bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Need for Multiple Measures of Hospital Quality
Authors: Hernandez Adrian F. , Fonarow Gregg C. , Liang Li , Heidenreich Paul A. , Yancy Clyde , Peterson Eric D. 
Published: July 2011

Background—
Process and outcome measures are often used to quantify quality of care in hospitals. Whether these quality measures correlate with one another and the degree to which hospital provider rankings shift on the basis of the performance metric is uncertain.

Methods and Results—
Heart failure patients ≥65 years of age hospitalized in the Get With the Guidelines–Heart Failure registry of the American Heart Association were linked to Medicare claims from 2005 to 2006. Hospitals were ranked by (1) composite adherence scores for 5 heart failure process measures, (2) composite adherence scores for emerging quality measures, (3) risk-adjusted 30-day death after admission, and (4) risk-adjusted 30-day readmission after discharge. Hierarchical models using shrinkage estimates were performed to adjust for case mix and hospital volume. There were 19 483 patients hospitalized from 2005 to 2006 from 153 hospitals. The overall median composite adherence rate to heart process measures was 85.8% (25th, 75th percentiles 77.5, 91.4). Median 30-day risk-adjusted mortality was 9.0% (7.9, 10.4). Median risk-adjusted 30-day readmission was 22.9% (22.1, 23.5). The weighted κ for remaining within the top 20th percentile or bottom 20th percentile was ≤0.15 and the Spearman correlation overall was ≤0.21 between the different measures of quality of care. The average shift in ranks was 33 positions (13, 68) when criteria were changed from 30-day mortality to readmission and 51 positions (22, 76) when ranking metric changed from 30-day mortality to composite process adherence.

Conclusions—
Agreement between different methods of ranking hospital-based quality of care and 30-day mortality or readmission rankings was poor. Profiling quality of care will require multidimensional ranking methods and/or additional measures.
NADPH Oxidase 4 Promotes Endothelial Angiogenesis Through Endothelial Nitric Oxide Synthase Activation
Authors: Craige Siobhan M. , Chen Kai , Pei Yongmei , Li Chunying , Huang Xiaoyun , Chen; Christine , Shibata Rei , Sato Kaori , Walsh Kenneth , Keaney John F. 
Published: July 2011

Background—
Reactive oxygen species serve signaling functions in the vasculature, and hypoxia has been associated with increased reactive oxygen species production. NADPH oxidase 4 (Nox4) is a reactive oxygen species–producing enzyme that is highly expressed in the endothelium, yet its specific role is unknown. We sought to determine the role of Nox4 in the endothelial response to hypoxia.

Methods and Results—

Hypoxia induced Nox4 expression both in vitro and in vivo and overexpression of Nox4 was sufficient to promote endothelial proliferation, migration, and tube formation. To determine the in vivo relevance of our observations, we generated transgenic mice with endothelial-specific Nox4 overexpression using the vascular endothelial cadherin promoter (VECad-Nox4 mice). In vivo, the VECad-Nox4 mice had accelerated recovery from hindlimb ischemia and enhanced aortic capillary sprouting. Because endothelial nitric oxide synthase (eNOS) is involved in endothelial angiogenic responses and eNOS is activated by reactive oxygen species, we probed the effect of Nox4 on eNOS. In cultured endothelial cells overexpressing Nox4, we observed a significant increase in eNOS protein expression and activity. To causally address the link between eNOS and Nox4, we crossed our transgenic Nox4 mice with eNOS
−/−
mice. Aortas from these mice did not demonstrate enhanced aortic sprouting, and VECad-Nox4 mice on the eNOS
−/−
background did not demonstrate enhanced recovery from hindlimb ischemia.

Conclusions—
Collectively, we demonstrate that augmented endothelial Nox4 expression promotes angiogenesis and recovery from hypoxia in an eNOS-dependent manner.
Potential effectiveness of three different treatment approaches to improve minimal to moderate arm and hand function after stroke – a pilot randomized clinical trial
Authors: Khan Christine Meier , Oesch Peter R , Gamper Urs N , Kool Jan P , Beer Serafin 
Published: July 2011

