bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunomodulation of Curcumin on Adoptive Therapy with T Cell Functional Imaging in Mice
Authors: Chang Ya-Fang , Chuang Hui-Yen , Hsu Chien-Hui , Liu Ren-Shyan , Gambhir Sanjiv Sam , Hwang Jeng-Jong 
Published: December 2011

AbstractAdoptive T-cell therapy involves the ex vivo expansion and subsequent transfusion of tumor-specific T lymphocytes to eliminate tumors. Using immune modulators to block immunosuppressive factors in the tumor microenvironment has emerged as a promising strategy to enhance T-cell–mediated tumor regression. Curcumin, a major component of turmeric, has been shown to possess antitumor and immunomodulatory effects by regulating a diverse range of molecular targets. Thus, we hypothesize that these beneficial effects of curcumin may improve the therapeutic efficacy of adoptive therapy. Here, we have shown that curcumin enhances cytotoxicity of CD8+ T cells toward tumors via alteration of the tumor microenvironment when combined with adoptive therapy. We found that T-cell accumulation and function were increased in combined treatment due to the blockade of different immunosuppressors, including TGF-β, indoleamine 2,3-dioxygenase, and regulatory T cells. Furthermore, bioluminescent imaging with a granzyme B promoter–conjugated optical reporter also reflected improved cytotoxicity of antigen-specific CD8+ T cells in tumor-bearing mice during treatment. These findings suggest that combination of multitargeting drugs, such as curcumin, with adoptive therapy may have potential for clinical application. In addition, using a granzyme B–specific imaging reporter to assess T-cell function may also be applied for the development and therapeutic evaluation of new immunotherapy in preclinical studies. Cancer Prev Res; 5(3); 444–52. ©2011 AACR.
Nuclear Receptors as Modulators of the Tumor Microenvironment
Authors: Sherman Mara H. , Downes Michael , Evans Ronald M. 
Published: December 2011

AbstractOver the past several decades of cancer research, the inherent complexity of tumors has become increasingly appreciated. In addition to acquired cell-intrinsic properties, tumor initiation and growth is supported by an abundance of parenchymal, inflammatory, and stromal cell types, which infiltrate and surround the tumor. Accumulating evidence shows that numerous components of this supportive milieu, referred to collectively as the tumor microenvironment, are indeed critical during the process of multistep tumorigenesis. These findings highlight the important interplay between neoplastic cells and tumor-associated cell types, and suggest that therapy should target both neoplastic cells and supportive stromal cells to effectively attenuate tumor growth. The nuclear receptor superfamily encompasses a druggable class of molecules expressed in numerous stromal and parenchymal cell types, whose established physiologic roles suggest their potential as therapeutic and preventive targets in the context of the reactive tumor microenvironment. In this minireview, we discuss recent evidence that tumor-associated inflammation, angiogenesis, and fibrosis can be modulated at the transcriptional level by nuclear receptors and their ligands. As these processes have been widely implicated in cancer initiation, progression, and resistance to current therapy, nuclear receptor ligands targeting the tumor microenvironment may be potent antitumor agents in combination therapies, including for preventing cancer development within high-risk populations. Cancer Prev Res; 5(1); 3–10. ©2011 AACR.
Imaging Study of Ventricular Scar in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Marra Martina Perazzolo , Leoni Loira , Bauce Barbara , Corbetti Francesco , Zorzi Alessandro , Migliore Federico , Silvano Maria , Rigato Ilaria , Tona Francesco , Tarantini Giuseppe , Cacciavillani Luisa , Basso Cristina , Buja Gianfranco , Thiene Gaetano , Iliceto Sabino , Corrado Domenico 
Published: December 2011

Background—
The hallmark lesion of arrhythmogenic right ventricular cardiomyopathy (ARVC) is fibrofatty scar replacement. We compared endocardial voltage mapping (EVM) and contrast-enhanced cardiac magnetic resonance (CE-CMR) for imaging scar lesions in ARVC patients.

