bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoter Methylation of CDO1 Identifies Clear-Cell Renal Cell Cancer Patients with Poor Survival Outcome
Authors: Deckers Ivette A.G. , Schouten Leo J. , Van Neste Leander , van Vlodrop Iris J.H. , Soetekouw Patricia M.M.B. , Baldewijns Marcella M.L.L. , Jeschke Jana , Ahuja Nita , Herman James G. , van den Brandt Piet A. , van Engeland Manon 
Published: April 2015

Abstract
Purpose: In this era of molecular diagnostics, prediction of clear-cell renal cell cancer (ccRCC) survival requires optimization, as current prognostic markers fail to determine individual patient outcome. Epigenetic events are promising molecular markers. Promoter CpG island methylation of cysteine dioxygenase type 1 (CDO1), which was identified as prognostic marker for breast cancer, is studied as a potential marker for ccRCC survival.
Experimental Design: We collected primary tissues of 365 ccRCC cases identified within the prospective Netherlands Cohort Study (NLCS). In this population-based series, CDO1 promoter methylation was observed in 124 of 324 (38.3%) patients with successful methylation-specific PCR analysis. Kaplan–Meier curves and Wilcoxon tests were used to evaluate 10-year ccRCC-specific survival. Cox regression analysis was used to obtain crude and multivariate HRs and 95% confidence intervals (CI). The relative prognostic value of multivariate models with and without CDO1 promoter methylation was compared using likelihood-ratio tests.
Results: Patients with CDO1 promoter methylation have a significantly poorer survival than those without (Wilcoxon P = 0.006). Differences in survival were independent of other prognostic factors, including age and sex (HR, 1.66; 95% CI, 1.12–2.45) and TNM stage, tumor size, and Fuhrman grade (HR, 1.89; 95% CI, 1.25–2.85). Multivariate models performed better with than without CDO1 promoter methylation status (likelihood-ratio P = 0.003). Survival curves were validated in an independent series of 280 ccRCC cases from The Cancer Genome Atlas (TCGA; Wilcoxon P &lt; 0.001).
Conclusions: CDO1 promoter methylation may not substitute common prognostic makers to predict ccRCC survival, but offers additional, relevant prognostic information, indicating that it might be a novel molecular marker to determine ccRCC prognosis. Clin Cancer Res; 21(15); 3492–500. ©2015 AACR.
Dendritic Cells in Irradiated Mice Trigger the Functional Plasticity and Antitumor Activity of Adoptively Transferred Tc17 Cells via IL12 Signaling
Authors: Bowers Jacob S. , Nelson Michelle H. , Kundimi Sreenath , Bailey Stefanie R. , Huff Logan W. , Schwartz Kristina M. , Cole David J. , Rubinstein Mark P. , Paulos Chrystal M. 
Published: April 2015

AbstractPurpose: The adoptive cell transfer (ACT) of CD8+ T cells is a promising treatment for advanced malignancies. Lymphodepletion before ACT enhances IFNγ+CD8+ T cell (Tc0)–mediated tumor regression. Yet, how lymphodepletion regulates the function and antitumor activity of IL17A+CD8+ T cells (Tc17) is unknown.Experimental Design: To address this question, pmel-1 CD8+ T cells were polarized to secrete either IL17A or IFNγ. These subsets were then infused into mice with B16F10 melanoma that were lymphoreplete [no total body irradiation (TBI)], or lymphodepleted with nonmyeloablative (5 Gy) or myeloablative (9 Gy with hematopoietic stem cell transplantation) TBI. The activation of innate immune cells and function of donor T-cell subsets were monitored in recipient mice.Results: Tc17 cells regress melanoma in myeloablated mice to a greater extent than in lymphoreplete or nonmyeloablated mice. TBI induced functional plasticity in Tc17 cells, causing conversion from IL17A to IFNγ producers. Additional investigation revealed that Tc17 plasticity and antitumor activity were mediated by IL12 secreted by irradiated host dendritic cells (DC). Neutralization of endogenous IL12 reduced the antitumor activity of Tc17 cells in myeloablated mice, whereas ex vivo priming with IL12 enhanced their capacity to regress melanoma in nonmyeloablated animals. This, coupled with exogenous administration of low-dose IL12, obviated the need for host preconditioning, creating curative responses in nonirradiated mice.Conclusions: Our findings indicate that TBI-induced IL12 augments Tc17 cell–mediated tumor immunity and underline the substantial implications of in vitro preparation of antitumor Tc17 cells with IL12 in the design of T-cell immunotherapies. Clin Cancer Res; 21(11); 2546–57. ©2015 AACR.
Activating stimuli induce platelet microRNA modulation and proteome reorganisation
Authors: Nassa Giovanni , Filippo Maria Rosaria De , Giurato Giorgio , Ravo Maria , Rizzo Francesca , Conte Stefano , Pellegrino Grazia , Cirillo Plinio , Calabrò Paolo , Öhman Tiina , Nyman Tuula A. , Cimmino Giovanni , Tarallo Roberta , Weisz Alessandro , Golino Paolo 
Published: April 2015

