bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Cluster-Randomized Effectiveness Trial of a Physician-Pharmacist Collaborative Model to Improve Blood Pressure Control
Authors: Carter Barry L. , Clarke William , Ardery Gail , Weber Cynthia A. , James Paul A. , Vander Weg Mark , Chrischilles Elizabeth A. , Vaughn Thomas , Egan Brent M. ,   on behalf of the Collaboration Among Pharmacists Physicians To Improve Outcomes Now (CAPTION) Trial Investigators*
Published: July 2010

Abstract—
Numerous studies have demonstrated the value of team-based care to improve blood pressure (BP) control, but there is limited information on whether these models would be adopted in diverse populations. The purpose of this study was to evaluate whether a collaborative model between physicians and pharmacists can improve BP control in multiple primary care medical offices with diverse geographic and patient characteristics and whether long-term BP control can be sustained. This study is a randomized prospective trial in 27 primary care offices first stratified by the percentage of underrepresented minorities and the level of clinical pharmacy services within the office. Each office is then randomized to either a 9- or 24-month intervention or a control group. Patients will be enrolled in this study until 2012. The results of this study should provide information on whether this model can be implemented in large numbers of diverse offices, if it is effective in diverse populations, and whether BP control can be sustained long term.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00935077.
Implementing IT in SCM—Understanding the Challenges
Authors: Mehrotra Ankit 
Published: July 2010

Technology offers the potential to change supply chain networks and processes to reduce non-value adding time spent and to support alternative ways of working. An efficient supply chain network can offer substantial improvements in productivity and in customer satisfaction by making available online, real-time information networked around the organization, giving full supply chain visibility. Thus, information is shared within and between the organization and decisions are made on the basis of this shared information. The technology needed to promote and support change, be it large or small, strategic or operational, if used appropriately offers the chance to improve supply chain, in turn, leading to increased productivity and profitability. However, despite the benefits associated with it, implementation of this technology is not always easy. The present study has been undertaken to understand the challenges faced in implementing information technology (IT)in supply chain management (SCM)and logistics. The study was conducted using the survey method. Data was collected through a structured questionnaire from a sample of 80 Indian companies. Perception map and discriminant analysis were used as the tools of analysis.
Becoming a pastor
Authors: Lauterbach Karen 
Published: July 2010

Ghana, like a number of other African countries, witnesses an increasing number of smaller independent Pentecostal churches founded by young pastors. These young pastors engage in pastoral careers as a way to achieve social mobility. It is an attractive career path for many young people as it offers opportunities of ascending religious and social hierarchies in a situation where the more conventional modes of achieving success, through education and employment as civil servant, are decreasing. By exploring the careers of young pastors, the article discusses how this particular group of youth are innovative and entrepreneurial in the sense that they create spaces, where they can build up status and where this status is socially recognized. At the same time the young pastors are dependent on more senior pastors in order to make a career. This points to the importance of approaching youth from the perspective of generational dynamics. The argument is that in order to become successful pastors, young people have to engage in complex relations of dependency and at the same time be innovative. A religious setting, like the small independent Pentecostal churches, enables young people to be involved in and transcend these generational relations by drawing on powerful religious repertoires of invoking and claiming access to divine powers.
Impaired Epstein-Barr virus–specific CD8+ T-cell function in X-linked lymphoproliferative disease is restricted to SLAM family–positive B-cell targets
Authors: Hislop Andrew D. , Palendira Umaimainthan , Leese Alison M. , Arkwright Peter D. , Rohrlich Pierre S. , Tangye Stuart G. , Gaspar H. Bobby , Lankester Arjan C. , Moretta Alessandro , Rickinson Alan B. 
Published: July 2010

