bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLAHRCs in practice: combined knowledge transfer and exchange strategies, cultural change, and experimentation
Authors: Soper Bryony , Yaqub Ohid , Hinrichs Saba , Marjanovich Sonja , Drabble Samuel , Hanney Stephen , Nolte Ellen 
Published: October 2013

Objectives The nine NIHR CLAHRCs are collaborations between universities and local NHS organizations that seek to improve patient outcomes through the conduct and application of applied health research. The theoretical and practical context within which the CLAHRCs were set up was characterized by a considerable degree of uncertainty, and the CLAHRCs were established as a natural experiment. Methods We adopted a formative and emergent evaluation approach. Drawing on in-depth, multi-method case studies of two CLAHRCs we explored how they pursued their remit by supporting efforts to increase the relevance and use of health research, and building relationships. Results Both CLAHRCs: strengthened local networks and relationships; built capacity in their local academic and NHS communities to undertake and use research that meets the needs of the service; developed research and implementation methodologies; and added to understanding of the complex relation between research and implementation. There was evidence of impact of CLAHRC projects on health and social care services. Informed by the literature on implementing collaborative research initiatives, knowledge transfer and exchange and cultural change, some key lessons can be drawn. Conclusion The CLAHRCs pursued a strategy that can be categorized as one of flexible comprehensiveness; i.e. their programmes have been flexible and responsive and they have used a range of approaches that seek to match the diverse aspects of the complex issues they face. Key features include their work on combining a range of knowledge transfer and exchange strategies, their efforts to promote cultural change, and the freedom to experiment, learn and adapt. Although the CLAHRCs do not, by themselves, have the remit or resources to bring about wholesale service improvement in health care, they do have features that would allow them to play a key role in some of the wider initiatives that encourage innovation.
cAMP signaling regulates platelet myosin light chain (MLC) phosphorylation and shape change through targeting the RhoA-Rho kinase-MLC phosphatase signaling pathway
Authors: Aburima Ahmed , Wraith Katie S. , Raslan Zaher , Law Robert , Magwenzi Simbarashe , Naseem Khalid M. 
Published: October 2013

Key PointsProtein kinase A (PKA) phosphorylates RhoA on serine188 to inhibit RhoA membrane translocation and RhoA kinase (ROCK) signaling. Inhibition of RhoA/ROCK2 promotes myosin light chain (MLC) phosphatase activity, which prevents the phosphorylation of MLC and platelet shape change.
Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects
Authors: Stockley Jacqueline , Morgan Neil V. , Bem Danai , Lowe Gillian C. , Lordkipanidzé Marie , Dawood Ban , Simpson Michael A. , Macfarlane Kirsty , Horner Kevin , Leo Vincenzo C. , Talks Katherine , Motwani Jayashree , Wilde Jonathan T. , Collins Peter W. , Makris Michael , Watson Steve P. , Daly Martina E. 
Published: October 2013

Key Points
Novel FLI1 and RUNX1 alterations were identified in 6 of 13 patients with excessive bleeding and platelet granule secretion defects. Two FLI1 alterations predicting amino acid substitutions in the DNA-binding domain of FLI1 abolished transcriptional activity of FLI1.
Activation of peripheral nerve fibers by electrical stimulation in the sole of the foot
Authors: Frahm Ken Steffen , Mørch Carsten Dahl , Grill Warren M , Lubock Nathan B , Hennings Kristian , Andersen Ole Kæseler 
Published: October 2013

Abstract

Background
Human nociceptive withdrawal reflexes (NWR) can be evoked by electrical stimulation applied to the sole of the foot. However, elicitation of NWRs is highly site dependent, and NWRs are especially difficult to elicit at the heel. The aim of the present study was to investigate potential peripheral mechanisms for any site dependent differences in reflex thresholds.

