bluuebunny/crossref_metadata_2025_split huggingface dataset:
RESTORE: REcovery after Serious Trauma—Outcomes, Resource use and patient Experiences study protocol
Authors: Gabbe Belinda J , Braaf Sandra , Fitzgerald Mark , Judson Rodney , Harrison James E , Lyons Ronan A , Ponsford Jennie , Collie Alex , Ameratunga Shanthi , Attwood David , Christie Nicola , Nunn Andrew , Cameron Peter A 
Published: August 2014

BackgroundTraumatic injury is a leading contributor to the overall global burden of disease. However, there is a worldwide shortage of population data to inform understanding of non-fatal injury burden. An improved understanding of the pattern of recovery following trauma is needed to better estimate the burden of injury, guide provision of rehabilitation services and care to injured people, and inform guidelines for the monitoring and evaluation of disability outcomes.ObjectiveTo provide a comprehensive overview of patient outcomes and experiences in the first 5 years after serious injury.DesignThis is a population-based, nested prospective cohort study using quantitative data methods, supplemented by a qualitative study of a seriously injured participant sample.ParticipantsAll 2547 paediatric and adult major trauma patients captured by the Victorian State Trauma Registry with a date of injury from 1 July 2011 to 30 June 2012 who survived to hospital discharge and did not opt-off from the registry.AnalysisTo analyse the quantitative data and identify factors that predict poor or good outcome, whether there is change over time, differences in rates of recovery and change between key participant subgroups, multilevel mixed effects regression models will be fitted. To analyse the qualitative data, thematic analysis will be used to identify important themes and the relationships between themes.Contribution to the fieldThe results of this project have the potential to inform clinical decisions and public health policy, which can reduce the burden of non-fatal injury and improve the lives of people living with the consequences of severe injury.
Alterations of insulin-like growth factor-1 receptor gene copy number and protein expression are common in non-small cell lung cancer
Authors: Tran T N , Selinger C I , Yu B , Ng C C , Kohonen-Corish M R J , McCaughan B , Kennedy C , O'Toole S A , Cooper W A 
Published: August 2014

AimsInsulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase membrane receptor involved in tumourigenesis that may be a potential therapeutic target. We aimed to investigate the incidence and prognostic significance of alterations inIGF1Rcopy number, and IGF1R protein expression in resected primary non-small cell lung cancer (NSCLC), and lymph node metastases.MethodsIGF1Rgene copy number status was evaluated by chromogenic silver in situ hybridisation and IGF1R protein expression was evaluated by immunohistochemistry in tissue microarray sections from a retrospective cohort of 309 surgically resected NSCLCs and results were compared with clinicopathological features, includingEGFRandKRASmutational status and patient survival.ResultsIGF1Rgene copy number status was positive (high polysomy or amplification) in 29.2% of NSCLC, and 12.1% exhibitedIGF1Rgene amplification. High IGF1R expression was found in 28.3%. There was a modest correlation betweenIGF1Rgene copy number and protein expression (r=0.2, p<0.05). Alterations ofIGF1Rgene copy number and protein expression in primary tumours were significantly associated with alterations in lymph node metastases (p<0.01). HighIGF1Rgene copy number and protein expression was significantly higher in squamous cell carcinomas (SCC) compared with other subtypes of NSCLC (p<0.05). There were no other associations between IGF1R status and other clinicopathological features including patient age, gender, smoking status, tumour size, stage, grade,EGFRorKRASmutational status or overall survival.ConclusionsHighIGF1Rgene copy number and protein overexpression are frequent in NSCLC, particularly in SCCs, but they are not prognostically relevant.
Angiographic factors influencing the success of endovascular treatment of arteriovenous malformations involving the corpus callosum
Authors: Robert Thomas , Blanc Raphaël , Ciccio Gabriele , Gilboa Boaz , Fahed Robert , Redjem Hocine , Pistocchi Silvia , Bartolini Bruno , Piotin Michel 
Published: August 2014