AbstractX-linked lymphoproliferative disease (XLP) is a condition associated with mutations in the signaling lymphocytic activation molecule (SLAM)–associated protein (SAP; SH2D1A). SAP functions as an adaptor, binding to and recruiting signaling molecules to SLAM family receptors expressed on T and natural killer cells. XLP is associated with extreme sensitivity to primary Epstein-Barr virus (EBV) infection, often leading to a lethal infectious mononucleosis. To investigate EBV-specific immunity in XLP patients, we studied 5 individuals who had survived EBV infection and found CD8+ T-cell responses numerically comparable with healthy donors. However, further investigation of in vitro–derived CD8+ T-cell clones established from 2 of these donors showed they efficiently recognized SLAM ligand–negative target cells expressing EBV antigens, but showed impaired recognition of EBV-transformed, SLAM ligand–positive, lymphoblastoid cell lines (LCLs). Importantly, LCL recognition was restored when interactions between the SLAM receptors CD244 and natural killer–, T-, and B-cell antigen (NTBA) and their ligands on LCLs were blocked. We propose that XLP patients' particular sensitivity to EBV, and not to other viruses, reflects at least in part EBV's strict tropism for B lymphocytes and the often inability of the CD8+ T-cell response to contain the primary infection of SLAM ligand–expressing target cells.
Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells
Authors: Gieseke Friederike , Böhringer Judith , Bussolari Rita , Dominici Massimo , Handgretinger Rupert , Müller Ingo 
Published: July 2010

Abstract
Human multipotent mesenchymal stromal cells (MSCs) suppress proliferation and alloreactivity of T cells. Several signaling molecules and enzymes contribute to this effect. We focused on carbohydrate-protein interactions and investigated whether lectins are involved in immune modulation by MSC. Gene expression profiling of MSCs revealed that one of the most important lectins in this setting, galectin-1, was highly expressed. Galectin-1 protein was detected intracellularly and on the cell surface of MSCs. In addition, galectin-1 was released into the cell culture supernatant by MSCs. To analyze the functional role of galectin-1, a stable knockdown of galectin-1 in MSCs with use of a retroviral transfection system was established. Galectin-1 knockdown in MSCs resulted in a significant loss of their immunomodulatory properties, compared with MSCs infected with nontargeting control sequences. The galectin-1 knockdown partially restored the proliferation of CD4+ and CD8+ T cells. By contrast, the effect of MSCs on nonalloreactive natural killer (NK) cells was unaffected by down-regulation of galectin-1 expression. Furthermore, MSC-derived galectin-1 significantly modulated the release of cytokines involved in graft-versus-host disease (GVHD) and autoimmunity (eg, tumor necrosis factor-α [TNFα], IFNγ, interleukin-2 [IL-2], and IL-10. These results identify galectin-1 as the first lectin mediating the immunomodulatory effect of MSCs on allogeneic T cells.
Shiga toxin B subunits induce VWF secretion by human endothelial cells and thrombotic microangiopathy in ADAMTS13-deficient mice
Authors: Huang Jing , Motto David G. , Bundle David R. , Sadler J. Evan 
Published: July 2010

AbstractDiarrhea–associated hemolytic uremic syndrome (D+HUS) is the most common cause of acute renal failure among children. Renal damage in D+HUS is caused by Shiga toxin (Stx), which is elaborated by Shigella dysenteriae and certain strains of Escherichia coli, in North America principally E coli O157:H7. Recent studies demonstrate that Stx also induces von Willebrand factor (VWF) secretion by human endothelial cells and causes thrombotic thrombocytopenic purpura, a disease with similarities to D+HUS, in Adamts13−/− mice. Stx occurs in 2 variants, Stx1 and Stx2, each of which is composed of 1 catalytically active A subunit that is responsible for cytotoxicity, and 5 identical B subunits that mediate binding to cell-surface globo-triaosylceramide. We now report that B subunits from Stx1 or Stx2 can stimulate the acute secretion of VWF in the absence of the cytotoxic A subunit. This rapid effect requires binding and clustering of globotriaosylceramide, and depends on plasma membrane cholesterol and caveolin-1 but not clathrin. Furthermore, similar to Stx2 holotoxin, the isolated Stx2B subunits induce thrombotic microangiopathy in Adamts13−/− mice. These results demonstrate the existence of a novel Stx B-induced lipid raft–dependent signaling pathway in endothelial cells that may be responsible for some of the biological effects attributed previously to the cytotoxic Stx A subunit.
IgA-mediated human autoimmune hemolytic anemia as a result of hemagglutination in the spleen, but independent of complement activation and FcαRI
Authors: Chadebech Philippe , Michel Marc , Janvier Daniel , Yamada Kazunori , Copie-Bergman Christiane , Bodivit Gwellaouen , Bensussan Armand , Fournie Jean-Jacques , Godeau Bertrand , Bierling Philippe , Izui Shozo , Noizat-Pirenne France 
Published: July 2010

