bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of BcaA, a Putative Classical Autotransporter Protein in Burkholderia pseudomallei
Authors: Campos Cristine G. , Borst Luke , Cotter Peggy A. 
Published: January 2013

ABSTRACT

Burkholderia pseudomallei
is a tier 1 select agent, and the causative agent of melioidosis, a disease with effects ranging from chronic abscesses to fulminant pneumonia and septic shock, which can be rapidly fatal. Autotransporters (ATs) are outer membrane proteins belonging to the type V secretion system family, and many have been shown to play crucial roles in pathogenesis. The open reading frame Bp1026b_II1054 (
bcaA
) in
B. pseudomallei
strain 1026b is predicted to encode a classical autotransporter protein with an approximately 80-kDa passenger domain that contains a subtilisin-related domain. Immediately 3′ to
bcaA
is Bp11026_II1055 (
bcaB
), which encodes a putative prolyl 4-hydroxylase. To investigate the role of these genes in pathogenesis, large in-frame deletion mutations of
bcaA
and
bcaB
were constructed in strain Bp340, an efflux pump mutant derivative of the melioidosis clinical isolate 1026b. Comparison of Bp340Δ
bcaA
and Bp340Δ
bcaB
mutants to wild-type
B. pseudomallei
in vitro
demonstrated similar levels of adherence to A549 lung epithelial cells, but the mutant strains were defective in their ability to invade these cells and to form plaques. In a BALB/c mouse model of intranasal infection, similar bacterial burdens were observed after 48 h in the lungs and liver of mice infected with Bp340Δ
bcaA
, Bp340Δ
bcaB
, and wild-type bacteria. However, significantly fewer bacteria were recovered from the spleen of Bp340Δ
bcaA
-infected mice, supporting the idea of a role for this AT in dissemination or in survival in the passage from the site of infection to the spleen.
Simultaneous hypertensive intracerebral haemorrhages: what are the odds?
Authors: Amin Osama S M 
Published: January 2013

The simultaneous development of two (or more) spontaneous, hypertensive, non-traumatic intraparenchymal cerebral haemorrhages is rare and constitutes less than 5.6% of all hypertensive cerebral haemorrhages. In addition to having a high early mortality, these haemorrhages carry a considerable morbidity figure in patients who survive the event. We report a 68-year-old hypertensive and diabetic woman who presented with a sudden onset of headache, vomiting, and dense right-sided weakness. In less than an hour, she became obtunded. An urgent non-contrast CT brain scan revealed two left-sided supratentorial hemispheric haemorrhages; putamenal and thalamic.
Preclinical and Clinical Studies of Gamma Secretase Inhibitors with Docetaxel on Human Breast Tumors
Authors: Schott Anne F. , Landis Melissa D. , Dontu Gabriela , Griffith Kent A. , Layman Rachel M. , Krop Ian , Paskett Lacey A. , Wong Helen , Dobrolecki Lacey E. , Lewis Michael T. , Froehlich Amber M. , Paranilam Jaya , Hayes Daniel F. , Wicha Max S. , Chang Jenny C. 
Published: January 2013

Abstract
Purpose: Accumulating evidence supports the existence of breast cancer stem cells (BCSC), which are characterized by their capacity to self-renew and divide indefinitely and resistance to conventional therapies. The Notch pathway is important for stem cell renewal and is a potential target for BCSC-directed therapy.
Experimental Design: Using human breast tumorgraft studies, we evaluated the impact of gamma secretase inhibitors (GSI) on the BCSC population and the efficacy of combining GSI with docetaxel treatment. The mouse experimental therapy paralleled a concurrent clinical trial in patients with advanced breast cancer, designed to determine the maximum-tolerated dose of the GSI, MK-0752, administered sequentially with docetaxel, and to evaluate BCSC markers in serial tumor biopsies.
Results: Treatment with GSI reduced BCSCs in MC1 and BCM-2147 tumorgrafts by inhibition of the Notch pathway. GSI enhanced the efficacy of docetaxel in preclinical studies. In the clinical trial, 30 patients with advanced breast cancer were treated with escalating doses of MK-0752 plus docetaxel. Clinically, meaningful doses of both drugs were possible with manageable toxicity and preliminary evidence of efficacy. A decrease in CD44+/CD24−, ALDH+, and mammosphere-forming efficiency were observed in tumors of patients undergoing serial biopsies.
Conclusions: These preclinical data show that pharmacologic inhibition of the Notch pathway can reduce BCSCs in breast tumorgraft models. The clinical trial shows feasibility of combination GSI and chemotherapy, and together these results encourage further study of Notch pathway inhibitors in combination with chemotherapy in breast cancer. Clin Cancer Res; 19(6); 1512–24. ©2012 AACR.
ZEB1 Promotes Invasiveness of Colorectal Carcinoma Cells through the Opposing Regulation of uPA and PAI-1
Authors: Sánchez-Tilló Ester , de Barrios Oriol , Siles Laura , Amendola Pier G. , Darling Douglas S. , Cuatrecasas Miriam , Castells Antoni , Postigo Antonio 
Published: January 2013