SummaryPlatelets carry megakaryocyte-derived mRNAs whose translation efficiency before and during activation is not known, although this can greatly affect platelet functions, both under basal conditions and in response to physiological and pathological stimuli, such as those involved in acute coronary syndromes. Aim of the present study was to determine whether changes in microRNA (miRNA) expression occur in response to activating stimuli and whether this affects activity and composition of platelet transcriptome and proteome. Purified platelet-rich plasmas from healthy volunteers were collected and activated with ADP, collagen, or thrombin receptor activating peptide. Transcriptome analysis by RNA-Seq revealed that platelet transcriptome remained largely unaffected within the first 2 hours of stimulation. In contrast, quantitative proteomics showed that almost half of > 700 proteins quantified were modulated under the same conditions. Global miRNA analysis indicated that reorganisation of platelet proteome occurring during activation reflected changes in mature miRNA expression, which therefore, appears to be the main driver of the observed discrepancy between transcriptome and proteome changes. Platelet functions significantly affected by modulated miRNAs include, among others, the integrin/cytoskeletal, coagulation and inflammatory-immune response pathways. These results demonstrate a significant reprogramming of the platelet miRNome during activation, with consequent significant changes in platelet proteome and provide for the first time substantial evidence that fine-tuning of resident mRNA translation by miRNAs is a key event in platelet pathophysiology.
Accumulation of tissue factor in endothelial cells induces cell apoptosis, mediated through p38 and p53 activation
Authors: Maraveyas Anthony , ElKeeb Azza , Collier Mary , Ettelaie Camille 
Published: April 2015

SummaryWe previously reported that high levels of tissue factor (TF) can induce cellular apoptosis in endothelial cells. In this study, TF-mediated mechanisms of induction of apoptosis were explored. Endothelial cells were transfected to express wild-type TF. Additionally, cells were transfected to express Asp253-substituted, or Ala253-substitued TF to enhance or prevent TF release, respectively. Alternatively, cells were pre-incubated with TF-rich and TF-poor microvesicles. Cell proliferation, apoptosis and the expression of cyclin D1, p53, bax and p21 were measured following activation of cells with PAR2-agonist peptide. Greatest levels of cell proliferation and cyclin D1 expression were observed in cells expressing wild-type or Asp253-substituted TF. In contrast, increased cellular apoptosis was observed in cells expressing Ala253-substituted TF, or cells pre-incubated with TF-rich microvesicles. The level of p53 protein, p53-phosphorylation at ser33, p53 nuclear localisation and transcriptional activity, but not p53 mRNA, were increased in cells expressing wild-type and Ala253-substituted TF, or in cells pre-incubated with TF-rich microvesicles. However, the expression of bax and p21 mRNA, and Bax protein were only increased in cells pre-incubated with TF-rich microvesicle and in cells expressing Ala253-substituted TF. Inhibition of the transcriptional activity of p53 using pifithrin-α suppressed the expression of Bax. Finally, siRNA- mediated suppression of p38α, or inhibition using SB202190 significantly reduced the p53 protein levels, p53 nuclear localisation and transcriptional activity, suppressed Bax expression and prevented cellular apoptosis. In conclusion, accumulation of TF within endothelial cells, or sequestered from the surrounding can induce cellular apoptosis through mechanisms mediated by p38, and involves the stabilisation of p53.
Atrial Ectopy Predicts Late Recurrence of Atrial Fibrillation After Pulmonary Vein Isolation
Authors: Gang Uffe J.O. , Nalliah Chrishan J. , Lim Toon Wei , Thiagalingam Aravinda , Kovoor Pramesh , Ross David L. , Thomas Stuart P. 
Published: April 2015

Background—
Late recurrence of atrial fibrillation (AF) after radiofrequency ablation remains significant. Asymptomatic recurrence poses a difficult clinical problem as it is associated with an equally increased risk of stroke and death compared with symptomatic AF events. Meta-analyses reveal that no single preablation patient characteristic efficiently predicts these AF recurrences. This study aimed to evaluate the prognostic value of premature atrial complex (PAC) occurrence with regard to the risk of late AF recurrence after radiofrequency ablation.