AbstractAutoimmune hemolytic anemia (AIHA) due to warm-acting IgA autoantibodies is rare. We explored the pathogenic mechanisms underlying destruction of red blood cells (RBCs) in a patient with severe AIHA mediated exclusively by polymeric immunoglobulin A (pIgA) anti-Band 3 autoantibodies. The follow-up period was 17 months. RBCs were not destroyed by complement activation as no deposition of complement was observed on the patient's RBCs. pIgA eluted from the patient's RBCs did not induce RBC destruction through phagocytosis by monocytes or antibody–dependent cell–mediated cytotoxicity by natural killer cells. Induction of eryptosis (ie, RBC apoptosis) due to direct alteration of the RBC membrane by pIgA autoantibodies was also excluded. By contrast, upon incubation with pIgA-opsonized RBCs, substantial RBC membrane transfers (ie, trogocytosis) to monocytes were observed that might contribute to RBC immune destruction. This effect was poorly inhibited by blockers of Fc receptors, excluding a major contribution of FcαRI to this process. Histologic analysis revealed a massive accumulation of agglutinated RBCs with little sign of erythrophagocytosis in the spleen. These results, together with the efficacy of splenectomy 17 months after AIHA onset, suggest that the trapping and subsequent sequestration of agglutinated RBCs in the spleen are the principal pathogenic mechanisms of pIgA-mediated AIHA.
Vesicle trafficking plays a novel role in erythroblast enucleation
Authors: Keerthivasan Ganesan , Small Sara , Liu Hui , Wickrema Amittha , Crispino John D. 
Published: July 2010

Abstract
Enucleation of mammalian erythroblasts is a process whose mechanism is largely undefined. The prevailing model suggests that nuclear extrusion occurs via asymmetric cytokinesis. To test this hypothesis, we treated primary erythroblasts with inhibitors of cytokinesis, including blebbistatin, hesperadin, and nocodazole, and then assayed for enucleation. Although these agents inhibited cell-cycle progression and subsequent enucleation when added early in culture, they failed to block enucleation proper when added to postmitotic cells. These results suggest that contraction of the actomyosin ring is not essential for nuclear expulsion. Next, by ultrastructural examination of primary erythroblasts, we observed an accumulation of vacuoles in the cytoplasm proximal to the extruding nucleus. This finding led us to hypothesize that vesicle trafficking contributes to erythroblast enucleation. Here, we show that chemical inhibitors of vesicle trafficking block enucleation of primary erythroblasts without affecting differentiation, cell division, or apoptosis. Moreover, knock-down of clathrin inhibited the enucleation of late erythroblasts. In contrast, vacuolin-1, a small molecule that induces vacuole formation, increased the percentage of enucleated cells. Together, these results illustrate that vesicle trafficking, specifically the formation, movement, and subsequent coalescence of vacuoles at the junction of the nucleus and the cytoplasm, is a critical component of mammalian erythroblast enucleation.
The combination of high-sensitivity cardiac troponin T (hs-cTnT) at presentation and changes in N-terminal natriuretic peptide type B (NT-proBNP) after chemotherapy best predicts survival in AL amyloidosis
Authors: Palladini Giovanni , Barassi Alessandra , Klersy Catherine , Pacciolla Rosana , Milani Paolo , Sarais Gabriele , Perlini Stefano , Albertini Riccardo , Russo Paola , Foli Andrea , Bragotti Letizia Zenone , Obici Laura , Moratti Remigio , Melzi d'Eril Gian Vico , Merlini Giampaolo 
Published: July 2010

AbstractIn light-chain (AL) amyloidosis, prognosis is dictated by cardiac dysfunction. N-terminal natriuretic peptide type B (NT-proBNP) and cardiac troponins (cTn) are used to assess the severity of cardiac damage. We evaluated the prognostic relevance of a high-sensitivity (hs) cTnT assay, NT-proBNP, and cardiac troponin I in 171 consecutive patients with AL amyloidosis at presentation and 6 months after treatment. Response and progression of NT-proBNP were defined as more than 30% and more than 300 ng/L changes. All 3 markers predicted survival, but the best multivariable model included hs-cTnT. The hs-cTnT prognostic cutoff was 77 ng/L (median survival 10.6 months for patients with hs-cTnT above the cutoff). After treatment, response and progression of NT-proBNP and a more than 75% increase of hs-cTnT were independent prognostic determinant. In AL amyloidosis, hs-cTnT is the best baseline prognostic marker. Therapy should be aimed at preventing progression of cardiac biomarkers, whereas NT-proBNP response confers an additional survival benefit.
Differentially regulated GPVI ectodomain shedding by multiple platelet–expressed proteinases
Authors: Bender Markus , Hofmann Sebastian , Stegner David , Chalaris Athena , Bösl Michael , Braun Attila , Scheller Jürgen , Rose-John Stefan , Nieswandt Bernhard 
Published: July 2010

