bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone Acetyltransferase PCAF Is Required for Hedgehog–Gli-Dependent Transcription and Cancer Cell Proliferation
Authors: Malatesta Martina , Steinhauer Cornelia , Mohammad Faizaan , Pandey Deo P. , Squatrito Massimo , Helin Kristian 
Published: August 2013

Abstract
The Hedgehog (Hh) signaling pathway plays an important role in embryonic patterning and development of many tissues and organs as well as in maintaining and repairing mature tissues in adults. Uncontrolled activation of the Hh–Gli pathway has been implicated in developmental abnormalities as well as in several cancers, including brain tumors like medulloblastoma and glioblastoma. Inhibition of aberrant Hh–Gli signaling has, thus, emerged as an attractive approach for anticancer therapy; however, the mechanisms that mediate Hh–Gli signaling in vertebrates remain poorly understood. Here, we show that the histone acetyltransferase PCAF/KAT2B is an important factor of the Hh pathway. Specifically, we show that PCAF depletion impairs Hh activity and reduces expression of Hh target genes. Consequently, PCAF downregulation in medulloblastoma and glioblastoma cells leads to decreased proliferation and increased apoptosis. In addition, we found that PCAF interacts with GLI1, the downstream effector in the Hh–Gli pathway, and that PCAF or GLI1 loss reduces the levels of H3K9 acetylation on Hh target gene promoters. Finally, we observed that PCAF silencing reduces the tumor-forming potential of neural stem cells in vivo. In summary, our study identified the acetyltransferase PCAF as a positive cofactor of the Hh–Gli signaling pathway, leading us to propose PCAF as a candidate therapeutic target for the treatment of patients with medulloblastoma and glioblastoma. Cancer Res; 73(20); 6323–33. ©2013 AACR.
FGFR4 Promotes Stroma-Induced Epithelial-to-Mesenchymal Transition in Colorectal Cancer
Authors: Liu Rui , Li Jingyi , Xie Ke , Zhang Tao , Lei Yunlong , Chen Yi , Zhang Lu , Huang Kai , Wang Kui , Wu Hong , Wu Min , Nice Edouard C. , Huang Canhua , Wei Yuquan 
Published: August 2013

Abstract
Tumor cells evolve by interacting with the local microenvironment; however, the tumor–stroma interactions that govern tumor metastasis are poorly understood. In this study, proteomic analyses reveal that coculture with tumor-associated fibroblasts (TAF) induces significant overexpression of FGFR4, but not other FGFRs, in colorectal cancer cell lines. Mechanistic study shows that FGFR4 plays crucial roles in TAF-induced epithelial-to-mesenchymal transition (EMT) in colorectal cancer cell lines. Accumulated FGFR4 in cell membrane phosphorylates β-catenin, leading to translocation of β-catenin into the nucleus. Further, TAF-derived CCL2 and its downstream transcription factor, Ets-1, are prerequisites for TAF-induced FGFR4 upregulation. Furthermore, FGFR4-associated pathways are shown to be preferentially activated in colorectal tumor samples, and direct tumor metastasis in a mouse metastasis model. Our study shows a pivotal role of FGFR4 in tumor–stroma interactions during colorectal cancer metastasis, and suggests novel therapeutic opportunities for the treatment of colorectal cancer. Cancer Res; 73(19); 5926–35. ©2013 AACR.
Prognostic Significance of AMPK Activation and Therapeutic Effects of Metformin in Hepatocellular Carcinoma
Authors: Zheng Longyi , Yang Wen , Wu Fuquan , Wang Chao , Yu Lexing , Tang Liang , Qiu Bijun , Li Yuqiong , Guo Linna , Wu Mengchao , Feng Gensheng , Zou Dajin , Wang Hongyang 
Published: August 2013