Results
The first part of the study investigated the neural innervation in different sites of the sole of the foot using two different staining techniques. 1) Staining for the Nav1.7 antigen (small nociceptive fibers) and 2) the Sihler whole nerve technique (myelinated part of the nerve). No differences in innervation densities were found across the sole of the foot using the two staining techniques: Nav1.7 immunochemistry (small nociceptive fibers (1-way ANOVA, NS)) and the Sihler’s method (myelinated nerve fibers (1-way ANOVA, NS)). However, the results indicate that there are no nociceptive intraepidermal nerve fibers (IENFs) innervating the heel.
Secondly, mathematical modeling was used to investigate to what degree differences in skin thicknesses affect the activation thresholds of Aδ and Aβ fibers in the sole of the foot. The modeling comprised finite element analysis of the volume conduction combined with a passive model of the activation of branching cutaneous nerve fibers. The model included three different sites in the sole of the foot (forefoot, arch and heel) and three different electrode sizes (diameters: 9.1, 12.9, and 18.3 mm). For each of the 9 combinations of site and electrode size, a total of 3000 Aβ fibers and 300 Aδ fibers was modeled. The computer simulation of the effects of skin thicknesses and innervation densities on thresholds of modeled Aδ and Aβ fibers did not reveal differences in pain and perception thresholds across the foot sole as have been observed experimentally. Instead a lack of IENFs at the heel decreased the electrical activation thresholds compared to models including IENFs.

Conclusions
The nerve staining and modeling results do not explain differences in NWR thresholds across the sole of the foot which may suggest that central mechanisms contribute to variation in NWR excitability across the sole of the foot.
The ORCA2 transcription factor plays a key role in regulation of the terpenoid indole alkaloid pathway
Authors: Li Chun Yao , Leopold Alex L , Sander Guy W , Shanks Jacqueline V , Zhao Le , Gibson Susan I 
Published: October 2013

Abstract

Background
The terpenoid indole alkaloid (TIA) pathway leads to the production of pharmaceutically important drugs, such as the anticancer compounds vinblastine and vincristine. Unfortunately, these drugs are produced in trace amounts, causing them to be very costly. To increase production of these drugs, an improved understanding of the TIA regulatory pathway is needed. Towards this end, transgenic Catharanthus roseus hairy roots that overexpress the ORCA2 TIA transcriptional activator were generated and characterized.

Results
Transcriptional profiling experiments revealed that overexpression of ORCA2 results in altered expression of key genes from the indole and terpenoid pathways, which produce precursors for the TIA pathway, and from the TIA pathway itself. In addition, metabolite-profiling experiments revealed that overexpression of ORCA2 significantly affects the levels of several TIA metabolites. ORCA2 overexpression also causes significant increases in transcript levels of several TIA regulators, including TIA transcriptional repressors.

Conclusions
Results presented here indicate that ORCA2 plays a critical role in regulation of TIA metabolism. ORCA2 regulates expression of key genes from both feeder pathways, as well as the genes (STR and SGD) encoding the enzymes that catalyze the first two steps in TIA biosynthesis. ORCA2 may play an especially important role in regulation of the downstream branches of the TIA pathway, as it regulates four out of five genes characterized from this part of the pathway. Regulation of TIA transcriptional repressors by ORCA2 may provide a mechanism whereby increases in TIA metabolite levels in response to external stimuli are transient and limited in magnitude.
Validity, intra- and inter-observer reliability of automated devices for the assessment of ankle brachial index using photo-plethysmography
Authors: Teren Andrej , Beutner Frank , Wirkner Kerstin , Loeffler Markus , Scholz Markus 
Published: October 2013

Abstract

Background
Ankle-brachial-Index (ABI) measured by manual Dopplersonography is an easily assessable marker of global cardiovascular risk. The aim of this study was to establish novel photo-plethysmography (PPG)-based ABI assessments in an epidemiologic context and to compare its results with those of Doppler.

Methods
Two devices for PPG-based ABI assessments (Vicorder, Vascular Explorer) were tested and compared against Doppler in 56 putatively healthy subjects. We determined acceptance, time requirements, agreement of repeat measurements, agreement with Doppler and intra- and inter-observer concordances for both devices and compared the results. Differences between cuff inflation- and deflation-based methods were also studied for Vascular Explorer.

Results
Acceptance was similar for both devices but Vascular Explorer was more time consuming. Agreement of multiple measurements was moderate for both methods highlighting the importance of measurement replicates. Both automated devices showed significantly higher ABI compared to Doppler which can be traced back to higher brachial pressures (Vicorder) or higher ankle pressures (Vascular Explorer). This effect is more pronounced for Vascular Explorer but can be ameliorated using the deflation method of measurement. Intra-observer concordances were similar. Inter-observer concordance was non-significantly better for Vicorder.

