bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Dendritic Cell p53 Peptide Vaccine for Head and Neck Cancer
Authors: Schuler Patrick J. , Harasymczuk Malgorzata , Visus Carmen , DeLeo Albert , Trivedi Sumita , Lei Yu , Argiris Athanassios , Gooding William , Butterfield Lisa H. , Whiteside Theresa L. , Ferris Robert L. 
Published: March 2014

AbstractBackground: p53 accumulation in head and neck squamous cell carcinoma (HNSCC) cells creates a targetable tumor antigen. Adjuvant dendritic cell (DC)–based vaccination against p53 was tested in a phase I clinical trial.Experimental Methods: Monocyte-derived DC from 16 patients were loaded with two modified HLA-class I p53 peptides (Arm 1), additional Th tetanus toxoid peptide (Arm 2), or additional Th wild-type (wt) p53-specific peptide (Arm 3). Vaccine DCs (vDC) were delivered to inguinal lymph nodes at three time points. vDC phenotype, circulating p53-specific T cells, and regulatory T cells (Treg) were serially monitored by flow cytometry and cytokine production by Luminex. vDC properties were compared with those of DC1 generated with an alternative maturation regimen.Results: No grade II–IV adverse events were observed. Two-year disease-free survival of 88% was favorable. p53-specific T-cell frequencies were increased postvaccination in 11 of 16 patients (69%), with IFN-γ secretion detected in four of 16 patients. Treg frequencies were consistently decreased (P = 0.006) relative to prevaccination values. The phenotype and function of DC1 were improved relative to vDC.Conclusion: Adjuvant p53-specific vaccination of patients with HNSCC was safe and associated with promising clinical outcome, decreased Treg levels, and modest vaccine-specific immunity. HNSCC patients' DC required stronger maturation stimuli to reverse immune suppression and improve vaccine efficacy. Clin Cancer Res; 20(9); 2433–44. ©2014 AACR.
Increased KIT Inhibition Enhances Therapeutic Efficacy in Gastrointestinal Stromal Tumor
Authors: Kim Teresa S. , Cavnar Michael J. , Cohen Noah A. , Sorenson Eric C. , Greer Jonathan B. , Seifert Adrian M. , Crawley Megan H. , Green Benjamin L. , Popow Rachel , Pillarsetty Nagavarakishore , Veach Darren R. , Ku Anson T. , Rossi Ferdinand , Besmer Peter , Antonescu Cristina R. , Zeng Shan , DeMatteo Ronald P. 
Published: March 2014

AbstractPurpose: Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and a model of targeted molecular therapy. GIST depends on oncogenic KIT signaling and responds to the tyrosine kinase inhibitor imatinib. However, imatinib is rarely curative. We hypothesized that PLX3397, which inhibits KIT and colony-stimulating-factor-1 receptor (CSF1R), would be more efficacious than imatinib in GIST by also depleting tumor-associated macrophages, which are generally thought to support tumor growth.Experimental Design: We treated KitV558del/+ mice that develop GIST or mice with subcutaneous human GIST xenografts with imatinib or PLX3397 and analyzed tumor weight, cellular composition, histology, molecular signaling, and fibrosis. In vitro assays on human GIST cell lines were also performed.Results: PLX3397 was more effective than imatinib in reducing tumor weight and cellularity in both KitV558del/+ murine GIST and human GIST xenografts. The superiority of PLX3397 did not depend on depletion of tumor-associated macrophages, because adding CSF1R inhibition did not improve the effects of imatinib. Instead, PLX3397 was a more potent KIT inhibitor than imatinib in vitro. PLX3397 therapy also induced substantial intratumoral fibrosis, which impaired the subsequent delivery of small molecules.Conclusions: PLX3397 therapy has greater efficacy than imatinib in preclinical GIST models and warrants study in patients with GIST. The resultant intratumoral fibrosis may represent one of the barriers to achieving complete tumor eradication. Clin Cancer Res; 20(9); 2350–62. ©2014 AACR.
Prevalence and Clinical Implications of Epstein–Barr Virus Infection in De Novo Diffuse Large B-Cell Lymphoma in Western Countries
Authors: Ok Chi Young , Li Ling , Xu-Monette Zijun Y. , Visco Carlo , Tzankov Alexander , Manyam Ganiraju C. , Montes-Moreno Santiago , Dybaer Karen , Chiu April , Orazi Attilio , Zu Youli , Bhagat Govind , Chen Jiayu , Richards Kristy L. , Hsi Eric D. , Choi William W. L. , van Krieken J. Han , Huh Jooryung , Ai Weiyun , Ponzoni Maurilio , Ferreri Andrés J.M. , Farnen John P. , Møller Michael B. , Bueso-Ramos Carlo E. , Miranda Roberto N. , Winter Jane N. , Piris Miguel A. , Medeiros L. Jeffrey , Young Ken H. 
Published: March 2014