ObjectiveArteriovenous malformations (AVMs) of the corpus callosum are rare lesions, accounting for 9–11% of brain AVMs. Microsurgical resection of such lesions is difficult because of their deep location, and also because of possible neuropsychological disasters resulting from extended callosal resection. The introduction of endovascular and radiation therapies has fundamentally changed the outcome of these lesions.MethodsWe prospectively collected clinical and angiographic data on cerebral AVMs from 1995. We reviewed data from patients treated for an AVM of the corpus callosum and identified the factors influencing the endovascular approach of such lesions.Results38 patients (mean age 31 years) were consecutively treated by endovascular techniques. 78.9% (30 cases) of patients presented with intracranial hemorrhage. 15 AVMs (39.5%) were anterior, 18 (47.4%) were posterior, and five (13.1%) were holocallosal. The Spetzler–Martin grade was I in two cases (5.2%), II in 20 cases (52.6%), III in nine cases (23.7%), IV in six cases (15.8%), and V in one case (2.6%). The nidus was compact in 19 cases (50%), diffuse in 13 (34.2%), and multifocal in six (15.8%). Both anterior and posterior circulation branches fed 14 nidi (36.8%). Venous drainage was superficial in three cases (7.9%), deep in 28 (73.7%), and both in seven cases (18.4%). 104 sessions were performed, with a procedural complication rate of 6.7%. Mean follow-up was 43.6 months, with the last modified Rankin Scale score <3 in 33 cases (86.8%). 22 patients (57.9%) were totally cured. Univariate analysis of factors influencing the success of endovascular treatment showed that Spetzler–Martin grade ≥3 (p=0.046), nidus >30 mm (p=0.02), extension in an eloquent area (p=0.03), and holocallosal type (p0.005) significantly diminished the chances of cure of the AVM.ConclusionsAVMs of the corpus callosum seems to be difficult to treat with endovascular therapy alone. The goal of embolization should be prevention of (re) bleeding and a decrease in nidus size. Our experience regarding this sub-pathology suggests that a combination of endovascular therapy and radiotherapy may be the best option.
Balloon-augmented Onyx embolization of cerebral arteriovenous malformations using a dual-lumen balloon: a multicenter experience
Authors: Spiotta Alejandro M , James Robert F , Lowe Stephen R , Vargas Jan , Turk Aquilla S , Chaudry M Imran , Bhalla Tarun , Janjua Rashid M , Delaney John J , Quintero-Wolfe Stacey , Turner Raymond D 
Published: August 2014

IntroductionConventional Onyx embolization of cerebral arteriovenous malformations (AVMs) requires lengthy procedure and fluoroscopy times to form an adequate ‘proximal plug’ which allows forward nidal penetration while preventing reflux and non-targeted embolization. We review our experience with balloon-augmented Onyx embolization of cerebral AVMs using a dual-lumen balloon catheter technique designed to minimize these challenges.MethodsRetrospectively acquired data for all balloon-augmented cerebral AVM embolizations performed between 2011 and 2014 were obtained from four tertiary care centers. For each procedure, at least one Scepter C balloon catheter was advanced into the AVM arterial pedicle of interest and Onyx embolization was performed through the inner lumen after balloon inflation via the outer lumen.ResultsTwenty patients underwent embolization with the balloon-augmented technique over 24 discreet treatment episodes. There were 37 total arterial pedicles embolized with the balloon-augmented technique, a mean of 1.9 per patient (range 1–5). The treated AVMs were heterogeneous in their location and size (mean 3.3±1.6 cm). Mean fluoroscopy time for each procedure was 48±26 min (28 min per embolized pedicle). Two Scepter C balloon catheter-related complications (8.3% of embolization sessions, 5.4% of pedicles embolized) were observed: an intraprocedural rupture of a feeding pedicle and fracture and retention of a catheter fragment.ConclusionsThis multicenter experience represents the largest reported series of balloon-augmented Onyx embolization of cerebral AVMs. The technique appears safe and effective in the treatment of AVMs, allowing more efficient and controlled injection of Onyx with a decreased risk of reflux and decreased fluoroscopy times.
The diagnostic and prognostic value of coronary CT angiography in asymptomatic high-risk patients: a cohort study
Authors: Plank Fabian , Friedrich Guy , Dichtl Wolfgang , Klauser Andrea , Jaschke Werner , Franz Wolfgang-Michael , Feuchtner Gudrun 
Published: August 2014