Abstract
Purpose: Carcinoma cells enhance their invasive capacity through dedifferentiation and dissolution of intercellular adhesions. A key activator of this process is the ZEB1 transcription factor, which is induced in invading cancer cells by canonical Wnt signaling (β-catenin/TCF4). Tumor invasiveness also entails proteolytic remodeling of the peritumoral stroma. This study aimed to investigate the potential regulation by ZEB1 of the plasminogen proteolytic system constituted by the urokinase plasminogen activator (uPA), and its inhibitor, plasminogen activator inhibitor-1 (PAI-1).
Experimental Design: Through multiple experimental approaches, colorectal carcinoma (CRC) cell lines and samples from human primary CRC and ZEB1 (−/−) mice were used to examine ZEB1-mediated regulation of uPA and PAI-1 at the protein, mRNA, and transcriptional level.
Results: ZEB1 regulates uPA and PAI-1 in opposite directions: induces uPA and inhibits PAI-1. In vivo expression of uPA depends on ZEB1 as it is severely reduced in the developing intestine of ZEB1 null (−/−) mice. Optimal induction of uPA by Wnt signaling requires ZEB1 expression. ZEB1 binds to the uPA promoter and activates its transcription through a mechanism implicating the histone acetyltransferase p300. In contrast, inhibition of PAI-1 by ZEB1 does not involve transcriptional repression but rather downregulation of mRNA stability. ZEB1-mediated tumor cell migration and invasion depend on its induction of uPA. ZEB1 coexpresses with uPA in cancer cells at the invasive front of CRCs.
Conclusions: ZEB1 promotes tumor invasiveness not only via induction in cancer cells of a motile dedifferentiated phenotype but also by differential regulation of genes involved in stroma remodeling. Clin Cancer Res; 19(5); 1071–82. ©2013 AACR.
Rab25 Regulates Invasion and Metastasis in Head and Neck Cancer
Authors: Amornphimoltham Panomwat , Rechache Kamil , Thompson Jamie , Masedunskas Andrius , Leelahavanichkul Kantima , Patel Vyomesh , Molinolo Alfredo , Gutkind J. Silvio , Weigert Roberto 
Published: January 2013

AbstractPurpose: Head and neck squamous cell carcinoma (HNSCC) is one of the 10 most common cancers with a 50% five-year survival rate, which has remained unchanged for the past three decades. One of the major reasons for the aggressiveness of this cancer is that HNSCCs readily metastasize to cervical lymph nodes that are abundant in the head and neck region. Hence, discovering new molecules controlling the metastatic process as well as understanding their regulation at the molecular level are essential for effective therapeutic strategies.Experimental Design: Rab25 expression level was analyzed in HNSCC tissue microarray. We used a combination of intravital microscopy in live animals and immunofluorescence in an in vitro invasion assay to study the role of Rab25 in tumor cell migration and invasion.Results: In this study, we identified the small GTPase Rab25 as a key regulator of HNSCC metastasis. We observed that Rab25 is downregulated in HNSCC patients. Next, we determined that reexpression of Rab25 in a metastatic cell line is sufficient to block invasion in a three-dimensional collagen matrix and metastasis to cervical lymph nodes in a mouse model for oral cancer. Specifically, Rab25 affects the organization of F-actin at the cell surface, rather than cell proliferation, apoptosis, or tumor angiogenesis.Conclusion: These findings suggest that Rab25 plays an important role in tumor migration and metastasis, and that understanding its function may lead to the development of new strategies to prevent metastasis in oral cancer patients. Clin Cancer Res; 19(6); 1375–88. ©2013 AACR.
Prognostic and Predictive Value of Tumor Vascular Endothelial Growth Factor Gene Amplification in Metastatic Breast Cancer Treated with Paclitaxel with and without Bevacizumab; Results from ECOG 2100 Trial
Authors: Schneider Bryan P. , Gray Robert J. , Radovich Milan , Shen Fei , Vance Gail , Li Lang , Jiang Guanglong , Miller Kathy D. , Gralow Julie R. , Dickler Maura N. , Cobleigh Melody A. , Perez Edith A. , Shenkier Tamara N. , Vang Nielsen Kirsten , Müller Sven , Thor Ann , Sledge George W. , Sparano Joseph A. , Davidson Nancy E. , Badve Sunil S. 
Published: January 2013