Abstract
Purpose: Epstein–Barr virus–positive (EBV+) diffuse large B-cell lymphoma (DLBCL) of the elderly is a variant of DLBCL with worse outcome that occurs most often in East-Asian countries and is uncommon in the Western hemisphere. We studied the largest cohort of EBV+ DLBCL, independent of age, treated with rituximab combined with CHOP (R-CHOP) in developed Western countries.
Experimental design: A large cohort (n = 732) of patients with DLBCL treated with R-CHOP chemotherapy is included from the multicenter consortium. This study group has been studied for expression of different biomarkers by immunohistochemistry, genetic abnormalities by FISH and mutation analysis, genomic information by gene expression profiling (GEP), and gene set enrichment analysis (GSEA).
Results: Twenty-eight patients (4.0%) were positive for EBV with a median age of 60.5 years. No clinical characteristics distinguished patients with EBV+ DLBCL from patients with EBV-negative (EBV−) DLBCL. Genetic aberrations were rarely seen. NF-κB p50, phosphorylated STAT-3, and CD30 were more commonly expressed in EBV+ DLBCLs (P &lt; 0.05). Significant differences in survival were not observed in patients with EBV+ DLBCL versus EBV− DLBCL. However, CD30 expression combined with EBV conferred an inferior outcome. GEP showed a unique expression signature in EBV+ DLBCL. GSEA revealed enhanced activity of the NF-κB and JAK/STAT pathways independent of molecular subtype.
Conclusions: The clinical characteristics of patients with EBV+ versus EBV− DLBCL are similar and EBV infection does not predict a worse outcome. EBV+ DLBCL, however, has a unique genetic signature. CD30 expression is more common in EBV+ DLBCL and, consistent CD30 and EBV is associated with an adverse outcome. Clin Cancer Res; 20(9); 2338–49. ©2014 AACR.
Is There Clinical Value to Prognostic Signatures in Early-Stage NSCLC?
Authors: Bunn Paul A. , Hirsch Fred R. , Aisner Dara L. 
Published: March 2014

Abstract
pAMPK and pmTOR favorably predicted outcome in early non–small cell lung cancer (NSCLC). The differences were small. Phosphoprotein lability makes routine clinical use and validation difficult. Protein immunohistochemistry is unlikely to be clinically useful, and numerous efforts to create predictive models to select resected patients for therapy have been unsuccessful. Clin Cancer Res; 20(7); 1727–9. ©2014 AACR.
Estrogen Receptor Mutations in Breast Cancer—New Focus on an Old Target
Authors: Segal Corrinne V. , Dowsett Mitch 
Published: March 2014

Abstract
Recent studies have provided strong evidence for the emergence of substantial numbers of constitutively active ESR1 mutations in estrogen receptor–positive metastatic breast cancer that are undetected in primary disease. Some of these mutants remain partially sensitive to current anti-estrogen therapies but effective therapeutics targeted at them may require new approaches. Clin Cancer Res; 20(7); 1724–6. ©2014 AACR.
New Approaches but the Same Flaws in the Search for Prognostic Signatures
Authors: Salazar Ramon , Tabernero Josep 
Published: March 2014

Abstract
A six-gene prognostic colorectal cancer hypoxia score was generated from expression data from in vitro experiments and microarray datasets and was validated in two distinct patient cohorts. The approach followed by the authors is original and biologically sound but could be limited by potential biases and other methodologic limitations. Clin Cancer Res; 20(8); 2019–22. ©2014 AACR.
Risk Prediction Model for Heart Failure and Cardiomyopathy After Adjuvant Trastuzumab Therapy for Breast Cancer
Authors: Ezaz Ghideon , Long Jessica B. , Gross Cary P. , Chen Jersey 
Published: March 2014

Background

Adjuvant trastuzumab improves survival for women with human epidermal growth factor receptor 2‐positive breast cancer, but increases risk for heart failure (
HF
) and cardiomyopathy (
CM
). However, clinical trials may underestimate
HF
/
CM
risk because they enroll younger subjects with fewer cardiac risk factors. We sought to develop a clinical risk score that identifies older women with breast cancer who are at higher risk of
HF
or
CM
after trastuzumab.

