bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salivary microRNAs Show Potential as a Noninvasive Biomarker for Detecting Resectable Pancreatic Cancer
Authors: Xie Zijun , Yin Xiaoyu , Gong Bo , Nie Wenjing , Wu Bin , Zhang Xuchao , Huang Jian , Zhang Pingyou , Zhou Zhiwei , Li Zijun 
Published: December 2014

Abstract
Early surgery is vital in the treatment of pancreatic cancer, which is often fatal. However, there is currently no useful noninvasive biomarker to screen for pancreatic cancer. Studies have documented that many salivary molecules can be used to detect systemic diseases. We investigated whether salivary miRNAs are useful biomarkers for detecting resectable pancreatic cancer. Using an Agilent microarray, salivary miRNAs were profiled from saliva samples of 8 patients with resectable pancreatic cancer and 8 healthy controls. Candidate biomarkers identified in the profiles were subjected to validation using quantitative PCR and an independent sample set of 40 patients with pancreatic cancer, 20 with benign pancreatic tumors (BPT), and 40 healthy controls. The validated salivary miRNA biomarkers were evaluated within three discriminatory categories: pancreatic cancer versus healthy control, pancreatic cancer versus BPT, and pancreatic cancer versus noncancer (healthy control + BPT). miR-3679-5p showed significant downregulation in the pancreatic cancer group within the three categories (P = 0.008, 0.007, and 0.002, respectively), whereas miR-940 showed significant upregulation in pancreatic cancer (P = 0.006, 0.004, and 0.0001, respectively). Logistic regression models combining the two salivary miRNAs were able to distinguish resectable pancreatic cancer within the three categories, showing sensitivities of 72.5%, 62.5%, and 70.0% and specificities of 70.0%, 80.0%, and 70.0%, respectively. Salivary miR-3679-5p and miR-940 possess good discriminatory power to detect resectable pancreatic cancer, with reasonable specificity and sensitivity. This report provides a new method for the early detection of pancreatic cancer and other systemic diseases by assessing salivary miRNAs. Cancer Prev Res; 8(2); 165–73. ©2014 AACR.
Spectrin Repeat Containing Nuclear Envelope 1 and Forkhead Box Protein E1 Are Promising Markers for the Detection of Colorectal Cancer in Blood
Authors: Melotte Veerle , Yi Joo Mi , Lentjes Marjolein H.F.M. , Smits Kim M. , Van Neste Leander , Niessen Hanneke E.C. , Wouters Kim A.D. , Louwagie Joost , Schuebel Kornel E. , Herman James G. , Baylin Stephen B. , van Criekinge Wim , Meijer Gerrit A. , Ahuja Nita , van Engeland Manon 
Published: December 2014

Abstract
Identifying biomarkers in body fluids may improve the noninvasive detection of colorectal cancer. Previously, we identified N-Myc downstream-regulated gene 4 (NDRG4) and GATA binding protein 5 (GATA5) methylation as promising biomarkers for colorectal cancer in stool DNA. Here, we examined the utility of NDRG4, GATA5, and two additional markers [Forkhead box protein E1 (FOXE1) and spectrin repeat containing nuclear envelope 1 (SYNE1)] promoter methylation as biomarkers in plasma DNA. Quantitative methylation-specific PCR was performed on plasma DNA from 220 patients with colorectal cancer and 684 noncancer controls, divided in a training set and a test set. Receiver operating characteristic analysis was performed to measure the area under the curve of GATA5, NDRG4, SYNE1, and FOXE1 methylation. Functional assays were performed in SYNE1 and FOXE1 stably transfected cell lines. The sensitivity of NDRG4, GATA5, FOXE1, and SYNE1 methylation in all stages of colorectal cancer (154 cases, 444 controls) was 27% [95% confidence interval (CI), 20%–34%), 18% (95% CI, 12%–24%), 46% (95% CI, 38%–54%), and 47% (95% CI, 39%–55%), with a specificity of 95% (95% CI, 93%–97%), 99% (95% CI, 98%–100%), 93% (95% CI, 91%–95%), and 96% (95% CI, 94%–98%), respectively. Combining SYNE1 and FOXE1, increased the sensitivity to 56% (95% CI, 48%–64%), while the specificity decreased to 90% (95% CI, 87%–93%) in the training set and to 58% sensitivity (95% CI, 46%–70%) and 91% specificity (95% CI, 80%–100%) in a test set (66 cases, 240 controls). SYNE1 overexpression showed no major differences in cell proliferation, migration, and invasion compared with controls. Overexpression of FOXE1 significantly decreased the number of colonies in SW480 and HCT116 cell lines. Overall, our data suggest that SYNE1 and FOXE1 are promising markers for colorectal cancer detection. Cancer Prev Res; 8(2); 157–64. ©2014 AACR.
Gla-Rich Protein Acts as a Calcification Inhibitor in the Human Cardiovascular System
Authors: Viegas Carla S.B. , Rafael Marta S. , Enriquez José L. , Teixeira Alexandra , Vitorino Rui , Luís Inês M. , Costa Rúben M. , Santos Sofia , Cavaco Sofia , Neves José , Macedo Anjos L. , Willems Brecht A.G. , Vermeer Cees , Simes Dina C. 
Published: December 2014

