bluuebunny/crossref_metadata_2025_split huggingface dataset:
A thrombospondin in the anthozoan Nematostella vectensis is associated with the nervous system and upregulated during regeneration
Authors: Tucker Richard P. , Hess John F. , Gong Qizhi , Garvey Katrina , Shibata Bradley , Adams Josephine C. 
Published: December 2012

Summary
Thrombospondins are multimeric extracellular matrix glycoproteins that play important roles in development, synaptogenesis and wound healing in mammals. We previously identified four putative thrombospondins in the genome of the starlet sea anemone Nematostella vectensis. This study presents the first analysis of these thrombospondins, with the goals of understanding fundamental roles of thrombospondins in the Eumetazoa. Reverse transcriptase PCR showed that each of the N. vectensis thrombospondins (Nv85341, Nv22035, Nv168100 and Nv30790) is transcribed. Three of the four thrombospondins include an RGD or KGD motif in their thrombospondin type 3 repeats at sites equivalent to mammalian thrombospondins, suggesting ancient roles as RGD integrin ligands. Phylogenetic analysis based on the C-terminal regions demonstrated a high level of sequence diversity between N. vectensis thrombospondins. A full-length cDNA sequence was obtained for Nv168100 (NvTSP168100), which has an unusual domain organization. Immunohistochemistry with an antibody to NvTSP168100 revealed labeling of neuron-like cells in the mesoglea of the retractor muscles and the pharynx. In situ hybridization and quantitative PCR showed that NvTSP168100 is upregulated during regeneration. Immunohistochemistry of the area of regeneration identified strong immunostaining of the glycocalyx, the carbohydrate-rich matrix coating the epidermis, and electron microscopy identified changes in glycocalyx organization during regeneration. Thus, N. vectensis thrombospondins share structural features with thrombospondins from mammals and may have roles in the nervous system and in matrix reorganization during regeneration.
Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules
Authors: Roubin Régine , Acquaviva Claire , Chevrier Véronique , Sedjaï Fatima , Zyss Déborah , Birnbaum Daniel , Rosnet Olivier 
Published: December 2012

Summary
The generation of cellular microtubules is initiated at specific sites such as the centrosome and the Golgi apparatus that contain nucleation complexes rich in γ-tubulin. The microtubule growing plus-ends are stabilized by plus-end tracking proteins (+TIPs), mainly EB1 and associated proteins. Myomegalin was identified as a centrosome/Golgi protein associated with cyclic nucleotide phosphodiesterase. We show here that Myomegalin exists as several isoforms. We characterize two of them. One isoform, CM-MMG, harbors a conserved domain (CM1), recently described as a nucleation activator, and is related to a family of γ-tubulin binding proteins, which includes Drosophila centrosomin. It localizes at the centrosome and at the cis-Golgi in an AKAP450-dependent manner. It recruits γ-tubulin nucleating complexes and promotes microtubule nucleation. The second isoform, EB-MMG, is devoid of CM1 domain and has a unique N-terminus with potential EB1-binding sites. It localizes at the cis-Golgi and can localize to microtubule plus-ends. EB-MMG binds EB1 and affects its loading on microtubules and microtubule growth. Depletion of Myomegalin by small interfering RNA delays microtubule growth from the centrosome and Golgi apparatus, and decreases directional migration of RPE1 cells. In conclusion, the Myomegalin gene encodes different isoforms that regulate microtubules. At least two of these have different roles, demonstrating a previously unknown mechanism to control microtubules in vertebrate cells.
Interplay between a Wnt-dependent organiser and the Notch segmentation clock regulates posterior development in Periplaneta americana
Authors: Chesebro John E. , Pueyo Jose Ignacio , Couso Juan Pablo 
Published: December 2012

