bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital Signal Processing Using Stream High Performance Computing
Authors: Kocz J. , Greenhill L. J. , Barsdell B. R. , Price D. , Bernardi G. , Bourke S. , Clark M. A. , Craig J. , Dexter M. , Dowell J. , Eftekhari T. , Ellingson S. , Hallinan G. , Hartman J. , Jameson A. , MacMahon D. , Taylor G. , Schinzel F. , Werthimer D. 
Published: March 2015

A “large-N” correlator that makes use of Field Programmable Gate Arrays and Graphics Processing Units has been deployed as the digital signal processing system for the Long Wavelength Array station at Owens Valley Radio Observatory (LWA-OV), to enable the Large Aperture Experiment to Detect the Dark Ages (LEDA). The system samples a [Formula: see text][Formula: see text]MHz baseband and processes signals from 512 antennas (256 dual polarization) over a [Formula: see text][Formula: see text]MHz instantaneous sub-band, achieving 16.8[Formula: see text]Tops[Formula: see text]s[Formula: see text] and 0.236 Tbit[Formula: see text]s[Formula: see text] throughput in a 9[Formula: see text]kW envelope and single rack footprint. The output data rate is 260 MB[Formula: see text]s[Formula: see text] for 9-s time averaging of cross-power and 1[Formula: see text]s averaging of total power data. At deployment, the LWA-OV correlator was the largest in production in terms of N and is the third largest in terms of complex multiply accumulations, after the Very Large Array and Atacama Large Millimeter Array. The correlator’s comparatively fast development time and low cost establish a practical foundation for the scalability of a modular, heterogeneous, computing architecture.
Genomic Landscape of Human Papillomavirus–Associated Cancers
Authors: Rusan Maria , Li Yvonne Y. , Hammerman Peter S. 
Published: March 2015

Abstract
Recent next-generation sequencing studies have generated a comprehensive overview of the genomic landscape of human papillomavirus (HPV)–associated cancers. This review summarizes these findings to provide insight into the tumor biology of these cancers and potential therapeutic opportunities for HPV-driven malignancies. In addition to the tumorigenic properties of the HPV oncoproteins, integration of HPV DNA into the host genome is suggested to be a driver of the neoplastic process. Integration may confer a growth and survival advantage via enhanced expression of viral oncoproteins, alteration of critical cellular genes, and changes in global promoter methylation and transcription. Alteration of cellular genes may lead to loss of function of tumor suppressor genes, enhanced oncogene expression, loss of function of DNA repair genes, or other vital cellular functions. Recurrent integrations in RAD51B, NR4A2, and TP63, leading to aberrant forms of these proteins, are observed in both HPV-positive head and neck squamous cell carcinoma (HNSCC) and cervical carcinoma. Additional genomic alterations, independent of integration events, include recurrent PIK3CA mutations (and aberrations in other members of the PI3K pathway), alterations in receptor tyrosine kinases (primarily FGFR2 and FGFR3 in HPV-positive HNSCC, and ERBB2 in cervical squamous cell carcinoma), and genes in pathways related to squamous cell differentiation and immune responses. A number of the alterations identified are potentially targetable, which may lead to advances in the treatment of HPV-associated cancers. Clin Cancer Res; 21(9); 2009–19. ©2015 AACR.
SLFN11 Is a Transcriptional Target of EWS-FLI1 and a Determinant of Drug Response in Ewing Sarcoma
Authors: Tang Sai-Wen , Bilke Sven , Cao Liang , Murai Junko , Sousa Fabricio G. , Yamade Mihoko , Rajapakse Vinodh , Varma Sudhir , Helman Lee J. , Khan Javed , Meltzer Paul S. , Pommier Yves 
Published: March 2015