Objective—
Vascular and valvular calcifications are pathological processes regulated by resident cells, and depending on a complex interplay between calcification promoters and inhibitors, resembling skeletal metabolism. Here, we study the role of the vitamin K–dependent Gla-rich protein (GRP) in vascular and valvular calcification processes.

Approach and Results—
Immunohistochemistry and quantitative polymerase chain reaction showed that GRP expression and accumulation are upregulated with calcification simultaneously with osteocalcin and matrix Gla protein (MGP). Using conformation-specific antibodies, both γ-carboxylated GRP and undercarboxylated GRP species were found accumulated at the sites of mineral deposits, whereas undercarboxylated GRP was predominant in calcified aortic valve disease valvular interstitial cells. Mineral-bound GRP, MGP, and fetuin-A were identified by mass spectrometry. Using an ex vivo model of vascular calcification, γ-carboxylated GRP but not undercarboxylated GRP was shown to inhibit calcification and osteochondrogenic differentiation through α-smooth muscle actin upregulation and osteopontin downregulation. Immunoprecipitation assays showed that GRP is part of an MGP–fetuin-A complex at the sites of valvular calcification. Moreover, extracellular vesicles released from normal vascular smooth muscle cells are loaded with GRP, MGP, and fetuin-A, whereas under calcifying conditions, released extracellular vesicles show increased calcium loading and GRP and MGP depletion.

Conclusions—
GRP is an inhibitor of vascular and valvular calcification involved in calcium homeostasis. Its function might be associated with prevention of calcium-induced signaling pathways and direct mineral binding to inhibit crystal formation/maturation. Our data show that GRP is a new player in mineralization competence of extracellular vesicles possibly associated with the fetuin-A–MGP calcification inhibitory system. GRP activity was found to be dependent on its γ-carboxylation status, with potential clinical relevance.
Changes in Functional Outcome Over the First Year After Stroke
Authors: Ullberg Teresa , Zia Elisabet , Petersson Jesper , Norrving Bo 
Published: December 2014

Background and Purpose—
Large longitudinal studies on stroke outcome are scarce. The aim of this study was to analyze predictors and changes in functional outcome during the first year poststroke.

Methods—
Data on patients who were independent in activities of daily living (ADL) and hospitalized for acute stroke in 2008 to 2010 were obtained from the Swedish Stroke Register. Case fatality was assessed by linkage to the Swedish Population Register. ADL was defined by independence or dependence in dressing, toileting, and indoor mobility and assessed at 3 and 12 months. Predictors of ADL dependency were assessed through multivariate analysis.

Results—

In total, 64 746 patients were included. Case fatality at 3 months was 13.1% (men 11.6% versus women 14.8%;
P
<0.0001) and at 12 months 18.2% (men 16.4% versus women 20.3%;
P
<0,0001). In the 35 064 followed-up survivors, ADL dependency rates at 3 and 12 months were 16.2% (men 15.9% versus women 19.2%;
P
<0.0001) and 28.3% (men 22.7% versus women 34.9%,
P
<0.0001), respectively. Factors predicting deterioration to ADL dependency between 3 and 12 months were female sex (relative risk [RR]=1.56; 95% confidence interval [CI], 1.50–1.70), diabetes mellitus (RR=1.50; 95% CI, 1.05–1.60), comatose at admittance (RR=2.34; 95% CI, 1.79–3.05), previous stroke (RR=1.52; 95% CI, 1.43–1.61), hemorrhagic or unspecified stroke (RR=1.14; 95% CI, 1.05–1.25), and atrial fibrillation (RR= 1.11; 95% CI, 1.04–1.17).