Objective: To test a study design and explore the feasibility and potential effects of conventional neurological therapy, constraint induced therapy and therapeutic climbing to improve minimal to moderate arm and hand function in patients after a stroke. Method: A pilot study with six-month follow-up in patients after stroke with minimal to moderate arm and hand function admitted for inpatient rehabilitation was performed. Participants were randomly allocated to one of three treatment approaches. Main outcomes were improvement of arm and hand function and adverse effects. Results: 283 patients with stroke were screened for inclusion over a two-year period, out of which fourtyfour were included. All patients could be treated according to the protocol. Improvement of arm and hand function was significantly higher in conventional neurological therapy and constraint induced therapy compared with therapeutic climbing at discharge, and at six months follow-up ( P < 0.05, effect size = 0.56–0.76). No significant differences in arm and hand function were observed between constraint induced therapy and conventional neurological therapy. Constraint induced therapy participants were significantly less at risk of developing shoulder pain at six months follow-up compared with the other participants ( P < 0.05, effect size = 0.82 and 1.79, respectively). Conclusions: The study design needs adaptation to accommodate the stringent inclusion criteria leading to prolonged study duration. Constraint induced therapy seems to be the optimal approach to improve arm and hand function and minimize the risk of shoulder pain for patients with minimal to moderate arm hand function after stroke in the intermediate term.
Thrombomodulin is a determinant of metastasis through a mechanism linked to the thrombin binding domain but not the lectin-like domain
Authors: Horowitz Netanel A. , Blevins Elizabeth A. , Miller Whitney M. , Perry Ashley R. , Talmage Kathryn E. , Mullins Eric S. , Flick Matthew J. , Queiroz Karla C. S. , Shi Kun , Spek C. Arnold , Conway Edward M. , Monia Brett P. , Weiler Hartmut , Degen Jay L. , Palumbo Joseph S. 
Published: July 2011

Abstract
Thrombomodulin (TM) is a predominantly endothelial transmembrane glycoprotein that modulates hemostatic function through a domain that controls thrombin-mediated proteolysis and an N-terminal lectin-like domain that controls inflammatory processes. To test the hypothesis that TM is a determinant of malignancy and dissect the importance of these functional domains in cancer biology, metastatic potential was evaluated in TMPro mice expressing a mutant form of TM with reduced thrombin affinity and TMLeD mice lacking the N-terminal lectin-like domain. Studies of TMPro mice revealed that TM is a powerful determinant of hematogenous metastasis. TMPro mice exhibited a strongly prometastatic phenotype relative to control mice that was found to result from increased survival of tumor cells newly localized to the lung rather than any alteration in tumor growth. The impact of the TMPro mutation on metastasis was dependent on both tumor cell-associated tissue factor and thrombin procoagulant function. In contrast, expression of a mutant form of TM lacking the lectin-like domain had no significant impact on metastasis. These studies directly demonstrate for the first time that TM-mediated regulation of tumor cell-driven procoagulant function strongly influences metastatic potential and suggest that endothelial cell-associated modulators of hemostasis may represent novel therapeutic targets in limiting tumor dissemination.
Hyperphosphorylation of autoantigenic targets of paraproteins is due to inactivation of PP2A
Authors: Preuss Klaus-Dieter , Pfreundschuh Michael , Fadle Natalie , Regitz Evi , Raudies Sybille , Murwaski Niels , Ahlgrimm Manfred , Bittenbring Joerg , Klotz Markus , Schäfer Karl-Herbert , Held Gerhard , Neumann Frank , Grass Sandra 
Published: July 2011

Abstract
Paratarg-7, a frequent autoantigenic target, and all other autoantigenic targets of human paraproteins molecularly defined to date are hyperphosphorylated in the respective patients compared with healthy controls, suggesting that hyperphosphorylation of autoantigenic paraprotein targets is a general mechanism underlying the pathogenesis of these paraproteins. We now show that hyperphosphorylation of paratarg-7 occurs because of an additional phosphorylation of Ser17, which is located within the paraprotein-binding epitope. Coimmunoprecipitation identified phosphokinase C ζ (PKCζ) as the kinase responsible for the phosphorylation of most, and phosphatase 2A (PP2A) as the phosphatase responsible for the dephosphorylation of all hyperphosphorylated autoantigenic targets of paraproteins. Single-nucleotide polymorphisms (SNPs) or mutations of PKCζ and PP2A were excluded. However, PP2A was inactivated by phosphorylation of its catalytic subunit at Y307. Stimulation of T cells from healthy carriers of wild-type paratarg-7 induced a partial and transient hyperphosphorylation between days 4 and 18, which was maintained by incubation with inhibitors of PP2A, again indicating that an inactivation of PP2A is responsible for the hyperphosphorylation of autoantigenic paraprotein targets. We conclude that the genetic defect underlying the dominantly inherited hyperphosphorylation of autoantigenic paraprotein targets is not in the PP2A itself, but in genes or proteins controlling PP2A activity by phosphorylation of its catalytic subunit.
Matrix metalloproteinase-19 inhibits growth of endothelial cells by generating angiostatin-like fragments from plasminogen
Authors: Brauer Rena , Beck Inken M , Roderfeld Martin , Roeb Elke , Sedlacek Radislav 
Published: July 2011