Abstract
Purpose: The AMP-activated protein kinase (AMPK) serves as an energy sensor in eukaryotic cells and occupies a central role in linking metabolism and cancer development. However, the phosphorylation status of AMPK and its therapeutic value in human hepatocellular carcinoma (HCC) remain unclear.
Experimental Design: The phosphorylation status of AMPK (Thr172) was determined by immunoblotting and immunostaining in specimens from 273 patients with HCC (including 253 patients with hepatitis B virus -related HCC). Kaplan–Meier survival analysis was used to determine the correlation with prognosis. The effects of therapeutic metformin/AMPK activation were assessed in cultured human HCC cell lines and primary HCC cells in vitro and in xenograft tumors model in vivo. To define the mechanisms of anticancer effects of metformin, we examined its influence on AMPK activation and NF-κB pathway.
Results: AMPK is dysfunctional in patients with HCC, and low p-AMPK staining is correlated with aggressive clinicopathologic features and poor prognosis. Activation of AMPK by metformin not only inhibited HCC cells growth in vitro and in vivo, but also augmented cisplatin-induced growth inhibition in HCC cells. Knockdown of AMPKα expression can greatly decrease the inhibitory effect of metformin, indicating that AMPK activation is required for the anticancer action of metformin. Mechanistically, metformin/AMPK activation inhibited NF-κB signaling through upregulation of IκBα. Activation of NF-κB signaling by ectopic expression of P65 or overexpression of an undegradable mutant form of IκBα attenuated the anticancer effects of metformin.
Conclusions: These results present novel insight into a critical role of AMPK in HCC progression. Anticancer effects of therapeutic metformin/AMPK activation unravel metformin's potential in treatment of HCC. Clin Cancer Res; 19(19); 5372–80. ©2013 AACR.
Histone Deacetylase Inhibition Overcomes Drug Resistance through a miRNA-Dependent Mechanism
Authors: Murray-Stewart Tracy , Hanigan Christin L. , Woster Patrick M. , Marton Laurence J. , Casero Robert A. 
Published: August 2013

Abstract
The treatment of specific tumor cell lines with poly- and oligoamine analogs results in a superinduction of polyamine catabolism that is associated with cytotoxicity; however, other tumor cells show resistance to analog treatment. Recent data indicate that some of these analogs also have direct epigenetic effects. We, therefore, sought to determine the effects of combining specific analogs with an epigenetic targeting agent in phenotypically resistant human lung cancer cell lines. We show that the histone deacetylase inhibitor MS-275, when combined with (N1, N11)-bisethylnorspermine (BENSpm) or (N1, N12)-bis(ethyl)-cis-6,7-dehydrospermine tetrahydrochloride (PG-11047), synergistically induces the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT), a major determinant of sensitivity to the antitumor analogs. Evidence indicates that the mechanism of this synergy includes reactivation of miR-200a, which targets and destabilizes kelch-like ECH-associated protein 1 (KEAP1) mRNA, resulting in the translocation and binding of nuclear factor (erythroid-derived 2)-like 2 (NRF2) to the polyamine-responsive element of the SSAT promoter. This transcriptional stimulation, combined with positive regulation of SSAT mRNA and protein by the analogs, results in decreased intracellular concentrations of natural polyamines and growth inhibition. The finding that an epigenetic targeting agent is capable of inducing a rate-limiting step in polyamine catabolism to overcome resistance to the antitumor analogs represents a completely novel chemotherapeutic approach. In addition, this is the first demonstration of miRNA-mediated regulation of the polyamine catabolic pathway. Furthermore, the individual agents used in this study have been investigated clinically; therefore, translation of these combinations into the clinical setting holds promise. Mol Cancer Ther; 12(10); 2088–99. ©2013 AACR.
Thrombolysis for Ischemic Stroke Associated With Infective Endocarditis
Authors: Asaithambi Ganesh , Adil Malik M. , Qureshi Adnan I. 
Published: August 2013

Background and Purpose—
Cerebral ischemic events are highly prevalent and associated with high rates of death and disability in patients with infective endocarditis (IE). However, the role of thrombolysis in these patients remains unclear. We sought to determine the rates and outcomes of acute ischemic stroke patients with IE treated with intravenous thrombolysis (IVT).

Methods—
We determined the rates of post-thrombolytic intracerebral hemorrhage and favorable outcome among acute ischemic stroke patients with IE treated with IVT. Patients were identified using Nationwide Inpatient Sample data from 2002 to 2010. We compared the rates of various outcomes with ischemic stroke patients without IE treated with IVT.

Results—

There were 222 patients (mean age 59±18 years; 46% women) who were treated with IVT for acute ischemic stroke associated with IE and 134 048 patients (mean age 69±15 years; 49% women) who were treated for stroke without IE. The rate of post-thrombolytic intracerebral hemorrhage was significantly higher in patients with IE compared with those without IE (20% versus 6.5%;
P
=0.006). There was a significantly lower rate of favorable outcome in the IE group (10% versus 37%;
P
=0.01).