Abstract
Purpose: Clinically validated biomarkers for anti-angiogenesis agents are not available. We have previously reported associations between candidate VEGFA single-nucleotide polymorphisms (SNP) and overall survival (OS) in E2100. The associations between tumor VEGFA amplification and outcome are evaluated here.
Experimental Design: E2100 was a phase III trial comparing paclitaxel with or without bevacizumab for patients with metastatic breast cancer. FISH to assess gene amplification status for VEGFA was conducted on paraffin-embedded tumors from 363 patients in E2100. Evaluation for association between amplification status and outcomes was conducted.
Results: Estrogen receptor (ER)+ or progesterone receptor (PR)+ tumors were less likely to have VEGFA amplification than ER/PR− tumors (P = 0.020). VEGFA amplification was associated with worse OS (20.2 vs. 25.3 months; P = 0.013) in univariate analysis with a trend for worse OS in multivariate analysis (P = 0.08). There was a significant interaction between VEGFA amplification, hormone receptor status, and study arm. Patients with VEGFA amplification and triple-negative breast cancers (TNBC) or HER2 amplification had inferior OS (P = 0.047); amplification did not affect OS for those who were ER+ or PR+ and HER2−. Those who received bevacizumab with VEGFA amplification had inferior progression-free survival (PFS; P = 0.010) and OS (P = 0.042); no association was seen in the control arm. Test for interaction between study arm and VEGFA amplification with OS was not significant.
Conclusion: VEGFA amplification in univariate analysis was associated with poor outcomes; this was particularly prominent in HER2+ or TNBCs. Additional studies are necessary to confirm the trend for poor OS seen on multivariate analysis for patients treated with bevacizumab. Clin Cancer Res; 19(5); 1281–9. ©2012 AACR.
Can the “Right” EGFR-Specific mAb Dramatically Improve EGFR-Targeted Therapy?
Authors: Sabbatino Francesco , Ferrone Soldano 
Published: January 2013

Abstract
EGF receptor (EGFR)–specific monoclonal antibodies (mAb) display limited therapeutic efficacy in EGFR-positive solid tumors. To overcome this limitation, the significant improvement of the antibody-dependent cell-mediated cytotoxicity–mediated antitumor activity of a novel EGFR-specific mAb is described. Its potential impact on the efficacy of immunotherapy for EGFR-positive solid tumors is discussed. Clin Cancer Res; 19(5); 958–60. ©2013 AACR.
Transcatheter Closure of Post-myocardial Infarction Ventricular Septal Rupture
Authors: Assenza Gabriele Egidy , McElhinney Doff B. , Valente Anne Marie , Pearson Disty D. , Volpe Massimo , Martucci Giuseppe , Landzberg Michael J. , Lock James E. 
Published: January 2013

Background—
Ventricular septal rupture (VSR) after acute myocardial infarction (AMI) is a potentially lethal mechanical complication of acute coronary syndromes. Given high surgical mortality, transcatheter closure has emerged as a potential strategy in selected cases. We report our single-center experience with double-umbrella device percutaneous closure of post-AMI VSR.

Methods and Results—

In this single-center, retrospective, cohort study, patients who underwent transcatheter closure of post-AMI VSR between 1988 and 2008 at Boston Children’s Hospital were included. Data were analysed according to whether the patients underwent direct percutaneous VSR closure or closure of a residual VSR after a previous surgical approach. Primary outcome was mortality rate at 30 days. Clinical predictors of primary outcome were investigated using univariate logistic regression. Thirty patients were included in the study (mean age, 67±8 years). A total of 40 closure devices were implanted. Major periprocedural complications occurred in 4 (13%) patients. Cardiogenic shock, increasing pulmonary/systemic flow ratio, and the use of the new generation (6-arm) STARFlex device all were associated with higher risk of mortality. The Model for End-Stage Liver Disease Excluding international normalized ratio (MELD-XI) score at the time of VSR closure seemed to be most strongly associated with death (odds ratio, 1.6; confidence interval, 1.1–2.2;
P
<0.001).

