bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational Combination of a MEK Inhibitor, Selumetinib, and the Wnt/Calcium Pathway Modulator, Cyclosporin A, in Preclinical Models of Colorectal Cancer
Authors: Spreafico Anna , Tentler John J. , Pitts Todd M. , Tan Aik Choon , Gregory Mark A. , Arcaroli John J. , Klauck Peter J. , McManus Martine C. , Hansen Ryan J. , Kim Jihye , Micel Lindsey N. , Selby Heather M. , Newton Timothy P. , McPhillips Kelly L. , Gustafson Daniel L. , DeGregori James V. , Messersmith Wells A. , Winn Robert A. , Eckhardt S. Gail 
Published: June 2013

Abstract
Purpose: The mitogen-activated protein kinase (MAPK) pathway is a crucial regulator of cell proliferation, survival, and resistance to apoptosis. MEK inhibitors are being explored as a treatment option for patients with KRAS-mutant colorectal cancer who are not candidates for EGFR-directed therapies. Initial clinical results of MEK inhibitors have yielded limited single-agent activity in colorectal cancer, indicating that rational combination strategies are needed.
Experimental Design: In this study, we conducted unbiased gene set enrichment analysis and synthetic lethality screens with selumetinib, which identified the noncanonical Wnt/Ca++ signaling pathway as a potential mediator of resistance to the MEK1/2 inhibitor selumetinib. To test this, we used shRNA constructs against relevant WNT receptors and ligands resulting in increased responsiveness to selumetinib in colorectal cancer cell lines. Further, we evaluated the rational combination of selumetinib and WNT pathway modulators and showed synergistic antiproliferative effects in in vitro and in vivo models of colorectal cancer.
Results: Importantly, this combination not only showed tumor growth inhibition but also tumor regression in the more clinically relevant patient-derived tumor explant (PDTX) models of colorectal cancer. In mechanistic studies, we observed a trend toward increased markers of apoptosis in response to the combination of MEK and WntCa++ inhibitors, which may explain the observed synergistic antitumor effects.
Conclusions: These results strengthen the hypothesis that targeting both the MEK and Wnt pathways may be a clinically effective rational combination strategy for patients with metastatic colorectal cancer. Clin Cancer Res; 19(15); 4149–62. ©2013 AACR.
microRNA 223 Is Upregulated in the Multistep Progression of Barrett's Esophagus and Modulates Sensitivity to Chemotherapy by Targeting PARP1
Authors: Streppel Mirte Mayke , Pai Shweta , Campbell Nathaniel R. , Hu Chaoxin , Yabuuchi Shinichi , Canto Marcia Irene , Wang Jean S. , Montgomery Elizabeth A. , Maitra Anirban 
Published: June 2013

Abstract
Purpose: Recent microarray and RNA-sequencing studies have uncovered aberrantly expressed microRNAs (miRNA) in Barrett's esophagus–associated esophageal adenocarcinoma. The functional significance of these miRNAs in esophageal adenocarcinoma initiation and progression is largely unknown.
Experimental Design: Expression levels of miR-199a/b-3p, -199a-5p, -199b-5p, -200b, -200c, -223, and -375 were determined in microdissected tissues from cardiac mucosa, Barrett's esophagus, dysplastic Barrett's esophagus, and esophageal adenocarcinoma using quantitative real-time PCR. miR-223 expression was validated in precursors and esophageal adenocarcinomas from 95 patients with esophageal adenocarcinoma by in situ hybridization (ISH). miR-223 was transfected into two esophageal adenocarcinoma cell lines, and in vitro assays were conducted. Target genes were identified using Illumina microarray, and results were validated in cell lines and human specimens.
Results: miR-199 family members and miR-223 were significantly overexpressed in esophageal adenocarcinoma, however, only miR-223 showed a stepwise increase during esophageal adenocarcinoma carcinogenesis. A similar trend was observed by ISH, which additionally showed that miR-223 is exclusively expressed by the epithelial compartment. miR-223–overexpressing cells had statistically significantly more migratory and invasive potential than scramble sequence–transfected cells. PARP1 was identified as a direct target gene of miR-223 in esophageal adenocarcinoma cells. Increased sensitivity to chemotherapy was observed in cells with enforced miR-223 expression and reduced PARP1.
Conclusions: miR-223 is significantly upregulated during the Barrett's esophagus–dysplasia–esophageal adenocarcinoma sequence. Although high miR-223 levels might contribute to an aggressive phenotype, our results also suggest that patients with esophageal adenocarcinoma with high miR-223 levels might benefit from treatment with DNA-damaging agents. Clin Cancer Res; 19(15); 4067–78. ©2013 AACR.
Modulation of OATP1B-Type Transporter Function Alters Cellular Uptake and Disposition of Platinum Chemotherapeutics
Authors: Lancaster Cynthia S. , Sprowl Jason A. , Walker Aisha L. , Hu Shuiying , Gibson Alice A. , Sparreboom Alex 
Published: June 2013