Abstract
Purpose: SLFN11 was identified as a critical determinant of response to DNA-targeted therapies by analyzing gene expression and drug sensitivity of NCI-60 and CCLE datasets. However, how SLFN11 is regulated in cancer cells remained unknown. Ewing sarcoma, which is characterized by the chimeric transcription factor EWS-FLI1, has notably high SLFN11 expression, leading us to investigate whether EWS-FLI1 drives SLFN11 expression and the role of SLFN11 in the drug response of Ewing sarcoma cells.
Experimental Design: Binding sites of EWS-FLI1 on the SLFN11 promoter were analyzed by chromatin immunoprecipitation sequencing and promoter-luciferase reporter analyses. The relationship between SLFN11 and EWS-FLI1 were further examined in EWS-FLI1-knockdown or -overexpressing cells and in clinical tumor samples.
Results: EWS-FLI1 binds near the transcription start site of SLFN11 promoter and acts as a positive regulator of SLFN11 expression in Ewing sarcoma cells. EWS-FLI1–mediated SLFN11 expression is responsible for high sensitivity of Ewing sarcoma to camptothecin and combinations of PARP inhibitors with temozolomide. Importantly, Ewing sarcoma patients with higher SLFN11 expression showed better tumor-free survival rate. The correlated expression between SLFN11 and FLI1 extends to leukemia, pediatric, colon, breast, and prostate cancers. In addition, expression of other ETS members correlates with SLFN11 in NCI-60 and CCLE datasets, and molecular experiments demonstrate that ETS1 acts as a positive regulator for SLFN11 expression in breast cancer cells.
Conclusions: Our results imply the emerging relevance of SLFN11 as an ETS transcription factor response gene and for therapeutic response to topoisomerase I inhibitors and temozolomide–PARP inhibitor combinations in ETS-activated cancers. Clin Cancer Res; 21(18); 4184–93. ©2015 AACR.
See related commentary by Kovar, p. 4033
A New and Validated Clinical Prognostic Model (EPI) for Enteropathy-Associated T-cell Lymphoma
Authors: de Baaij Laura R. , Berkhof Johannes , van de Water Jolanda M.W. , Sieniawski Michal K. , Radersma Marijn , Verbeek Wieke H.M. , Visser Otto J. , Oudejans Joost J. , Meijer Chris J.L.M. , Mulder Chris J.J. , Lennard Anne L. , Cillessen Saskia A.G.M. 
Published: March 2015

Abstract
Purpose: Enteropathy-associated T-cell lymphoma (EATL) is a rare intestinal non–Hodgkin lymphoma with a poor, though variable prognosis. The International Prognostic Index (IPI) and the prognostic index for peripheral T-cell lymphoma (PIT) have limited predictive value for outcome of EATL. The purpose of this study was to develop and validate a prognostic model for EATL, which can identify high-risk patients who need more aggressive therapy.
Experimental Design: This retrospective multicenter study was based on 92 patients and included 45 patients diagnosed with EATL between 1999 and 2009 from the Netherlands and 47 patients from England and Scotland, diagnosed with EATL between 1994 and 1998. A new EATL prognostic index (EPI) was constructed using the RPART (recursive partitioning and regression trees) procedure. Validation was performed applying the bootstrap method.
Results: Three risk groups were distinguished (P &lt; 0.0001): a high-risk group, characterized by the presence of B-symptoms [median overall survival (OS) of 2 months]; an intermediate-risk group, comprising patients without B-symptoms and an IPI score ≥ 2 (7 months); and a low-risk group, representing patients without B-symptoms and an IPI score of 0 to 1 (34 months). Internal validation showed stability of statistical significance and prognostic discrimination. In contrast with the IPI and PIT, the EPI better classified patients in risk groups according to their clinical outcome.
Conclusions: Our new, validated, prognostic model EPI accurately predicts survival outcome in EATL and may be used for patient selection for new therapeutic strategies and evaluation of clinical trials. Clin Cancer Res; 21(13); 3013–9. ©2015 AACR.
PLEKHA5: A Key to Unlock the Blood–Brain Barrier?
Authors: Eisele Sylvia C. , Gill Corey M. , Shankar Ganesh M. , Brastianos Priscilla K. 
Published: March 2015