Methods and Results—
We studied 23 consecutive ARVC patients (16 males; mean age, 38±12 years) who underwent RV EVM and CE-CMR and 37 control subjects. In 21 (91%) of 23 ARVC patients, RV EVM was abnormal, with a total of 45 electroanatomical scars (EAS): 17 (38%) in the inferobasal region, 12 (26.6%) in the anterolateral region, 8 (17.7%) in the RV outflow tract (RVOT), and 8 (17.7%) in the apex. RV delayed contrast enhancement (DCE) was found in 9 (39%) of 23 patients, with a total of 23 RV DCE scars: 4 (17.4%) in the inferobasal region, 9 (39.1%) in the anterolateral region, 4 (17.4%) in the RVOT, and 6 (26.1%) in the apex. There was a mismatch in 24 RV scars, with 22 EAS not confirmed by DCE and 2 DCE scars (both in the RVOT) undetected by EVM. In 9 (75%) of 12 patients with abnormal RV EVM/normal RV DCE, ≥1 DCEs were identified in the left ventricle (LV). Overall, ventricular DCE was detected in 78% of patients. No control subjects showed either EAS or DCE.

Conclusions—
EVM and CE-CMR allow identification of RV scar lesions in most ARVC patients. CE-CMR is less sensitive than EVM in identifying RV scar lesions. The high prevalence of LV DCE confirms the frequent biventricular involvement and indicates the diagnostic relevance of LV scar detection by CE-CMR.
Randomized Ablation Strategies for the Treatment of Persistent Atrial Fibrillation
Authors: Dixit Sanjay , Marchlinski Francis E. , Lin David , Callans David J. , Bala Rupa , Riley Michael P. , Garcia Fermin C. , Hutchinson Mathew D. , Ratcliffe Sarah J. , Cooper Joshua M. , Verdino Ralph J. , Patel Vickas V. , Zado Erica S. , Cash Nancy R. , Killian Tony , Tomson Todd T. , Gerstenfeld Edward P. 
Published: December 2011

Background—
The single-procedure efficacy of pulmonary vein isolation (PVI) is less than optimal in patients with persistent atrial fibrillation (AF). Adjunctive techniques have been developed to enhance single-procedure efficacy in these patients. We conducted a study to compare 3 ablation strategies in patients with persistent AF.

Methods and Results—

Subjects were randomized as follows: arm 1, PVI + ablation of non-PV triggers identified using a stimulation protocol (standard approach); arm 2, standard approach + empirical ablation at common non-PV AF trigger sites (mitral annulus, fossa ovalis, eustachian ridge, crista terminalis, and superior vena cava); or arm 3, standard approach + ablation of left atrial complex fractionated electrogram sites. Patients were seen at 6 weeks, 6 months, and 1 year; transtelephonic monitoring was performed at each visit. Antiarrhythmic drugs were discontinued at 3 to 6 months. The primary study end point was freedom from atrial arrhythmias off antiarrhythmic drugs at 1 year after a single-ablation procedure. A total of 156 patients (aged 59±9 years; 136 males; AF duration, 47±50 months) participated (arm 1, 55 patients; arm 2, 50 patients; arm 3, 51 patients). Procedural outcomes (procedure, fluoroscopy, and PVI times) were comparable between the 3 arms. More lesions were required to target non-PV trigger sites than a complex fractionated electrogram (33±9 versus 22±9;
P
<0.001). The primary end point was achieved in 71 patients and was worse in arm 3 (29%) compared with arm 1 (49%;
P
=0.04) and arm 2 (58%;
P
=0.004).

Conclusions—
These data suggest that additional substrate modification beyond PVI does not improve single-procedure efficacy in patients with persistent AF.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00379301.
The 719Arg Variant of KIF6 and Cardiovascular Outcomes in Statin-Treated, Stable Coronary Patients of the Treating to New Targets and Incremental Decrease in End Points Through Aggressive Lipid-Lowering Prospective Studies
Authors: Arsenault Benoit J. , Boekholdt S. Matthijs , Hovingh G. Kees , Hyde Craig L. , DeMicco David A. , Chatterjee Aurobindo , Barter Philip , Deedwania Prakash , Waters David D. , LaRosa John C. , Pedersen Terje R. , Kastelein John J.P. 
Published: December 2011

Background—
Carriers of the KIF6 719Arg variant may be at increased risk for CVD and may benefit more from statin therapy, in terms of CVD risk reduction, than noncarriers. Our objective was to investigate whether carriers of the KIF6 719Arg genetic variant (rs20455) are at increased cardiovascular risk and obtain more benefit from high-dose statin therapy than do noncarriers.

