bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of Androgen Receptor, Lipogenesis, and Oxidative Stress Converged by SREBP-1 Is Responsible for Regulating Growth and Progression of Prostate Cancer Cells
Authors: Huang Wen-Chin , Li Xiangyan , Liu Jian , Lin Jentai , Chung Leland W.K. 
Published: November 2011

Abstract
We previously reported that sterol regulatory element-binding protein-1 (SREBP-1) is involved in the transcriptional regulation of androgen receptor (AR) and formation of fatty acid through altered expression of fatty acid synthase (FASN). In this article, we provide a new finding that SREBP-1 induced oxidative stress in prostate cancer cells through increased production of reactive oxygen species (ROS) and expression of NADPH oxidase 5 (Nox5). We have shown that (i) expression of SREBP-1 protein is positively associated with the clinical Gleason grades in human prostate cancer; (ii) genetic overexpression or knockdown of SREBP-1 in prostate cancer cells resulted in corresponding increased or decreased AR, FASN and Nox5 expression, fatty acid and lipid droplet accumulation, and ROS generation; and (iii) SREBP-1 induces and promotes the growth, migration, invasion, and castration-resistant progression of prostate cancer cells in vitro and in vivo. Our data show a novel molecular mechanism by which SREBP-1 promotes prostate cancer growth and progression through alterations in the concerted intracellular metabolic and signaling networks involving AR, lipogenesis, and ROS in prostate cancer cells. Mol Cancer Res; 10(1); 133–42. ©2011 AACR.
High-Throughput Detection of Actionable Genomic Alterations in Clinical Tumor Samples by Targeted, Massively Parallel Sequencing
Authors: Wagle Nikhil , Berger Michael F. , Davis Matthew J. , Blumenstiel Brendan , DeFelice Matthew , Pochanard Panisa , Ducar Matthew , Van Hummelen Paul , MacConaill Laura E. , Hahn William C. , Meyerson Matthew , Gabriel Stacey B. , Garraway Levi A. 
Published: November 2011

AbstractKnowledge of “actionable” somatic genomic alterations present in each tumor (e.g., point mutations, small insertions/deletions, and copy-number alterations that direct therapeutic options) should facilitate individualized approaches to cancer treatment. However, clinical implementation of systematic genomic profiling has rarely been achieved beyond limited numbers of oncogene point mutations. To address this challenge, we utilized a targeted, massively parallel sequencing approach to detect tumor genomic alterations in formalin-fixed, paraffin-embedded (FFPE) tumor samples. Nearly 400-fold mean sequence coverage was achieved, and single-nucleotide sequence variants, small insertions/deletions, and chromosomal copynumber alterations were detected simultaneously with high accuracy compared with other methods in clinical use. Putatively actionable genomic alterations, including those that predict sensitivity or resistance to established and experimental therapies, were detected in each tumor sample tested. Thus, targeted deep sequencing of clinical tumor material may enable mutation-driven clinical trials and, ultimately, “personalized” cancer treatment.Significance: Despite the rapid proliferation of targeted therapeutic agents, systematic methods to profile clinically relevant tumor genomic alterations remain underdeveloped. We describe a sequencing-based approach to identifying genomic alterations in FFPE tumor samples. These studies affirm the feasibility and clinical utility of targeted sequencing in the oncology arena and provide a foundation for genomics-based stratification of cancer patients. Cancer Discovery; 2(1); 82–93. ©2011 AACR.Read the Commentary on this article by Corless and Spellman, p. 23This article is highlighted in the In This Issue feature, p. 1
Endocardial Left Ventricular Pacing Improves Cardiac Resynchronization Therapy in Chronic Asynchronous Infarction and Heart Failure Models
Authors: Strik Marc , Rademakers Leonard M. , van Deursen Caroline J.M. , van Hunnik Arne , Kuiper Marion , Klersy Catherine , Auricchio Angelo , Prinzen Frits W. 
Published: November 2011

Background—
Studies in canine hearts with acute left bundle branch block (LBBB) showed that endocardial left ventricular (LV) pacing improves the efficacy of cardiac resynchronization therapy (CRT) compared with conventional epicardial LV pacing. The present study explores the efficacy of endocardial CRT in more compromised hearts and the mechanisms of such beneficial effects.