Abstract
Brain metastases represent a devastating complication of melanoma. Our understanding of the mechanisms driving metastasis to the brain is limited. PLEKHA5 functions as a regulator of brain metastasis in melanoma, and further investigation is warranted to explore the use of PLEKHA5 as a potential therapeutic target. Clin Cancer Res; 21(9); 1978–80. ©2015 AACR.
See related article by Jilaveanu et al., p. 2138
TBCRC 019: A Phase II Trial of Nanoparticle Albumin-Bound Paclitaxel with or without the Anti-Death Receptor 5 Monoclonal Antibody Tigatuzumab in Patients with Triple-Negative Breast Cancer
Authors: Forero-Torres Andres , Varley Katherine E. , Abramson Vandana G. , Li Yufeng , Vaklavas Christos , Lin Nancy U. , Liu Minetta C. , Rugo Hope S. , Nanda Rita , Storniolo Anna M. , Traina Tiffany A. , Patil Sujata , Van Poznak Catherine H. , Nangia Julie R. , Irvin William J. , Krontiras Helen , De Los Santos Jennifer F. , Haluska Paul , Grizzle William , Myers Richard M. , Wolff Antonio C. 
Published: March 2015

Abstract
Purpose: Tigatuzumab (TIG), an agonistic anti-DR5 antibody, triggers apoptosis in DR5+ human tumor cells without crosslinking. TIG has strong in vitro/in vivo activity against basal-like breast cancer cells enhanced by chemotherapy agents. This study evaluates activity of TIG and chemotherapy in patients with metastatic triple-negative breast cancer (TNBC).
Experimental Design: Randomized 2:1 phase II trial of albumin-bound paclitaxel (nab-PAC) ± TIG in patients with TNBC stratified by prior chemotherapy. Patients received nab-PAC weekly × 3 ± TIG every other week, every 28 days. Primary objective was within-arm objective response rate (ORR). Secondary objectives were safety, progression-free survival (PFS), clinical benefit, and TIG immunogenicity. Metastatic research biopsies were required.
Results: Among 64 patients (60 treated; TIG/nab-PAC n = 39 and nab-PAC n = 21), there were 3 complete remissions (CR), 8 partial remissions (PR; 1 almost CR), 11 stable diseases (SD), and 17 progressive diseases (PD) in the TIG/nab-PAC arm (ORR, 28%), and no CRs, 8 PRs, 4 SDs, and 9 PDs in the nab-PAC arm (ORR, 38%). There was a numerical increase in CRs and several patients had prolonged PFS (1,025+, 781, 672, 460, 334) in the TIG/nab-PAC arm. Grade 3 toxicities were 28% and 29%, respectively, with no grade 4–5. Exploratory analysis suggests an association of ROCK1 gene pathway activation with efficacy in the TIG/nab-PAC arm.
Conclusions: ORR and PFS were similar in both. Preclinical activity of TIG in basal-like breast cancer and prolonged PFS in few patients in the combination arm support further investigation of anti-DR5 agents. ROCK pathway activation merits further evaluation. Clin Cancer Res; 21(12); 2722–9. ©2015 AACR.
See related article by Paoletti et al., p. 2771
The Use of Transcriptional Profiling to Improve Personalized Diagnosis and Management of Cutaneous T-cell Lymphoma (CTCL)
Authors: Litvinov Ivan V. , Netchiporouk Elena , Cordeiro Brendan , Doré Marc-André , Moreau Linda , Pehr Kevin , Gilbert Martin , Zhou Youwen , Sasseville Denis , Kupper Thomas S. 
Published: March 2015