Conclusions—
Transition from ADL independence to dependence was observed in a high proportion of patients between 3 and 12 months, challenging the common belief that functioning after stroke is stable beyond 3 months. Deterioration occurred more commonly in women, among whom 1/6 converted to dependency.
Activation of the High-Mobility Group Box 1 Protein-Receptor for Advanced Glycation End-Products Signaling Pathway in Rats During Neurogenesis After Intracerebral Hemorrhage
Authors: Lei Chunyan , Wu Bo , Cao Tian , Zhang Shuting , Liu Ming 
Published: December 2014

Background and Purpose—
Following intracerebral hemorrhage (ICH), high-mobility group box 1 protein (HMGB1) may promote neurogenesis that supports functional recovery. How HMGB1 regulates or participates in this process is unclear, as are the pattern recognition receptors and signaling pathways involved.

Methods—
ICH was induced by injection of collagenase in Sprague–Dawley rats, which were treated 3 days later with saline, with the HMGB1 inhibitor ethyl pyruvate or with FPS-ZM1, an antagonist of the receptor for advanced glycation end-products. A Sham group was treated with saline solution instead of collagenase and then treated 3 days later with saline again or with ethyl pyruvate or N-benzyl-4-chloro-N-cyclohexylbenzamide (FPS-ZM1). Expression of the following proteins was measured by Western blot, immunohistochemistry, or immunofluorescence: HMGB1, receptor for advanced glycation end-products, toll-like receptor (TLR)-2, TLR4, brain-derived neurotrophic factor, and matrix metalloproteinase-9. The number of cells positive for 5-bromo-2-deoxyuridine or doublecortin was determined by immunohistochemistry and immunofluorescence.

Results—
Levels of HMGB1, receptor for advanced glycation end-products, TLR4, TLR2, brain-derived neurotrophic factor, and matrix metalloproteinase-9 were significantly higher 14 days after ICH than at baseline, as were the numbers of 5-bromo-2-deoxyuridine- or doublecortin-positive cells. At the same time, HMGB1 moved from the nucleus into the cytoplasm. Administering ethyl pyruvate significantly reduced all these ICH-induced increases, except the increase in TLR4 and TLR2. Administering FPS-ZM1 reduced the ICH-induced increases in the expression of brain-derived neurotrophic factor and matrix metalloproteinase-9 and in the numbers of 5-bromo-2-deoxyuridine- or doublecortin-positive cells.

Conclusions—
These findings suggest that HMGB1 acts via the receptor for advanced glycation end-products signaling pathway to promote neurogenesis in later phases of ICH.
Comparing National Institutes of Health Stroke Scale Among a Stroke Team and Helicopter Emergency Medical Service Providers
Authors: Kesinger Matthew R. , Sequeira Denisse J. , Buffalini Samantha , Guyette Francis X. 
Published: December 2014

Background and Purpose—
The use of tissue-type plasminogen activator is limited to a maximum of 4.5 hours after symptom-onset. Endovascular recanalization may improve outcomes for large-vessel occlusions (LVO), but efficacy decreases with time from symptom-onset. A National Institutes of Health Stroke Scale (NIHSS) score ≥12 is predictive of LVOs and could be used to triage patients if appropriately used by prehospital providers. The NIHSS has been considered too complex and has not been validated in the prehospital setting.

Methods—
We reviewed all patients with ischemic stroke transported by helicopter emergency medical services (HEMS) to a single comprehensive stroke center in 2010. HEMS NIHSS were compared with in-hospital stroke team physician scores. NIHSS was categorized based on 3 clinically relevant groupings and ability to predict LVO was investigated.

Results—
Three-hundred five patients met inclusion criteria, 68.9% having LVO. Moderate agreement existed between HEMS and physicians (72.1%; κ=0.571). Interclass correlation was 0.879 (95% confidence interval, 0.849–0.904). Excluding patients with tissue-type plasminogen activator before HEMS transport, there were 216 patients and good agreement (82.7%; κ=0.619). Among patients presenting within 8 hours postonset and NIHSS≥12, HEMS had a sensitivity of 55.9% and positive predictive value of 83.7% in predicting LVO.