Summary
Sequential addition of segments in the posteriorly growing end of the embryo is a developmental mechanism common to many bilaterians. However, posterior growth and patterning in most animals also entails the establishment of a ‘posterior organiser’ that expresses the Caudal and Wnt proteins and has been proposed to be an ancestral feature of animal development. We have studied the functional relationships between the Wnt-driven organiser and the segmentation mechanisms in a basal insect, the cockroach Periplaneta americana. Here, posteriorly-expressed Wnt1 promotes caudal and Delta expression early in development to generate a growth zone from which segments will later bud off. caudal maintains the undifferentiated growth zone by dampening Delta expression, and hence Notch-mediated segmentation occurs just outside the caudal domain. In turn, Delta expression maintains Wnt1, maintaining this posterior gene network until all segments have formed. This feedback between caudal, Wnt and Notch-signalling in regulating growth and segmentation seems conserved in other arthropods, with some aspects found even in vertebrates. Thus our findings not only support an ancestral Wnt posterior organiser, but also impinge on the proposals for a common origin of segmentation in arthropods, annelids and vertebrates.
Preventable Hospital Mortality: Learning from Retrospective Case Record Review
Authors: Sorinola Olanrewaju O , Weerasinghe Chamindri , Brown Ruth 
Published: December 2012

Summary Objective To determine the proportion of hospital deaths associated with preventable problems in care and how they can be reduced. Design A two phase before and after evaluation of a hospital mortality reduction programme. Setting A district general hospital in Warwickshire, England. Participants In Phase 1, 400 patients who died in 2009 at South Warwickshire NHS Foundation Trust had their case notes reviewed. In Phase 2, Trust wide measures were introduced across the whole Trust population to bring about quality improvements. Main outcome measures To reduce the crude mortality and in effect the risk adjusted mortality index (RAMI) by 45 in the three years following the start of the programme, from 145 in 2009 to 100 or less in 2012. Results In total, 34 (8.5%) patients experienced a problem in their care that contributed to death. The principal problems were lack of senior medical input (24%), poor clinical monitoring or management (24%), diagnostic errors (15%) and infections (15%). In total, 41% (14) of these were judged to have been preventable (3.5% of all deaths). Following the quality improvement programme, crude mortality fell from 1.95% (2009) to 1.56% (2012) while RAMI dropped from 145 (2009) to 87 (2012). Conclusion A quality improvement strategy based on good local evidence is effective in improving the quality of care sufficiently to reduce mortality.
Critical Appraisal of Translational Research Models for Suitability in Performance Assessment of Cancer Centers
Authors: Rajan Abinaya , Sullivan Richard , Bakker Suzanne , van Harten Wim H. 
Published: December 2012

Abstract

Background.
Translational research is a complex cumulative process that takes time. However, the operating environment for cancer centers engaged in translational research is now financially insecure. Centers are challenged to improve results and reduce time from discovery to practice innovations. Performance assessment can identify improvement areas that will help reduce translational delays. Currently, no standard method exists to identify models for use in performance assessment. This study aimed to critically appraise translational research models for suitability in performance assessment of cancer centers.

Methods.
We conducted a systematic review to identify models and developed a set of criteria based on scientometrics, complex adaptive systems, research and development processes, and strategic evaluation. Models were assessed for linkage between research and care components, new knowledge, systems integration, performance assessment, and review of other models.

Results.
Twelve models were identified; six described phases/components for translational research in different blocks (T models) and six described the process of translational research (process models). Both models view translational research as an accumulation of new knowledge. However, process models more clearly address systems integration, link research and care components, and were developed for evaluating and improving the performance of translational research. T models are more likely to review other models.

Conclusion.
Process models seem to be more suitable for performance assessment of cancer centers than T models. The most suitable process models (the Process Marker Model and Lean and Six Sigma applications) must be thoroughly tested in practice.
TGF Expression and Macrophage Accumulation in Atherosclerotic Renal Artery Stenosis
Authors: Gloviczki Monika L. , Keddis Mira T. , Garovic Vesna D. , Friedman Hanna , Herrmann Sandra , McKusick Michael A , Misra Sanjay , Grande Joseph P. , Lerman Lilach O. , Textor Stephen C. 
Published: December 2012

Summary

Background and objectives
Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow and is a potential cause of chronic kidney injury, yet little is known regarding inflammatory pathways in this disorder in human participants. This study aimed to examine the hypothesis that reduced renal blood flow (RBF) in ARAS would be associated with tissue TGF-β activation and inflammatory cell accumulation.

