bluuebunny/crossref_metadata_2025_split huggingface dataset:
Executive functioning in children with unilateral cerebral palsy: protocol for a cross-sectional study
Authors: Bodimeade Harriet L , Whittingham Koa , Lloyd Owen , Boyd Roslyn N 
Published: April 2013

IntroductionEarly brain injury, as found in children with unilateral cerebral palsy (CP), may cause deficits in higher-order cognitive tasks known as executive functions (EF). EF has been conceptualised as comprised of four distinct yet inter-related components: (1) attentional control, (2) cognitive flexibility, (3) goal setting and (4) information processing. The aim of this study was to examine EF in children with unilateral CP and compare their performance with a typically developing reference group (TDC). The potential laterality effects of unilateral CP on EF will be explored, as will the relationship between the cognitive measures of EF, behavioural manifestations of EF, psychological functioning and clinical features of unilateral CP.Methods and analysisThis cross-sectional study aims to recruit a total of 42 children with unilateral CP (21 right unilateral CP and 21 left unilateral CP) and 21 TDC aged between 8 and 16 years. Clinical severity will be described for gross motor function and manual ability. Outcomes for cognitive EF measureswill include subtests from the Wechsler Intelligence Scale for Children—Fourth Edition, Delis-Kaplan Executive Function System, Rey Complex Figure Test and the Test of Everyday Attention for Children. Behavioural manifestations of EF will be assessed using the Behaviour Rating Inventory of Executive Function, Parent and Teacher versions. Psychological functioning will be examined using the Strengths and Difficulties Questionnaire. Between-groups differences will be examined in a series of one-way analyses of covariance and followed up using linear comparisons. An overall composite of cognitive EF measures will be created. Bivariate correlations between the EF composite and psychological measures will be calculated.Ethics and disseminationThis protocol describes a study that, to our knowledge, is the first to examine multiple components of EF using a cohort of children with unilateral CP. Exploration of potential laterality effects of EF among children with a congenital, unilateral brain injury is also novel. Possible relationships between EF and psychological functioning will also be investigated. Ethics have been obtained through the University of Queensland School of Psychology Ethics Committee and the Queensland Children's Health Services Human Research Ethics Committee. Results will be disseminated in peer reviewed publications and presentations at national and international conferences. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12611000263998).
Web-based general public opinion study of automated versus manual external chest compression
Authors: Lapostolle Frédéric , Bertrand Philippe , Agostinucci Jean-Marc , Pradeau Catherine , Tazarourte Karim , Grave Mélanie , Galinski Michel , Adnet Frédéric 
Published: April 2013

BackgroundOnly a few cardiac-arrest victims receive external chest compression (ECC) by a bystander.ObjectiveTo test the hypothesis that the general public might start ECC more often if they used an automated device rather than a manual massage.MethodsWeb-based public opinion survey based on two short videos, one showing manual ECC and the other automated ECC (Autopulse, Zoll, France). Advantages and disadvantages (perceived efficacy, reproducibility, hazard, apprehension and acceptability) of the two techniques were evaluated on a visual analogue scale (VAS). A VAS of 1–3 was considered to indicate preference for manual ECC, 8–10 for automated ECC and 4–7 for no clear preference. The final global score was the difference between advantage and disadvantage scores.ResultsOverall, 1769 persons answered the questionnaire. The median VAS score for each variable was as follows: 7 (25–75 percentiles, 5–9) for efficacy, 8 (3–10) for reproducibility, 5 (3–8) for hazard, 5 (2–8) for apprehension and 5 (2–8) for acceptability. The overall median score indicated that 1034 persons (58%) preferred use of the device, 618 (35%) preferred manual ECC and 117 (7%) had no preference. There was no significant difference in the preference according to gender, education and training in first aid. However, older persons (0) preferred the use of device.ConclusionsThe better ‘advantages over disadvantages’ score for the automated ECC device over manual ECC indicated that the general public might envisage use of the device. This could contribute to increase the frequency of resuscitation attempts by bystanders.
How emergency physicians use biomarkers: insights from a qualitative assessment of script concordance tests
Authors: Claessens Yann-Erick , Wannepain Sophie , Gestin Stéphanie , Magdelein Xavier , Ferretti Elsa , Guilly Marine , Charlin Bernard , Pelaccia Thierry 
Published: April 2013