Methods and Results—

We used an adjusted Cox proportional hazard model to assess the hazard ratio (HR) for the reduction of major cardiovascular events by 80 mg/d atorvastatin over 10 mg/d atorvastatin in 4599 patients of the Treating to New Targets (TNT) study and by 80 mg/d atorvastatin over 20–40 mg/d simvastatin in 6541 patients of the Incremental Decrease in End Points Through Aggressive Lipid-Lowering (IDEAL) study. A total of 381 and 648 patients had a cardiovascular event during follow-up in TNT and IDEAL, respectively. Heterozygotes and homozygotes for the minor allele were not at increased risk compared with noncarriers. In TNT, for noncarriers of the 719Arg allele, the HR for high- versus low-dose atorvastatin was 0.81 (95% confidence interval, 0.59–1.11). In carriers of 1 or 2 minor alleles, the HR was 0.85 (0.66–1.11) and carriers of 2 copies of the minor allele obtained a significant risk reduction (HR: 0.44, 95% confidence interval, 0.23–0.84). In IDEAL, the respective HRs were 0.85 (0.67–1.10), 0.88 (0.62–1.07) and 0.91 (0.58–1.43). The interaction term for carrier status by treatment was also nonsignificant (
P
=0.810 in TNT and
P
=0.909 in IDEAL).

Conclusions—
In these 2 large, randomized clinical trials, carriers of the KIF6 719Arg allele were not at increased cardiovascular risk and did not obtain consistent cardiovascular benefit from high-dose statin therapy compared with noncarriers.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00327691.
Serial Measurement of Cardiac Troponin T Using a Highly Sensitive Assay in Patients With Chronic Heart Failure
Authors: Masson Serge , Anand Inder , Favero Chiara , Barlera Simona , Vago Tarcisio , Bertocchi Federico , Maggioni Aldo P. , Tavazzi Luigi , Tognoni Gianni , Cohn Jay N. , Latini Roberto 
Published: December 2011

Background—
Cardiac troponins are emerging as important prognostic markers in chronic cardiovascular conditions like stable coronary artery disease or chronic heart failure (HF). Less is known about the relation between serial measurements of high-sensitivity cardiac troponin T (hs-cTnT) and future events in HF. We determined the association between changes over time in hs-cTnT and outcome in patients with chronic HF.

Methods and Results—
We analyzed 5284 patients with chronic HF from 2 independent randomized clinical trials, the Valsartan Heart Failure Trial (Val-HeFT) (n=4053) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca–Heart Failure (GISSI-HF) trial (n=1231). hs-cTnT was measured at randomization and after 3 months (GISSI-HF) or 4 months of follow-up (Val-HeFT). The association between changes over time of hs-cTnT and various outcomes was tested in multivariable models. In both studies, increases in hs-cTnT levels over time were associated with age, diabetes mellitus, worsening of renal function (reduction in estimated glomerular filtration rate), and baseline and increases in N-terminal pro-brain natriuretic peptide concentrations. Increases in hs-cTnT concentrations were associated with all-cause mortality (incidence rates, 8.19 [7.51–8.88] and 6.79 [5.98–7.61] per 100 person-years in Val-HeFT and GISSI-HF, respectively, with hazard ratios [95% confidence intervals] of 1.59 [1.39–1.82] and 1.88 [1.50–2.35]) after adjustment for conventional risk factors and baseline levels of hs-cTnT and N-terminal pro-brain natriuretic peptide. Changes in hs-cTnT concentration modestly improved prognostic discrimination beyond baseline values for fatal outcomes only.

Conclusions—
Despite very low circulating concentrations, changes in hs-cTnT concentrations over time are robust predictors of future cardiovascular events in patients with chronic HF but add limited prognostic discrimination.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00336336.
Predictors of Tissue-Type Plasminogen Activator Nonresponders According to Location of Vessel Occlusion
Authors: Mendonça Nuno , Rodriguez-Luna David , Rubiera Marta , Boned-Riera Sandra , Ribo Marc , Pagola Jorge , Piñeiro Socorro , Meler Pilar , Alvarez-Sabin Jose , Montaner Joan , Molina Carlos A. 
Published: December 2011

Background and Purpose—
Information on the clinical and hemodynamic profile of intravenous tissue-type plasminogen activator nonresponders, at different locations of arterial occlusion, may improve the selection of candidates for rescue reperfusion therapies. Therefore, we aim to investigate predictors of failing intravenous tissue-type plasminogen activator therapy according to occluded vessel and location of the clot.

