bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site recognition and substrate screens for PKN family proteins
Authors: Collazos Alejandra , Michael Nicholas , Whelan Richard D. H. , Kelly Gavin , Mellor Harry , Pang Leon C. H. , Totty Nick , Parker Peter J. 
Published: July 2011

The PRKs [protein kinase C-related kinases; also referred to as PKNs (protein kinase Ns)] are a kinase family important in diverse functions including migration and cytokinesis. In the present study, we have re-evaluated and compared the specificity of PKN1 and PKN3 and assessed the predictive value in substrates. We analysed the phosphorylation consensus motif of PKNs using a peptide library approach and demonstrate that both PKN1 and PKN3 phosphorylate serine residues in sequence contexts that have an arginine residue in position −3. In contrast, PKN1 and PKN3 do not tolerate arginine residues in position +1 and −1 respectively. To test the predictive value of this motif, site analysis was performed on the PKN substrate CLIP-170 (cytoplasmic linker protein of 170 kDa); a PKN target site was identified that conformed to the predicted pattern. Using a protein array, we identified 22 further substrates for PKN1, of which 20 were previously undescribed substrates. To evaluate further the recognition signature, the site on one of these hits, EGFR (epidermal growth factor receptor), was identified. This identified Thr654 in EGFR as the PKN1 phosphorylation site and this retains an arginine residue at the −3 position. Finally, the constitutive phosphorylation of EGFR on Thr654 is shown to be modulated by PKN in vivo.
Acetylsalicylic acid regulates overexpressed small GTPase RhoA in vascular smooth muscle cells through prevention of new synthesis and enhancement of protein degradation
Authors: Li Dong-Bo , Fu Zhi-Xuan , Ruan Shu-Qin , Hu Shen-Jiang , Li Xia 
Published: July 2011

RhoA has been shown to play a major role in vascular processes and acetylsalicylic acid (aspirin) is known to exert a cytoprotective effect via multiple mechanisms. In the present study, we aimed at investigating the effect of aspirin on RhoA expression under a stress state in rat VSMCs (vascular smooth muscle cells) and the underlying mechanisms. The expression of iNOS (inducible nitric oxide synthase) and iNOS activity as well as NO concentration was significantly promoted by LPS (lipopolysaccharide) accompanying the elevation of RhoA expression, which was blocked by the addition of the iNOS inhibitor L-NIL [L-N6-(1-iminoethyl)lysine dihydrochloride]. Aspirin (30 μM) significantly attenuated the elevation of RhoA, while indomethacin and salicylate had no similar effect. The sGC (soluble guanylate cyclase) inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) showed the same effect as aspirin in down-regulating RhoA but was reversed by the addition of the cGMP analogue 8-Br-PET-cGMP (β-phenyl-1,N2-ethano-8-bromoguanosine 3′,5′-cyclic monophosphorothioate). 8-Br-PET-cGMP solely enhanced the RhoA expression that was abrogated by preincubation with aspirin. Degradation analysis indicated that aspirin enhanced the protein degradation rate of RhoA and GDP-bound RhoA seemed to be more susceptible to aspirin-enhanced degradation compared with the GTP-bound form. Our results indicate that aspirin attenuates the LPS-induced overexpression of RhoA both by inhibiting new synthesis and accelerating protein degradation, which may help elucidate the multiple beneficial effects of aspirin.
Electronic Measures of Surgical Site Infection: Implications for Estimating Risks and Costs
Authors: Hollenbeak Christopher S. , Boltz Melissa M. , Nikkel Lucas E. , Schaefer Eric , Ortenzi Gail , Dillon Peter W. 
Published: July 2011