Conclusions—
High rates of post-thrombolytic intracerebral hemorrhage and low rates of favorable outcome mandate caution in using IVT in acute ischemic stroke patients with IE.
Dynamic Cerebral Autoregulation in Acute Intracerebral Hemorrhage
Authors: Oeinck Maximilian , Neunhoeffer Florian , Buttler Klaus-Juergen , Meckel Stephan , Schmidt Bernhard , Czosnyka Marek , Weiller Cornelius , Reinhard Matthias 
Published: August 2013

Background and Purpose—
Cerebral autoregulation (CA) is not universally impaired in acute intracerebral hemorrhage (ICH); however, the dynamic components of CA are probably more vulnerable. This study, therefore, evaluates the time course of dynamic CA in acute ICH and its relationship to clinical outcome.

Methods—
Twenty-six patients with ICH were studied on days 1, 3, and 5 after ictus. Dynamic CA was measured from spontaneous fluctuations in blood pressure and middle cerebral artery flow velocity by transfer function phase (reflecting rapidity of CA) and gain (reflecting damping characteristics of CA) in the low frequency range. Results were compared with those from 55 controls and related with clinical factors and 90-day outcome (modified Rankin scale).

Results—

Phase did not fluctuate significantly over time, nor did it differ between sides or differ from controls. Gain was always higher in patients than in controls but showed no significant association with outcome or other clinical factors. At day 1, poorer ipsilateral phase was associated with lower blood pressure and higher ICH volume. Poorer phase always coincided with lower Glasgow Coma Scale values. Poorer ipsilateral phase on day 5 was related with poorer clinical outcome according to multivariate analysis (
P
=0.013).

Conclusions—
Dynamic temporal characteristics of CA (phase) are not generally altered in acute ICH. Poorer individual phase values are, however, associated with larger ICH volume, lower blood pressure, and worsened outcome. Dampening characteristics of CA (gain) are generally impaired in acute ICH but not related to clinical factors or outcome.
Cost-Effectiveness of Surgical Decompression for Space-Occupying Hemispheric Infarction
Authors: Hofmeijer Jeannette , van der Worp H. Bart , Kappelle L. Jaap , Eshuis Sara , Algra Ale , Greving Jacoba P. 
Published: August 2013

Background and Purpose—
Surgical decompression reduces mortality and increases the probability of a favorable functional outcome after space-occupying hemispheric infarction. Its cost-effectiveness is uncertain.

Methods—
We assessed clinical outcomes, costs, and cost-effectiveness for the first 3 years in patients who were randomized to surgical decompression or best medical treatment within 48 hours after symptom onset in the Hemicraniectomy After Middle Cerebral Artery Infarction With Life-Threatening Edema Trial (HAMLET). Data on medical consumption were derived from case record files, hospital charts, and general practitioners. We calculated costs per quality-adjusted life year (QALY). Uncertainty was assessed with bootstrapping. A Markov model was constructed to estimate costs and health outcomes after 3 years.

Results—
Of 39 patients enrolled within 48 hours, 21 were randomized to surgical decompression. After 3 years, 5 surgical (24%) and 14 medical patients (78%) had died. In the first 3 years after enrollment, operated patients had more QALYs than medically treated patients (mean difference, 1.0 QALY [95% confidence interval, 0.6–1.4]), but at higher costs (mean difference, €127 000 [95% confidence interval, 73 100–181 000]), indicating incremental costs of €127 000 per QALY gained. Ninety-eight percent of incremental cost-effectiveness ratios replicated by bootstrapping were >€80 000 per QALY gained. Markov modeling suggested costs of ≈€60 000 per QALY gained for a patient’s lifetime.