Methods and Results—
Measurements were performed in 22 dogs, 9 with acute LBBB, 7 with chronic LBBB combined with infarction (embolization; LBBB plus myocardial infarction, and concentric remodeling), and 6 with chronic LBBB and heart failure (rapid pacing, LBBB+HF, and eccentric remodeling). A head-to-head comparison was performed of the effects of endocardial and epicardial LV pacing at 8 sites. LV activation times were measured using ≈100 endocardial and epicardial electrodes and noncontact mapping. Pump function was assessed from right ventricular and LV pressures. Endocardial CRT resulted in better electric resynchronization than epicardial CRT in all models, although the benefit was larger in concentrically remodeled LBBB plus myocardial infarction than in eccentrically remodeled LBBB+HF hearts (19% versus 10%). In LBBB and LBBB+HF animals, endocardial conduction was ≈50% faster than epicardial conduction; in all models, transmural impulse conduction was ≈25% faster when pacing from the endocardium than from the epicardium. Hemodynamic effects were congruent with electric effects.

Conclusions—
Endocardial CRT improves electric synchrony of activation and LV pump function compared with conventional epicardial CRT in compromised canine LBBB hearts. This benefit can be explained by a shorter path length along the endocardium and by faster circumferential and transmural impulse conduction during endocardial LV pacing.
Frailty Is Independently Associated With Short-Term Outcomes for Elderly Patients With Non–ST-Segment Elevation Myocardial Infarction
Authors: Ekerstad Niklas , Swahn Eva , Janzon Magnus , Alfredsson Joakim , Löfmark Rurik , Lindenberger Marcus , Carlsson Per 
Published: November 2011

Background—
For the large and growing population of elderly patients with cardiovascular disease, it is important to identify clinically relevant measures of biological age and their contribution to risk. Frailty is an emerging concept in medicine denoting increased vulnerability and decreased physiological reserves. We analyzed the manner in which the variable frailty predicts short-term outcomes for elderly non–ST-segment elevation myocardial infarction patients.

Methods and Results—
Patients aged ≥75 years, with diagnosed non–ST-segment elevation myocardial infarction were included at 3 centers, and clinical data including judgment of frailty were collected prospectively. Frailty was defined according to the Canadian Study of Health and Aging Clinical Frailty Scale. The impact of the comorbid conditions on risk was quantified by the coronary artery disease–specific index. Of 307 patients, 149 (48.5%) were considered frail. By multiple logistic regression, frailty was found to be strongly and independently associated with risk for the primary composite outcome (death from any cause, myocardial reinfarction, revascularization due to ischemia, hospitalization for any cause, major bleeding, stroke/transient ischemic attack, and need for dialysis up to 1 month after inclusion) (odds ratio, 2.2; 95% confidence interval, 1.3–3.7), in-hospital mortality (odds ratio, 4.6; 95% confidence interval, 1.3–16.8), and 1-month mortality (odds ratio, 4.7; 95% confidence interval, 1.7–13.0).

Conclusions—
Frailty is strongly and independently associated with in-hospital mortality, 1-month mortality, prolonged hospital care, and the primary composite outcome. The combined use of frailty and comorbidity may constitute an ultimate risk prediction concept in regard to cardiovascular patients with complex needs.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT01049997.
Somatosensory Anticipatory Alpha Activity Increases to Suppress Distracting Input
Authors: Haegens Saskia , Luther Lisa , Jensen Ole 
Published: November 2011