Objective.Electronic measures of surgical site infections (SSIs) are being used more frequently in place of labor-intensive measures. This study compares performance characteristics of 2 electronic measures of SSIs with a clinical measure and studies the implications of using electronic measures to estimate risk factors and costs of SSIs among surgery patients.Methods.Data included 1,066 general and vascular surgery patients at a single academic center between 2007 and 2008. Clinical data were from the National Surgical Quality Improvement Program (NSQIP) database, which includes a nurse-derived measure of SSI. We compared the NSQIP SSI measure with 2 electronic measures of SSI: MedMined Nosocomial Infection Marker (NIM) and International Classification of Diseases, Ninth Revision (ICD-9) coding for SSIs. We compared infection rates for each measure, estimated sensitivity and specificity of electronic measures, compared effects of SSI measures on risk factors for mortality using logistic regression, and compared estimated costs of SSIs for measures using linear regression.Results.SSIs were observed in 8.8% of patients according to the NSQIP definition, 2.6% of patients according to the NIM definition, and 5.8% according to the ICD-9 definition. Logistic regression for each SSI measure revealed large differences in estimated risk factors. NIM and ICD-9 measures overestimated the cost of SSIs by 134% and 33%, respectively.Conclusions.Caution should be taken when relying on electronic measures for SSI surveillance and when estimating risk and costs attributable to SSIs. Electronic measures are convenient, but in this data set they did not correlate well with a clinical measure of infection.
Public Reporting of Health Care–Associated Infections (HAIs): Approach to Choosing HAI Measures
Authors: Passaretti C. L. , Barclay P. , Pronovost P. , Perl T. M. ,   Maryland Health Care Commission Health Care–Associated Infection Technical Advisory Committee
Published: July 2011

Objective.To develop a method for selecting health care–associated infection (HAI) measures for public reporting.Context.HAIs are common, serious, and costly adverse outcomes of medical care that affect 2 million people in the United States annually. Thirty-seven states have introduced or passed legislation requiring public reporting of HAI measures. State legislation varies widely regarding which HAIs to report, how the data are collected and reported, and public availability of results.Design.The Maryland Health Care Commission developed an HAI Technical Advisory Committee (TAC) that consisted of a group of experts in the field of healthcare epidemiology, infection prevention and control (IPC), and public health. This group reviewed public reporting systems in other states, surveyed Maryland hospitals to determine the current state of IPC programs, performed a literature review on HAI measures, and developed six criteria for ranking the measures: impact, unprovability, inclusiveness, frequency, functionality, and feasibility. The committee and experts in the field then ranked each of 18 proposed HAI measures. A composite score was determined for each measure.Results.Among outcome measures, the rate of central line–associated bloodstream infections ranked highest, followed by the rate of post–coronary artery bypass grafting surgical-site infections. Among process measures, perioperative antimicrobial prophylaxis, compliance with central-line bundles, compliance with hand hygiene, and healthcare-worker influenza vaccination ranked highest.Conclusions.Our qualitative criteria facilitated consensus on the HAI TAC and provided a useful framework for public reporting of HAI measures. Validation will be important for such approaches to be supported by the scientific community.
An Outbreak ofBurkholderia cepaciaComplex Associated with Intrinsically Contaminated Nasal Spray
Authors: Dolan Susan A. , Dowell Elaine , LiPuma John J. , Valdez Sondra , Chan Kenny , James John F. 
Published: July 2011

Objective.To determine the source ofBurkholderia cepaciacomplex associated with a hospital outbreak and describe the measures taken to identify and confirm the source.Setting.A 250-bed, tertiary care pediatric hospital in Denver, Colorado.Methods.An epidemiologic investigation was used to identify possible causes for an apparent outbreak ofB. cepaciacomplex in pediatric patients who had new positive cultures with this organism from December 2003 to February 2004. Chart review, microbiology reports, surgical records, site visits, literature review, staff interviews, and cultures of common products and equipment were performed to determine a source of contamination. Random amplified polymorphic DNA and pulsed-field gel electrophoresis typing, performed by 2 independent laboratories, were used for molecular typing of patient and source isolates.Results.Five pediatric patients had new positiveB. cepaciacomplex cultures from either the sinus or the respiratory tract, and all 5 patients had prior exposure to 0.05% oxymetazoline hydrochloride Major Twice-A-Day 12-hour nasal spray (Proforma, Miami, FL). Four of the 5 patients had isolates that were identical to theB. cepaciacomplex isolates recovered from the unopened Twice-A-Day 12-hour nasal spray.Conclusions.Intrinsic contamination of Major Twice-A-Day 12-hour nasal spray withB. cepaciacomplex resulted in nosocomial transmission to 4 patients at our facility and resulted in a voluntary product recall by the manufacturer.B. cepaciacomplex species are common contaminants of an increasing variety of nonsterile medical products. Enhanced culture techniques may be useful in evaluating possible product contamination, suggesting additional measures that should be considered to assure the safety of products that may be used in high-risk patients.
Elemental composition determination based on MSn
Authors: Rojas-Chertó Miguel , Kasper Piotr T. , Willighagen Egon L. , Vreeken Rob J. , Hankemeier Thomas , Reijmers Theo H. 
Published: July 2011