Abstract
Expression of the human organic anion transporting polypeptides OATP1B1 and OATP1B3 has been previously believed to be restricted to hepatocytes. Here we show that the gene encoding OATP1B3, but not OATP1B1, is abundantly expressed in multiple human solid tumors that include hepatocellular, lung, and ovarian carcinomas. Surprisingly, OATP1B3 gene expression in a panel of 60 human tumor cell lines was linked with sensitivity to multiple cytotoxic agents, including the platinum anticancer drugs cisplatin, carboplatin, and oxaliplatin. In addition, overexpression of OATP1B3 in mammalian cells increased cellular accumulation of platinum agents and decreased cell survival. In mice with a targeted disruption of the ortholog transporter Oatp1b2, the liver-to-plasma ratio of cisplatin was significantly reduced compared with wild-type mice, without concurrent changes in expression profiles of other transporter genes. Our findings indicate an unexpected role for tumoral and host OATP1B-type carriers in the toxicity and disposition of platinum anticancer drugs, and may provide a foundation for understanding the extensive interindividual pharmacodynamic variability seen with these drugs in patients. Mol Cancer Ther; 12(8); 1537–44. ©2013 AACR.
Validation and Prognosis of Coronary Artery Calcium Scoring in Nontriggered Thoracic Computed Tomography
Authors: Xie Xueqian , Zhao Yingru , de Bock Geertruida H. , de Jong Pim A. , Mali Willem P. , Oudkerk Matthijs , Vliegenthart Rozemarijn 
Published: June 2013

Background—
Coronary calcium score (CS), traditionally based on electrocardiography-triggered computed tomography (CT), predicts cardiovascular risk. Currently, nontriggered thoracic CT is extensively used, such as in lung cancer screening. The purpose of the study was to determine the correlation in CS between nontriggered and electrocardiography-triggered CT, and to evaluate the prognostic performance of the CS derived from nontriggered CT.

Methods and Results—
PubMed, Embase, and Web of Knowledge were searched until November 2012. Two reviewers independently screened 2120 records to identify studies reporting the CS in nontriggered CT and extracted information. Study quality was evaluated by standardized assessment tools. Cohen κ was extracted for agreement of CS categories between nontriggered and electrocardiography-triggered CT (validation). Hazard ratio (HR) was extracted for prognostic performance. Five studies about validation comprising 1316 individuals were included. Five studies about prognosis comprising 34 028 cardiac asymptomatic individuals, mainly from lung cancer screening trials, were included. All studies were of high quality. Meta-analysis could only be performed for validation studies because studies on prognostic performance were highly heterogeneous. Pooled Cohen κ for agreement between the 2 techniques was 0.89 (95% confidence interval, 0.83–0.95) for increasing CS categories. Increasing CS categories were associated with increasing risk of cardiovascular death or events. Nontriggered CT yielded false-negative CS in 8.8% of individuals and underestimated high CS in 19.1% of individuals.

Conclusions—
Our analysis shows the prognostic value and potential role of nontriggered assessment of coronary calcium, but it does not suggest that electrocardiography-triggered CT should be replaced by nontriggered examinations.
Vasodilatory Capacity of the Coronary Microcirculation is Preserved in Selected Patients With Non–ST-Segment–Elevation Myocardial Infarction
Authors: Layland Jamie , Carrick David , McEntegart Margaret , Ahmed Nadeem , Payne Alex , McClure John , Sood Arvind , McGeoch Ross , MacIsaac Andrew , Whitbourn Robert , Wilson Andrew , Oldroyd Keith , Berry Colin 
Published: June 2013

Background—
The use of fractional flow reserve in patients with non–ST-segment–elevation myocardial infarction (NSTEMI) is a controversial issue. We undertook a study to assess the vasodilatory capacity of the coronary microcirculation in patients with NSTEMI when compared with a model of preserved microcirculation (stable angina [SA] cohort: culprit and nonculprit vessel) and acute microcirculatory dysfunction (ST-segment–elevation myocardial infarction [STEMI] cohort). We hypothesized that the vasodilatory response of the microcirculation would be preserved in NSTEMI.