Conclusions—
Surgical decompression for space-occupying infarction results in an increase in QALYs, but at very high costs.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier: ISRCTN94237756.
From Sensation to Oblivion: Boven Digoel in Sino-Malay Novels
Authors: Chandra Elizabeth 
Published: August 2013

Abstract
The so-called ‘Sino-Malay literature’ has often been characterized as literary publications that were commercial and very rarely political. This essay however draws attention to three novels written by prominent Indies Chinese authors on the colonial internment camp for communist activists, Boven Digoel. Written in three different decades, Kwee Tek Hoay’s Drama di Boven Digoel (Drama in Boven Digoel, 1928-1932), Liem Khing Hoo’s Merah (Red, 1937), and Njoo Cheong Seng’s Taufan gila (Mad typhoon, 1950) reflect not only individual journeys of Digoel-bound activists, but also the political landscapes in which they were written.
Displaced Archives, Displaced History: Recovering the Seized Archives of Indonesia
Authors: Karabinos Michael Joseph 
Published: August 2013

Abstract
This article examines the post-war conflict of colonial retention that the Netherlands engaged in with Indonesia, and the invasion of Yogyakarta on 19 December 1948. While arresting high-ranking members of the Republican government, Dutch troops seized papers that were left behind. These documents were not returned to Indonesia until nearly 50 years later. By studying the archival collection, fluctuations in the relationship between Indonesia and the Netherlands are revealed. The seized archives relate directly to the building of a new nation; their history reflects the history of Indonesia.
Vigilante Citizenship: Sovereign Practices and the Politics of Insult in Indonesia
Authors: Telle Kari 
Published: August 2013

Abstract
This article examines the informal authority wielded by civilian security groups (pamswakarsa) on the island of Lombok. Taking as its point of departure the Balinese minority’s plan to build a large Hindu temple in northern Lombok, the article shows how the project was thwarted by a combination of rumours, pamphlets, violence as well as legal obstacles from district and provincial authorities. Outlining how the campaign against the temple gained momentum, I suggest that rumours and documents issued by a security force claiming to represent the island’s Muslim majority played an important role in preventing the realization of the temple. Discussing the ‘conviviality’ between non-state security groups and state officials in post-Suharto Lombok, I argue that civilian security groups exercise a form of vigilante citizenship.
Projected Changes in Late-Twenty-First-Century Tropical Cyclone Frequency in 13 Coupled Climate Models from Phase 5 of the Coupled Model Intercomparison Project
Authors: Tory K. J. , Chand S. S. , McBride J. L. , Ye H. , Dare R. A. 
Published: August 2013

Abstract
Changes in tropical cyclone (TC) frequency under anthropogenic climate change are examined for 13 global models from phase 5 of the Coupled Model Intercomparison Project (CMIP5), using the Okubo–Weiss–Zeta parameter (OWZP) TC-detection method developed by the authors in earlier papers. The method detects large-scale conditions within which TCs form. It was developed and tuned in atmospheric reanalysis data and then applied without change to the climate models to ensure model and detector independence. Changes in TC frequency are determined by comparing TC detections in the CMIP5 historical runs (1970–2000) with high emission scenario (representative concentration pathway 8.5) future runs (2070–2100). A number of the models project increases in frequency of higher-latitude tropical cyclones in the late twenty-first century. Inspection reveals that these high-latitude systems were subtropical in origin and are thus eliminated from the analysis using an objective classification technique. TC detections in 8 of the 13 models reproduce observed TC formation numbers and geographic distributions reasonably well, with annual numbers within ±50% of observations. TC detections in the remaining five models are particularly low in number (10%–28% of observed). The eight models with a reasonable TC climatology all project decreases in global TC frequency varying between 7% and 28%. Large intermodel and interbasin variations in magnitude and sign are present, with the greatest variations in the Northern Hemisphere basins. These results are consistent with results from earlier-generation climate models and thus confirm the robustness of coupled model projections of globally reduced TC frequency.
A gradient-based iterative algorithm for generalized coupled Sylvester matrix equations over generalized centro-symmetric matrices
Authors: Hajarian Masoud 
Published: August 2013

An [Formula: see text] real matrix [Formula: see text] is said to be a symmetric orthogonal matrix if [Formula: see text]. An [Formula: see text] real matrix [Formula: see text] is called a generalized centro-symmetric matrix with respect to [Formula: see text], if [Formula: see text]. It is obvious that every [Formula: see text] matrix is also a generalized centro-symmetric matrix with respect to [Formula: see text] (identity matrix). In the present paper, we propose a gradient-based iterative algorithm to solve the generalized coupled Sylvester matrix equations [Formula: see text] over the generalized centro-symmetric matrix pair [Formula: see text]. It is proved that the iterative method is always convergent for any initial generalized centro-symmetric matrix pair [Formula: see text] Finally, a numerical example is discussed to illustrate the results.
Safety and efficacy of recombinant activated factor VII for refractory hemorrhage in pediatric patients on extracorporeal membrane oxygenation: a single center review
Authors: Long MT , Wagner D , Maslach-Hubbard A , Pasko DA , Baldridge P , Annich GM 
Published: August 2013