Abstract
Motivation: Identification of metabolites is essential for its use as biomarkers, for research in systems biology and for drug discovery. The first step before a structure can be elucidated is to determine its elemental composition. High-resolution mass spectrometry, which provides the exact mass, together with common constraint rules, for rejecting false proposed elemental compositions, cannot always provide one unique elemental composition solution.
Results: The Multistage Elemental Formula (MEF) tool is presented in this article to enable the correct assignment of elemental composition to compounds, their fragment ions and neutral losses that originate from the molecular ion by using multistage mass spectrometry (MSn). The method provided by MEF reduces the list of predicted elemental compositions for each ion by analyzing the elemental compositions of its parent (precursor ion) and descendants (fragments). MSn data of several metabolites were processed using the MEF tool to assign the correct elemental composition and validate the efficacy of the method. Especially, the link between the mass accuracy needed to generate one unique elemental composition and the topology of the MSn tree (the width and the depth of the tree) was addressed. This method makes an important step toward semi-automatic de novo identification of metabolites using MSn data.
Availability: Software available at: http://abs.lacdr.gorlaeus.net/people/rojas-cherto
Contact: m.rojas@lacdr.leidenuniv.nl; t.reijmers@lacdr.leidenuniv.nl
Supplementary information: Supplementary data are available at Bioinformatics online.
Utility of a spatial habitat classification system as a surrogate of marine benthic community structure for the Australian margin
Authors: Przeslawski Rachel , Currie David R. , Sorokin Shirley J. , Ward Tim M. , Althaus Franziska , Williams Alan 
Published: July 2011

Abstract
Przeslawski, R., Currie, D. R., Sorokin, S. J., Ward. T. M., Althaus, F., and Williams, A. 2011. Utility of a spatial habitat classification system as a surrogate of marine benthic community structure for the Australian margin. – ICES Journal of Marine Science, 68: 1954–1962. This study tests whether a continental-scale classification of Australian benthic habitats (termed “seascapes”) and the interpolated environmental data from which they are derived are useful as abiotic surrogates of biodiversity at a local [tens of kilometres, Great Australian Bight (GAB)] and regional scale [hundreds of kilometres, Western Australian (WA) margin]. Benthic invertebrate community structure is moderately associated with specific seascapes in both the GAB (R = 0.418) and WA margin (excluding hard substrata, R = 0.375; all substrata, R = 0.313). Mud content, seafloor slope, and seafloor temperature are significantly correlated with invertebrate communities at both scales, with disturbance and primary production correlated with GAB communities. Seascapes are not consistently useful surrogates because the strength and significance of relationships between seascapes and community structure differs among seascapes, regions, and spatial scales. Nevertheless, a national system of seascapes is an appropriate surrogate for broad-scale benthic invertebrate community patterns when biological data are limited, provided the uncertainty is acknowledged and, where possible, an assessment made of each seascape's ability to differentiate biological communities. Further refinement of seascape derivations may include updated and additional environmental data (particularly for hard vs. soft substrata) and validation among biological datasets from a range of habitats and scales.
Somatostatinoma
Authors: Wass John A.H. 
Published: July 2011

Somatostatin was isolated in 1973 by Paul Brazeau in Roger Guillemin’s laboratory. It was found to have a widespread distribution, not only in the hypothalamus and brain but also in the gastrointestinal tract. Sixty-five per cent of the body’s somatostatin is in the gut, mostly in the D cells of the gastric and intestinal epithelium. It is also present in the myometric and submucosal plexuses. The highest concentration is in the antrum of the stomach and there is a gradual decrease of concentrations down the gastrointestinal tract. Five per cent of the body’s somatostatin is in the pancreas.

