bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal Heterogeneity Characterizes the Genetic Landscape of Pheochromocytoma and Defines Early Events in Tumorigenesis
Authors: Crona Joakim , Backman Samuel , Maharjan Rajani , Mayrhofer Markus , Stålberg Peter , Isaksson Anders , Hellman Per , Björklund Peyman 
Published: May 2015

Abstract
Purpose: Pheochromocytoma and paraganglioma (PPGL) patients display heterogeneity in the clinical presentation and underlying genetic cause. The degree of inter- and intratumor genetic heterogeneity has not yet been defined.
Experimental Design: In PPGLs from 94 patients, we analyzed LOH, copy-number variations, and mutation status of SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, EPAS1, NF1, RET, TMEM127, MAX, and HRAS using high-density SNP array and targeted deep sequencing, respectively. Genetic heterogeneity was determined through (i) bioinformatics analysis of individual samples that estimated absolute purity and ploidy from SNP array data and (ii) comparison of paired tumor samples that allowed reconstruction of phylogenetic trees.
Results: Mutations were found in 61% of the tumors and correlated with specific patterns of somatic copy-number aberrations (SCNA) and degree of nontumoral cell admixture. Intratumor genetic heterogeneity was observed in 74 of 136 samples using absolute bioinformatics estimations and in 22 of 24 patients by comparison of paired samples. In addition, a low genetic concordance was observed between paired primary tumors and distant metastases. This allowed for reconstructing the life history of individual tumors, identifying somatic mutations as well as copy-number loss of 3p and 11p (VHL subgroup), 1p (Cluster 2), and 17q (NF1 subgroup) as early events in PPGL tumorigenesis.
Conclusions: Genomic landscapes of PPGL are specific to mutation subtype and characterized by genetic heterogeneity both within and between tumor lesions of the same patient. Clin Cancer Res; 21(19); 4451–60. ©2015 AACR.
Untouched GMP-Ready Purified Engineered Immune Cells to Treat Cancer
Authors: Straetemans Trudy , Gründer Cordula , Heijhuurs Sabine , Hol Samantha , Slaper-Cortenbach Ineke , Bönig Halvard , Sebestyen Zsolt , Kuball Jürgen 
Published: May 2015

AbstractPurpose: Engineering T cells with receptors to redirect the immune system against cancer has most recently been described as a scientific breakthrough. However, a main challenge remains the GMP-grade purification of immune cells selectively expressing the introduced receptor in order to reduce potential side effects due to poorly or nonengineered cells.Experimental Design: In order to test a novel purification strategy, we took advantage of a model γδT cell receptor (TCR), naturally interfering with endogenous TCR expression and designed the optimal retroviral expression cassette to achieve maximal interference with endogenous TCR chains. Following retroviral transduction, nonengineered and poorly engineered immune cells characterized by a high endogenous αβTCR expression were efficiently depleted with GMP-grade anti-αβTCR beads. Next, the engineered immune cells were validated for TCR expression, function against a panel of tumor cell lines and primary tumors and potential allo-reactivity. Engineered immune cells were further validated in two humanized mouse tumor models.Results: The untouched enrichment of engineered immune cells translated into highly purified receptor-engineered cells with strong antitumor reactivity both in vitro and in vivo. Importantly, this approach eliminated residual allo-reactivity of engineered immune cells. Our data demonstrate that even with long-term suboptimal interference with endogenous TCR chains such as in resting cells, allo-reactivity remained absent and tumor control preserved.Conclusions: We present a novel enrichment method for the production of untouched engineered immune cells, ready to be translated into a GMP-grade method and potentially applicable to all receptor-modified cells even if interference with endogenous TCR chains is far from complete. Clin Cancer Res; 21(17); 3957–68. ©2015 AACR.
Autoantibody Signatures Combined with Epstein–Barr Virus Capsid Antigen-IgA as a Biomarker Panel for the Detection of Nasopharyngeal Carcinoma
Authors: Peng Yu-Hui , Xu Yi-Wei , Huang Li-Sheng , Zhai Tian-Tian , Dai Li-Hua , Qiu Si-Qi , Yang Yu-Su , Chen Wei-Zheng , Zhang Li-Qun , Li En-Min , Xu Li-Yan 
Published: May 2015