Methods and Results

Using the Surveillance, Epidemiology and End Results (
SEER
)‐Medicare database, we identified women with breast cancer who received adjuvant trastuzumab. Using a split‐sample design, we used a proportional hazards model to identify candidate predictors of
HF
/
CM
in a derivation cohort. A risk score was constructed using regression coefficients, and
HF
/
CM
rates were calculated in the validation cohort. The sample consisted of 1664 older women (mean age 73.6 years) with 3‐year
HF
/
CM
rate of 19.1%. A risk score consisting of age, adjuvant chemotherapy, coronary artery disease, atrial fibrillation or flutter, diabetes mellitus, hypertension, and renal failure was able to classify
HF
/
CM
risk into low (0 to 3 points), medium (4 to 5 points), and high (≥6 points) risk strata with 3‐year rates of 16.2%, 26.0%, and 39.5%, respectively.

Conclusions

A 7‐factor risk score was able to stratify 3‐year risk of
HF
/
CM
after trastuzumab between the lowest and highest risk groups by more than 2‐fold in a Medicare population. These findings will inform future research aimed at further developing a clinical risk score for
HF
/
CM
for breast cancer patients of all ages.
Acute Intravenous Injection of Serelaxin (Recombinant Human Relaxin‐2) Causes Rapid and Sustained Bradykinin‐Mediated Vasorelaxation
Authors: Leo Chen Huei , Jelinic Maria , Parkington Helena C. , Tare Marianne , Parry Laura J. 
Published: March 2014

Background

A recent clinical trial (
RELAX
in in Acute Heart Failure [
RELAX
‐
AHF
]) demonstrated that 48 hours of continuous intravenous infusion of the vasorelaxant peptide serelaxin (recombinant human relaxin‐2) to patients with acute heart failure reduced cardiovascular mortality at 180 days. The persistence of a vasorelaxant response as a potential mechanism for this long‐term benefit and the vascular effects of a bolus intravenous injection of serelaxin have not been examined. This study investigates changes in resistance artery reactivity and passive mechanical wall properties following an intravenous serelaxin injection and whether these vascular effects persist in the absence of detectable circulating serelaxin.

Methods and Results
Male rats were injected with 13.3 μg/kg serelaxin into the tail vein; mesenteric arteries were assessed 3 and 24 hours after treatment by using wire‐myography. Serelaxin increased basal nitric oxide synthase activity and reduced maximal contraction to endothelin‐1 at 3 hours after administration. Serelaxin treatment also selectively enhanced bradykinin‐mediated endothelium‐dependent relaxation. This effect was sustained for 24 hours in the absence of circulating serelaxin. Serelaxin‐mediated augmentation of bradykinin‐evoked relaxation involved endothelium‐derived hyperpolarization after 3 hours and prostacyclin‐mediated relaxation after 24 hours. Furthermore, upregulation of inducible nitric oxide synthase, phosphorylation of protein kinase B at Ser473 and endothelial nitric oxide synthase at Ser1177 was observed at 24 hours after serelaxin injection. There were no effects of serelaxin on passive arterial wall stiffness.

Conclusion
Our data show that a bolus intravenous injection of serelaxin modulates endothelial vasodilator function 3 hours after administration, an effect that was sustained for 24 hours. The prolonged bradykinin‐mediated vasorelaxation is principally mediated through prostacyclin.
The Importance of Purkinje Activation in Long Duration Ventricular Fibrillation
Authors: Huang Jian , Dosdall Derek J. , Cheng Kang‐An , Li Li , Rogers Jack M. , Ideker Raymond E. 
Published: March 2014

Background

The mechanisms that maintain long duration ventricular fibrillation (
LDVF
) are unclear. The difference in distribution of the Purkinje system in dogs and pigs was explored to determine if Purkinje activation propagates to stimulate working myocardium (
WM
) during
LDVF
and
WM
pacing.

Methods and Results

In‐vivo extracellular recordings were made from 1044 intramural plunge and epicardial plaque electrodes in 6 pig and 6 dog hearts. Sinus activation propagated sequentially from the endocardium to the epicardium in dogs but not pigs. During epicardial pacing, activation propagated along the endocardium and traversed the
LV
wall almost parallel to the epicardium in dogs, but in pigs propagated away from the pacing site approximately perpendicular to the epicardium. After 1 minute of
VF
, activation rate near the endocardium was significantly faster than near the epicardium in dogs (
P
<0.01) but not pigs (
P
>0.05). From 2 to 10 minutes of
LDVF
, recordings exhibiting Purkinje activations were near the endocardium in dogs (
P
<0.01) but were scattered transmurally in pigs, and the
WM
activation rate in recordings in which Purkinje activations were present was significantly faster than the
WM
activation rate in recordings in which Purkinje activations were absent (
P
<0.01). In 10 isolated perfused dog hearts, the
LV
endocardium was exposed and 2 microelectrodes were inserted into Purkinje and adjacent myocardial cells. After 5 minutes of
LDVF
, mean Purkinje activation rate was significantly faster than mean
WM
activation rate (
P
<0.01).