Background: Medically refractory hemorrhage in patients on ECMO (extracorporeal membrane oxygenation) support can have catastrophic complications. Recombinant-Activated Factor VII (rFVIIa; NovoSeven®) may provide lifesaving hemostasis; however, there are reports of catastrophic thrombosis related to its administration. Objective: This review attempts to add safety and efficacy data to existing literature regarding the use of rFVIIa for refractory hemorrhage in pediatric patients on ECMO support. Design/Methods: A retrospective chart review was performed for all pediatric patients on ECMO who received rFVIIa for refractory hemorrhage from 2004 to 2009. Data was extracted for each refractory bleeding event, including patient blood loss and transfused blood products in the 6 hours before the first dose, between rFVIIa doses and in the 6 hours after the final dose. For purposes of data collection, a hemorrhagic event was defined as new onset hemorrhage or a hemorrhage occurring at least 12 hours after the most recent dose of rFVIIa. Results: In total, seven patients aged 1 month to 15 years received rFVIIa for 14 different hemorrhagic events. There was no significant difference in blood loss or blood product transfusion associated with rFVIIa administration. There was one patient-related and one ECMO-related complication temporally associated with rFVIIa administration: decreased ECMO circuit oxygenator efficiency and the development of an intra-gastric clot requiring surgical evacuation. Conclusion: These data suggest limited efficacy for rFVIIa use for refractory hemorrhage in pediatric patients on ECMO support. There were two non-catastrophic complications temporally associated with its administration.
Incidence, Mechanisms, and Severity of Match-Related Collegiate Women’s Soccer Injuries on FieldTurf and Natural Grass Surfaces
Authors: Meyers Michael C. 
Published: August 2013

Background: Numerous injuries have been attributed to playing on artificial turf. Over the past 2 decades, however, newer generations of synthetic turf have been developed to duplicate the playing characteristics of natural grass. Although synthetic turf has been determined to be safer than natural grass in some studies, few long-term studies have been conducted comparing match-related collegiate soccer injuries between the 2 playing surfaces. Hypothesis: Collegiate female soccer athletes do not experience any difference in the incidence, mechanisms, and severity of match-related injuries on FieldTurf and on natural grass. Study Design: Cohort study: Level of evidence, 2. Methods: Female soccer athletes from 13 universities were evaluated over 5 competitive seasons for injury incidence, injury category, time of injury, injury time loss, player position, injury mechanism and situation, primary type of injury, injury grade and anatomic location, field location at the time of injury, injury severity, head and lower extremity trauma, cleat design, turf age, and environmental factors. In sum, 797 collegiate games were evaluated for match-related soccer injuries sustained on FieldTurf or natural grass during 5 seasons. Results: Overall, 355 team games (44.5%) were played on FieldTurf versus 442 team games (55.5%) on natural grass. A total of 693 injuries were documented, with 272 (39.2%) occurring during play on FieldTurf and 421 (60.8%) on natural grass. Multivariate analysis per 10 team games indicated a significant playing surface effect: F2,690 = 6.435, P = .002, n – β = .904. A significantly lower total injury incidence rate (IIR) of 7.7 (95% confidence interval [CI], 7.2-8.1) versus 9.5 (95% CI, 9.3-9.7) ( P = .0001) and lower rate of substantial injuries, 0.7 (95% CI, 0.5-1.0) versus 1.5 (95% CI, 1.2-1.9) ( P = .001), were documented on FieldTurf versus natural grass, respectively. Analyses also indicated significantly less trauma on FieldTurf when comparing injury time loss, player position, injury grade, injuries under various field conditions and temperatures, cleat design, and turf age. Conclusion: Although similarities existed between FieldTurf and natural grass during competitive match play, FieldTurf is a practical alternative when comparing injuries in collegiate women’s soccer. It must be reiterated that the findings of this study may be generalizable to only collegiate competition and this specific artificial surface.