Abstract
Nasopharyngeal carcinoma (NPC) is prevalent in Southern China and Southeast Asia, and autoantibody signatures may improve early detection of NPC. In this study, serum levels of autoantibodies against a panel of six tumor-associated antigens (p53, NY-ESO-1, MMP-7, Hsp70, Prx VI, and Bmi-1) and Epstein–Barr virus capsid antigen-IgA (VCA-IgA) were tested by enzyme-linked immunosorbent assay in a training set (220 NPC patients and 150 controls) and validated in a validation set (90 NPC patients and 68 controls). We used receiver-operating characteristics (ROC) to calculate diagnostic accuracy. ROC curves showed that use of these 6 autoantibody assays provided an area under curve (AUC) of 0.855 [95% confidence interval (CI), 0.818–0.892], 68.2% sensitivity, and 90.0% specificity in the training set and an AUC of 0.873 (95% CI, 0.821–0.925), 62.2% sensitivity, and 91.2% specificity in the validation set. Moreover, the autoantibody panel maintained diagnostic accuracy for VCA-IgA–negative NPC patients [0.854 (0.809–0.899), 67.8%, and 90.0% in the training set; 0.879 (0.815–0.942), 67.4%, and 91.2% in the validation set]. Importantly, combination of the autoantibody panel and VCA-IgA improved diagnostic accuracy for NPC versus controls compared with the autoantibody panel alone [0.911 (0.881–0.940), 81.4%, and 90.0% in the training set; 0.919 (0.878–0.959), 78.9%, and 91.2% in the validation set), as well as for early-stage NPC (0.944 (0.894–0.994), 87.9%, and 94.0% in the training set; 0.922 (0.808–1.000), 80.0%, and 92.6% in the validation set]. These results reveal autoantibody signatures in an optimized panel that could improve the identification of VCA-IgA–negative NPC patients, may aid screening and diagnosis of NPC, especially when combined with VCA-IgA. Cancer Prev Res; 8(8); 729–36. ©2015 AACR.
Standardized Outcome Measurement for Patients With Coronary Artery Disease: Consensus From the International Consortium for Health Outcomes Measurement (ICHOM)
Authors: McNamara Robert L. , Spatz Erica S. , Kelley Thomas A. , Stowell Caleb J. , Beltrame John , Heidenreich Paul , Tresserras Ricard , Jernberg Tomas , Chua Terrance , Morgan Louise , Panigrahi Bishnu , Rosas Ruiz Alba , Rumsfeld John S. , Sadwin Lawrence , Schoeberl Mark , Shahian David , Weston Clive , Yeh Robert , Lewin Jack 
Published: May 2015

Background
Coronary artery disease (CAD) outcomes consistently improve when they are routinely measured and provided back to physicians and hospitals. However, few centers around the world systematically track outcomes, and no global standards exist. Furthermore, patient‐centered outcomes and longitudinal outcomes are under‐represented in current assessments.

Methods and Results
The nonprofit International Consortium for Health Outcomes Measurement (ICHOM) convened an international Working Group to define a consensus standard set of outcome measures and risk factors for tracking, comparing, and improving the outcomes of CAD care. Members were drawn from 4 continents and 6 countries. Using a modified Delphi method, the ICHOM Working Group defined who should be tracked, what should be measured, and when such measurements should be performed. The ICHOM CAD consensus measures were designed to be relevant for all patients diagnosed with CAD, including those with acute myocardial infarction, angina, and asymptomatic CAD. Thirteen specific outcomes were chosen, including acute complications occurring within 30 days of acute myocardial infarction, coronary artery bypass grafting surgery, or percutaneous coronary intervention; and longitudinal outcomes for up to 5 years for patient‐reported health status (Seattle Angina Questionnaire [SAQ‐7], elements of Rose Dyspnea Score, and Patient Health Questionnaire [PHQ‐2]), cardiovascular hospital admissions, cardiovascular procedures, renal failure, and mortality. Baseline demographic, cardiovascular disease, and comorbidity information is included to improve the interpretability of comparisons.

Conclusions
ICHOM recommends that this set of outcomes and other patient information be measured for all patients with CAD.
Soluble Epoxide Hydrolase in Hydrocephalus, Cerebral Edema, and Vascular Inflammation After Subarachnoid Hemorrhage
Authors: Siler Dominic A. , Berlow Yosef A. , Kukino Ayaka , Davis Catherine M. , Nelson Jonathan W. , Grafe Marjorie R. , Ono Hirohisa , Cetas Justin S. , Pike Martin , Alkayed Nabil J. 
Published: May 2015

Background and Purpose—
Acute communicating hydrocephalus and cerebral edema are common and serious complications of subarachnoid hemorrhage (SAH), whose causes are poorly understood. Using a mouse model of SAH, we determined whether soluble epoxide hydrolase (sEH) gene deletion protects against SAH-induced hydrocephalus and edema by increasing levels of vasoprotective eicosanoids and suppressing vascular inflammation.