ObjectiveTo prospectively assess the value of coronary CT angiography (CTA) in asymptomatic patients with high ‘a priori’ risk of coronary artery disease (CAD).Methods711 consecutive asymptomatic patients (61.8 years; 40.1% female) with high ‘a priori’ risk of CAD were prospectively examined with a coronary calcium score (CCS) and CTA. Coronary arteries were evaluated for atherosclerotic plaque (non-calcified and calcified) and stenosis (mild <50%, intermediate 50–70% or high-grade >70%). Coronary Segment Involvement Score (SIS, total number of segments with plaque) and nc (non-calcified) SIS were calculated. Primary end points were major adverse cardiac events (ST-elevation MI, non-ST-elevation MI and cardiac death); secondary end points were coronary revascularisation and >50% stenosis by invasive angiography.ResultsOf 711 patients, 28.3% were negative for CAD and 71.7% positive (CAD+) by CTA (15.6% had plaques without stenosis, 23.9% mild, 10.7% intermediate and 21.5% high-grade stenosis). CCS zero prevalence was 306 (43%), out of those 100 (32.7%) had non-calcified plaque only. Mean follow-up period was 2.65 years. MACE rate was 0% in CAD negative and higher (1.2%) in CAD positive by CTA. Coronary revascularisation rate was 5.5%. Patients with SIS ≥5 had an HR of 6.5 (95% CI 1.6 to 25.8, p<0.013) for MACE, patients with ncSIS ≥1 had an HR of 2.4 (95% CI 1.2 to 4.6, p<0.01) for secondary end point. The sensitivity of CTA for stenosis >50% compared with invasive angiography was 92.9% (95% CI 83.0% to 98.1%). Negative predictive value of CTA was 99.4% (95% CI 98.3% to 99.8%) for combined end points.ConclusionsCAD prevalence by CTA in asymptomatic high-risk patients is high. CCS zero does not exclude CAD. CTA is highly accurate to exclude CAD. Total coronary plaque burden and nc plaques, even if only one segment is involved, are associated with an increased risk of adverse outcome.
Petroleum column-height controls in the western Hammerfest Basin, Barents Sea
Authors: Hermanrud Christian , Halkjelsvik Malene Eikås , Kristiansen Kine , Bernal Asdrúbal , Strömbäck Anna Christiana 
Published: August 2014

Hydrocarbon leakage is a major exploration challenge in the western Hammerfest Basin. Most exploration failures in the area have been attributed to leakage; hydrocarbon-bearing traps are rarely filled to their structural capacity, and almost all traps have hydrocarbon shows down to their structural spillpoint or below.
We have investigated to what extent the hydrocarbon column heights can be explained by vertical leakage along faults or at fault intersections. For the fields that we evaluated we observe that: (a) all dry structures have fault intersections at top reservoir level up dip of the well position: (b) the only structure where no faults intersect at top reservoir level is the only structure that is clearly filled to structural spillpoint; and (c) all fluid contacts in underfilled structures broadly coincide with the position of intersecting faults. The underfilled structures have less than two fault intersections up dip and above the gas-bearing reservoir. We suggest that vertical leakage at fault intersections has exerted a main control on the position of the gas–water contacts in the western Hammerfest Basin, and therefore that hydrocarbon column-height predictions can be improved by addressing the positions of such intersections at the top reservoir surface.
Denotational Semantics with Nominal Scott Domains
Authors: Lösch Steffen , Pitts Andrew M. 
Published: August 2014

When defining computations over syntax as data, one often runs into tedious issues concerning
α
-equivalence and semantically correct manipulations of binding constructs. Here we study a semantic framework in which these issues can be dealt with automatically by the programming language. We take the user-friendly “nominal” approach in which bound objects are named. In particular, we develop a version of Scott domains within nominal sets and define two programming languages whose denotational semantics are based on those domains. The first language,
λν
-PCF, is an extension of Plotkin’s PCF with names that can be swapped, tested for equality and locally scoped; although simple, it already exposes most of the semantic subtleties of our approach. The second language, PNA, extends the first with name abstraction and concretion so that it can be used for metaprogramming over syntax with binders.