Design, setting, participants, & measurements
This cross-sectional study of ARAS of varying severity compared transjugular biopsy specimens in patients with ARAS (n=12, recruited between 2008 and 2012) with tissue from healthy kidney donors (n=15) and nephrectomy specimens from individuals with total vascular occlusion (n=65). ARAS patients were studied under controlled conditions to measure RBF by multidetector computed tomography and tissue oxygenation by blood oxygen level–dependent magnetic resonance imaging.

Results
Compared with the nonstenotic contralateral kidneys, RBF was reduced in poststenotic kidneys (242±149 versus 365+174 ml/min; P<0.01) as was single-kidney GFR (28±17 versus 41±19 ml/min; P<0.01), whereas cortical and medullary oxygenation were relatively preserved. Tissue TGF-β immunoreactivity was higher in ARAS patients compared with those with both normal kidneys and those with total occlusion (mean score 2.4±0.7 versus 1.5+1.1 in the nephrectomy group and versus 0±0 in donors; P<0.01). By contrast, the number of CD68+ macrophages was higher with greater disease severity (from 2.2±2.7 in normal to 22.4±18 cells/high-power field in nephrectomy samples; P<0.001).

Conclusions
The results of this study indicate robust stimulation of TGF-β associated with macrophage infiltration within the human kidney with vascular occlusive disease.
Characteristics and long-term outcome of 251 patients with dural arteriovenous fistulas in a defined population
Authors: Piippo Anna , Niemelä Mika , van Popta Jouke , Kangasniemi Marko , Rinne Jaakko , Jääskeläinen Juha E. , Hernesniemi Juha 
Published: December 2012

Object
Management of dural arteriovenous fistulas (DAVFs) has changed during the last decades due to increased knowledge of their pathophysiology and natural history as well as advances in treatment modalities. The authors describe the characteristics and long-term outcome of a large consecutive series of patients with DAVFs.

Methods
Altogether 251 patients with 261 DAVFs were treated in 2 of the 5 neurosurgery departments at Helsinki and Kuopio University Hospitals between 1944 and 2006. Clinical data and radiological examinations were reviewed to assess patients' overall long-term clinical outcome.

Results
The detection rate of DAVFs increased markedly in the 1970s and again in the 1990s when digital subtraction angiography was introduced. The incidence of DAVFs in a defined southern Finnish population was 0.51 per 100,000 individuals per year, which represents 32% of all the brain arteriovenous malformations. In the early part of the series, DAVFs were treated by proximal ligation of the feeding arteries. Later, most of the patients underwent preoperative embolization and subsequent craniotomy, and since 2000 stereotactic radiosurgery has been increasingly used in the treatment of DAVFs. Fifty-nine percent of the 261 fistulas were totally occluded. Treatment-related major complications were seen in 21 patients.

Conclusions
The advances in diagnostic methods (digital subtraction angiography, CT, and MRI) increased the detection rate of DAVFs, and as treatment modalities developed, the results of treatment and outcome of patients markedly improved with the introduction of endovascular techniques and stereotactic radiosurgery. Microsurgery is of limited use in DAVFs resistant to other treatment modalities.
A single center's experience with the bedside subdural evacuating port system: a useful alternative to traditional methods for chronic subdural hematoma evacuation
Authors: Safain Mina , Roguski Marie , Antoniou Alexander , Schirmer Clemens M. , Malek Adel M. , Riesenburger Ron 
Published: December 2012

Object
The traditional methods for managing symptomatic chronic subdural hematoma (SDH) include evacuation via a bur hole or craniotomy, both with or without drain placement. Because chronic SDH frequently occurs in elderly patients with multiple comorbidities, the bedside approach afforded by the subdural evacuating port system (SEPS) is an attractive alternative method that is performed under local anesthesia and conscious sedation. The goal of this study was to evaluate the radiographic and clinical outcomes of SEPS as compared with traditional methods.

Methods
A prospectively maintained database of 23 chronic SDHs treated by bur hole or craniotomy and of 23 chronic SDHs treated by SEPS drainage at Tufts Medical Center was compiled, and a retrospective chart review was performed. Information regarding demographics, comorbidities, presenting symptoms, and outcome was collected. The volume of SDH before and after treatment was semiautomatically measured using imaging software.