Conclusions—
HEMS providers can administer NIHSS with moderate to good agreement with the receiving stroke team. The use of the NIHSS in HEMS may identify patients with LVO and inform triage decisions for patients ineligible for tissue-type plasminogen activator.
Making Cognitive Latent Variables Manifest: Distinct Neural Networks for Fluid Reasoning and Processing Speed
Authors: Habeck Christian , Steffener Jason , Barulli Daniel , Gazes Yunglin , Razlighi Qolamreza , Shaked Danielle , Salthouse Timothy , Stern Yaakov 
Published: December 2014

Abstract
Cognitive psychologists posit several specific cognitive abilities that are measured with sets of cognitive tasks. Tasks that purportedly tap a specific underlying cognitive ability are strongly correlated with one another, whereas performances on tasks that tap different cognitive abilities are less strongly correlated. For these reasons, latent variables are often considered optimal for describing individual differences in cognitive abilities. Although latent variables cannot be directly observed, all cognitive tasks representing a specific latent ability should have a common neural underpinning. Here, we show that cognitive tasks representing one ability (i.e., either perceptual speed or fluid reasoning) had a neural activation pattern distinct from that of tasks in the other ability. One hundred six participants between the ages of 20 and 77 years were imaged in an fMRI scanner while performing six cognitive tasks, three representing each cognitive ability. Consistent with prior research, behavioral performance on these six tasks clustered into the two abilities based on their patterns of individual differences and tasks postulated to represent one ability showed higher similarity across individuals than tasks postulated to represent a different ability. This finding was extended in the current report to the spatial resemblance of the task-related activation patterns: The topographic similarity of the mean activation maps for tasks postulated to reflect the same reference ability was higher than for tasks postulated to reflect a different reference ability. Furthermore, for any task pairing, behavioral and topographic similarities of underlying activation patterns are strongly linked. These findings suggest that differences in the strengths of correlations between various cognitive tasks may be because of the degree of overlap in the neural structures that are active when the tasks are being performed. Thus, the latent variable postulated to account for correlations at a behavioral level may reflect topographic similarities in the neural activation across different brain regions.
High-Resolution GNSS-Tracked Drifter for Studying Surface Dispersion in Shallow Water
Authors: Suara Kabir , Wang Charles , Feng Yanming , Brown Richard J. , Chanson Hubert , Borgas Michael 
Published: December 2014

AbstractThe use of Global Navigation Satellite System (GNSS)-tracked Lagrangian drifters allows more realistic quantification of fluid motion and dispersion coefficients than Eulerian techniques because such drifters are analogs of particles that are relevant to flow field characterization and pollutant dispersion. Using the fast-growing real-time kinematic (RTK) positioning technique derived from GNSS, drifters are developed for high-frequency (10 Hz) sampling with position estimates with centimeter accuracy. The drifters are designed with small size and less direct wind drag to follow the subsurface flow that characterizes dispersion in shallow waters. An analysis of position error from stationary observation indicates that the drifter can efficiently resolve motion up to 1 Hz. The result of the field deployments of the drifter in conjunction with acoustic Eulerian devices shows a higher estimate of the drifter streamwise velocities. Single particle statistical analysis of field deployments in a shallow estuarine zone yielded estimates of dispersion coefficients comparable to those of dye tracer studies. The drifters capture the tidal elevation during field studies in a tidal estuary.
Morphometric description of the feline radius and ulna generated from computed tomography
Authors: Preston Timothy , Glyde Mark , Hosgood Giselle , Snow Lynne 
Published: December 2014

Objectives This study aimed to describe the length, internal and external diameters, cancellous bone volume and extent, and cortical thickness at predetermined locations in the radius and ulna of a cohort of skeletally mature, disease-free feline cadavers using radiography and computed tomography (CT). Methods Five feline cadavers were used (mean weight 3.31 kg, range 2.55–4.24 kg). Antebrachii (n = 10) were radiographed to confirm skeletal maturity and normal radiographic appearance prior to CT. Reconstructed CT images were used to measure bone length, cortical thickness, internal and external diameters, and cancellous extent. Cancellous bone volume was calculated automatically using OsiriX after manual segmentation (350–850 Hounsfield units window) from axial CT slices. Results CT images were used to measure bone length, cortical thickness, internal and external diameters, and cancellous extent and volume. Mean radial length was 95.89 mm (95% confidence interval [CI] 88.52–103.26 mm) and mean ulna length was 114.67 mm (95% CI 105.53–123.81 mm). The olecranon had the largest mean cancellous bone volume (94.16 mm3; 95% CI 72.09–116.23 mm3) and it extended a mean of 13.12 mm (95% CI 11.73–14.51 mm) distally. The radius at the level of the trochlea and the ulna at the level of the coronoid processes had the largest external diameters, respectively. The medullary canal narrowed at the level of the coronoid processes and became cranially eccentric at the proximal third of the diaphysis. The cranial cortex at the level of the coronoid processes and the caudal cortex of the olecranon were markedly thicker than other cortices at those levels. Conclusions and relevance Morphometry of the feline antebrachium was described using CT, and should be a useful reference for future research investigations and clinical applications.
WWOX: A fragile tumor suppressor
Authors: Schrock Morgan S , Huebner Kay 
Published: December 2014