AbstractGlycoprotein VI (GPVI) mediates platelet activation on exposed subendothelial collagens at sites of vascular injury and thereby contributes to normal hemostasis, but also to the occlusion of diseased vessels in the setting of myocardial infarction or stroke. GPVI is an attractive target for antithrombotic therapy, particularly because previous studies have shown that anti-GPVI antibodies induce irreversible down-regulation of the receptor in circulating platelets by internalization and/or ectodomain shedding. Metalloproteinases of the a disintegrin and metalloproteinase (ADAM) family have been proposed to mediate this ectodomain shedding, but direct evidence for this is lacking. Here, we studied GPVI shedding in vitro and in vivo in newly generated mice with a megakaryocyte–specific ADAM10 deficiency and in Adam17ex/ex mice, which lack functional ADAM17. We demonstrate that GPVI cleavage in vitro can occur independently through either ADAM10 or ADAM17 in response to distinct stimuli. In contrast, antibody (JAQ1)–induced GPVI shedding in vivo occurred in mice lacking both ADAM10/ADAM17 in their platelets, suggesting the existence of a third GPVI cleaving platelet enzyme. This was supported by in vitro studies on ADAM10/ADAM17 double–deficient platelets. These results reveal that ectodomain shedding of GPVI can be mediated through multiple differentially regulated platelet–expressed proteinases with obvious therapeutic implications.
EPSVR and EPMeta: prediction of antigenic epitopes using support vector regression and multiple server results
Authors: Liang Shide , Zheng Dandan , Standley Daron M , Yao Bo , Zacharias Martin , Zhang Chi 
Published: July 2010

Abstract

Background
Accurate prediction of antigenic epitopes is important for immunologic research and medical applications, but it is still an open problem in bioinformatics. The case for discontinuous epitopes is even worse - currently there are only a few discontinuous epitope prediction servers available, though discontinuous peptides constitute the majority of all B-cell antigenic epitopes. The small number of structures for antigen-antibody complexes limits the development of reliable discontinuous epitope prediction methods and an unbiased benchmark to evaluate developed methods.

Results
In this work, we present two novel server applications for discontinuous epitope prediction: EPSVR and EPMeta, where EPMeta is a meta server. EPSVR, EPMeta, and datasets are available at http://sysbio.unl.edu/services.

Conclusion
The server application for discontinuous epitope prediction, EPSVR, uses a Support Vector Regression (SVR) method to integrate six scoring terms. Furthermore, we combined EPSVR with five existing epitope prediction servers to construct EPMeta. All methods were benchmarked by our curated independent test set, in which all antigens had no complex structures with the antibody, and their epitopes were identified by various biochemical experiments. The area under the receiver operating characteristic curve (AUC) of EPSVR was 0.597, higher than that of any other existing single server, and EPMeta had a better performance than any single server - with an AUC of 0.638, significantly higher than PEPITO and Disctope (p-value < 0.05).
Aquaporins in the wild: natural genetic diversity and selective pressure in the PIP gene family in five Neotropical tree species
Authors: Audigeos Delphine , Buonamici Anna , Belkadi Laurent , Rymer Paul , Boshier David , Scotti-Saintagne Caroline , Vendramin Giovanni G , Scotti Ivan 
Published: July 2010

Abstract

Background
Tropical trees undergo severe stress through seasonal drought and flooding, and the ability of these species to respond may be a major factor in their survival in tropical ecosystems, particularly in relation to global climate change. Aquaporins are involved in the regulation of water flow and have been shown to be involved in drought response; they may therefore play a major adaptive role in these species. We describe genetic diversity in the PIP sub-family of the widespread gene family of Aquaporins in five Neotropical tree species covering four botanical families.