AbstractBackgroundAngiogenesis is the process of forming new blood vessels from existing ones and requires degradation of the vascular basement membrane and remodeling of extracellular matrix (ECM) in order to allow endothelial cells to migrate and invade into the surrounding tissue. Matrix metalloproteinases (MMPs) are considered to play a central role in the remodeling of basement membranes and ECM. However, MMPs contribute to vascular remodeling not only by degrading ECM components. Specific MMPs enhance angiogenesis via several ways; they help pericytes to detach from vessels undergoing angiogenesis, release ECM-bound angiogenic growth factors, expose cryptic pro-angiogenic integrin binding sites in the ECM, generate promigratory ECM component fragments, and cleave endothelial cell-cell adhesions. MMPs can also negatively influence the angiogenic process through generating endogenous angiogenesis inhibitors by proteolytic cleavage. Angiostatin, a proteolytic fragment of plasminogen, is one of the most potent antagonists of angiogenesis that inhibits migration and proliferation of endothelial cells. Reports have shown that metalloelastase, pancreas elastase, plasmin reductase, and plasmin convert plasminogen to angiostatin.ResultsWe report here that MMP-19 processes human plasminogen in a characteristic cleavage pattern to generate three angiostatin-like fragments with a molecular weight of 35, 38, and 42 kDa. These fragments released by MMP-19 significantly inhibited the proliferation of HMEC cells by 27% (p = 0.01) and reduced formation of capillary-like structures by 45% (p = 0.05) compared with control cells. As it is known that angiostatin blocks hepatocyte growth factor (HGF)-induced pro-angiogenic signaling in endothelial cells due to structural similarities to HGF, we have analyzed if the plasminogen fragments generated by MMP-19 interfere with this pathway. As it involves the activation of c-met, the receptor of HGF, we could show that MMP-19-dependent processing of plasminogen decreases the phosphorylation of c-met.ConclusionAltogether, MMP-19 exhibits an anti-angiogenic effect on endothelial cells via generation of angiostatin-like fragments.
Chromosomal painting and ZW sex chromosomes differentiation in Characidium (Characiformes, Crenuchidae)
Authors: Machado Tatiana C , Pansonato-Alves José C , Pucci Marcela B , Nogaroto Viviane , Almeida Mara C , Oliveira Claudio , Foresti Fausto , Bertollo Luiz AC , Moreira-Filho Orlando , Artoni Roberto F , Vicari Marcelo R 
Published: July 2011

Abstract

Background
The Characidium (a Neotropical fish group) have a conserved diploid number (2n = 50), but show remarkable differences among species and populations in relation to sex chromosome systems and location of nucleolus organizer regions (NOR). In this study, we isolated a W-specific probe for the Characidium and characterized six Characidium species/populations using cytogenetic procedures. We analyzed the origin and differentiation of sex and NOR-bearing chromosomes by chromosome painting in populations of Characidium to reveal their evolution, phylogeny, and biogeography.

Results
A W-specific probe for efficient chromosome painting was isolated by microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR) amplification of W chromosomes from C. gomesi. The W probe generated weak signals dispersed on the proto sex chromosomes in C. zebra, dispersed signals in both W and Z chromosomes in C. lauroi and, in C. gomesi populations revealed a proximal site on the long arms of the Z chromosome and the entire W chromosome. All populations showed small terminal W probe sites in some autosomes. The 18S rDNA revealed distinctive patterns for each analyzed species/population with regard to proto sex chromosome, sex chromosome pair, and autosome location.