Conclusions
Both devices proved to be feasible in epidemiologic studies, but compared to Doppler, do not constitute an advantage regarding time requirement and accuracy of ABI assessment. Since PPG-based ABI values are inflated compared to Doppler, it will be necessary to adjust Doppler-based cut-offs for risk stratification.
High-level expression of a novel thermostable and mannose-tolerant β-mannosidase from Thermotoga thermarum DSM 5069 in Escherichia coli
Authors: Shi Hao , Huang Yingjuan , Zhang Yu , Li Wenqian , Li Xun , Wang Fei 
Published: October 2013

Abstract

Background
Mannan is one of the primary polysaccharides in hemicellulose and is widely distributed in plants. β-Mannosidase is an important constituent of the mannan-degrading enzyme system and it plays an important role in many industrial applications, such as food, feed and pulp/paper industries as well as the production of second generation bio-fuel. Therefore, the mannose-tolerant β-mannosidase with high catalytic efficiency for bioconversion of mannan has a great potential in the fields as above.

Results
A β-mannosidase gene (Tth man5) of 1,827 bp was cloned from the extremely thermophilic bacterium Thermotoga thermarum DSM 5069 that encodes a protein containing 608 amino acid residues, and was over-expressed in Escherichia coli BL21 (DE3). The results of phylogenetic analysis, amino acid alignment and biochemical properties indicate that the Tth Man5 is a novel β-mannosidase of glycoside hydrolase family 5. The optimal activity of the Tth Man5 β-mannosidase was obtained at pH 5.5 and 85°C and was stable over a pH range of 5.0 to 8.5 and exhibited 2 h half-life at 90°C. The kinetic parameters K

m
and V

max
values for p-nitrophenyl-β-D-mannopyranoside and 1,4-β-D-mannan were 4.36±0.5 mM and 227.27±1.59 μmol min-1 mg-1, 58.34±1.75 mg mL-1 and 285.71±10.86 μmol min-1 mg-1, respectively. The k

cat
/K

m
values for p-nitrophenyl-β-D-mannopyranoside and 1,4-β-D-mannan were 441.35±0.04 mM-1 s-1 and 41.47±1.58 s-1 mg-1 mL, respectively. It displayed high tolerance to mannose, with a K

i
value of approximately 900 mM.

Conclusions
This work provides a novel and useful β-mannosidase with high mannose tolerance, thermostability and catalytic efficiency, and these characteristics constitute a powerful tool for improving the enzymatic conversion of mannan through synergetic action with other mannan-degrading enzymes.
Overtraining is associated with DNA damage in blood and skeletal muscle cells of Swiss mice
Authors: Pereira Bruno Cesar , Pauli José Rodrigo , Antunes LusâniaMaria Greggi , de Freitas Ellen Cristini , de Almeida Mara Ribeiro , de Paula Venâncio Vinícius , Ropelle Eduardo Rochete , de Souza Claudio Teodoro , Cintra Dennys Esper , Papoti Marcelo , da Silva AdelinoSanchez Ramos 
Published: October 2013

Abstract

Background
The alkaline version of the single-cell gel (comet) assay is a useful method for quantifying DNA damage. Although some studies on chronic and acute effects of exercise on DNA damage measured by the comet assay have been performed, it is unknown if an aerobic training protocol with intensity, volume, and load clearly defined will improve performance without leading to peripheral blood cell DNA damage. In addition, the effects of overtraining on DNA damage are unknown. Therefore, this study aimed to examine the effects of aerobic training and overtraining on DNA damage in peripheral blood and skeletal muscle cells in Swiss mice. To examine possible changes in these parameters with oxidative stress, we measured reduced glutathione (GSH) levels in total blood, and GSH levels and lipid peroxidation in muscle samples.

Results
Performance evaluations (i.e., incremental load and exhaustive tests) showed significant intra and inter-group differences. The overtrained (OTR) group showed a significant increase in the percentage of DNA in the tail compared with the control (C) and trained (TR) groups. GSH levels were significantly lower in the OTR group than in the C and TR groups. The OTR group had significantly higher lipid peroxidation levels compared with the C and TR groups.