Methods and Results—

The study cohort consisted of 124 patients with 7-day Holter recordings at 6 months post radiofrequency ablation for AF. No patients had AF recurrence before this time. Patients were followed-up every 6 months. Holter-detected PACs were defined as any supraventricular complexes occurring >30% earlier than expected. During a median follow-up of 4.2 years (first quartile to third quartile [Q1–Q3]=1.6–4.5), 32 patients (26%) had late recurrences of AF at a median of 462 days (Q1–Q3=319–1026) post radiofrequency ablation. The number of PACs per 24 hours was 248 (Q1–Q3=62–1026) in patients with and 77 (Q1–Q3=24–448) in patients without recurrence of AF (
P
=0.02). Multivariate analysis of the risk of late AF recurrence found ≥142 PACs per 24 hours to have a hazard ratio 2.84 (confidence interval, 1.26–6.43),
P
=0.01.

Conclusions—
This study showed that occurrence of ≥142 PACs per day at 6 months after PVI was independently associated with a significantly increased risk of late AF recurrence. These results could have important clinical implications for the design of post-PVI follow-up.

Clinical Trial Registration—

URL:
http://www.anzctr.org.au
. Unique identifier: ACRTN12606000467538.
Prediction of Mortality by Stress Echocardiography in 2835 Diabetic and 11 305 Nondiabetic Patients
Authors: Cortigiani Lauro , Borelli Lucia , Raciti Mauro , Bovenzi Francesco , Picano Eugenio , Molinaro Sabrina , Sicari Rosa 
Published: April 2015

Background—
To compare the capability by stress echocardiography results to predict overall mortality in a large unselected cohort of diabetic and nondiabetic patients.

Methods and Results—

The study group comprised 14 140 patients (2835 diabetics and 11 305 nondiabetics) who underwent stress echocardiography for evaluation of known (n=5671) or suspected (n=8469) coronary artery disease. Ischemia at stress echocardiography was observed in 768 (27%) diabetics and 2644 (23%) nondiabetics. During a median follow-up of 30 months (first quartile, 9; third quartile, 63), 1213 patients died. In diabetics, multivariable indicators of mortality were age (hazard ratio [HR], 1.07, 95% confidence interval [CI], 1.06–1.09), rest wall motion abnormality (HR, 2.43; 95% CI, 1.83–3.22), and ischemia at stress echocardiography (HR, 1.71; 95% CI, 1.34–2.18). In nondiabetics, multivariable indicators of mortality were age (HR, 1.07; 95% CI, 1.06–1.08), rest wall motion abnormality (HR, 2.19; 95% CI, 1.86–2.57), male sex (HR, 1.65; 95% CI, 1.41–1.93), ischemia at stress echocardiography (HR, 1.54; 95% CI, 1.32–1.80), and antischemic therapy at the time of test (HR, 1.15; 95% CI, 1.00–1.32). In stress echo negative subjects for ischemia, antischemic therapy showed increased annual mortality in nondiabetic patients with (3.8% versus 3.1%;
P
=0.04) or without rest wall motion abnormality (1.6% versus 0.9%;
P
<0.0001); it failed to do so in diabetic patients with (5.7% versus 5.8%;
P
=0.89) or without rest wall motion abnormality (2.6% versus 1.9%;
P
=0.10).

Conclusions—
Ischemia at stress echocardiography is a strong and independent predictor of total mortality in diabetic as well as nondiabetic patients. Antischemic therapy markedly affects the negative predictive value of stress echocardiography in nondiabetic patients, whereas it is prognostically neutral in the diabetic population.
New Method for Noninvasive Quantification of Central Venous Pressure by Ultrasound
Authors: Xing Chang-Yang , Liu Yuan-Ling , Zhao Mei-Ling , Yang Rui-Jing , Duan Yun-You , Zhang Lian-Hua , Sun Xu-De , Yuan Li-Jun , Cao Tie-Sheng 
Published: April 2015

Background—
The central venous pressure (CVP) is essential for assessing the cardiac preload and circulating blood volume in clinic. The invasive CVP measurement by central venous catheter has been reported with various complications. The aim of this study was to develop a new noninvasive method for quantification of CVP by ultrasound.