Conclusions
The results from dual-color fluorescence in situ hybridization (dual-color FISH) using W and 18S rDNA probes allowed us to infer the putative evolutionary pathways for the differentiation of sex chromosomes and NORs, from structural rearrangements in a sex proto-chromosome, followed by gene erosion and heterochromatin amplification, morphological differentiation of the sex chromosomal pair, and NOR transposition, giving rise to the distinctive patterns observed among species/populations of Characidium. Biogeographic isolation and differentiation of sex chromosomes seem to have played a major role in the speciation process in this group of fish.
Identification of a human immunodominant T-cell epitope of mycobacterium tuberculosis antigen PPE44
Authors: Cuccu Barbara , Freer Giulia , Genovesi Alessandro , Garzelli Carlo , Rindi Laura 
Published: July 2011

AbstractBackgroundRecently our group has identified a novel antigen ofMycobacterium tuberculosis, protein PPE44, belonging to the "PPE protein" family. Although its role in infection is largely unknown, PPE44-specific immune responses were detected in mice infected withM. tuberculosis; moreover, immunization of mice with PPE44 subunit vaccines resulted in protective efficacy comparable to the one afforded by BCG againstM. tuberculosis(Romanoet al., Vaccine 26, 6053-6063, 2008).ResultsIn the present paper, we investigated anti-PPE44 T-lymphocyte responses during human infection by evaluating the frequency of PPE44-specific interferon (IFN)-γ-secreting cells by ELISpot and flow cytometry in a small cohort of healthy subjects that had proven positive to PPD (PPD+)in vitro, in patients with active tuberculosis, in subjects vaccinated with BCG and in unvaccinated, PPD-healthy controls. We showed IFN-γ+T cell immune responses to recombinant PPE44 in at least a very high proportion of PPD+individuals tested and, to a lower extent, in subjects vaccinated with BCG. By the use of a panel of overlapping synthetic 20-mer peptides spanning the PPE44 primary amino acid sequence, we identified a strong CD4+T-cell epitope, encompassed by peptide p1L (VDFGALPPEVNSARMYGGAG), in the NH2-terminus of the PPE44 molecule at the amino acid position 1-20. Conversely, our experiments did not provide evidence of a significant IFN-γ+CD4+T cell response to PPE44 or its immunodominant peptide p1L in most (7 out of 8) patients with active TB.ConclusionsOur data suggest an important immunological role of PPE44 and its immunodominant epitope p1L that could be useful in the design of anti-tuberculosis vaccines and in the immunological diagnosis ofM. tuberculosisinfection.
Endotoxin-free purification for the isolation of Bovine Viral Diarrhoea Virus E2 protein from insoluble inclusion body aggregates
Authors: Cavallaro Antonino S , Mahony Donna , Commins Margaret , Mahony Timothy J , Mitter Neena 
Published: July 2011

Abstract

Background
Protein expression in Escherichia coli may result in the recombinant protein being expressed as insoluble inclusion bodies. In addition, proteins purified from E. coli contain endotoxins which need to be removed for in vivo applications. The structural protein, E2, from Bovine Viral Diarrhoea Virus (BVDV) is a major immunogenic determinant, and is an ideal candidate as a subunit vaccine. The E2 protein contains 17 cysteine residues creating difficulties in E. coli expression. In this report we outline a procedure for successfully producing soluble and endotoxin-free BVDV E2 protein from inclusion bodies (IB).

Results
The expression of a truncated form of BVDV-E2 protein (E2-T1) in E. coli resulted in predominantly aggregated insoluble IB. Solubilisation of E2-T1 with high purity and stability from IB aggregates was achieved using a strong reducing buffer containing 100 mM Dithiothreitol. Refolding by dialysis into 50 mM Tris (pH 7.0) containing 0.2% Igepal CA630 resulted in a soluble but aggregated protein solution. The novel application of a two-phase extraction of inclusion body preparations with Triton X-114 reduced endotoxin in solubilised E2-T1 to levels suitable for in vivo use without affecting protein yields. Dynamic light scattering analyses showed 37.5% of the protein was monomeric, the remaining comprised of soluble aggregates. Mice immunised with E2-T1 developed a high titre antibody response by ELISA. Western hybridisation analysis showed E2-T1 was recognised by sera from immunised mice and also by several BVDV-E2 polyclonal and monoclonal antibodies.

Conclusion
We have developed a procedure using E. coli to produce soluble E2-T1 protein from IB, and due to their insoluble nature we utilised a novel approach using Triton X-114 to efficiently remove endotoxin. The resultant protein is immunogenic and detectable by BVDV-E2 specific antibodies indicating its usefulness for diagnostic applications and as a subunit vaccine. The optimised E. coli expression system for E2-T1 combined with methodologies for solubilisation, refolding and integrated endotoxin removal presented in this study should prove useful for other vaccine applications.
Scaling analysis for the investigation of slip mechanisms in nanofluids
Authors: Savithiri S , Pattamatta Arvind , Das Sarit K 
Published: July 2011