Abstract
Purpose: Although many patients with mycosis fungoides presenting with stage I disease enjoy an indolent disease course and normal life expectancy, about 15% to 20% of them progress to higher stages and most ultimately succumb to their disease. Currently, it is not possible to predict which patients will progress and which patients will have a stable disease. Previously, we conducted microarray analyses with RT-PCR validation of gene expression in biopsy specimens from 60 patients with stage I–IV cutaneous T-cell lymphoma (CTCL), identified three distinct clusters based upon transcription profile, and correlated our molecular findings with 6 years of clinical follow-up.
Experimental Design: We test by RT-PCR within our prediction model the expression of about 240 genes that were previously reported to play an important role in CTCL carcinogenesis. We further extend the clinical follow-up of our patients to 11 years. We compare the expression of selected genes between mycosis fungoides/Sézary syndrome and benign inflammatory dermatoses that often mimic this cancer.
Results: Our findings demonstrate that 52 of the about 240 genes can be classified into cluster 1–3 expression patterns and such expression is consistent with their suggested biologic roles. Moreover, we determined that 17 genes (CCL18, CCL26, FYB, T3JAM, MMP12, LEF1, LCK, ITK, GNLY, IL2RA, IL26, IL22, CCR4, GTSF1, SYCP1, STAT5A, and TOX) are able to both identify patients who are at risk of progression and also distinguish mycosis fungoides/Sézary syndrome from benign mimickers.
Conclusions: This study, combined with other gene expression analyses, prepares the foundation for the development of personalized molecular approach toward diagnosis and treatment of CTCL. Clin Cancer Res; 21(12); 2820–9. ©2015 AACR.
Rho Guanine Nucleotide Exchange Factor 5 Increases Lung Cancer Cell Tumorigenesis via MMP-2 and Cyclin D1 Upregulation
Authors: He Ping , Wu Wei , Yang Kang , Tan Deli , Tang Meng , Liu Hongxiang , Wu Tao , Zhang Shixin , Wang Haidong 
Published: March 2015

Abstract
We sought to elucidate the role of Rho guanine nucleotide exchange factor 5 (ARHGEF5) in tumorigenesis of lung adenocarcinoma cells. ARHGEF5 protein levels were assessed in 91 human lung adenocarcinoma specimens, and A549 and NCI-H1650 cells, by IHC and Western blotting. In addition, ARHGEF5 mRNA expression was evaluated by quantitative reverse transcriptase-PCR. Furthermore, ARHGEF5 long and short isoform coexpression was detected by immunofluorescence. Finally, flow cytometry; CCK8 and wound-healing assays; cell invasion, migration and adhesion; and xenografts were used to evaluate the biologic significance of ARHGEF5. ARHGEF5 was significantly increased in lung adenocarcinoma tissues and cell lines. Interestingly, ARHGEF5 levels were significantly associated with tumor grade and pathologic stage, but not age, gender, T stage, or lymph node metastasis status. ARHGEF5 knockdown by RNAi resulted in dramatically reduced proliferation, adhesion, invasion, and migratory capability of A549 and NCI-H1650 cells. Likewise, protein levels of p-Src, p-Akt, and NF-κB were significantly decreased after ARHGEF5 knockdown. In parallel, increased S-phase population and MMP-2/cyclin D1 expression were observed in the cancer cells, which were not apoptotic. In addition, ARHGEF5 knockdown A549 and NCI-H1650 cells injected s.c. and i.v. into nude mice exhibited decreased xenograft volume and overtly reduced metastasis. Conversely, ARHGEF5 overexpression in A549 and NCI-H1650 cells increased their tumorigenicity in vitro. ARHGEF5 acts as a proto-oncogene in human lung adenocarcinoma cell tumorigenesis. Mol Cancer Ther; 14(7); 1671–9. ©2015 AACR.
Status of Cardiovascular Health in US Children Up to 11 Years of Age
Authors: Ning Hongyan , Labarthe Darwin R. , Shay Christina M. , Daniels Stephen R. , Hou Lifang , Van Horn Linda , Lloyd-Jones Donald M. 
Published: March 2015

Background—
The American Heart Association recently defined cardiovascular health (CVH) to monitor it over time for all Americans. Nationally representative prevalence estimates for children under 12 years according to sex and race/ethnicity have not been reported.