Conclusions
Aerobic and anaerobic performance parameters can be improved in training at maximal lactate steady state during 8 weeks without leading to DNA damage in peripheral blood and skeletal muscle cells or to oxidative stress in skeletal muscle cells. However, overtraining induced by downhill running training sessions is associated with DNA damage in peripheral blood and skeletal muscle cells, and with oxidative stress in skeletal muscle cells and total blood.
Combining glycosylated hemoglobin A1c and fasting plasma glucose for diagnosis of type 2 diabetes in Chinese adults
Authors: Mo Miao , Zhong Weijian , Zhao Genming , Ruan Ye , Zhang Hua , Shi Liang , Lu Dajiang , Yang Qundi , Li Yanyun , Jiang Qingwu , Li Rui , Xu Wang-Hong 
Published: October 2013

Abstract

Background
Glycosylated hemoglobin A1c (HbA1c) has been applied to identify type 2 diabetes (T2DM) in the U.S. and European countries. It has not been used in China mainly due to lack of a standardized approach to measure HbA1c, short of knowledge about racial-specific standard and deficiency of an optimal cut-off point.

Methods
To evaluate combination of HbA1c and fasting plasma glucose (FPG) in diagnosing T2DM in Chinese adults, a multistage sampling cross-sectional study was conducted in Shanghai, China, in 2009. The FPG measurement, HbA1c assay, and oral glucose tolerance test (OGTT) were performed in 6,661 Chinese adults (3057 men, 3604 women) who had no prior history of diabetes to identify the unrecognized T2DM.

Results
A total of 454 participants were identified as T2DM based on the 1999 World Health Organization (WHO) diagnostic criteria. Of these patients, 239 were detected using an FPG ≥ 7.0 mmol/l and 141 were further identified using an HbA1c ≥ 43 mmol/mol (6.1%), achieving a sensitivity of 83.7% and a specificity of 89.3% for combining use of FPG and HbA1c. In subjects at high risk of diabetes, the combining use of FPG and HbA1c produced a higher sensitivity and an improved positive predictive value (PPV), and had a satisfactory specificity and negative predictive value (NPV).

Conclusions
The combining use of FPG and HbA1c is a potential screening and diagnosis approach for T2DM in Chinese adults, especially among those at high risk of the disease.
The status of HBV infection influences metastatic pattern and survival in Chinese patients with pancreatic cancer
Authors: Wei Xiao-li , Qiu Miao-zhen , Chen Wei-wei , Jin Ying , Ren Chao , Wang Feng , Luo Hui-yan , Wang Zhi-qiang , Zhang Dong-sheng , Wang Feng-hua , Li Yu-hong , Xu Rui-hua 
Published: October 2013

Abstract

Background
It has been proved that hepatitis B virus (HBV) infection alters the metastatic pattern and affects survival in colorectal cancer (CRC) and hepatocellular carcinoma (HCC), while the influence of HBV infection on metastatic pattern and survival in patients with pancreatic cancer (PC) has not been investigated yet.

Methods
We conducted an investigation to evaluate the impact of HBV infection on metastatic pattern and overall survival in PC. We collected the data of 460 PC patients treated in our hospital from 1999 to 2010. Serum HBV markers were tested with enzyme-linked immunosorbent assay. The impact of HBV infection on metastatic pattern and overall survival was analyzed.

Results
We found that the incidence of synchronous liver metastasis was significantly higher in patients with HBsAg positive than those with HBsAg negative (46.0% vs 32.0%, P < 0.05), and higher in chronic HBV infection (CHB) group than both non HBV infection and resolved HBV infection group (61.1% vs 33.9%, P < 0.05, and 61.1% vs 28.7%, P < 0.05, respectively). What’s more, Kaplan-Meier analysis showed that CHB, resolved HBV infection and non HBV infection group had significant longer overall survival (OS) compared with inactive HBsAg carriers (IC) group (P=0.037, P=0.009, and P=0.019 respectively). But, in the multivariate analysis, only the CHB and non HBV infection group had significant better overall survival compared with IC group (P=0.010 and P=0.018 respectively).