Methods—
We prospectively evaluated consecutive patients with an acute ischemic stroke admitted within the first 6 hours of onset. Five hundred forty-eight patients with documented intracranial occlusion were included. Patients were categorized according to site of vessel occlusion into 4 distinct groups: proximal middle cerebral artery occlusion (n=251), distal middle cerebral artery occlusion (n=194), internal carotid artery bifurcation occlusion (n=61), and basilar artery occlusion (n=42). Recanalization was assessed on transcranial Doppler at 1 hour of tissue-type plasminogen activator bolus.

Results—

Among patients with proximal middle cerebral artery occlusion, the presence of severe extracranial internal carotid artery stenosis or occlusion (OR, 2.36; 95% CI, 1.15–4.84;
P
=0.02) and age >74 years (OR, 1.84; 95% CI, 1.02–3.31;
P
=0.04) independently predicted no recanalization. No independent predictors of no recanalization were identified in patients with distal middle cerebral artery occlusion. In patients with internal carotid artery bifurcation occlusion, a previous diagnosis of hypertension (OR, 12.77; 95% CI, 2.12–76.88;
P
=0.05), and absence of atrial fibrillation (OR, 8.15; 95% CI, 1.40–47.44;
P
=0.02) emerged as independent predictors of no recanalization. Similarly, among patients with basilar artery occlusion, absence of atrial fibrillation was as an independent predictor of no recanalization (OR, 7.50; 95% CI, 1.40–40.35;
P
=0.02).

Conclusions—
The use of relevant predictors of no recanalization and a rapid neurovascular evaluation may improve the selection of patients for more aggressive rescue strategies.
The Evolution of Third-Party Mediation in Sharīʿa Courts in 19th- and early 20th-century Central Asia
Authors: Sartori Paolo 
Published: December 2011

AbstractWhile in the Ottoman Empire reconciling disputing parties insharīʿacourts occurred without the direct involvement of state officials, in modern Central Asia functionaries appointed by the ruler’s chancellery acted as mediators and mediation procedures were consistent with the state’s intervention in the resolution of a conflict. This ended with Russian colonization. Conflict resolution was left to thesharīʿacourts; mediation continued to be important but state appointees were no longer officially involved in bringing it about. The Russian colonial and Soviet administrations made the community responsible for seeking amicable settlements. Only afterwards did they realize how easy this made it for local groups to circumvent the state’s supervision.
Assimilation of Reflectivity Data in a Convective-Scale, Cycled 3DVAR Framework with Hydrometeor Classification
Authors: Gao Jidong , Stensrud David J. 
Published: December 2011

Abstract
The impact of assimilating radar reflectivity and radial velocity data with an intermittent, cycled three-dimensional variational assimilation (3DVAR) system is explored using an idealized thunderstorm case and a real data case on 8 May 2003. A new forward operator for radar reflectivity is developed that uses a background temperature field provided by a numerical weather prediction model for automatic hydrometeor classification. Three types of experiments are performed on both the idealized and real data cases. The first experiment uses radial velocity data only, the second experiment uses both radial velocity and reflectivity data without hydrometeor classification, and the final experiment uses both radial velocity and reflectivity data with hydrometeor classification. All experiments advance the analysis state to the next observation time using a numerical model prediction, which is then used as the background for the next analysis. Results from both the idealized and real data cases show that, assimilating only radial velocity data, the model can reconstruct the supercell thunderstorm after several cycles, but the development of precipitation is delayed because of the well-known spinup problem. The spinup problem is reduced dramatically when assimilating reflectivity without hydrometeor classification. The analyses are further improved using the new reflectivity formulation with hydrometeor classification. This study represents a successful first effort in variational convective-scale data assimilation to partition hydrometeors using a background temperature field from a numerical weather prediction model.
Predicting Maximum Acceptable Efforts for Repetitive Tasks
Authors: Potvin Jim R. 
Published: December 2011