Methods and Results—

Seventy-six patients who had their CVP monitored for intraoperative or postoperative management were recruited. By accurate location of the collapse point of the internal jugular vein and the center of the right atrium using ultrasound imaging, the height of the fluid column between those 2 points was measured as the noninvasive CVP (CVPn). A total of 118 measurements were performed and compared with the invasive CVP (CVPi). Linear correlation analysis revealed a significant correlation between CVPi and CVPn (preoperative measurements,
r
=0.90;
P
<0.01 and postoperative measurements,
r
=0.93;
P
<0.01). Bland–Altman plots showed a good agreement between CVPi and CVPn with the mean difference of 0.22 mm Hg (preoperative measurements) and −0.09 mm Hg (postoperative measurements), respectively.

Conclusions—
The new noninvasive CVP quantification method based on the location of both the collapse point of internal jugular vein and the center of right atrium by ultrasound could be used as a reliable approach for monitoring the hemodynamic status in clinic.
Trends in Myocardial Infarction Secondary Prevention: The National Health and Nutrition Examination Surveys (NHANES), 1999–2012
Authors: Shah Nilay S. , Huffman Mark D. , Ning Hongyan , Lloyd‐Jones Donald M. 
Published: April 2015

Background
Nationally representative data evaluating recent trends and future projections of vascular risk factor treatment and control rates in secondary prevention of ischemic heart disease are sparse.

Methods and Results

We evaluated sex‐ and race‐stratified cholesterol, blood pressure, and hemoglobin A1c levels and risk factor treatment and control rates in 1580 individuals who self‐reported a history of myocardial infarction from The National Health and Nutrition Examination Surveys (
NHANES
) 1999 to 2012. We used weighted linear regression to estimate time trends and created forward linear projections to 2020. Participants were 30% to 41% women, 73% to 85% white, and had a mean age of 63 to 66 years. Cholesterol treatment rates increased and reached above 80% in men and women by 2011–2012, with significant increases in control rates (as then defined) in men to 85% in 2011–2012, with projections to reach 100% by 2020. Cholesterol treatment rates significantly increased in non‐Hispanic whites and Hispanics. Statin use increased significantly to 73% of myocardial infarction survivors by 2011–2012, and aspirin use increased significantly but only to 28% by 2011–2012. There were no changes in blood pressure treatment or control rates by sex, and hypertension treatment increased only in non‐Hispanic blacks. Projected hypertension control rates remained suboptimal.

Conclusions
While temporal trends suggest improvements in cholesterol treatment, unchanged treatment and control of blood pressure and persistently low aspirin use represent missed opportunities. Urgent action is needed to improve secondary prevention rates projected by 2020 to reduce recurrent events in this high‐risk group.
Female belly colour and bobbing behaviour advertise sexual receptivity in a pelagic-spawning coral reef fish
Authors: LaPlante Lori Hosaka 
Published: April 2015

Female nuptial signals (FNSs) advertise reproductive state, individual quality, and are used in intrasexual competition. I explored whether pelagic-spawning pink-belly wrasse (Halichoeres margaritaceus) used red belly colouration and a unique bobbing behaviour as FNSs to advertise spawning readiness. I examined (i) if there was a temporal pattern in belly colour and incidence of bobbing, as each related to spawning; (ii) response of female belly colouration during male courtship behaviours; and (iii) pink belly area as it related to body area and bobbing rate. Temporal patterns were detected, females displayed ephemeral red belly colour and bobbing behaviour prior to spawning; females displaying red belly colouration elicited more courtship behaviour from males than females with white or pink belly colouration, and larger females displayed larger red belly areas. Benefits to advertising spawning readiness in pink-belly wrasse are discussed, including a reduction in mate-searching costs and potential for increased reproductive success through sex-change.
Defences of a Neotropical harvestman against different levels of threat by the recluse spider
Authors: Segovia Júlio M.G. , Del-Claro Kleber , Willemart Rodrigo Hirata 
Published: April 2015