Conclusions—
Transcatheter closure of post-AMI VSR using CardioSEAL or STARFlex devices is feasible and effective. The MELD-XI score, a marker of multiorgan dysfunction, is a promising risk stratifier in this population of patients. Early closure of post-AMI VSR is advisable before establishment of multiorgan failure.
Duration of Cardiopulmonary Resuscitation and Illness Category Impact Survival and Neurologic Outcomes for In-hospital Pediatric Cardiac Arrests
Authors: Matos Renée I. , Watson R. Scott , Nadkarni Vinay M. , Huang Hsin-Hui , Berg Robert A. , Meaney Peter A. , Carroll Christopher L. , Berens Richard J. , Praestgaard Amy , Weissfeld Lisa , Spinella Philip C. 
Published: January 2013

Background—
Pediatric cardiopulmonary resuscitation (CPR) for >20 minutes has been considered futile after pediatric in-hospital cardiac arrests. This concept has recently been questioned, although the effect of CPR duration on outcomes has not recently been described. Our objective was to determine the relationship between CPR duration and outcomes after pediatric in-hospital cardiac arrests.

Methods and Results—
We examined the effect of CPR duration for pediatric in-hospital cardiac arrests from the Get With The Guidelines–Resuscitation prospective, multicenter registry of in-hospital cardiac arrests. We included 3419 children from 328 US and Canadian Get With The Guidelines–Resuscitation sites with an in-hospital cardiac arrest between January 2000 and December 2009. Patients were stratified into 5 patient illness categories: surgical cardiac, medical cardiac, general medical, general surgical, and trauma. Survival to discharge was 27.9%, but only 19.0% of all cardiac arrest patients had favorable neurological outcomes. Between 1 and 15 minutes of CPR, survival decreased linearly by 2.1% per minute, and rates of favorable neurological outcome decreased by 1.2% per minute. Adjusted probability of survival was 41% for CPR duration of 1 to 15 minutes and 12% for >35 minutes. Among survivors, favorable neurological outcome occurred in 70% undergoing <15 minutes of CPR and 60% undergoing CPR >35 minutes. Compared with general medical patients, surgical cardiac patients had the highest adjusted odds ratios for survival and favorable neurological outcomes, 2.5 (95% confidence interval, 1.8–3.4) and 2.7 (95% confidence interval, 2.0–3.9), respectively.

Conclusions—
CPR duration was independently associated with survival to hospital discharge and neurological outcome. Among survivors, neurological outcome was favorable for the majority of patients. Performing CPR for >20 minutes is not futile in some patient illness categories.
Levels of Subjective Globalization: Ideologies, Imaginaries, Ontologies
Authors: Steger Manfred B. , James Paul 
Published: January 2013

AbstractThe subjective dimensions of globalization have not received even close to the level of attention that has been paid to the objective dimensions of global interchange and extension. Seeking to rectify this neglect, we argue that the subjective dimensions of globalization can be conceptualized in terms of three dimensions or levels: ideologies, imaginaries, and ontologies. The Occupy Movement in several global locations seeks to challenge global capitalism as the dominant system of economics. At the ideological level, activists connected to Occupy tend to engage in fierce contestation of the global structuring of greed, thus exhibiting clear signs of global rebellion. However, the terms of debate and critique tend to become increasingly uncontested as we go deeper into examining the dominant social imaginary and the ontologies of modern time and space that underpin this general sense of the global. Occupy is clearly an important variant of “justice globalism” that has inspired scores of young activists to protest against increasing inequality and the growing concentration of wealth in the hands of a tiny minority. Still, we suggest that this important alter-globalization movement often works within many of the same subjective frameworks and precepts as the market-globalist world that it criticizes.
New Social Movements and the Egyptian Spring: A Comparative Analysis between the April 6 Movement and the Revolutionary Socialists
Authors: Hafez Bassem Nabil 
Published: January 2013

Abstract
In this article I will comparatively analyze the conceptual foundations of two Egyptian protest movements, the April 6 Movement and the Revolutionary Socialists, two prominent instigators of the Egyptian revolution, as part of the global rebellion against the dystopia perceived as the creation of neo-liberalism and globalization. In Egypt, the limitations of conventional opposition led to the mushrooming of New Social Movements (NSMs) over the past decade. The political dynamics since 2000 have yielded, among many, the aforementioned youth movements that represent two different approaches to the rebellion against the dystopia, which speeded up the downfall of Mubarak.
The Korean Wave: An Asian Reaction to Western-Dominated Globalization
Authors: Hogarth Hyun-key Kim 
Published: January 2013