Methods and Results—

A total of 140 patients undergoing single vessel percutaneous coronary intervention were included: 50 stable angina, 50 NSTEMI, and 40 STEMI. The index of microvascular resistance (IMR), fractional flow reserve, and coronary flow reserve were measured before stenting in the culprit vessel and in an angiographically normal nonculprit vessel in patients with SA. The resistive reserve ratio, a measure of the vasodilatory capacity of the microcirculation and calculated using the equation: baseline resistance index (
Tmn
Base
×
Pa
Base
[
Pd
Base
–
Pw
/
Pa
Base
–
Pw
])–IMR/IMR, where
Tmn
Base
referred to nonhyperemic transit time;
Pa
Base
and
Pd
Base
, the nonhyperemic aortic and distal coronary pressures, respectively; and
Pw
referred to the coronary wedge pressure, was also measured. Troponin was also measured ≤24 hours after percutaneous coronary intervention. The resistive reserve ratio was significantly lower in the STEMI patients compared with the stable angina patients both culprit and nonculprit vessel (STEMI, 1.7 versus SA culprit, 2.8;
P
≤0.001 and SA nonculprit, 2.9;
P
<0.0001) and compared with NSTEMI patients (NSTEMI, 2.46;
P
≤0.001). The resistive reserve ratio was similar in stable angina and NSTEMI patients (
P
=0.6). IMR was significantly higher pre-PCI in STEMI compared with SA and NSTEMI (IMR STEMI, 36.51 versus IMR NSTEMI, 22.73 [
P
=0.01] versus IMR SA, 18.26 [
P
<0.0001]). However, there was no significant difference in IMR pre-PCI between NSTEMI and SA (IMR NSTEMI, 22.73; IMR SA, 18.26 [
P
=0.1]).

Conclusions—
The vasodilatory capacity of the microcirculation is preserved in selected patients with NSTEMI. The clinical use of fractional flow reserve in the culprit vessel may be preserved in selected patents with NSTEMI.
Bloodstream Infections Occurring in Patients With Percutaneously Implanted Bioprosthetic Pulmonary Valve
Authors: Buber Jonathan , Bergersen Lisa , Lock James E. , Gauvreau Kimberlee , Esch Jesse J. , Landzberg Michael J. , Valente Anne Marie , Sandora Thomas J. , Marshall Audrey C. 
Published: June 2013

Background—
Percutaneous pulmonary valve implantation using a stent-based bioprosthetic valve provides an alternative to surgery in select patients. Systemic infections in Melody valve–implanted patients with and without identified valve involvement have been reported, yet the incidence is unknown, and risk factors remain unidentified.

Methods and Results—
Between 2007 and 2012, a total of 147 consecutive patients with congenital heart disease underwent Melody percutaneous pulmonary valve implantation at our institution. Demographic and clinical variables were collected at baseline and at follow-up and analyzed as predictors. The occurrence of bloodstream infection (BSI), defined as a bacterial infection treated with ≥4 weeks of antibiotics, served as our primary outcome. The mean age at implantation for the study population was 21.5±11 years, and tetralogy of Fallot was the cardiac condition in 59%. During a median follow-up of 19 months, 14 patients experienced BSI (9.5%; 95% confidence interval, 5.3%–15%). Of these, 4 (2.7%) patients had Melody valve endocarditis. Two patients died during the event, neither of whom had known valve involvement. The median procedure to infection time was 15 months (range, 1–56). In univariate analysis, male sex, previous endocarditis, in situ stents in the right ventricular outflow tract, and presence of outflow tract irregularities at the implant site were associated with BSI occurrence.