Results
PIP Aquaporin subfamily genes were isolated, and their DNA sequence polymorphisms characterised in natural populations. Sequence data were analysed with statistical tests of standard neutral equilibrium and demographic scenarios simulated to compare with the observed results. Chloroplast SSRs were also used to test demographic transitions. Most gene fragments are highly polymorphic and display signatures of balancing selection or bottlenecks; chloroplast SSR markers have significant statistics that do not conform to expectations for population bottlenecks. Although not incompatible with a purely demographic scenario, the combination of all tests tends to favour a selective interpretation of extant gene diversity.

Conclusions
Tropical tree PIP genes may generally undergo balancing selection, which may maintain high levels of genetic diversity at these loci. Genetic variation at PIP genes may represent a response to variable environmental conditions.
Relationship between EGFR expression, copy number and mutation in lung adenocarcinomas
Authors: Liang Zhiyong , Zhang Jing , Zeng Xuan , Gao Jie , Wu Shafei , Liu Tonghua 
Published: July 2010

AbstractBackgroundThis study was designed to investigate EGFR protein expression, EGFR copy number and EGFR mutations in lung adenocarcinomas, to explore the relationship of the three markers.MethodsEGFR status was analyzed in surgically resected lung adenocarcinoma samples from 133 Chinese patients by three methods: protein expression (n = 133) by standardized immunohistochemistry (IHC), gene copy number (n = 133) by fluorescence in situ hybridization (FISH), and mutation analysis using the Scorpion amplification refractory mutation system (ARMS) (n = 133).ResultsThe results showed that 68.4% of the samples were positive by IHC, 42.1% were positive by FISH, and 63.9% contained activating kinase domain mutations. EGFR mutations were more frequent in non-smoking patients (p = 0.008), and EGFR mutations were associated with EGFR FISH positivity (p < 0.0001). When using 10% positivity and 2+ as cutoffs, EGFR protein expression was significantly correlated with EGFR FISH positivity (p = 0.012) and EGFR mutations (p = 0.008) after Bonferroni correction.ConclusionEGFR protein expression, EGFR copy number and EGFR mutations were closely related to each other. Standard methods and interpretation criteria need to be established.
Hind limb unloading of mice modulates gene expression at the protein and mRNA level in mesenchymal bone cells
Authors: Visigalli Davide , Strangio Antonella , Palmieri Daniela , Manduca Paola 
Published: July 2010

Abstract

Background
We investigated the extent, modalities and reversibility of changes at cellular level in the expression of genes and proteins occurring upon Hind limb unloading (HU) in the tibiae of young C57BL/6J male mice. We focused on the effects of HU in chondrogenic, osteogenic, and marrow mesenchymal cells.

Methods
We analyzed for expression of genes and proteins at two time points after HU (7 and 14 days), and at 14 days after recovery from HU. Levels of mRNAs were tested by in situ hybridization. Protein levels were tested by immunohistochemistry. We studied genes involved in osteogenesis (alkaline phosphatase (AP), osteocalcin (OC), bonesialoprotein (BSP), membrane type1 matrix metalloproteinase (MT1-MMP)), in extracellular matrix (ECM) formation (procollagenases (BMP1), procollagenase enhancer proteins (PCOLCE)) and remodeling (metalloproteinase-9 (MMP9), RECK), and in bone homeostasis (Stro-1, CXCL12, CXCR4, CD146).

Results
We report the following patterns and timing of changes in gene expression induced by HU: 1) transient or stable down modulations of differentiation-associated genes (AP, OC), genes of matrix formation, maturation and remodelling, (BMP1, PCOLCEs MMP9) in osteogenic, chondrogenic and bone marrow cells; 2) up modulation of MT1-MMP in these same cells, and uncoupling of its expression from that of AP; 3) transient down modulation of the osteoblast specific expression of BSP; 4) for genes involved in bone homeostasis, up modulation in bone marrow cells at distal epiphysis for CXCR4, down modulation of CXCL12, and transient increases in osteoblasts and marrow cells for Stro1. 14 days after limb reloading expression returned to control levels for most genes and proteins in most cell types, except AP in all cells, and CXCL12, only in bone marrow.

Conclusions
HU induces the coordinated modulation of gene expression in different mesenchymal cell types and microenvironments of tibia. HU also induces specific patterns of expression for homeostasis related genes and modulation of mRNAs and proteins for ECM deposition, maturation and remodeling which may be key factors for bone maintenance.