Abstract
The primary objective of this study is to investigate the effect of slip mechanisms in nanofluids through scaling analysis. The role of nanoparticle slip mechanisms in both water- and ethylene glycol-based nanofluids is analyzed by considering shape, size, concentration, and temperature of the nanoparticles. From the scaling analysis, it is found that all of the slip mechanisms are dominant in particles of cylindrical shape as compared to that of spherical and sheet particles. The magnitudes of slip mechanisms are found to be higher for particles of size between 10 and 80 nm. The Brownian force is found to dominate in smaller particles below 10 nm and also at smaller volume fraction. However, the drag force is found to dominate in smaller particles below 10 nm and at higher volume fraction. The effect of thermophoresis and Magnus forces is found to increase with the particle size and concentration. In terms of time scales, the Brownian and gravity forces act considerably over a longer duration than the other forces. For copper-water-based nanofluid, the effective contribution of slip mechanisms leads to a heat transfer augmentation which is approximately 36% over that of the base fluid. The drag and gravity forces tend to reduce the Nusselt number of the nanofluid while the other forces tend to enhance it.
Molecular analysis of lipoid proteinosis: identification of a novel nonsense mutation in the ECM1 gene in a Pakistani family
Authors: Nasir Muhammad , Latif Amir , Ajmal Muhammad , Qamar Reem , Naeem Muhammad , Hameed Abdul 
Published: July 2011

AbstractLipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood that is caused by homozygous or compound heterozygous mutations in theECM1gene located on chromosome 1q21. The aim of the study was to investigate the molecular genetic defect underlying lipoid proteinosis in a consanguineous Pakistani family.MethodsGenotyping of seven members of the family was performed by amplifying microsatellite markers, tightly linked to theECM1gene. To screen for mutations in theECM1gene, all of its exons and splice junctions were PCR amplified from genomic DNA and analyzed by SSCP and sequenced directly in an ABI 3130 genetic analyzer.ResultsThe results revealed linkage of the LP family to theECM1locus. Sequence analysis of the coding exons and splice junctions of theECM1gene revealed a novel homozygous mutation (c.616C > T) in exon 6, predicted to replace glutamine with stop codon (p.Q206X) at amino acid position 206.ConclusionsThe finding of a novel mutation in Pakistani family extends the body of evidence that supports the importance ofECM1gene for the development of lipoid proteinosis.
Time and frequency domain analysis of heart rate variability in cattle affected by bovine spongiform encephalopathy
Authors: Konold Timm , Bone Gemma E , Simmons Marion M 
Published: July 2011

AbstractBackgroundHeart rate variability (HRV) analysis is a method to assess the function of the autonomic nervous system. Brainstem nuclei that influence HRV are affected by vacuolar changes and accumulation of disease-associated prion protein (PrPd) in bovine spongiform encephalopathy (BSE) resulting in clinical signs suggestive of an increased parasympathetic tone. It was hypothesised that BSE in cattle causes changes in the autonomic nervous system; this was tested by comparing HRV indices derived from 1048 electrocardiograms, which were recorded from 51 naturally or experimentally infected cattle with BSE confirmed by postmortem tests, 321 clinical suspect cases or cattle inoculated with potentially infectious tissue without disease confirmation and 78 BSE-free control cattle.FindingsStatistically significant differences were found for low or high frequency power, their normalised values and ratio when the last recording prior to cull or repeated recordings were compared but only between male and female cattle of the three groups and not between groups of the same gender, even though BSE cases of each gender appeared to be more nervous during the recording. The same findings were made for heart rate, deviation from the mean RR interval and vasovagal tonus index when repeated recordings were compared. BSE cases with severe vacuolar changes in the parasympathetic nucleus of the vagus nerve had a significantly lower low:high frequency power ratio but not a lower heart rate than BSE cases with mild vacuolation, whereas severity of vacuolar changes in the solitary tract nucleus or intensity of PrPdaccumulation in both nuclei did not appear to have any affect on either index. Abnormalities in the electrocardiogram were detected in 3% of the recordings irrespective of the BSE status; sinus arrhythmia was present in 93% of the remaining recordings.ConclusionsHRV analysis was not useful to distinguish BSE-positive from BSE-negative cattle grouped by gender, and HRV indices appeared to be mainly influenced by gender. There is agreement with earlier studies that vacuolar changes in the brainstem may be associated with an increased parasympathetic tone in BSE and that abnormalities in an electrocardiogram can be detected in cattle without evidence of heart disease.