Conclusions
Our study found that HBV infection increased synchronous liver metastasis rate, and HBV infection status was an independent prognostic factor in PC patients.
The microwave-assisted ionic liquid nanocomposite synthesis: platinum nanoparticles on graphene and the application on hydrogenation of styrene
Authors: Lee Jer-Yeu , Yung Tung-Yuan , Liu Ling-Kang 
Published: October 2013

Abstract
The microwave-assisted nanocomposite synthesis of metal nanoparticles on graphene or graphite oxide was introduced in this research. With microwave assistance, the Pt nanoparticles on graphene/graphite oxide were successfully produced in the ionic liquid of 2-hydroxyethanaminium formate [HOCH2CH2NH3][HCO2]. On graphene/graphite oxide, the sizes of Pt nanoparticles were about 5 to 30 nm from transmitted electron microscopy (TEM) results. The crystalline Pt structures were examined by X-ray diffraction (XRD). Since hydrogenation of styrene is one of the important well-known chemical reactions, herein, we demonstrated then the catalytic hydrogenation capability of the Pt nanoparticles on graphene/graphite oxide for the nanocomposite to compare with that of the commercial catalysts (Pt/C and Pd/C, 10 wt.% metal catalysts on activated carbon from Strem chemicals, Inc.). The conversions with the Pt nanoparticles on graphene are >99% from styrene to ethyl benzene at 100°C and under 140 psi H2 atmosphere. However, ethyl cyclohexane could be found as a side product at 100°C and under 1,520 psi H2 atmosphere utilizing the same nanocomposite catalyst.
Dysfunction of orbitofrontal and dorsolateral prefrontal cortices in children and adolescents with high-functioning pervasive developmental disorders
Authors: Sawa Tetsuji , Kodaira Masaki , Oiji Arata , Sasayama Daimei , Iwadare Yoshitaka , Ushijima Hirokage , Usami Masahide , Watanabe Kyota , Saito Kazuhiko 
Published: October 2013

Abstract

Background
Several lines of evidence suggest that dysfunction of the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) contributes to the pathophysiology of pervasive developmental disorders (PDD). The purpose of this study was to investigate neuropsychological dysfunctions in both the DLPFC and OFC of children and adolescents with high-functioning PDD.

Methods
The Iowa gambling task (IGT), which reflects OFC function, and the Wisconsin Card Sorting Test (WCST), which reflects DLPFC function, were assigned to 19 children and early adolescents with high-functioning PDD and 19 healthy controls matched for gender, age, and intelligence.

Results
Compared to healthy controls, patients with high-functioning PDD displayed poorer performance on the IGT and the WCST.

Conclusions
These results indicate that both the DLPFC and OFC could be impaired in children and early adolescents with high-functioning PDD.
Expressions of oxidative stress-related genes and antioxidant enzyme activities in Mytilus galloprovincialis (Bivalvia, Mollusca) exposed to hypoxia
Authors: Woo Seonock , Denis Vianney , Won Hyokyung , Shin Kyungsoon , Lee Gunsup , Lee Taek-Kyun , Yum Seungshic 
Published: October 2013

Abstract

Background
In this study, we investigated transcription and enzyme level responses of mussels Mytilus galloprovincialis exposed to hypoxic conditions. Genes for catalase (CAT), cytochrome P450, glutathione S-transferase (GST), metallothionein, superoxide dismutase (SOD), cytochrome c oxidase subunit 1 (COX-1), and NADH dehydrogenase subunit 2 were selected for study. Transcriptional changes were investigated in mussels exposed to hypoxia for 24 and 48 h and were compared to changes in control mussels maintained at normal oxygen levels. Activities of CAT, GST, and SOD enzymes, and lipid peroxidation (LPO) were also investigated in mussels following exposure to hypoxia for 24, 48, and 72 h.

Results
Relative to the control group, the CAT activity decreased in all hypoxia treatments, while the activity of GST significantly increased in mussels exposed to hypoxia for 24 and 48 h, but decreased in those exposed for 72 h. The LPO levels were significantly higher in mussels in the 24- and 48-h hypoxia treatments than those in the control mussels, but there was no significant change in the SOD activities among all hypoxia treatments. Messenger RNA levels for the CAT, cytochrome P450, GST, metallothionein, and SOD genes were not significantly affected by hypoxic conditions for 48 h, but the expressions of the COX-1 and NADH dehydrogenase subunit 2 genes were significantly repressed in mussels in both the 24- and 48-h exposure treatments.

Conclusions
These results demonstrate the transcriptional stability and changes among several genes related to oxidative stress under oxygen-depletion conditions in M. galloprovincialis and provide useful information about the modulation of antioxidant enzyme activities induced by hypoxia in a marine animal.