AbstractEffective processing of sensory input in daily life requires attentional selection and amplification of relevant input and, just as importantly, attenuation of irrelevant information. It has been proposed that top–down modulation of oscillatory alpha band activity (8–14 Hz) serves to allocate resources to various regions, depending on task demands. In previous work, we showed that contralateral somatosensory alpha activity decreases to facilitate processing of an anticipated target stimulus in a tactile discrimination task. In the current study, we asked whether somatosensory alpha activity is also modulated when expecting incoming distracting stimuli on the nonattended side. We hypothesized that an ipsilateral increase of alpha to suppress distracters would be required for optimal task performance. We recorded magneto-encephalography while subjects performed a tactile stimulus discrimination task where a cue directed attention either to their left or right hand. Distracters were presented simultaneously to the unattended hand. We found that alpha power contralateral to the attended hand decreased, whereas ipsilateral alpha power increased. In addition, posterior alpha power showed a general increase. Importantly, these three alpha components all contributed to discrimination performance. This study further extends the notion that alpha band activity is involved in shaping the functional architecture of the working brain by determining the engagement and disengagement of specific regions: Contralateral alpha decreases to facilitate stimulus detection, whereas ipsilateral alpha increases when active suppression of distracters is required. Importantly, the ipsilateral alpha increase is crucial for optimal task performance.
Equatorial Planetary Waves and Their Signature in Atmospheric Variability
Authors: Grise Kevin M. , Thompson David W. J. 
Published: November 2011

Abstract
Equatorial planetary waves are a fundamental component of the tropical climate system. Previous studies have examined their structure in the climatological-mean circulation, their role in the climatological-mean momentum balance of the tropics, and their contribution to the climatological-mean upwelling across the tropical tropopause. In this study, the authors focus on the contribution of the equatorial planetary waves to variability in the tropical circulation about its climatological-mean state.
The equatorial planetary waves that dominate the climatological mean exhibit considerable variability on intraseasonal and interannual time scales. Variability in the amplitude of the equatorial planetary waves is associated with a distinct pattern of equatorially symmetric climate variability that also emerges from empirical orthogonal function analysis of various tropical dynamical fields. Variability in the equatorial planetary waves is characterized by variations in 1) convection in the deep tropics, 2) eddy momentum flux convergence and zonal-mean zonal wind in the tropical upper troposphere, 3) the mean meridional circulation of the tropical and subtropical troposphere, 4) temperatures in the tropical lower stratosphere and subtropical troposphere of both hemispheres, and 5) the amplitude of the upper tropospheric anticyclones over the western tropical Pacific Ocean.
It is argued that pulsation of the equatorial planetary waves provides an alternative framework for interpreting the response of the tropical circulation to a range of climate phenomena. Pulsation of the equatorial planetary waves is apparent in association with opposing phases of El Niño–Southern Oscillation and select phases of the Madden–Julian oscillation. Pulsation of the equatorial planetary waves also contributes to variability in measures of the width of the tropical belt.
Implementation and evaluation of an education program to guide palliative care for people with motor neurone disease
Authors: McConigley Ruth , Aoun Samar , Kristjanson Linda , Colyer Sue , Deas Kathy , O’Connor Margaret , Harris Rod , Currow David , Yates Patsy 
Published: November 2011

Background: Despite a recognized need for a palliative approach to caring for people with motor neurone disease (MND), access to palliative care is often limited. Aim: This project aimed to improve the knowledge of health professionals about a palliative approach to MND care. Design: A three-phase study was undertaken to develop, implement and evaluate an education program for health professionals that promoted a palliative approach to MND care. This paper discusses the second and third phases: the implementation and evaluation of the project. Education workshops were held for health professionals. Their knowledge of palliative care was measured before and after the workshops and one month later. Attitudes to providing MND care were also measured. Setting: Workshops were held in South Australia and Western Australia. Participants were health professionals working in the areas of MND care or palliative care. Some aged care and generalist health professionals were included if they had a role in providing care to people with MND. Results: The participants demonstrated an improvement in MND knowledge (χ2 = 64.13(2), p = 0.000) and palliative care knowledge (χ2 = 17.24(2), p = 0.000); both were sustained at one month. Attitudes to providing MND care also improved (χ2 = 11.85(2), p = 0.003) and were maintained at the six-month follow-up. Participants indicated that the knowledge gained positively influenced their clinical practice. Conclusions: A targeted education program for health professionals improved understanding about end-of-life care for people with MND. Health care providers also reported having made improvements in the care provided to patients and carers, particularly communication, psychosocial care and symptom management.
Repeat Victimisation and the Policing of Communities
Authors: Chenery Sylvia , Henshaw Chris , Pease Ken 
Published: November 2011