ObjectivesBiomarkers have been developed in emergency medicine to improve decision at bedside using Bayesian approach. We intend to determine the cognitive process actually utilised by emergency physicians to incorporate biomarkers in clinical reasoning.DesignWe invited eight emergency physicians to answer eight script concordance tests. Interviews were tape-recorded and qualitatively analysed using predetermined categories until saturation.ResultsEmergency physicians mainly mobilised intuition and non-Bayesian reasoning to incorporate biomarkers for diagnosis or treatment strategies.ConclusionsAlthough biomarkers have been developed to be used in a Bayesian approach, emergency physicians mainly use other analytical and non-analytical cognitive processes to introduce these tools in their clinical reasoning.
Strong expression of the neuronal transcription factor FOXP2 is linked to an increased risk of early PSA recurrence in ERG fusion-negative cancers
Authors: Stumm Laura , Burkhardt Lia , Steurer Stefan , Simon Ronald , Adam Meike , Becker Andreas , Sauter Guido , Minner Sarah , Schlomm Thorsten , Sirma Hüseyin , Michl Uwe 
Published: April 2013

Background and aimsTranscription factors of the forkhead box P (FOXP1-4) family have been implicated in various human cancer types before. The relevance and role of neuronal transcription factor FOXP2 in prostate cancer is unknown.MethodsA tissue microarray containing samples from more than 11 000 prostate cancers from radical prostatectomy specimens with clinical follow-up data was analysed for FOXP2 expression by immunohistochemistry. FOXP2 data were also compared with pre-existing ERG fusion (by fluorescence in situ hybridisation and immunohistochemistry) and cell proliferation (Ki67 labelling index) data.ResultsThere was a moderate to strong FOXP2 protein expression in basal and secretory cells of normal prostatic glands. As compared with normal cells, FOXP2 expression was lost or reduced in 25% of cancers. Strong FOXP2 expression was linked to advanced tumour stage, high Gleason score, presence of lymph node metastases and early tumour recurrence (p<0.0001; each) in ERG fusion-negative, but not in ERG fusion-positive cancers. High FOXP2 expression was linked to high Ki67 labelling index (p<0.0001) in all cancers irrespective of ERG fusion status.ConclusionsThese data demonstrate that similar high FOXP2 protein levels as in normal prostate epithelium exert a ‘paradoxical’ oncogenic role in ‘non fusion-type’ prostate cancer. It may be speculated that interaction of FOXP2 with members of pathways that are specifically activated in ‘non fusion-type’ cancers may be responsible for this phenomenon.
Mitochondrial myopathy with autophagic vacuoles in patients with the m.8344A>G mutation
Authors: Yuan Jun-Hui , Sakiyama Yusuke , Higuchi Itsuro , Inamori Yukie , Higuchi Yujiro , Hashiguchi Akihiro , Higashi Keiko , Yoshimura Akiko , Takashima Hiroshi 
Published: April 2013

Background and aimsIn mitochondrial myopathy, autophagy is presumed to play an important role in mitochondrial dysfunction. Rimmed vacuoles (RVs), a sign of autophagy, can be seen as a secondary phenomenon in muscle ragged-red fibres (RRFs), whereas the uncommon presentation is that some fibres contain RVs, but without any mitochondrial abnormalities. To investigate the pathogenesis beneath this pathological phenomenon.MethodsWe reviewed 783 skeletal muscle specimens and selected five obtained from patients with suspected mitochondrial myopathy, characterised by clearly visible autophagic vacuoles in non-RRFs, besides the coexistence of RRFs and cytochrome oxidase-negative fibres. Immunohistochemical staining with LC-3, and electron microscopy studies were performed. Using resequencing microarray and a next-generation sequencing system, the mitochondrial DNA was screened for mutations and the heteroplasmic level was measured in skeletal muscle and blood.ResultsMuscle fibres with RVs and RRFs, as well as some morphologically normal fibres, stained strongly for LC-3. Electron microscopy disclosed significant abnormal mitochondrial proliferation and existence of autophagic vacuoles. After mutation screening, m.8344A>G in the tRNALysgene was detected in two patients. The heteroplasmy of mutated G was 45.1% in skeletal muscle and 17.8% in blood in patient 1; patient 2 exhibited 80.3% mutated G in skeletal muscle and 25.2% in blood.ConclusionsThese findings demonstrate a new pathological phenotype for the m.8344A>G mutation- related disease and also provide pathological evidence of a correlation between mitochondrial abnormalities and autophagy.
Diacylglycerol Kinase α Is a Critical Signaling Node and Novel Therapeutic Target in Glioblastoma and Other Cancers
Authors: Dominguez Charli L. , Floyd Desiree H. , Xiao Aizhen , Mullins Garrett R. , Kefas Benjamin A. , Xin Wenjun , Yacur Melissa N. , Abounader Roger , Lee Jae K. , Wilson Gabriela Mustata , Harris Thurl E. , Purow Benjamin W. 
Published: April 2013