The threat sensitive hypothesis predicts that animals modulate the defensive behaviour with the level of threat. Therefore, responses to predator cues may differ from responses to the actual predator in close range. Also, in high threat situations, prey would be expected to use their most dangerous defences. The recluse spider Loxosceles gaucho (Araneae, Sicariidae) is known to prey upon well defended harvestmen such as the laniatorid Mischonyx cuspidatus (Opiliones, Gonyleptidae), which has been reported to use tanathosis, chemical defences, pinching with sharp apophyses on legs, chelicerae and pedipalps. Because of harvestmen’s dependence on chemical stimuli, we tested if M. cuspidatus would change its locomotory behaviour in the presence of chemicals of the recluse spider (low threat situation: spider vs blank vs chemical control; one at a time). Subsequently, we tested harvestmen behaviour in the presence of the spider in close range, a high-threat situation. Finally, we looked at the survival rate of spiders after being pierced by sharp apophyses that M. cuspidatus have on legs IV. The harvestmen only showed defensive behaviours in the high threat situation. Surprisingly, their mostly known defensive behaviours (chemical defence, tanathosis, pinching with chelicerae and pedipalps) were not seen even in the high threat situation. This is the first evidence that these behaviours are not used against a natural predator that has an almost 80% predation success when attacking harvestmen. Pinching with the sharp legs IV apophyses may perforate but do not kill the spiders. We highlight the importance of the traditional descriptive approach with natural predators to understand the specificities of defensive behaviours against different types of predator.
A new species of Regabellator Siebenaller & Hessler, 1981 (Isopoda, Asellota, Nannoniscidae) from the Amundsen Sea shelf (Southern Ocean)
Authors: Kaiser S. S. M. 
Published: April 2015

Based on benthic material collected during the BIOPEARL (Biodiversity, Phylogeny, Evolution and Adaptive Radiation of Life in Antarctica) II expedition on board RRS “James Clark Ross” a new nannoniscid species,Regabellator brixorumsp. n., is described from the Pine Island Bay continental shelf, western Amundsen Sea (Antarctica). The new species most closely resemblesRegabellator armatus(Hansen, 1916) but can be distinguished from this species by possessing ventral spines on pereonites 1-4, the shape of the cephalothorax anterior margin and the length of the pereonite 7 ventral spine. The genusRegabellatorhas been previously recorded from the North and South-eastern Atlantic and here exclusively from the deep sea (1946 m and below). The new species represents the first record of the genusRegabellatorfrom the Antarctic continental shelf and thus greatly extends hitherto known latitudinal and bathymetric ranges for this genus.
Effective Buoyancy, Inertial Pressure, and the Mechanical Generation of Boundary Layer Mass Flux by Cold Pools
Authors: Jeevanjee Nadir , Romps David M. 
Published: April 2015

Abstract
The Davies-Jones formulation of effective buoyancy is used to define inertial and buoyant components of vertical force and to develop an intuition for these components by considering simple cases. This decomposition is applied to the triggering of new boundary layer mass flux by cold pools in a cloud-resolving simulation of radiative–convective equilibrium (RCE). The triggering is found to be dominated by inertial forces, and this is explained by estimating the ratio of the inertial forcing to the buoyancy forcing, which scales as H/h, where H is the characteristic height of the initial downdraft and h is the characteristic height of the mature cold pool’s gust front. In a simulation of the transition from shallow to deep convection, the buoyancy forcing plays a dominant role in triggering mass flux in the shallow regime, but the force balance tips in favor of inertial forcing just as precipitation sets in, consistent with the RCE results.
Finding the Minimum Potential Energy State by Adiabatic Parcel Rearrangements with a Nonlinear Equation of State: An Exact Solution in Polynomial Time
Authors: Hieronymus Magnus , Nycander Jonas 
Published: April 2015

AbstractThe problem of finding the state of minimum potential energy through the rearrangement of water parcels with a nonlinear equation of state is discussed in the context of a combinatorial optimization problem. It is found that the problem is identical to a classical optimization problem called the linear assignment problem. This problem belongs to a problem class known as P, a class of problems that have known efficient solutions. This is very fortunate since this study’s problem has been suggested to be an asymmetric traveling salesman problem. A problem that belongs to a class called NP-hard, for which no efficient solutions are known. The difference between the linear assignment problem and the traveling salesman problem is discussed and made clear by looking at the different constraints used for the two problems. It is also shown how the rearrangement of water parcels that minimizes the potential energy can be found in polynomial time using the so-called Hungarian algorithm. The Hungarian algorithm is then applied to a simplified ocean stratification, and the result is compared to a few different approximate solutions to the minimization problem. It is found that the improved accuracy over the approximate methods comes at a high computational cost. Last, the algorithm is applied to a realistic ocean stratification using a technique that splits the minimization problem into smaller bits.