Methods and Results—
The study sample comprised 8961 children aged 2 to 11 years from 2003 to 2010 National Health and Nutrition Examination Surveys. National prevalence of ideal, intermediate, and poor CVH as defined by American Heart Association was estimated for each of 4 available metrics (body mass index [BMI], healthy diet score, total cholesterol, and blood pressure). No children had ideal levels for either zero or all 4 metrics. Ideal healthy diet score was least prevalent, ranging from 0 to 0.1%, whereas ideal blood pressure was most prevalent ranging from 88% to 93% across sex, race/ethnicity groups. Ideal BMI was less frequent at ages 6 to 11 years than at ages 2 to 5 years (67% versus 77%). Approximately 40% of children had intermediate or poor total cholesterol levels. The dietary intake of diet score components was associated with BMI, which was associated with blood pressure and total cholesterol.

Conclusions—
Ideal CVH status for BMI, total cholesterol, and blood pressure was prevalent in young children, whereas ideal diet was rare. Diet and BMI were important components to achieve ideal CVH metrics in children. Limited availability of data for all CVH metrics is a major obstacle for CVH assessment in the youngest age groups and represents an important missed opportunity for surveillance and secular trends analyses with aging.
Differential Effect of Baseline Computed Tomographic Angiography Collaterals on Clinical Outcome in Patients Enrolled in the Interventional Management of Stroke III Trial
Authors: Menon Bijoy K. , Qazi Emmad , Nambiar Vivek , Foster Lydia D. , Yeatts Sharon D. , Liebeskind David , Jovin Tudor G. , Goyal Mayank , Hill Michael D. , Tomsick Thomas A. , Broderick Joseph P. , Demchuk Andrew M. 
Published: March 2015

Background and Purpose—
In the Interventional Management of Stroke (IMS) III trial, we sought to demonstrate evidence of a differential treatment effect of endovascular treatment of acute ischemic stroke compared with intravenous tissue-type plasminogen activator, according to baseline collateral status measured using computed tomographic angiography.

Methods—
Of 656 patients enrolled in Interventional Management of Stroke III trial, 306 had baseline computed tomographic angiography. Of these, 185 patients had M1 middle cerebral artery ± intracranial internal carotid artery occlusion, where baseline collateral status could be measured. Collateral status was assessed by consensus using 3 different ordinal scales and categorized as good, intermediate, and poor. Multivariable modeling was used to assess the effect of collateral status and treatment type on clinical outcome by modified Rankin Scale (mRS 0–2, mRS 0–1, and the ordinal mRS).

Results—

Of 185 patients, 126 randomized to endovascular therapy (87.6% recanalized, 41.3% 90-day mRS 0–2) and 59 to intravenous tissue-type plasminogen activator only (60.5% recanalized, 30.5% 90-day mRS 0–2). In multivariable modeling, collateral status was a significant predictor of all clinical outcomes (
P
<0.05). Maximal benefit with endovascular treatment across all clinical outcomes was seen in patients with intermediate collaterals, some benefit in patients with good collaterals, and none in patients with poor collaterals, although small sample size limited the power of the analysis to show a statistically significant interaction between collateral status and treatment type (
P
>0.05).

Conclusion—
Using data from a large randomized controlled trial (IMS III), we show that baseline computed tomographic angiography collaterals are a robust determinant of final clinical outcome and could be used to select patients for endovascular therapy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov/ct2/show/
. Unique identifier: 0020NCT00359424.
Attitudes toward Human Papilloma Virus Vaccination and Head and Neck Cancer Prevention in a Diverse, Urban Population
Authors: Kram Yoseph A. , Schmidt Timothy H. , Saghezchi Sohail , Russell Marika D. 
Published: March 2015