AbstractAlthough diacylglycerol kinase α (DGKα) has been linked to several signaling pathways related to cancer cell biology, it has been neglected as a target for cancer therapy. The attenuation of DGKα activity via DGKα-targeting siRNA and small-molecule inhibitors R59022 and R59949 induced caspase-mediated apoptosis in glioblastoma cells and in other cancers, but lacked toxicity in noncancerous cells. We determined that mTOR and hypoxia-inducible factor-1α (HIF-1α) are key targets of DGKα inhibition, in addition to its regulation of other oncogenes. DGKα regulates mTOR transcription via a unique pathway involving cyclic AMP. Finally, we showed the efficacy of DGKα inhibition with short hairpin RNA or a small-molecule agent in glioblastoma and melanoma xenograft treatment models, with growth delay and decreased vascularity. This study establishes DGKα as a central signaling hub and a promising therapeutic target in the treatment of cancer.Significance: DGKα, which converts diacylglycerol to phosphatidic acid, regulates critical oncogenic pathways, notably HIF-1α and mTOR. DGKα knockdown and small-molecule inhibition are selectively toxic to human cancer cells but not normal human cells, and DGKα inhibition slows tumor growth, decreases angiogenesis, and increases mouse survival in xenograft models. Cancer Discov; 3(7); 782–97. ©2013 AACR.See related commentary by Bhat and Aldape, p. 726This article is highlighted in the In This Issue feature, p. 705
Anti-Inflammatory and Antiatherogenic Role of BMP Receptor II in Endothelial Cells
Authors: Kim Chan Woo , Song Hannah , Kumar Sandeep , Nam Douglas , Kwon Hyuk Sang , Chang Kyung Hwa , Son Dong Ju , Kang Dong-Won , Brodie Seth A. , Weiss Daiana , Vega J. David , Alberts-Grill Noah , Griendling Kathy , Taylor W. Robert , Jo Hanjoong 
Published: April 2013

Objective—
Atherosclerosis is an inflammatory disease with multiple underlying metabolic and physical risk factors. Bone morphogenic protein 4 (BMP4) expression is increased in endothelium in atherosclerosis-prone regions and is known to induce endothelial inflammation, endothelial dysfunction, and hypertension. BMP actions are mediated by 2 different types of BMP receptors (BMPRI and BMPRII). Here, we show a surprising finding that loss of BMPRII expression causes endothelial inflammation and atherosclerosis.

Approach and Results—

Using BMPRII siRNA and BMPRII
+/−
mice, we found that specific knockdown of BMPRII, but not other BMP receptors (Alk1, Alk2, Alk3, Alk6, ActRIIa, and ActRIIb), induced endothelial inflammation in a ligand-independent manner by mechanisms mediated by reactive oxygen species, nuclear factor-KappaB, and reduced nicotinamide adenine dinucleotide phosphate oxidases. Further, BMPRII
+/−
ApoE
−/−
mice developed accelerated atherosclerosis compared with BMPRII
+/+
ApoE
−/−
mice. Interestingly, we found that multiple proatherogenic stimuli, such as hypercholesterolemia, disturbed flow, prohypertensive angiotensin II, and the proinflammatory cytokine (tumor necrosis factor-α), downregulated BMPRII expression in endothelium, whereas antiatherogenic stimuli, such as stable flow and statin treatment, upregulated its expression in vivo and in vitro. Moreover, BMPRII expression was significantly diminished in human coronary advanced atherosclerotic lesions. Also, we were able to rescue the endothelial inflammation induced by BMPRII knockdown by overexpressing the BMPRII wild type, but not by the BMPRII short form lacking the carboxyl-terminal tail region.

Conclusions—
These results suggest that BMPRII is a critical, anti-inflammatory, and antiatherogenic protein that is commonly targeted by multiple pro- and antiatherogenic factors. BMPRII may be used as a novel diagnostic and therapeutic target in atherosclerosis.
Walking Versus Running for Hypertension, Cholesterol, and Diabetes Mellitus Risk Reduction
Authors: Williams Paul T. , Thompson Paul D. 
Published: April 2013

Objective—
To test whether equivalent energy expenditure by moderate-intensity (eg, walking) and vigorous-intensity exercise (eg, running) provides equivalent health benefits.