Infused somatostatin, which has a short half-life of 3 min, has a large number of actions on the pituitary gland, the endocrine and exocrine pancreas, gastrointestinal tract, other hormones, and on the nervous system (Box 6.8.1). Among its various actions of importance in the gastrointestinal tract is the inhibition of gastrin and cholecystokinin (CCK). In the pancreas, insulin and glucagon are inhibited. Nonendocrine actions include inhibition of gastric acid secretion, pancreatic exocrine function, gall bladder contraction, and intestinal motility. Intestinal absorption of nutrients, including glucose, triglycerides, and amino acids, is also inhibited (1).

Somatostatin exists in two main forms, as a 14-amino acid peptide (somatostatin 14) present mainly in the pancreas and the stomach, and as a 28-amino acid peptide present mainly in the intestine. Somatostatin 14 is the peptide present in enteric neurons.

Somatostatin receptors are present on many cell types, including the parietal cells of the stomach, G cells, D cells themselves, and cells of the exocrine and endocrine pancreas. A large number of tumours also have somatostatin receptors and these include pituitary adenomas, endocrine pancreatic tumours, carcinoid tumours, paragangliomas, phaeochromocytomas, small cell lung carcinomas, lymphomas, and meningiomas. Five different somatostatin receptors (SSTRs) have been cloned (SSTR1–SSTR5) and all are on different chromosomes. These have a varying affinity for somatostatin 14 and somatostatin 28 and a varying tissue distribution with SSTR2 and 5 being predominant in the pituitary (2).

Somatostatin can act either as an endocrine hormone or in a paracrine or autocrine way. It probably also has luminal effects in the gastrointestinal tract. Lastly, it can act as a neurotransmitter (3).
Diabetic nephropathy
Authors: Karalliedde Janaka , Janaka Giancarlo 
Published: July 2011

Diabetic nephropathy is classically defined as a rise in urinary albumin excretion rate (UAER), often associated with an increase in blood pressure, with concomitant retinopathy but without evidence of

other causes of renal disease (1). It is characterized by a progressive decline in glomerular filtration rate (GFR), eventually resulting in end-stage renal disease. Diabetic nephropathy occurs in approximately 30–35% of type 1 and type 2 patients and tends to cluster in families. These families also show a predisposition to cardiovascular disease and hypertension—and, hypertension, or a predisposition to it, appears a major determinant of diabetic renal disease. These data taken together clearly suggest an individual susceptibility to this complication.

The phases of diabetic nephropathy based on urine albumin excretion status and GFR are shown in Table 13.5.3.1 (2). Histological changes of diabetic glomerulopathy are present in over 95% of patients with type 1 diabetes and albuminuria (UAER >300 mg/day) and in approximately 85% of type 2 diabetic patients who develop albuminuria with concomitant diabetic retinopathy (1, 2). In the absence of diabetic retinopathy nearly 30% of patients with type 2 diabetes and proteinuria have nondiabetic renal lesions (1).

The all-cause mortality in patients with diabetic nephropathy is nearly 20–40 times higher than that in patients without nephropathy. In recent years it has become apparent that renal disease and cardiovascular disease are closely related and diabetic nephropathy is acknowledged as an independent and powerful risk factor for cardiovascular disease (3). Many patients with diabetes and renal impairment die from a cardiovascular disease event before they progress to end-stage renal disease. Diabetic nephropathy is the most common cause of end-stage renal disease worldwide and represent about 30–40% of all patients receiving renal replacement therapy in the Western World.
Tectonic setting of Cretaceous basins on the NE Tibetan Plateau: insights from the Jungong basin
Authors: Craddock William H. , Kirby Eric , Dewen Zheng , Jianhui Liu 
Published: July 2011