WWOX, the WW domain-containing oxidoreductase gene at chromosome region 16q23.3–q24.1, spanning chromosomal fragile site FRA16D, encodes the 46 kDa Wwox protein, a tumor suppressor that is lost or reduced in expression in a wide variety of cancers, including breast, prostate, ovarian, and lung. The function of Wwox as a tumor suppressor implies that it serves a function in the prevention of carcinogenesis. Indeed, in vitro studies show that Wwox protein interacts with many binding partners to regulate cellular apoptosis, proliferation, and/or maturation. It has been reported that newborn Wwox knockout mice exhibit nascent osteosarcomas while Wwox+/− mice exhibit increased incidence of spontaneous and induced tumors. Furthermore, absence or reduction of Wwox expression in mouse xenograft models results in increased tumorigenesis, which can be rescued by Wwox re-expression, though there is not universal agreement among investigators regarding the role of Wwox loss in these experimental models. Despite this proposed tumor suppressor function, the overlap of the human WWOX locus with FRA16D sensitizes the gene to protein-inactivating deletions caused by replication stress. The high frequency of deletions within the WWOX locus in cancers of various types, without the hallmark protein inactivation-associated mutations of “classical” tumor suppressors, has led to the proposal that WWOX deletions in cancers are passenger events that occur in early cancer progenitor cells due to fragility of the genetic locus, rather than driver events which provide the cancer cell a selective advantage. Recently, a proposed epigenetic cause of chromosomal fragility has suggested a novel mechanism for early fragile site instability and has implications regarding the involvement of tumor suppressor genes at chromosomal fragile sites in cancer. In this review, we provide an overview of the evidence for WWOX as a tumor suppressor gene and put this into the context of fragility associated with the FRA16D locus.
P-Rex and Vav Rac-GEFs in platelets control leukocyte recruitment to sites of inflammation
Authors: Pan Dingxin , Amison Richard T. , Riffo-Vasquez Yanira , Spina Domenico , Cleary Simon J. , Wakelam Michael J. , Page Clive P. , Pitchford Simon C. , Welch Heidi C. E. 
Published: December 2014

Key Points
P-Rex and Vav Rac-GEFs cooperate in leukocyte recruitment during inflammation by facilitating leukocyte adhesion to the vascular endothelium. P-Rex/Vav expression in platelets is required for vascular adhesion and recruitment of neutrophils and eosinophils into lung tissue.
Systematic qualitative review of randomised trials conducted in nonsmall cell lung cancer with a noninferiority or equivalence design
Authors: Paesmans Marianne , Grigoriu Bogdan , Ocak Sebahat , Roelandts Martine , Lafitte Jean-Jacques , Holbrechts Stéphane , Berghmans Thierry , Meert Anne-Pascale , Moretti Luigi , Danyi Sophie , Pasleau Françoise , Ameye Lieveke , Van Meerhaeghe Alain , Sculier Jean-Paul 
Published: December 2014

The use of noninferiority randomised trials for patients with advanced non-small cell lung cancer has emerged during the past 10–15 years but has raised some issues related to their justification and methodology. The present systematic review aimed to assess trial characteristics and methodological aspects.All randomised clinical trials with a hypothesis of noninferiority/equivalence, published in English, were identified. Several readers extracteda prioridefined methodological information. A qualitative analysis was then performed.We identified 20 randomised clinical trials (three phase II and 17 phase III), 11 of them being conducted in strong collaboration with industry. We highlighted some deficiencies in the reports like the lack of justification for both the noninferiority assumption and the definition of the noninferiority margin, as well as inconsistencies between the results and the authors' conclusions. CONSORT guidelines were better followed for general items than for specific items (p<0.001).Improvement in the reporting of the meth"odology of noninferiority/equivalence trials is needed to avoid misleading interpretation and to allow readers to be fully aware of the assumptions underlying the trial designs. They should be restricted to limited specific situations with a strong justification why a noninferiority hypothesis is acceptable.