Conclusions—
In this cohort, 9.5% of patients who underwent Melody percutaneous pulmonary valve implantation experienced subsequent BSI, occurring 1 to 56 months after implant, and 2.7% of patients had prosthetic endocarditis. Our findings suggest that patient and nonvalve anatomic factors may be associated with BSI after percutaneous pulmonary valve implantation.
End of Study Transition From Study Drug to Open-Label Vitamin K Antagonist Therapy
Authors: Mahaffey Kenneth W. , Hellkamp Anne S. , Patel Manesh R. , Hannan Karen L. , Schwabe Kimberly , Nessel Christopher C. , Berkowitz Scott D. , Halperin Jonathan L. , Hankey Graeme J. , Becker Richard C. , Piccini Jonathan P. , Breithardt Günter , Hacke Werner , Singer Daniel E. , Califf Robert M. , Fox Keith A.A. 
Published: June 2013

Background—
To evaluate the previously reported excess of thromboembolic events during the 30 days after the end of study (EOS) visit when participants transitioned from blinded therapy to open-label vitamin K antagonist.

Methods and Results—

At the EOS visit, open-label vitamin K antagonist was recommended, and the international normalized ratio (INR) was not to be measured until 3 days later to preserve blinding. We analyzed transition strategies, clinical outcomes, and INR values. Event rates are per 100 patient-years. A total of 9248 (65%) participants were taking study drug at EOS, and, between days 3 and 30, an excess of stroke and systemic embolic events were observed in participants assigned to rivaroxaban (rivaroxaban 22 events, event rate 6.42; warfarin 6 events, event rate 1.73; hazard ratio, 3.72; 95% confidence interval, 1.51–9.16;
P
=0.0044). No INR values were reported for ≈5% of participants transitioned to warfarin. By 30 days after EOS, 83% of the warfarin group and 52% of the rivaroxaban group had ≥1 therapeutic INR value. Median time to first therapeutic INR was 3 days in the warfarin group and 13 days in the rivaroxaban group.

Conclusions—
The excess of events at EOS was likely because of a period of inadequate anticoagulation in rivaroxaban participants switched to vitamin K antagonist therapy. If transition from rivaroxaban to vitamin K antagonist is needed, timely monitoring and careful dosing should be used to ensure consistent and adequate anticoagulation.
Timing-Invariant Imaging of Collateral Vessels in Acute Ischemic Stroke
Authors: Smit Ewoud J. , Vonken Evert-jan , van Seeters Tom , Dankbaar Jan Willem , van der Schaaf Irene C. , Kappelle L. Jaap , van Ginneken Bram , Velthuis Birgitta K. , Prokop Mathias 
Published: June 2013

Background and Purpose—
Although collateral vessels have been shown to be an important prognostic factor in acute ischemic stroke, patients with lack of collaterals on standard imaging techniques may still have good clinical outcome. We postulate that in these cases collateral vessels are present though not visible on standard imaging techniques that are based on a single time frame.

Methods—
This study included 40 consecutive patients with acute ischemic stroke with a large-vessel occlusion. Standard computed tomography angiography (CTA, single time frame) and CT perfusion (multiple time frames) were obtained at admission and timing-invariant (TI)-CTA was created from the CT perfusion data. Clinical outcome data (modified Rankin Scale) were assessed at 3-month follow-up. Four experienced observers independently assessed collateral status twice on both standard CTA and TI-CTA in an independent, blinded, randomized manner. Collateral status was rated as good if ≥50% and poor if <50% of collaterals were present compared with the contralateral hemisphere.

Results—

Collateral status was rated higher on TI-CTA (good in 84%) compared with standard CTA (good in 49%;
P
<0.001). Thirty-one percent of patients with poor collateral status on standard CTA still had good clinical outcome. All of those patients, however, showed good collaterals on TI-CTA. All cases with poor collateral status rated on TI-CTA had poor clinical outcome.

Conclusions—
Collateral vessels may not always be visible on standard single time-frame CTA because of delayed contrast arrival. Future prognostic studies in acute stroke should consider delay-insensitive techniques, such as TI-CTA, instead of standard single time-frame imaging, such as standard CTA.
A “Greek God” in a Japanese New Religion: On Hermes in Kōfuku-no-Kagaku
Authors: Winter Franz 
Published: June 2013

Abstract
The article deals with the presence of the “Greek god” Hermes in the Japanese new religious movement Kōfuku-no-Kagaku, which was founded in 1986. The various references are interpreted in light of the history and development of the movement and with regard to its setting in present-day Japanese religious culture. In addition to the importance of several aspects of the reception of the Euro-American New Age tradition and the prophecies of Nostradamus, the fact that the figure of Hermes is presented as the hero of several manga and anime productions of Kōfuku-no-Kagaku is also taken into consideration. This leads to the theoretical question of the importance of the new media of representation of religious content and the effect this approach has on the development of the various groups.
‘Un paradigma in cielo’. Platone politico da Aristotele al Novecento, Mario Vegetti, Rome: Carocci, 2009
Authors: Arruzza Cinzia 
Published: June 2013

