in infrared microscopy.

Conclusions
We demonstrate that interactive similarity maps may identify more accurate segmentations than hierarchical clustering based approaches, and thus are a viable and due to their interactive nature attractive alternative to hierarchical clustering. Our validation scheme furthermore shows that performance of hierarchical two-means is comparable to the traditionally used Ward’s clustering. As the former is much more efficient in time and memory, our results suggest another less resource demanding alternative for annotating large spectral images.
Existence results for p-Laplacian boundary value problems of impulsive dynamic equations on time scales
Authors: Ozen Ozlem B , Karaca Ilkay Y , Tokmak Fatma 
Published: November 2013

Abstract
In this paper, Bai-Ge’s fixed point theorem is used to investigate the existence of positive solutions for second-order boundary value problems of p-Laplacian impulsive dynamic equations on time scales. As an application, we give an example to demonstrate our results.

MSC:34B18, 34N05, 39B37.
Exact solutions of unsteady MHD free convection in a heat absorbing fluid flow past a flat plate with ramped wall temperature
Authors: Nandkeolyar Raj , Das Mrutyunjay , Sibanda Precious 
Published: November 2013

Abstract
Unsteady MHD free convection and mass transfer from a viscous, incompressible, electrically conducting and heat absorbing fluid flow past a vertical infinite flat plate is investigated. The flow is induced by a general time-dependent movement of the vertical plate, and the cases of ramped temperature and isothermal plates are studied. Exact solutions of the governing equations are obtained. The Sherwood number, Nusselt number and skin friction coefficients are obtained for both ramped temperature and isothermal plates. Some applications of practical interest are discussed for different types of plate motions. The numerical values of species concentration, fluid temperature and fluid velocity are displayed graphically whereas the numerical values of Sherwood number, the Nusselt number and skin friction are presented in tabular form, for different parameter values for both ramped and isothermal plates.
Epitope analysis of anti-myeloperoxidase antibodies in propylthiouracil-induced antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Wang Chen , Gou Shen-ju , Xu Peng-cheng , Zhao Ming-hui , Chen Min 
Published: November 2013

Abstract
Introduction
Increasing evidence has suggested that linear epitopes of antineutrophil cytoplasmic antibody (ANCA) directed to myeloperoxidase (MPO) might provide clues to the pathogenesis of propylthiouracil (PTU)-induced ANCA-associated vasculitis (AAV). This study mapped epitopes of MPO-ANCA in sera from patients with PTU-induced MPO-ANCA (with or without vasculitis) and primary AAV, aiming to analyze certain epitopes associated with the development of PTU-induced AAV.

Methods
Six recombinant linear fragments, covering the whole amino acid sequence of a single chain of MPO, were produced from Escherichia coli. Sera from 17 patients with PTU-induced AAV, 17 patients with PTU-induced MPO-ANCA but without clinical evidence of vasculitis, and 64 patients with primary AAV were collected at presentation. Of the 17 patients with PTU-induced AAV, 12 also had sera at remission. The epitope specificities were detected by enzyme-linked immunosorbent assay by using the recombinant fragments as solid-phase ligands.

Results
Compared with patients with PTU-induced MPO-ANCA but without clinical vasculitis, sera from PTU-induced AAV patients showed significantly higher reactivity against the H1 fragment of MPO (optical density values: 0.17 (0.10 to 0.35) versus 0.10 (0.04 to 0.21), P = 0.038) and could recognize a significantly higher number of fragments (two (none to four) versus one (none to two), P = 0.026). Compared with sera from primary AAV patients, sera from PTU-induced AAV patients had significantly higher reactivity to the P fragment and the H4 fragment (47.1% versus 14.1% P < 0.001; 41.2% versus 14.1%, P = 0.034, respectively), and could recognize a significantly higher number of fragments (two (none to four) versus one (none to two), P = 0.013]. Among the 12 PTU-induced AAV patients with sequential samples, the number of fragments recognized in remission was significantly less than that in initial onset (two (none to four) versus none (none to 0.75), P < 0.001].

Conclusions
Linear epitopes of MPO molecules might be associated closely with PTU-induced AAV. In particular, the P and H4 fragments may be important epitopes in PTU-induced AAV.