Objective: The objective was to develop an equation, for repetitive tasks, that uses frequency and/or duty cycle (DC) to predict maximum acceptable efforts (MAE) relative to maximum voluntary efforts (MVE). Background: Ergonomists must determine acceptable physical demands for a wide variety of tasks. Although a large database exists in the literature for maximum single-effort strength, far fewer repetitive tasks have psychophysical and/or physiological data available to guide the prediction of acceptable submaximal, repeated efforts. Method: DC represents the total effort duration divided by the cycle time. MAEs were calculated by dividing average psychophysics-based acceptable loads by corresponding single-effort maximum strength using 69 values from studies of the upper extremities. The author developed an equation to characterize the relationship between MAE and DC. Results: The resulting equation had DC taken to the exponent 0.24, and it predicted MAE very well ( r2 = 0.87%, root mean square [RMS] difference = 7.2% of the maximum strength). At higher DC values, the equation also demonstrated good agreement with the published physiological data. Conclusion: The limited psychophysical database in the literature makes it difficult for ergonomists and engineers to recommend acceptable efforts for the large variety of repetitive tasks they evaluate. However, the proposed equation now allows for a correction of the large strength database to estimate acceptable force and torque limits for repetitive occupational tasks. Application: The proposed equation will have wide applications for ergonomic practitioners performing evaluations of repetitive tasks.
Theater of the Oppressed as a Rhizome
Authors: Ferreira Mariana Leal , Devine Dominique 
Published: December 2011

The spread of Augusto Boal’s Theater of the Oppressed across the Americas and the rest of the world can be understood in terms of Deleuze and Guattari’s metaphor of the rhizome, whose nomadic habit of growth and propagation mirrors the power of Theater of the Oppressed to reproduce itself in more than 70 countries worldwide. The Theater of the Oppressed rhizome is now deeply rooted in academia and has sprouted in classrooms and in the streets, bringing together students, scholars, administrators, policy makers, and community activists in the pursuit of social justice and human rights. An examination of its use as a pedagogical tool calls attention to its potential for creating a world in which human rights are appreciated and protected. Its use is particularly timely today given the worldwide attention to the rights of the indigenous peoples represented by the adoption of the United Nations Declaration on the Rights of Indigenous Peoples in 2007. La difusión del Teatro del oprimido de Augusto Boal a través las Américas y el resto del mundo puede verse en términos de la metáfora del rizoma utilizada por Deleuze y Guattari, donde el hábito de crecimiento nomádico y propagación refleja el poder de dicho método de reproducirse en más de 70 países alrededor del mundo. El rizoma del Teatro del oprimido se ha enraizado profundamente en el ámbito académico y florecido en aulas y calles, uniendo estudiantes, investigadores, administradores, responsables políticos y activistas comunitarios interesados en la justicia social y los derechos humanos. Un análisis de su uso como herramienta pedagógica muestra su potencial para crear un mundo que reconozca y proteja los derechos humanos. Esto resulta de particular relevancia hoy día dada la atención mundial conferida a los derechos de los pueblos indígenas a partir de la Declaración de las Naciones Unidas sobre los derechos de los pueblos indígenas de 2007.
Performing Mulata-ness
Authors: Pravaz Natasha 
Published: December 2011

In Rio de Janeiro, mulatas—brown-skinned women of mixed racial descent who dance the samba in Carnival parades and in nightclubs—have become multifocal symbols eliciting associations that resonate both with colonial morality and with mestiçagem, the narrative of racial and cultural mixing as a cornerstone of nationhood. Because of these associations, a dangerous border crossing takes place whenever they dance the samba in public: they may become icons of nationhood, but this may call into question their moral standing. Women who occupy this subject position attempt to maintain a modicum of respectability as they manipulate the objectifying gaze of Brazilians and foreigners to the best of their ability. They also attempt to portray their dance skills as culturally “authentic” in the search for legitimacy and racial pride. Ultimately, samba is a stage upon which the economic needs, embodied desires, and ethnic identities of Brazilian women clash and collude with the neo-colonial dreams of tourists and cosmopolitans. Na cidade do Rio de Janeiro, as mulatas—mulheres de ascendência racial misturada que dançam o samba nos desfiles de carnaval e nas boites—se tornaram símbolos polivalentes que evocam associações ressonantes com a moralidade colonial e com o discurso da mestiçagem (mistura racial e cultural) comofundamento da brasilidade. Por causa destas associações, elas negociam um espaço perigoso cada vez que sambam em público: podem tornar-se símbolos da nação, mas isto pode gerar dúvidas sobre a sua reputação moral. As mulheres nesta posição social tentam manter um mínimo de respeito social através da manipulação dos olhares brasileiros e estrangeiros que as reificam. Em busca de legitimidade e orgulho racial, elas procuram definir suas habilidades artísticas comoculturalmente “autênticas.” Por fim, o samba é um palco onde as necessidades econômicas, os desejos encarnados e as identidades étnicas da mulher brasileira se embatem e conspiram com os sonhos neo-coloniais de turistas e cosmopolitas.