Conclusion

These extracellular and intracellular findings about activation support the hypothesis that Purkinje activation propagates to stimulate
WM
during sinus rhythm, pacing, and
LDVF
.
Endothelial Cell‐, Platelet‐, and Monocyte/Macrophage‐Derived Microparticles are Elevated in Psoriasis Beyond Cardiometabolic Risk Factors
Authors: Takeshita Junko , Mohler Emile R. , Krishnamoorthy Parasuram , Moore Jonni , Rogers Wade T. , Zhang Lifeng , Gelfand Joel M. , Mehta Nehal N. 
Published: March 2014

Background
Psoriasis, especially when severe, is a risk factor for cardiometabolic disease beyond traditional risk factors. The mechanism of atherogenesis in psoriasis remains unknown. Cell membrane vesicles (ie, microparticles), released upon cell activation or apoptosis, have recently been associated with cardiometabolic disease and may play a pathogenic role. Microparticle levels, particularly from endothelial cells and platelets, are elevated in patients with cardiovascular disorders, metabolic syndrome, other inflammatory diseases, autoimmune conditions, and have been shown to be predictive of cardiovascular outcomes.

Methods and Results

Concentrations of microparticles with positive expression for any of 7 cell surface markers (Annexin V,
CD
3,
CD
31,
CD
41a,
CD
64,
CD
105, and
CD
144) were measured in blood samples from psoriasis patients (n=53) and control subjects without psoriasis (n=41). Platelet‐free plasma was separated from whole blood by one‐step centrifugation for microparticle analysis. Microparticles were fluorescently labeled and characterized by flow cytometry. Higher concentrations of
CD
105 (5.5/μL versus 2.5/μL,
P
<0.001),
CD
31 (31/μL versus 18/μL,
P
=0.002),
CD
41a (50/μL versus 22/μL,
P
<0.001), and
CD
64 (5.0/μL versus 4.1/μL,
P
=0.02) singly positive microparticles corresponding to endothelial cell‐, platelet‐, and monocyte/macrophage‐derived microparticles, respectively, were found in psoriasis patients compared with controls. These differences persisted after adjustment for traditional cardiometabolic risk factors including body mass index.

Conclusions
Increased microparticle concentrations, independent of cardiometabolic risk factors, in patients with psoriasis suggest that the presence of increased endothelial cell, platelet, and monocyte/macrophage activation with cell turnover may contribute to the heightened atherogenesis associated with psoriasis.
Cardiovascular and Mortality Risk of Apparent Resistant Hypertension in Women With Suspected Myocardial Ischemia: A Report From the NHLBI‐Sponsored WISE Study
Authors: Smith Steven M. , Huo Tianyao , Delia Johnson B. , Bittner Vera , Kelsey Sheryl F. , Vido Thompson Diane , Noel Bairey Merz C. , Pepine Carl J. , Cooper‐DeHoff Rhonda M. 
Published: March 2014

Background

Women are more likely than men to develop resistant hypertension, which is associated with excess risk of major adverse outcomes; however, the impact of resistant hypertension in women with ischemia has not been explicitly studied. In this Women's Ischemia Syndrome Evaluation (
WISE
) analysis, we assessed long‐term adverse outcomes associated with apparent treatment‐resistant hypertension (
aTRH
) among women with suspected myocardial ischemia referred for coronary angiography.

Methods and Results

Women (n=927) were grouped according to baseline blood pressure (
BP
): normotensive (no hypertension history,
BP
<140/90 mm Hg, no antihypertensive drugs); controlled (
BP
<140/90 mm Hg and a hypertension diagnosis or on 1 to 3 drugs); uncontrolled (
BP
≥140/90 mm Hg on ≤2 drugs); or
aTRH
(
BP
≥140/90 mm Hg on 3 drugs or anyone on ≥4 drugs). Adverse outcomes (first occurrence of death [any cause], nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure or angina) were collected over 10 years of follow‐up. Apparent treatment‐resistant hypertension prevalence was 10.4% among those with hypertension. Women with
aTRH
had a greater incidence of adverse outcomes, compared with normotensive women (adjusted hazard ratio [
HR],
3.25; 95% confidence interval [
CI],
1.94 to 5.43), and women with controlled (
HR,
1.77; 95%
CI,
1.26 to 2.49) and uncontrolled (
HR,
1.62; 95%
CI,
1.15 to 2.27) hypertension; outcome differences were evident early in follow‐up. Risk of all‐cause death was greater in the
aTRH
group, compared to the normotensive women and women with controlled and uncontrolled hypertension.