For both languages, we prove a full abstraction result for nominal Scott domains analogous to Plotkin’s classic result about PCF and conventional Scott domains: two program phrases have the same observable operational behaviour in all contexts if and only if they denote equal elements of the nominal Scott domain model. This is the first full abstraction result we know of for languages combining higher-order functions with some form of locally scoped names which uses a domain theory based on ordinary extensional functions, rather than using the more intensional approach of game semantics.
To obtain full abstraction, we need to add two functionals, one for existential quantification over names and one for “definite description” over names. Only adding one of them is not enough, as we give counter-examples to full abstraction in both cases.
BRG1/SMARCA4 Inactivation Promotes Non–Small Cell Lung Cancer Aggressiveness by Altering Chromatin Organization
Authors: Orvis Tess , Hepperla Austin , Walter Vonn , Song Shujie , Simon Jeremy , Parker Joel , Wilkerson Matthew D. , Desai Nisarg , Major Michael B. , Hayes D. Neil , Davis Ian J. , Weissman Bernard 
Published: August 2014

Abstract
SWI/SNF chromatin remodeling complexes regulate critical cellular processes, including cell-cycle control, programmed cell death, differentiation, genomic instability, and DNA repair. Inactivation of this class of chromatin remodeling complex has been associated with a variety of malignancies, including lung, ovarian, renal, liver, and pediatric cancers. In particular, approximately 10% of primary human lung non–small cell lung cancers (NSCLC) display attenuations in the BRG1 ATPase, a core factor in SWI/SNF complexes. To evaluate the role of BRG1 attenuation in NSCLC development, we examined the effect of BRG1 silencing in primary and established human NSCLC cells. BRG1 loss altered cellular morphology and increased tumorigenic potential. Gene expression analyses showed reduced expression of genes known to be associated with progression of human NSCLC. We demonstrated that BRG1 losses in NSCLC cells were associated with variations in chromatin structure, including differences in nucleosome positioning and occupancy surrounding transcriptional start sites of disease-relevant genes. Our results offer direct evidence that BRG1 attenuation contributes to NSCLC aggressiveness by altering nucleosome positioning at a wide range of genes, including key cancer-associated genes. Cancer Res; 74(22); 6486–98. ©2014 AACR.
Gangliosides Drive the Tumor Infiltration and Function of Myeloid-Derived Suppressor Cells
Authors: Wondimu Assefa , Liu Yihui , Su Yan , Bobb Daniel , Ma Jennifer S.Y. , Chakrabarti Lina , Radoja Saša , Ladisch Stephan 
Published: August 2014

AbstractAlthough it is now widely appreciated that antitumor immunity is critical to impede tumor growth and progression, there remain significant gaps in knowledge about the mechanisms used by tumors to escape immune control. In tumor cells, we hypothesized that one mechanism of immune escape used by tumors involves the synthesis and extracellular shedding of gangliosides, a class of biologically active cell surface glycosphingolipids with known immunosuppressive properties. In this study, we report that tumor cells engineered to be ganglioside deficient exhibit impaired tumorigenicity, supporting a link between ganglioside-dependent immune escape and tumor outgrowth. Notably, we documented a dramatic reduction in the numbers and function of tumor-infiltrating myeloid-derived suppressor cells (MDSC) in ganglioside-deficient tumors, in contrast with the large MDSC infiltrates seen in ganglioside-rich littermate control tumors. Transient ganglioside reconstitution of the tumor cell inoculum was sufficient to increase MDSC infiltration, supporting a direct connection between ganglioside production by tumor cells and the recruitment of immunosuppressive MDSC into the tumor microenvironment. Our results reveal a novel mechanism of immune escape that supports tumor growth, with broad implications given that many human tumors produce and shed high levels of gangliosides. Cancer Res; 74(19); 5449–57. ©2014 AACR.
Downregulation of MHC-I Expression Is Prevalent but Reversible in Merkel Cell Carcinoma
Authors: Paulson Kelly G. , Tegeder Andrew , Willmes Christoph , Iyer Jayasri G. , Afanasiev Olga K. , Schrama David , Koba Shinichi , Thibodeau Renee , Nagase Kotaro , Simonson William T. , Seo Aaron , Koelle David M. , Madeleine Margaret , Bhatia Shailender , Nakajima Hideki , Sano Shigetoshi , Hardwick James S. , Disis Mary L. , Cleary Michele A. , Becker Jürgen C. , Nghiem Paul 
Published: August 2014