Results
There was no significant difference in initial SDH volume (94.5 cm3 vs 112.6 cm3, respectively; p = 0.25) or final SDH volume (31.9 cm3 vs 28.2 cm3, respectively; p = 0.65) between SEPS drainage and traditional methods. In addition, there was no difference in mortality (4.3% vs 9.1%, respectively; p = 0.61), length of stay (11 days vs 9.1 days, respectively; p = 0.48), or stability of subdural evacuation (94.1% vs 83.3%, respectively; p = 0.60) for the SEPS and traditional groups at an average follow-up of 12 and 15 weeks, respectively. Only 2 of 23 SDHs treated by SEPS required further treatment by bur hole or craniotomy due to inadequate evacuation of subdural blood.

Conclusions
The SEPS is a safe and effective alternative to traditional methods of evacuation of chronic SDHs and should be considered in patients presenting with a symptomatic chronic SDH.
Radiographic and clinical outcome of syringomyelia in patients treated for tethered cord syndrome without other significant imaging abnormalities
Authors: Kulwin Charles G. , Patel Neal B. , Ackerman Laurie L. , Smith Jodi L. , Boaz Joel C. , Fulkerson Daniel H. 
Published: December 2012

Object
The surgical management of patients with symptoms of tethered cord syndrome (TCS) who lack significant radiographic abnormalities is controversial. One potential MRI marker for TCS is a spinal cord syrinx or syringomyelia. Alternatively, a syrinx may be a benign and incidental finding. In this report the authors evaluated a highly selected cohort of patients with symptoms of TCS with minimal radiographic abnormalities other than syringomyelia. They analyzed clinical and radiographic outcomes after tethered cord release (TCR).

Methods
A retrospective review of data from 16 children who met the study inclusion criteria was performed. All patients had been surgically treated at Riley Hospital for Children in Indianapolis, Indiana, between 2006 and 2011. All children had clinical symptoms of TCS as well as available pre- and postoperative MRI data.

Results
The most common presentation (12 [75%] of 16 patients) was urinary dysfunction, defined as symptoms of urgency or incontinence with abnormal urodynamic studies. Clinical follow-up data were available in 11 of these 12 patients. All 11 had improvement in symptoms at an average follow-up of 17 months. Seven (87.5%) of 8 patients presenting with back or leg pain had improvement. Three patients had progressive scoliosis; 2 had stabilization of the curve or mild improvement, and 1 patient had worsening deformity.
Radiographic follow-up data were obtained an average of 14.5 months after surgery. Twelve patients (75%) had stable syringomyelia after TCR. Four patients showed improvement, with 2 having complete radiographic resolution.

Conclusions
Highly selected patients with symptoms of TCS did very well clinically. Patients with abnormal urodynamic studies, pain, and gait disturbances showed a high rate of symptomatic improvement. However, a smaller percentage of patients had radiographic improvement of the syrinx. Therefore, the authors suggest that the decision to perform TCR should be based on clinical symptoms in this population. Symptomatic improvement was not necessarily related to radiographic resolution of the syrinx.
Qu'est-ce que l'esprit d'un peuple ?
Authors: Coignard Tristan 
Published: December 2012

Résumé Les rapports entre langue et nation dans l’espace germanophone sont marqués par une longue quête de cohésion. Écrivains et philosophes ont entrepris de lever les contradictions multiples qu’ils ont pu rencontrer : entre une langue commune et des dialectes germaniques, entre la langue allemande et la langue française, entre la tentation du particularisme et l’ambition d’incarner le général. La vision d’une nation homogène a peu à peu cédé le pas au concept de peuple qui permet de recentrer la quête identitaire autour des valeurs portées par une langue unique.
Safety and Feasibility of Obtaining Wedged Pulmonary Artery Samples and Differential Distribution of Biomarkers in Pulmonary Hypertension
Authors: Fares Wassim H. , Ford Hubert James , Ghio Andrew J. , Aris Robert M. 
Published: December 2012