Methods—

SAH was induced via endovascular puncture in wild-type and sEH knockout mice. Hydrocephalus and tissue edema were assessed by T
2
-weighted magnetic resonance imaging. Endothelial activation was assessed in vivo using T2*-weighted magnetic resonance imaging after intravenous administration of iron oxide particles linked to anti–vascular cell adhesion molecule-1 antibody 24 hours after SAH. Behavioral outcome was assessed at 96 hours after SAH with the open field and accelerated rotarod tests.

Results—
SAH induced an acute sustained communicating hydrocephalus within 6 hours of endovascular puncture in both wild-type and sEH knockout mice. This was followed by tissue edema, which peaked at 24 hours after SAH and was limited to white matter fiber tracts. sEH knockout mice had reduced edema, less vascular cell adhesion molecule-1 uptake, and improved outcome compared with wild-type mice.

Conclusions—
Genetic deletion of sEH reduces vascular inflammation and edema and improves outcome after SAH. sEH inhibition may serve as a novel therapy for SAH.
Hemodynamic Characteristics of Cerebral Arteriovenous Malformation Feeder Vessels With and Without Aneurysms
Authors: Shakur Sophia F. , Amin-Hanjani Sepideh , Mostafa Hassan , Charbel Fady T. , Alaraj Ali 
Published: May 2015

Background and Purpose—
The pathogenesis of aneurysms associated with cerebral arteriovenous malformation (AVM) feeder vessels is poorly understood. We sought to determine the hemodynamic characteristics of AVM feeder vessels with and without aneurysms.

Methods—
Patients with AVMs associated with feeder aneurysms who had flow, vessel diameter, and wall shear stress measured before treatment using quantitative magnetic resonance angiography were retrospectively reviewed. Feeders within each AVM were classified into 2 groups based on presence or absence of aneurysms. Hemodynamic parameters were calculated for each arterial feeder and then compared between the 2 groups.

Results—

Eleven patients had AVMs with feeder aneurysms. Of 35 total feeder arteries, 12 had an aneurysm and 23 feeders did not have any aneurysms. Absolute mean flow was higher (510.2 versus 438.4 mL/min;
P
=0.53) and vessel diameter was lower (4.0 versus 4.8 mm;
P
=0.24) in feeders with aneurysms but not significantly. However, wall shear stress (96.2 versus 28.0 dynes/cm
2
;
P
=0.04) was significantly higher in feeders with aneurysms.

Conclusions—
Wall shear stress is significantly higher among cerebral AVM feeders harboring aneurysms. Despite similarly high flows, feeder artery diameter tended to be smaller if an aneurysm was present, suggesting that AVM feeders with aneurysms are a subgroup in which vessel remodeling cannot compensate for increased blood flow.
Dual-Polarization Radar Data Analysis of the Impact of Ground-Based Glaciogenic Seeding on Winter Orographic Clouds. Part I: Mostly Stratiform Clouds
Authors: Jing Xiaoqin , Geerts Bart , Friedrich Katja , Pokharel Binod 
Published: May 2015

AbstractThe impact of ground-based glaciogenic seeding on wintertime orographic, mostly stratiform clouds is analyzed by means of data from an X-band dual-polarization radar, the Doppler-on-Wheels (DOW) radar, positioned on a mountain pass. This study focuses on six intensive observation periods (IOPs) during the 2012 AgI Seeding Cloud Impact Investigation (ASCII) project in Wyoming. In all six storms, the bulk upstream Froude number below mountaintop exceeded 1 (suggesting unblocked flow), the clouds were relatively shallow (with bases below freezing), some liquid water was present, and orographic flow conditions were mostly steady. To examine the silver iodide (AgI) seeding effect, three study areas are defined (a control area, a target area upwind of the crest, and a lee target area), and comparisons are made between measurements from a treated period and those from an untreated period. Changes in reflectivity and differential reflectivity observed by the DOW at low levels during seeding are consistent with enhanced snow growth, by vapor diffusion and/or aggregation, for a case study and for the composite analysis of all six IOPs, especially at close range upwind of the mountain crest. These low-level changes may have been affected by natural changes aloft, however, as evident from differences in the evolution of the echo-top height in the control and target areas. Even though precipitation in the target region is strongly correlated with that in the control region, the authors cannot definitively attribute the change to seeding because there is a lack of knowledge about natural variability, nor can the outcome be generalized, because the sample size is small.
Does External Forcing Interfere with the AMOC’s Influence on North Atlantic Sea Surface Temperature?
Authors: Tandon Neil F. , Kushner Paul J. 
Published: May 2015