Abstract
Merkel cell carcinoma (MCC) is an aggressive, polyomavirus-associated skin cancer. Robust cellular immune responses are associated with excellent outcomes in patients with MCC, but these responses are typically absent. We determined the prevalence and reversibility of major histocompatibility complex class I (MHC-I) downregulation in MCC, a potentially reversible immune-evasion mechanism. Cell-surface MHC-I expression was assessed on five MCC cell lines using flow cytometry as well as immunohistochemistry on tissue microarrays representing 114 patients. Three additional patients were included who had received intralesional IFN treatment and had evaluable specimens before and after treatment. mRNA expression analysis of antigen presentation pathway genes from 35 MCC tumors was used to examine the mechanisms of downregulation. Of note, 84% of MCCs (total n = 114) showed reduced MHC-I expression as compared with surrounding tissues, and 51% had poor or undetectable MHC-I expression. Expression of MHC-I was lower in polyomavirus-positive MCCs than in polyomavirus-negative MCCs (P &lt; 0.01). The MHC-I downregulation mechanism was multifactorial and did not depend solely on HLA gene expression. Treatment of MCC cell lines with ionizing radiation, etoposide, or IFN resulted in MHC-I upregulation, with IFNs strongly upregulating MHC-I expression in vitro, and in 3 of 3 patients treated with intralesional IFNs. MCC tumors may be amenable to immunotherapy, but downregulation of MHC-I is frequently present in these tumors, particularly those that are positive for polyomavirus. This downregulation is reversible with any of several clinically available treatments that may thus promote the effectiveness of immune-stimulating therapies for MCC. Cancer Immunol Res; 2(11); 1071–9. ©2014 AACR.
A Feasibility Study of Cyclophosphamide, Trastuzumab, and an Allogeneic GM-CSF–Secreting Breast Tumor Vaccine for HER2+ Metastatic Breast Cancer
Authors: Chen Gang , Gupta Richa , Petrik Silvia , Laiko Marina , Leatherman James M. , Asquith Justin M. , Daphtary Maithili M. , Garrett-Mayer Elizabeth , Davidson Nancy E. , Hirt Kellie , Berg Maureen , Uram Jennifer N. , Dauses Tianna , Fetting John , Duus Elizabeth M. , Atay-Rosenthal Saadet , Ye Xiaobu , Wolff Antonio C. , Stearns Vered , Jaffee Elizabeth M. , Emens Leisha A. 
Published: August 2014

Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF)–secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide augments vaccine activity in tolerant neu mice and in patients with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance vaccine activity in neu mice. We hypothesized that cyclophosphamide-modulated vaccination with HER2-specific mAb safely induces relevant HER2-specific immunity in neu mice and patients with HER2+ metastatic breast cancer. Adding both cyclophosphamide and the HER2-specific mAb 7.16.4 to vaccination maximized HER2-specific CD8+ T-cell immunity and tumor-free survival in neu transgenic mice. We, therefore, conducted a single-arm feasibility study of cyclophosphamide, an allogeneic HER2+ GM-CSF–secreting breast tumor vaccine, and weekly trastuzumab in 20 patients with HER2+ metastatic breast cancer. Primary clinical trial objectives were safety and clinical benefit, in which clinical benefit represents complete response + partial response + stable disease. Secondary study objectives were to assess HER2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Patients received three monthly vaccinations, with a boost 6 to 8 months from trial entry. This combination immunotherapy was safe, with clinical benefit rates at 6 months and 1 year of 55% [95% confidence interval (CI), 32%–77%; P = 0.013] and 40% (95% CI, 19%–64%), respectively. Median progression-free survival and overall survival durations were 7 months (95% CI, 4–16) and 42 months (95% CI, 22–70), respectively. Increased HER2-specific DTH developed in 7 of 20 patients [of whom 4 had clinical benefit (95% CI, 18–90)], with a trend toward longer progression-free survival and overall survival in DTH responders. Polyfunctional HER2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of cyclophosphamide-modulated vaccination with trastuzumab is warranted. (Clinicaltrials.gov identifier: NCT00399529) Cancer Immunol Res; 2(10); 949–61. ©2014 AACR.