Three types of police service can be distinguished. • Reaction to relevant emergencies; • Identifying and processing crime perpetrators; • Proaction to prevent crime and disorder (referred to below as ‘unity policing’). The central problem for the organisation of policing is arguably the integration of the first two elements of work with the third. In this paper, the writers contend that focusing on identifying and providing relevant help to those previously victimised by crime offers a platform for such integration. The advantages conferred by this approach will be identified. The Huddersfield Biting Back project is described as an example of how such an approach can be implemented. The implications of risk-based targeting, of which repeat victimisation provides the easiest example to implement, are spelled out.
Collaborative Problem-Solving Partnerships: Advancing Community Policing Philosophy to Domestic Violence Victim Services
Authors: Laszlo Anna T. , Rinehart Tammy A. 
Published: November 2011

Throughout the last three decades, victims and victim advocates have significantly advanced victim's rights and services and have altered the fabric of police-victim interactions from viewing victims as necessary witnesses (Laszlo and Burgess, 1979; Waller, 1990) to engaging victims and victim organizations as collaborative partners in developing victim-oriented criminal justice services. As criminal justice agencies seek to engage stakeholders in problem-solving strategies, victims and victim organizations are becoming active partners in prevention, intervention, and restitution initiatives, and have been instrumental in tailoring criminal justice systems services to the needs of special populations. This paper describes four ongoing efforts to effect prevention, intervention, and restitution activities for special populations of victims and, in particular, to advancing community policing and community government in or for special populations. Within the historical contexts of the victim's movement, these efforts manifest the expanding role of victims as collaborative partners of police (including tribal police), prosecutors, and the courts.
Coronary artery disease is detectable by multi-slice computed tomography in most asymptomatic type 2 diabetic patients at high cardiovascular risk
Authors: Nasti Rodolfo , Carbonara Ornella , di Santo Stefano Maria L Mangoni , Auriemma Roberta , Esposito Sabato , Picardi Giuseppe , Lascar Nadia , Pagano Antonio , Ruggiero Roberto , Torella Roberto , Sasso Ferdinando C 
Published: November 2011

Objective: Non-invasive testing often does not identify coronary artery disease (CAD) in diabetic subjects. This study was designed in order to examine the prevalence of CAD in a cohort of asymptomatic type 2 diabetic patients at high cardiovascular risk and negative nuclear imaging, using multi-slice computed tomography (MSCT) angiography. Methods: In total, 770 type 2 diabetic patients were screened from January 2008 through July 2010. Of these, 132 Caucasians with diabetic nephropathy and asymptomatic for angina were eligible for a cross-sectional study. Patients underwent MSCT after ischaemia was excluded by myocardial Single Photon Emission Computed Tomography (SPECT) at rest and after dynamic exercise. When obstructive plaques were found (≥50% lumen narrowing), patients were sent to conventional coronary angiography (CCA). Results: Six subjects were not included in the analysis because of motion artefacts. MSCT was positive for CAD in 114 patients (90%). Within patients with positive MSCT, 60 (48% of all) showed one or more obstructive plaques. CCA confirmed significant stenosis (≥50%) in 48 of these 60 patients (80%). Some 21 (35%) showed stenosis ≥75% and were submitted to the revascularisation procedure. Conclusion: MSCT seems to better identify CAD than myocardial SPECT in asymptomatic patients with type 2 diabetes and diabetic nephropathy.
The cell cycle regulator CDC25A is a target for JAK2V617F oncogene
Authors: Gautier Emilie-Fleur , Picard Muriel , Laurent Camille , Marty Caroline , Villeval Jean-Luc , Demur Cécile , Delhommeau François , Hexner Elizabeth , Giraudier Stéphane , Bonnevialle Nicolas , Ducommun Bernard , Récher Christian , Laurent Guy , Manenti Stéphane , Mansat-De Mas Véronique 
Published: November 2011