Objective(1) To understand if awareness of the human papilloma virus (HPV) vaccination’s potential to prevent head and neck cancer improves acceptability of the vaccine in a large urban population and (2) to identify characteristics of those in whom such discussions would have the greatest impact.Study DesignIn‐person, anonymous survey.SettingAcademic public hospital between March 2014 and June 2014.SubjectsPatients aged 12 to 24 years and their parents or guardians awaiting scheduled outpatient pediatric appointments.MethodsDemographics and modified Carolina HPV Immunization Attitudes and Beliefs Scales data were cross‐analyzed, followed by univariate binomial logistic regression to identify predictors for major outcomes of interest.ResultsMore than 78% of those surveyed indicated they would be more receptive to the HPV vaccine if given strong evidence that it prevented head and neck cancer. Respondents were more likely to increase receptivity to HPV vaccination if they held the belief that they did not have enough information about the vaccine or indicated they preferred to wait because the vaccine was too new.ConclusionIncreasing public awareness of head and neck cancer prevention with HPV vaccination could increase HPV vaccination acceptance.
An assistive decision-and-control architecture for force-sensitive hand–arm systems driven by human–machine interfaces
Authors: Vogel J. , Haddadin S. , Jarosiewicz B. , Simeral J.D. , Bacher D. , Hochberg L.R. , Donoghue J.P. , van der Smagt P. 
Published: March 2015

Fully autonomous applications of modern robotic systems are still constrained by limitations in sensory data processing, scene interpretation, and automated reasoning. However, their use as assistive devices for people with upper-limb disabilities has become possible with recent advances in “soft robotics”, that is, interaction control, physical human–robot interaction, and reflex planning. In this context, impedance and reflex-based control has generally been understood to be a promising approach to safe interaction robotics. To create semi-autonomous assistive devices, we propose a decision-and-control architecture for hand–arm systems with “soft robotics” capabilities, which can then be used via human–machine interfaces (HMIs). We validated the functionality of our approach within the BrainGate2 clinical trial, in which an individual with tetraplegia used our architecture to control a robotic hand–arm system under neural control via a multi-electrode array implanted in the motor cortex. The neuroscience results of this research have previously been published by Hochberg et al. In this paper we present our assistive decision-and-control architecture and demonstrate how the semi-autonomous assistive behavior can help the user. In our framework the robot is controlled through a multi-priority Cartesian impedance controller and its behavior is extended with collision detection and reflex reaction. Furthermore, virtual workspaces are added to ensure safety. On top of this we employ a decision-and-control architecture that uses sensory information available from the robotic system to evaluate the current state of task execution. Based on a set of available assistive skills, our architecture provides support in object interaction and manipulation and thereby enhances the usability of the robotic system for use with HMIs. The goal of our development is to provide an easy-to-use robotic system for people with physical disabilities and thereby enable them to perform simple tasks of daily living. In an exemplary real-world task, the participant was able to serve herself a beverage autonomously for the first time since her brainstem stroke, which she suffered approximately 14 years prior to this research.
BET bromodomain inhibition suppresses graft-versus-host disease after allogeneic bone marrow transplantation in mice
Authors: Sun Yaping , Wang Ying , Toubai Tomomi , Oravecz-Wilson Katherine , Liu Chen , Mathewson Nathan , Wu Julia , Rossi Corinne , Cummings Emily , Wu Depei , Wang Shaomeng , Reddy Pavan 
Published: March 2015

Key Points
Demonstrates that targeting BET bromodomain is a novel strategy to mitigate acute GVHD. BET bromodomain inhibition regulates DCs and T cells and causes disruption of interaction between BRD4 and acetyl-310 RelA of nuclear factor kappa B.
Phase 1/2 study of carfilzomib plus melphalan and prednisone in patients aged over 65 years with newly diagnosed multiple myeloma
Authors: Moreau Philippe , Kolb Brigitte , Attal Michel , Caillot Denis , Benboubker Lotfi , Tiab Mourad , Touzeau Cyrille , Leleu Xavier , Roussel Murielle , Chaleteix Carine , Planche Lucie , Chiffoleau Anne , Fortin June , Avet-Loiseau Hervé , Mary Jean-Yves , Hulin Cyrille , Facon Thierry 
Published: March 2015

Key Points
CMP is an effective induction regimen for transplant-ineligible MM patients. The CMP regimen is safe and well tolerated with a notable lack of peripheral neuropathy.