This study aims to evaluate the safety and feasibility of obtaining wedged pulmonary artery (PA) samples and investigate the differential vascular beds' distribution of select inflammatory and cellular adhesion molecules that are implicated in pulmonary arterial hypertension (PAH) pathogenesis. This is a cross‐sectional study of adult patients. Serum samples were simultaneously drawn from three different vascular sites during right heart catheterization as part of PAH evaluation: The superior vena cava, distal pulmonary artery prior to wedging, and distal pulmonary artery after (and distal to) wedging. The study group was comprised of patients with either PAH or chronic thromboembolic pulmonary hypertension (i.e., WHO/Dana Point Group 1 or 4). The internal control group included patients whose hemodynamics were not consistent with pulmonary hypertension. The external control group consisted of healthy volunteers who had a peripheral venous sample drawn. The mean age of the 25 study patients was 55 ± 14 years and mean BMI was 31 ± 10, and those of the 25 internal control patients were 49 ± 14 years and 26 ± 5, respectively. There were no complications resulting from obtaining wedged PA samples. Obtaining adequate wedged samples was successful in 80% of patients. More severe pulmonary hypertension was associated with lower success rates. There were no significant differences in the concentrations of the different biomarkers studied amongst the different vascular sites (n = 25 study patients). There was a nonsignificant trend of decreasing biomarkers concentrations from peripheral to wedged to un‐wedged PA samples. Compared to the healthy external controls, sVCAM‐1 levels were higher in the study group. Obtaining wedged PA blood samples is safe and feasible in adult patients with pulmonary hypertension. There were no differences in the distribution of markers between the vascular beds within patients.
Peroxisome Proliferator‐Activated Receptor Gamma (PPARγ) Regulates Thrombospondin‐1 and Nox4 Expression in Hypoxia‐Induced Human Pulmonary Artery Smooth Muscle Cell Proliferation
Authors: Green David E. , Kang Bum‐Yong , Murphy Tamara C. , Hart C. Michael 
Published: December 2012

Transforming growth factor‐β1 (TGF‐ β1) and thrombospondin‐1 (TSP‐1) are hypoxia‐responsive mitogens that promote vascular smooth muscle cell (SMC) proliferation, a critical event in the pathogenesis of pulmonary hypertension (PH). We previously demonstrated that hypoxia‐induced human pulmonary artery smooth muscle (HPASMC) cell proliferation and expression of the NADPH oxidase subunit, Nox4, were attenuated by the peroxisome proliferator‐activated receptor γ (PPARγ) agonist, rosiglitazone. The current study examines the hypothesis that rosiglitazone regulates Nox4 expression and HPASMC proliferation by attenuating TSP‐1 signaling. Selected HPASMC were exposed to normoxic or hypoxic (1% O2) environments or TSP‐1 (0‐1 μg/ml) for 72 hours ± administration of rosiglitazone (10 μM). Cellular proliferation, Nox4, TSP‐1, and TGF‐β1 expression and reactive oxygen species generation were measured. Mice exposed to hypoxia (10% O2) for three weeks were treated with rosiglitazone (10 mg/kg/day) for the final 10 days, and lung TSP‐1 expression was examined. Hypoxia increased TSP‐1 and TGF‐P1 expression and HPASMC proliferation, and neutralizing antibodies to TSP‐1 or TGF‐β1 attenuated proliferation. Rosiglitazone attenuated hypoxia‐induced HPASMC proliferation and increases in mouse lung and HPASMC TSP‐1 expression, but failed to reduce increases in TGF‐β1 expression or Nox4 expression and activity caused by direct TSP‐1 stimulation. Transfecting HPASMC with siRNA to Nox4 attenuated hypoxia‐ ∗∗∗or TSP‐1‐stimulated HPASMC proliferation. These findings provide novel evidence that TSP‐1‐mediated Nox4 expression plays a critical role in hypoxia‐induced HPASMC proliferation. PPARγ activation with exogenous ligands attenuates TSP‐1 expression to reduce Nox4 expression. These results clarify mechanisms of hypoxia‐induced SMC proliferation and suggest additional pathways by which PPARγ agonists may regulate critical steps in the pathobiology of PH.