Abstract
Numerous studies have suggested that variations in the strength of the Atlantic meridional overturning circulation (AMOC) may drive predictable variations in North Atlantic sea surface temperature (NASST). However, two recent studies have presented results suggesting that coupled models disagree on both the sign and the phasing of the correlation between AMOC and NASST indices. These studies analyzed linearly detrended output from twentieth-century historical simulations in phases 3 and 5 of the Coupled Model Intercomparison Project (CMIP3 and CMIP5). The present study argues that the apparent disagreement among models arises from a comingling of two processes: 1) a bottom-up effect in which unforced AMOC changes lead to NASST changes of the same sign and 2) a top-down effect in which forced NASST changes lead to AMOC changes of the opposite sign. Linear detrending is not appropriate for separating these two effects because the time scales of forced and unforced variations are not well separated. After forced variations are properly removed, the models come into much closer agreement with each other. This argument is supported by analysis of CMIP5 historical simulations, as well as preindustrial control simulations and a 29-member ensemble of the Community Earth System Model, version 1, covering the period 1920–2005. Additional analysis is presented suggesting that, even after the data are linearly detrended, a significant portion of observed NASST persistence may be externally forced.
Alar Suspension Sutures in the Management of Nasal Valve Collapse
Authors: Manickavasagam Jaiganesh , Iqbal Isma , Wong Smeeta , Raghavan Ullas 
Published: May 2015

Objective: This study assesses the efficacy of alar suspension sutures in the management of nasal valve collapse causing nasal obstruction. These sutures are inserted between the vestibular skin and lateral crura and hitched to the periosteum of the medial inferior orbital margin; this is a variation of the alar (change everywhere) suspension suture technique. Method: A retrospective review of patients who underwent alar suspension suture insertion between January 2009 and December 2010 in the management of nasal obstruction was undertaken. Symptoms of nasal obstruction were assessed using the Visual Analogue Scale (VAS) and peak inspiratory flow rate (PIFR). This was measured preprocedure and repeated at 3, 6, and 12 months postoperatively. Results: A total of 35 patients were identified, and 26 were included in the study; 90% of patients were satisfied with the outcome of surgery, supported by improvement in the VAS and PIFR scores. The mean difference in VAS preprocedure and postprocedure was 4.97 ( P value = 0.00), and the average improvement in PIFR was 25.5 L/min ( P value = 0.00). Conclusion: Our study shows a significant improvement in patient’s symptoms following insertion of alar suspension sutures. It is, therefore, a reliable, safe, and effective technique in treating nasal obstruction secondary to nasal valve collapse.
Defining the Morphology and Distribution of the Alar Fascia
Authors: Scali Frank , Nash Lance G. , Pontell Matthew E. 
Published: May 2015

Objectives: This study aims to delineate the morphology, integrity, and distribution of the alar fascia using dissection and E12 sheet plastination. This is the first study that employs E12 sheet plastination to investigate the alar fascia and its adjacent potential spaces. Methods: Twenty-nine manual dissections and 3 sets of E12 sheet plastinations were used to examine the posterior pharyngeal region for the architecture and distribution of the alar fascia. Specimens were examined from the inferior nuchal line to C6. Results: The alar fascia originated as a well-defined midline structure at the level of C1 and could be identified down to C6. There was no evidence of the alar fascia between the inferior nuchal line and the base of the skull. Notably, the alar fascia permitted resistance to manual traction. Conclusions: E12 sheet plastination allowed for visualization of the alar fascia’s superior attachments within the deep cervical region. Resistance to traction suggests that the alar fascia may be more than just a loose fibroareolar matrix. The findings in this study suggest an alternative point of entry into the danger space. Understanding the continuity of this fascial layer is critically important with regard to the pathophysiology of deep neck space infections.
Treatment Selection for T3/T4a Laryngeal Cancer
Authors: Timme David W. , Jonnalagadda Sashikanth , Patel Raunak , Rao Krishna , Robbins K. Thomas 
Published: May 2015