Approach and Results—

We used the National Runners’ (n=33 060) and Walkers’ (n=15 945) Health Study cohorts to examine the effect of differences in exercise mode and thereby exercise intensity on coronary heart disease (CHD) risk factors. Baseline expenditure (metabolic equivant hours per day [METh/d]) was compared with self-reported, physician-diagnosed incident hypertension, hypercholesterolemia, diabetes mellitus, and CHD during 6.2 years follow-up. Running significantly decreased the risks for incident hypertension by 4.2% (
P
<10
−7
), hypercholesterolemia by 4.3% (
P
<10
−14
), diabetes mellitus by 12.1% (
P
<10
−5
), and CHD by 4.5% per METh/d (
P
=0.05). The corresponding reductions for walking were 7.2% (
P
<10
−6
), 7.0% (
P
<10
−8
), 12.3% (
P
<10
−4
), and 9.3% (
P
=0.01). Relative to <1.8 METh/d, the risk reductions for 1.8 to 3.6, 3.6 to 5.4, 5.4 to 7.2, and ≥7.2 METh/d were as follows: (1) 10.1%, 17.7%, 25.1%, and 34.9% from running and 14.0%, 23.8%, 21.8%, and 38.3% from walking for hypercholesterolemia; (2) 19.7%, 19.4%, 26.8%, and 39.8% from running and 14.7%, 19.1%, 23.6%, and 13.3% from walking for hypertension; and (3) 43.5%, 44.1%, 47.7%, and 68.2% from running, and 34.1%, 44.2% and 23.6% from walking for diabetes mellitus (walking >5.4 METh/d excluded for too few cases). The risk reductions were not significantly different for running than walking for diabetes mellitus (
P
=0.94), hypertension (
P
=0.06), or CHD (
P
=0.26), and only marginally greater for walking than running for hypercholesterolemia (
P
=0.04).

Conclusions—
Equivalent energy expenditures by moderate (walking) and vigorous (running) exercise produced similar risk reductions for hypertension, hypercholesterolemia, diabetes mellitus, and possibly CHD.
Targeting Platelet GPIbβ Reduces Platelet Adhesion, GPIb Signaling and Thrombin Generation and Prevents Arterial Thrombosis
Authors: Maurer Eric , Tang Chaojun , Schaff Mathieu , Bourdon Catherine , Receveur Nicolas , Ravanat Catherine , Eckly Anita , Hechler Béatrice , Gachet Christian , Lanza Francois , Mangin Pierre H. 
Published: April 2013

Objective—
The glycoprotein (GP) Ib-V-IX complex regulates the adhesion, activation, and procoagulant activity of platelets. We previously reported that RAM.1, a rat monoclonal antibody directed against the extracellular domain of mouse GPIbβ, diminished adhesion of platelets and chinese hamster ovary cells transfected with the human GPIb-IX complex to von Willebrand factor under flow conditions. Here, we further evaluated the functional importance of GPIbβ by studying the impact of RAM.1 on GPIb-mediated platelet responses and in vitro and in vivo thrombus formation.

Approach and Results—

We show that RAM.1 dramatically reduced GPIb-mediated filopodia extension of chinese hamster ovary GPIb-IX cells after adhesion to von Willebrand factor. RAM.1 also reduced filopodia extension and GPIb-mediated Ca
2+
signaling after adhesion of mouse platelets to von Willebrand factor. RAM.1 inhibited thrombin generation in platelet-rich plasma without impairing phosphatidylserine exposure. In addition, RAM.1 reduced thrombus formation after perfusion of mouse whole blood over collagen in a shear-dependent manner. This effect was confirmed in vivo, because injection of F(ab)′2 fragments of RAM.1 diminished thrombus formation induced by laser beam injury of mesenteric arterioles and forceps injury of the abdominal aorta. In contrast, RAM.1 F(ab)′2 did not prolong the tail-bleeding time or increase the volume of blood lost.

Conclusions—
These findings are the first evidence that targeting a subunit other than GPIbα can lead to an antithrombotic effect via the GPIb-V-IX complex. This could represent an alternative way to reduce thrombus formation with a minor impact on hemostasis.
Chemerin Connects Fat to Arterial Contraction
Authors: Watts Stephanie W. , Dorrance Anne M. , Penfold Mark E. , Rourke Jillian L. , Sinal Christopher J. , Seitz Bridget , Sullivan Timothy J. , Charvat Trevor T. , Thompson Janice M. , Burnett Robert , Fink Gregory D. 
Published: April 2013

Objective—
Obesity and hypertension are comorbid in epidemic proportion, yet their biological connection is largely a mystery. The peptide chemerin is a candidate for connecting fat deposits around the blood vessel (perivascular adipose tissue) to arterial contraction. We presently tested the hypothesis that chemerin is expressed in perivascular adipose tissue and is vasoactive, supporting the existence of a chemerin axis in the vasculature.