ABSTRACTQuantifying the Cenozoic growth of high topography in the Indo‐Asian collision zone remains challenging, due in part to significant shortening that occurred within Eurasia before collision. A growing body of evidence suggests that regions far removed from the suture zone experienced deformation before and during the early phases of Himalayan orogenesis. In the present‐day north‐eastern Tibetan Plateau, widespread deposits of Cretaceous sediment attest to significant basin formation; however, the tectonic setting of these basins remains enigmatic. We present a study of a regionally extensive network of sedimentary basins that are spatially associated with a system of SE‐vergent thrust faults and are now exposed in the high ranges of the north‐eastern corner of the Tibetan Plateau. We focus on a particularly well‐exposed basin, located ∼20 km north of the Kunlun fault in the Anyemaqen Shan. The basin is filled by ∼900 m of alluvial sediments that become finer‐grained away from the basin‐bounding fault. Additionally, beds in the proximal footwall of the basin‐bounding fault exhibit progressive, up‐section shallowing and several intraformational unconformities which can be traced into correlative conformities in the distal part of the basin. The observations show sediment accumulated in the basin during fault motion. Regional constraints on the timing of sediment deposition are provided by both fossil assemblages from the Early Cretaceous, and by K–Ar dating of volcanic rocks that floor and cross‐cut sedimentary fill. We argue that during the Cretaceous, the interior NE Tibetan Plateau experienced NW–SE contractional deformation similar to that documented throughout the Qinling–Dabie orogen to the east. The Songpan‐Ganzi terrane apparently marked the southern limit of this deformation, such that it may have been a relatively rigid block in the Tibetan lithosphere, separating regions experiencing deformation north of the convergent Tethyan margin from regions deforming inboard of the east Asian margin.
A randomized, double‐blind, placebo‐controlled study of the CRTH2 antagonist OC000459 in moderate persistent asthma
Authors: Barnes N. , Pavord I. , Chuchalin A. , Bell J. , Hunter M. , Lewis T. , Parker D. , Payton M. , Collins L. Pearce , Pettipher R. , Steiner J. , Perkins C. M. 
Published: July 2011

Summary
Background CRTH2 is a G‐protein‐coupled receptor that mediates the activation of Th2 lymphocytes, eosinophils and basophils in response to prostaglandin D2 and may be involved in the pathogenesis of airway inflammation and dysfunction in asthma.
Objective To evaluate the effects of a potent and selective CRTH2 antagonist, OC000459, on the lung function, symptoms and eosinophilic airway inflammation in a double‐blind, parallel group trial in steroid‐free subjects with moderate persistent asthma.
Methods Adult subjects were randomized to oral OC000459 200 mg twice daily (N=65) or a placebo (N=67) for 28 days. The primary end‐point was the change from baseline in pre‐bronchodilator forced expiratory volume in 1 s (FEV1); eosinophilic airway inflammation was assessed by induced sputum differential eosinophil count. The trial was registered on the clinicaltrials.gov database (Identifier NCT01057927).
Results Data were analysed for both the Full Analysis (FA) population and the Per Protocol (PP) population (55 treated with OC000459 and 52 with placebo), which excluded non‐compliant subjects. In the FA population, the mean change in FEV1 was 7.1% on OC000459 compared with 4.3% on placebo (not significant); in the PP population, the mean changes were 9.2% and 1.8%, respectively (P=0.037). Improvement in quality of life was apparent in both FA and PP populations [difference from the placebo in AQLQ(S) total score of 0.29, P=0.0113 and 0.37, P=0.0022, respectively]. OC000459 also improved the night‐time symptom scores (mean reduction of 0.36 vs. 0.11, P=0.008, FA population; 0.37 vs. 0.12, P=0.022, PP population). The geometric mean sputum eosinophil count reduced from 2.1% to 0.7% (P=0.03) after OC000459, but this effect was not significant when compared with the change on placebo (P=0.37). Adverse events on OC000459 were comparable to those on placebo; respiratory infections were notably less common during OC000459 than the placebo treatment.
Conclusion and Clinical Relevance This study provides the first clinical evidence that CRTH2 receptors contribute to airflow limitation, symptoms and eosinophilic airway inflammation in asthma. OC000459 shows promise as a novel oral treatment for asthma and related disorders.
Cite this as: N. Barnes, I. Pavord, A. Chuchalin, J. Bell, M. Hunter, T. Lewis, D. Parker, M. Payton, L. Pearce Collins, R. Pettipher, J. Steiner and C. M. Perkins, Clinical & Experimental Allergy, 2012 (42) 38–48.