Objective: We report the treatment outcomes, including organ preservation, for patients with locally advanced (T3/T4a) laryngeal cancer receiving both surgical and nonsurgical approaches. We hypothesize that selection of treatment protocols aimed to optimize organ preservation does not compromise survival provided careful selection is done through the process of multidisciplinary treatment planning. Methods: Patients with T3-4a laryngeal squamous cell cancer were evaluated and recommended for primary treatment with total or partial laryngectomy (37 patients) or chemoradiotherapy (34 patients). Treatment outcomes were compared between the 2 cohorts. In addition, the laryngeal preservation rate and laryngoesophageal dysfunction-free survival (LEDFS) were determined for the chemoradiation group. Results: The 5-year overall survival rate for patients with T3 lesions was 41% and 40% for the surgical and nonsurgical groups, respectively, and for T4 lesions it was 54% and 53%, respectively. For the chemoradiation group, the rate of overall laryngeal preservation was 79%. LEDFS at 2 years was 40% for T3 lesions and 33% for T4 lesions. Conclusion: Through careful selection, some patients with locally advanced laryngeal cancer can be offered chemoradiation (organ preservation) without compromising survival. However, the patients selected to receive chemoradiation have a high rate of laryngeal and esophageal dysfunction.
Age at first tobacco use and risk of subsequent psychosis-related outcomes: A birth cohort study
Authors: McGrath John J , Alati Rosa , Clavarino Alexandra , Williams Gail M , Bor William , Najman Jake M , Connell Melissa , Scott James G 
Published: May 2015

Objective: Compared to the substantial body of research examining links between cannabis use and psychosis, there has been relatively little attention to the role of tobacco as a potential risk factor for psychosis. This study explored the association between age at first tobacco use and psychosis-related outcomes in a birth cohort. Method: This study is based on a large birth cohort (the Mater-University Study of Pregnancy). At approximately 21 years of age, cohort members ( N = 3752) were assessed for three psychosis-related outcomes (International Classification of Diseases non-affective psychosis, the presence of any hallucination and total count of delusional-like experiences) with the Composite International Diagnostic Interview and the Peters Delusional Inventory. Associations between age at first tobacco use and psychosis-related outcomes were examined using logistic regression in a model (a) adjusted for sex and age and (b) in a second model excluding all respondents who had a history of past problematic and current cannabis use. Results: When adjusted for age and sex, those who commenced tobacco at 15 years of age or younger were significantly more likely to (a) have non-affective psychosis, (b) be in the highest quartile of total score of the Peters Delusional Inventory and (c) report hallucinations. After excluding all those with a history of a cannabis use disorder, or who were current (last month) cannabis users, a significant association between age at first tobacco use and the presence of hallucinations persisted. Conclusion: There is an association between age at first tobacco use and subsequent psychosis-related outcomes in young adults. While the findings cannot be used to deduce causality, it adds weight to the hypothesis that early tobacco use may contribute to the risk of developing psychosis-related outcomes.
Minimally invasive aortic valve replacement: Comparison of long-term outcomes
Authors: Ariyaratnam Priyadharshanan , Loubani Mahmoud , Griffin Steven C 
Published: May 2015

Background Minimally invasive aortic valve replacement tends to be performed in specialist centers. Little data exists with regard to long-term outcomes of the upper hemi-sternotomy technique. We sought to evaluate the short- and long-term outcomes of this procedure in our institution. Methods Data were collected from our cardiac surgical database. We compared the outcomes of all patients who underwent minimally invasive aortic valve replacement with all who underwent conventional aortic valve replacement between July 1999 and December 2013. Propensity-matching analysis was performed to evaluate hospital outcomes. Results There were 125 patients who underwent minimally invasive aortic valve replacement and 1446 who had conventional surgery. After propensity score matching, there were no differences in postoperative mortality or complications between the 2 groups. The only significant differences were longer bypass (62.69 ± 10.12 vs. 68.94 ± 14.79 min, p = 0.002) and crossclamp times (45.48 ± 8.08 vs. 52.30 ± 16.29 min, p < 0.001) in conventional surgery. Long-term survival after minimally invasive aortic valve replacement at 2, 6, and 10 years was 88% ± 3.0%, 79% ± 4.0%, and 66% ± 6.0%, respectively. Predictors of long-term survival were age, peripheral vascular disease, and low ejection fraction ( p < 0.005). Conclusion Minimally invasive aortic valve replacement has similar hospital outcomes compared to conventional aortic valve replacement. The operation is quicker and does not confer any significant increase in complications or length of hospital stay. The long-term outcomes are favorable and justify its continued use by specialist surgeons in the United Kingdom.