Approach and Results—
Real-time polymerase chain reaction, immunohistochemistry, and Western analyses supported the synthesis and expression of chemerin in perivascular adipose tissue, whereas the primary chemerin receptor ChemR23 was expressed both in the tunica media and endothelial layer. The ChemR23 agonist chemerin-9 caused receptor, concentration-dependent contraction in the isolated rat thoracic aorta, superior mesenteric artery, and mesenteric resistance artery, and contraction was significantly amplified (more than 100%) when nitric oxide synthase was inhibited and the endothelial cell mechanically removed or tone was placed on the arteries. The novel ChemR23 antagonist CCX832 inhibited phenylephrine-induced and prostaglandin F2α-induced contraction (+perivascular adipose tissue), suggesting that endogenous chemerin contributes to contraction. Arteries from animals with dysfunctional endothelium (obese or hypertensive) demonstrated a pronounced contraction to chemerin-9. Finally, mesenteric arteries from obese humans demonstrate amplified contraction to chemerin-9.

Conclusions—
These data support a new role for chemerin as an endogenous vasoconstrictor that operates through a receptor typically attributed to function only in immune cells.
Capturing the Voices of Pseudepigraphic Personae: On the Form and Function of Incipits in the Aramaic Dead Sea Scrolls
Authors: Perrin Andrew B. 
Published: April 2013

Abstract
It is widely recognized that the authors of the Aramaic Dead Sea Scrolls often shrouded their tales in first person voices and exhibited a perennial interest in the production and transmission of ancestral booklore. The present study explores the literary convention of the incipit in light of these interrelated methods of pseudepigraphy. Throughout the Aramaic Scrolls incipits introduce entire compositions and putative texts within narratives. Comparative philological analysis reveals that these incipits feature strikingly similar literary-linguistic idioms. However, it is equally apparent that that these common elements were uniquely patterned by individual authors. It is suggested that these commonalities should inform how we conceive of the scribal milieu(s) from which the Aramaic Scrolls emerged and our understanding of pseudepigraphy in early Judaism. The article concludes with a fresh proposal for the function of the title “A Copy of the Writing of the Words of Noah” in 1QapGen 5:29.
Archaeometry of the Dead Sea Scrolls
Authors: Rabin Ira 
Published: April 2013

Abstract
For many years after the discovery of the Dead Sea Scrolls, text analysis and fragment attribution were the main concern of the scholars dealing with them. The uncertain archaeological provenance of a large part of the collection added an additional difficulty to the formidable task of sorting thousands of fragments. After sixty years of scholarly research, the questions of origin, archaeological provenance, and correct attribution of the fragments are still debated. In many cases, material characterization of the scroll writing media delivers answers to these questions.
Physical and chemical examination of the skin-based material of the Dead Sea Scrolls started shortly after their discovery. Subsequent studies dedicated to long-term preservation resulted in a respectable body of knowledge about this material, in many ways very different from medieval parchment.
A new multi-instrumental approach, developed for an accurate characterization of the highly inhomogeneous “parchment” of the Dead Sea Scrolls, might lead to a reliable reconstruction of their history. This approach is illustrated by the case studies, in which we discuss the specific questions of origin (1QHa), archaeological provenance (11QTa), and post-discovery interventions (1QapGen ar).
C-Band Polarimetric Radar QPE Based on Specific Differential Propagation Phase for Extreme Typhoon Rainfall
Authors: Wang Yadong , Zhang Jian , Ryzhkov Alexander V. , Tang Lin 
Published: April 2013

Abstract
To obtain accurate radar quantitative precipitation estimation (QPE) for extreme rainfall events such as land-falling typhoon systems in complex terrain, a new method was developed for C-band polarimetric radars. The new methodology includes a correction method based on vertical profiles of the specific differential propagation phase (VPSDP) for low-level blockage and an optimal relation between rainfall rate () and the specific differential phase (). In the VPSDP-based correction approach, a screening process is applied to fields, where missing or unreliable data from lower tilts caused by severe beam blockage are replaced with data from upper and unblocked tilts. The data from upper tilts are adjusted to account for variations in the vertical profile of . The corrected field is then used for rain-rate estimations. To acquire an accurate QPE result, a new relation for C-band polarimetric radars was derived through simulations using drop size distribution (DSD) and drop shape relation (DSR) observations from typhoon systems in Taiwan. The VPSDP-based correction method with the new relation was evaluated using the typhoon cases of Morakot (2009) and Fanapi (2010).