AbstractIn this article I analyze “the Korean Wave (hallyu),” the term coined by Chinese media towards the end of the last millennium to describe the meteoric rise in the popularity of Korean pop culture in Asian countries. It has attracted the attention of not only the general public, but also academic and other researchers because of the far-reaching ramifications in terms of the Korean national economy and the cultural unity and exchange among the Asian peoples.The world of popular entertainment has seen a high degree of globalization with Hollywood as its utopia. However, Hollywood has proved to be a dystopia to the peoples of Asia, in that it is dominated by non-Asians, and underpinned by the contemporary Western ethos, i.e. individualism, commercialism and sensationalism. Scenes containing unadulterated sex and violence, which offend the sensitivities of the Asian general public, are almost an integral part of many a commercially successful film. Opportunities for big roles are almost non-existent to ethnic Asian actors. Romantic heroes and heroines are very rarely played by Asian actors, who usually appear as weird villains or, very rarely, wizards with supernatural powers.In contemporary Korean cinemas, TV dramas and pop music, globalization is also evident. The stars follow the world trend in performance, presentation and fashion, and emulate their Western compatriots. English is often used as lyrics in songs. However, the big difference is that the performers have distinct Asian physical features, and the dramas reflect the traditional Asian values and ethos, which helps to make the Asian fans feel at home. The “Asian-ness” is no longer something weird or marginal, but takes center stage. Therefore there is a sense in which the Korean Wave is a reaction of the Asian people to the West-dominated globalization in popular culture. But what distinguishes the Korean Wave from other similar phenomena, such as Bollywood and Nollywood, is the juxtaposition of globalized and traditional Korean cultures.
“Occupying” Our Social Imagination: The Necessity of Utopian Discourses in an Anti-Utopian Age
Authors: Webb Graeme 
Published: January 2013

AbstractWe are in the depths of multiple catastrophes that Western society is seemingly unwilling and unable to address: growing inequalities between the rich and the poor, a willful blindness to climate change, and a political system mired in uncompromising and ever increasing extremism. However, there are no reality transcending dialogues, no new social imaginaries to drive change—our own dystopic reality has no utopian response. The greatest importance that the Occupy movements may play in spurring social change and revolution is their success at bringing radical discourses into mainstream society. Occupy not only occupied fixed public locations, but also occupied our social imagination.
Governmentality and the Analytics of Development
Authors: Ove Peter 
Published: January 2013

AbstractIn this article, I discuss the extension of Foucault’s work on governmentality into the fields of global studies in general and development studies in particular. Drawing on insights from postdevelopment theory and critical race theory, I present an adaptation of governmentality—labeled developmentality—that is intended to bridge the gap between those studies dealing with the regulatory aspects of development in the global South and those dealing with construction of ethical identities in the North.
Two Hoards of Coins and Jewellery Items from the Time of the Roman-Bosporan War of AD 45–49 from the Site of Artezian
Authors: Abramzon Mikhail G. , Treister Mikhail Yu. , Vinokurov Nikolaï I. 
Published: January 2013

Abstract
This article is the publication of two hoards found in 2009 during excavations of the fortified settlement of Artezian in the Eastern Crimea, which met its end at the very beginning of the Roman-Bosporan war of AD 45–49. The assemblages contain 244 bronze Bosporan coins from the end of the 1st century BC to the first half of the 1st century AD (Caesarea, Agrippia, Aspurgus, Gepaepyris, Mithridates VIII), 10 silver denarii of the Roman emperors Augustus and Tiberius, and also various items of gold, silver and bronze jewellery and glass vessels. The discovery of these hoards not only provides further archaeological confirmation of the historical events of the mid-1st century BC, but also makes it possible to establish, with more precision, the chronology of certain categories of jewellery items and glass vessels, which in a number of cases had only been represented by rare specimens of Bosporan, Eastern-Mediterranean and Roman workmanship of a high level. Deserving of special attention is the find, in the context of hoards, of a well-preserved gladius of the Mainz type. For the first time it has proved possible reliably to record the initial phase of the Bosporan-Roman War of AD 45–49 at an archaeological site, situated within the territory of the European Bosporus. The unique nature of the materials from Artezian lies in their diversity and the narrow chronological range of their hoarding, linked to important events of not only Bosporan but also Mediterranean history, which had a considerable influence on the military-political situation in the Pontic region.