Conclusions

In this cohort of women with evidence of ischemia,
aTRH
was associated with a profoundly increased long‐term risk of major adverse events, including death, that emerged early during follow‐up.
Splenectomy Is Modifying the Vascular Remodeling of Thrombosis
Authors: Frey Maria K. , Alias Sherin , Winter Max P. , Redwan Bassam , Stübiger Gerald , Panzenboeck Adelheid , Alimohammadi Arman , Bonderman Diana , Jakowitsch Johannes , Bergmeister Helga , Bochkov Valery , Preissner Klaus T. , Lang Irene M. 
Published: March 2014

Background
Splenectomy is a clinical risk factor for complicated thrombosis. We hypothesized that the loss of the mechanical filtering function of the spleen may enrich for thrombogenic phospholipids in the circulation, thereby affecting the vascular remodeling of thrombosis.

Methods and Results

We investigated the effects of splenectomy both in chronic thromboembolic pulmonary hypertension (
CTEPH
), a human model disease for thrombus nonresolution, and in a mouse model of stagnant flow venous thrombosis mimicking deep vein thrombosis. Surgically excised thrombi from rare cases of
CTEPH
patients who had undergone previous splenectomy were enriched for anionic phospholipids like phosphatidylserine. Similar to human thrombi, phosphatidylserine accumulated in thrombi after splenectomy in the mouse model. A postsplenectomy state was associated with larger and more persistent thrombi. Higher counts of procoagulant platelet microparticles and increased leukocyte–platelet aggregates were observed in mice after splenectomy. Histological inspection revealed a decreased number of thrombus vessels. Phosphatidylserine‐enriched phospholipids specifically inhibited endothelial proliferation and sprouting.

Conclusions

After splenectomy, an increase in circulating microparticles and negatively charged phospholipids is enhanced by experimental thrombus induction. The initial increase in thrombus volume after splenectomy is due to platelet activation, and the subsequent delay of thrombus resolution is due to inhibition of thrombus angiogenesis. The data illustrate a potential mechanism of disease in
CTEPH
.
Never Good Enough
Authors: Alamillo-Martinez Laura 
Published: March 2014

AbstractIn different schooling systems throughout the world children of socially advantaged groups experience a higher degree of academic success than children of minority or underprivileged groups. However, there is evidence that academic success comes at a cost. In this paper, based on the findings of an ethnographic research at a Spanish middle-upper class high school, it is argued that secondary school socialization has a strong focus on the future, and it fosters feelings of anxiety in the children of elites. Students believe that a good academic trajectory is the cornerstone to a successful career and they try to take individual control of their future lives without learning how to influence their competitive social context.
Beauty, the Beast, and the Baseball Bat: Ethnography of Self-Defense Training for Upper-Class Women in Revolutionary Cairo (Egypt)
Authors: Lachenal Perrine 
Published: March 2014

AbstractJanuary 2011, Egypt: a huge revolutionary movement began. Since this moment, the perception of insecurity has clearly increased among the upper class. This feeling of vulnerability has opened the doors to new market opportunities related to personal security. In charming neighborhoods of Cairo, offers of self-defense training for women flourished. These training classes offer a valuable and fascinating ethnographic field for addressing the way emotional narratives shape social mobilizations. In class, self-defense participants confirm their shared social belonging while expressing feelings of anxiety in specific terms. Through the Egyptian case, I illustrate that anxiety constitutes a relevant analytical tool to better understand the social and emotional dynamics playing out in revolutionary societies.
Feeling Bad and Being Elite: A Comparative Analysis of the Anxieties and Uncertainties of Aspiring Barristers
Authors: Rogers Justine 
Published: March 2014

AbstractThis paper examines the anxieties and uncertainties of aspiring barristers in order to understand the workings of elite professional status. The literature poses two diverging conceptions of negative feelings: as mechanisms for power and solidarity, concentrated at initiation, or else indicators of diminished control and breakdown. To allow for both potential meanings, this paper draws on an ethnographic study of two cohorts of trainee English barristers: one private, one public. The findings detail and compare the sources, nature, and consequences of bad feeling across the sectors. This innovative analysis detects the modes and blends of authority and cohesion, as well as differentiation, declining status, and even separation. This paper argues for intra-professional analyses as valuable groundwork for wider comparisons.