Abstract
The JAK2V617F mutation is present in the majority of patients with polycythemia vera and one-half of those with essential thrombocythemia and primary myelofibrosis. JAK2V617F is a gain-of-function mutation resulting in constitutive JAK2 signaling involved in the pathogenesis of these diseases. JAK2V617F has been shown to promote S-phase entry. Here, we demonstrate that the CDC25A phosphatase, a key regulator of the G1/S cell-cycle transition, is constitutively overexpressed in JAK2V617F-positive cell lines, JAK2-mutated patient CD36+ progenitors, and in vitro–differentiated proerythroblasts. Accordingly, CDC25A is overexpressed in BM and spleen of Jak2V617F knock-in mice compared with wild-type littermates. By using murine FDC-P1–EPOR and human HEL and SET-2 cell lines, we found that JAK2V617F-induced CDC25A up-regulation was caused neither by increased CDC25A transcription or stability nor by the involvement of its upstream regulators Akt and MAPK. Instead, our results suggest that CDC25A is regulated at the translational level through STAT5 and the translational initiation factor eIF2α. CDC25A inhibition reduces the clonogenic and proliferative potential of JAK2V617F-expressing cell lines and erythroid progenitors while moderately affecting normal erythroid differentiation. These results suggest that CDC25A deregulation may be involved in hematopoietic cells expansion in JAK2V617F patients, making this protein an attracting potential therapeutic target.
VIP and endothelin receptor antagonist: An effective combination against experimental pulmonary arterial hypertension
Authors: Hamidi Sayyed A , Lin Richard Z , Szema Anthony M , Lyubsky Sergey , Jiang Ya Ping , Said Sami I 
Published: November 2011

Abstract

Background
Pulmonary Arterial Hypertension (PAH) remains a therapeutic challenge, and the search continues for more effective drugs and drug combinations. We recently reported that deletion of the vasoactive intestinal peptide (VIP) gene caused the spontaneous expression of a PH phenotype that was fully corrected by VIP. The objectives of this investigation were to answer the questions: 1) Can VIP protect against PH in other experimental models? and 2) Does combining VIP with an endothelin (ET) receptor antagonist bosentan enhance its efficacy?

Methods
Within 3 weeks of a single injection of monocrotaline (MCT, s.c.) in Sprague Dawley rats, PAH developed, manifested by pulmonary vascular remodeling, lung inflammation, RV hypertrophy, and death within the next 2 weeks. MCT-injected animals were either untreated, treated with bosentan (p.o.) alone, with VIP (i.p.) alone, or with both together. We selected this particular combination upon finding that VIP down-regulates endothelin receptor expression which is further suppressed by bosentan. Therapeutic outcomes were compared as to hemodynamics, pulmonary vascular pathology, and survival.

Results
Treatment with VIP, every other day for 3 weeks, begun on the same day as MCT, almost totally prevented PAH pathology, and eliminated mortality for 45 days. Begun 3 weeks after MCT, however, VIP only partially reversed PAH pathology, though more effectively than bosentan. Combined therapy with both drugs fully reversed the pathology, while preventing mortality for at least 45 days.

Conclusions
1) VIP completely prevented and significantly reversed MCT-induced PAH; 2) VIP was more effective than bosentan, probably because it targets a wider range of pro-remodeling pathways; and 3) combination therapy with VIP plus bosentan was more effective than either drug alone, probably because both drugs synergistically suppressed ET-ET receptor pathway.