Abstract
Vegetti’s book tries to decipher and recast the complex history of the interpretation of the political Plato in a compelling historical and philosophical analysis. This review article presents an intellectual profile of Mario Vegetti and a critical engagement with his historical and politico-philosophical approach. It concludes with the suggestion that we should investigate the vicious circle of philosophy and politics in Plato’s Republic in light of Marx’s Theses on Feuerbach.
Imagining the King’s Death: Figurative Treason, Fantasies of Regicide, 1793–1796, John Barrell, Oxford: Oxford University Press, 2000
Authors: Hayward Danny 
Published: June 2013

AbstractThis review essay has two divisions. In its first division it sets out a brief overview of recent Marxist research in the field of ‘Romanticism’, identifying two major lines of inquiry. On the one hand, the attempt to expand our sense of what might constitute a ruthless critique of social relations; on the other, an attempt to develop a materialist account of aesthetic disengagement. This first division concludes with an extended summary of John Barrell’s account of the treason trials of the middle 1790s, as set out in his bookImagining the King’s Death. It argues that Barrell’s book is the most significant recent work belonging to the second line of inquiry. In its second division the review responds to Barrell’s concluding discussion, in which the aesthetic consequences of the treason trials are established by means of a close reading of some of the poetry of Samuel Taylor Coleridge. The division finishes with some more general remarks on the subject of a materialist aesthetics of disengagement.
Sohn-Rethel and the Origin of ‘Real Abstraction’: A Critique of Production or a Critique of Circulation?
Authors: Jappe Anselm 
Published: June 2013

AbstractAlfred Sohn-Rethel did not just elaborate a materialist theory of knowledge, he also introduced the term ‘real abstraction’ into Marxist debate. However, he locates the origin of commodity abstraction solely in the sphere of circulation, conceiving of production itself as a mere metabolism with nature. This conception, in which the critique of capitalism aims exclusively at distribution, and which rejects the Marxian concept of ‘abstract labour’, remains widespread. It is our express intention here to undertake a critique of such a conception for the benefit of a critique of the very mode of capitalist production.
Manifeste pour une philosophie sociale, Franck Fischbach, Paris: La Découverte, 2009
Authors: Toscano Alberto 
Published: June 2013

AbstractIn this polemical intervention within the field of French and European social theory, Franck Fischbach proposes to revive and radicalise the tradition of social philosophy. The latter is understood, following Axel Honneth, in terms of the normatively-driven analysis of socio-economic processes that may be characterised as pathologies of the social. Fischbach contrasts the lessons of social philosophy from Rousseau to the Frankfurt School with the recent ascendance to intellectual hegemony of a formalistic, procedural liberalism which is oblivious to social negativity. The review questions the capacity of social philosophy to synthesise stances as politically and methodologically different as those of de Maistre, Nietzsche and Marx, as well as the very pertinence of the appellation ‘philosophy’. Fischbach’s more historically determinate definition of social philosophy as arising out of the critique of Jacobin revolutionary political thought, with its supposed abstraction and voluntarism, fails to contend with the claims of ruptural politics, as well as with those positions that would regard crisis and pathology not just as a menace, but also as an opportunity for liberation. In the end, in spite of its able historical and conceptual mapping, and its commendable demand for totalising critique, Fischbach fails to persuade in his claim that social philosophy is the name for emancipatory thought in the present.
Census and Censure: Sacred Threshing Floors and Counting Taboos in 2 Samuel 24
Authors: Park Song-Mi Suzie 
Published: June 2013

Abstract
Focusing on the mythological features in the story of David’s census and the plague at the threshing floor of Araunah in 2 Samuel 24, this paper argues that David, by conducting a census, transgressed the power of God by mimicking God’s creator/counter role. By examining the mythological aspects of the story, such as cosmogony, threshing floors, counting taboos, sacrifice and temple building, this paper argues that the narrative disparages David’s kingly status in order to assert God’s position as the ultimate king, creator and counter. Moreover, the story points towards the future function of Araunah’s threshing floor as the site of Solomon’s Temple, a place that would symbolize the continual presence, power and rule of the Israelite deity.