bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome, Use of Resources and Their Relationship in the Treatment of AMI, Stroke and Hip Fracture at European Hospitals
Authors: Häkkinen Unto , Rosenqvist Gunnar , Iversen Tor , Rehnberg Clas , Seppälä Timo T. ,   on behalf of the EuroHOPE study group
Published: December 2015

AbstractThe aim of the present study was to compare the quality (survival), use of resources and their relationship in the treatment of three major conditions (acute myocardial infarction (AMI), stroke and hip fracture), in hospitals in five European countries (Finland, Hungary, Italy, Norway and Sweden). The comparison of quality and use of resources was based on hospital‐level random effects models estimated from patient‐level data. After examining quality and use of resources separately, we analysed whether a cost–quality trade‐off existed between the hospitals. Our results showed notable differences between hospitals and countries in both survival and use of resources. Some evidence would support increasing the horizontal integration: higher degrees of concentration of regional AMI care were associated with lower use of resources. A positive relation between cost and quality in the care of AMI patients existed in Hungary and Finland. In the care of stroke and hip fracture, we found no evidence of a cost–quality trade‐off. Thus, the cost–quality association was inconsistent and prevailed for certain treatments or patient groups, but not in all countries. Copyright © 2015 John Wiley & Sons, Ltd.
Phase 1 Study of ABT‐751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer
Authors: Rudek Michelle A. , Dasari Arvind , Laheru Daniel , He Ping , Jin Runyan , Walker Rosalind , Taylor Gretchen E. , Jimeno Antonio , Donehower Ross C. , Hidalgo Manuel , Messersmith Wells A. , Purcell W. Thomas 
Published: December 2015

AbstractABT‐751 is an orally bioavailable sulfonamide with antimitotic properties. A nonrandomized phase 1 dose‐escalation study of ABT‐751 in combination with CAPIRI (capecitabine and irinotecan) and bevacizumab was conducted to define the maximum tolerated dose, dose‐limiting toxicity (DLT), and pharmacokinetics in patients with advanced colorectal cancer. Patients were treated with ABT‐751 daily for 7 days (alone) and then began 21‐day cycles of treatment with ABT‐751 daily and capecitabine twice daily for 14 days plus irinotecan on day 1 intravenously. Bevacizumab was added as standard of care at 7.5 mg/kg on day 1 after the first 2 dose levels. Because of intolerance to the regimen, a reduced dose of ABT‐751 was also explored with reduced‐dose and full‐dose CAPIRI with bevacizumab. ABT‐751 and irinotecan pharmacokinetics, ABT‐751 glucuronidation, and protein binding were explored. Twenty‐four patients were treated over 5 dose levels. The maximum tolerated dose was ABT‐751 125 mg combined with full‐dose CAPIRI and bevacizumab 7.5 mg/kg on day 1. DLTs were hypokalemia, elevated liver tests, and febrile neutropenia. ABT‐751 is metabolized by UGT1A8 and to a lesser extent UGT1A4 and UGT1A1. Irinotecan and APC exposure were increased, SN‐38 exposure was similar, and SN‐38 glucuronide exposure was decreased. Clinically relevant alterations in ABT‐751 and irinotecan pharmacokinetics were not observed. Despite modest efficacy, the combination of ABT‐751, CAPIRI, and bevacizumab will not be studied further in colorectal cancer.
Comparison of natural crosslinking agents for the stabilization of xenogenic articular cartilage
Authors: Pinheiro Amanda , Cooley Avery , Liao Jun , Prabhu Rajkumar , Elder Steven 
Published: December 2015

ABSTRACTOsteochondral xenografts are potentially inexpensive, widely available alternatives to fresh allografts. However, antigen removal from xenogenic cartilage may damage the extracellular matrix and reduce compressive stiffness. Non‐crosslinked xenogenic cartilage may also undergo rapid enzymatic degradation in vivo. We hypothesized that natural crosslinking agents could be used in place of glutaraldehyde to improve the mechanical properties and enzymatic resistance of decellularized cartilage. This study compared the effects of genipin (GNP), proanthocyanidin (PA), and epigallocatechin gallate (EGCG), on the physical and mechanical properties of decellularized porcine cartilage. Glutaraldehyde (GA) served as a positive control. Porcine articular cartilage discs were decellularized in 2% sodium dodecyl sulfate and DNase I followed by fixation in 0.25% GNP, 0.25% PA, 0.25% EGCG, or 2.5% GA. Decellularization decreased DNA by 15% and GAG by 35%. For natural crosslinkers, the average degree of crosslinking ranged from approximately 50% (EGCG) to 78% (GNP), as compared to 83% for the GA control. Among the natural crosslinkers, only GNP significantly affected the disc diameter, and shrinkage was under 2%. GA fixation had no significant effect on disc diameter. Decellularization decreased aggregate modulus; GA and GNP, but not EGCG and PA, were able to restore it to its original level. GNP, PA, and GA conferred a similar, almost complete resistance to collagenase degradation. EGCG also conferred substantial resistance but to a lesser degree. Overall, the data support our hypothesis and suggest that natural crosslinkers may be suitable alternatives to glutaraldehyde for stabilization of decellularized cartilage. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1037–1046, 2016.
Thermomechanical Properties and Shape‐Memory Behavior of Bisphenol A Diacrylate‐Based Shape‐Memory Polymers
Authors: Santiago David , De la Flor Silvia , Ferrando Francesc , Ramis Xavier , Sangermano Marco 
Published: December 2015

A series of acrylate‐based shape‐memory materials are synthesized from bisphenol A diacrylate monomers as crosslinking agents. Networks are synthesized by keeping constant the content of bisphenol A‐based crosslinking agent and systematically varying the content ratio of different monofunctional chain builder monomers. The implications of the structure of bisphenol A‐based monomers and the chemical structure and content of monofunctional monomers on thermomechanical properties are discussed. Thermomechanical properties are analyzed using dynamic mechanical analyses and mechanical properties are studied at room temperature and at the onset of the glass transition temperature. Shape‐memory performances under isothermal and transient temperature conditions are also carried out. Tensile tests show excellent values of stress at break up to 45 and 15 MPa at room and high temperature, respectively. The measurements show excellent shape recovery and shape fixity ratios, ≈95% and 97%, respectively. These materials also show very high recovery velocities under transient temperature conditions, up to 24% min−1, and very short recovery times, up to 1.5 s, under isothermal conditions in a water bath. The results confirm that networks synthesized from bisphenol A crosslinkers are promising shape‐memory materials.image
Block of CDK1‐dependent polyadenosine elongation of Cyclin B mRNA in metaphase‐i‐arrested starfish oocytes is released by intracellular pH elevation upon spawning
Authors: Ochi Hiroe , Aoto Saki , Tachibana Kazunori , Hara Masatoshi , Chiba Kazuyoshi 
Published: December 2015

SUMMARYMeiotic progression requires the translation of maternal mRNAs in a strict temporal order. In isolated animal oocytes, translation of maternal mRNAs containing a cytoplasmic polyadenylation element (CPE), such as cyclin B, is activated by in vitro stimulation of meiotic resumption which induces phosphorylation of CPEB (CPE‐binding protein) and elongation of their polyadenosine (poly(A)) tails; whether or not this model can be applied in vivo to oocytes arrested at metaphase of meiosis I in ovaries is unknown. In this study, we found that active CDK1 (cyclin‐dependent kinase 1) phosphorylated CPEB in ovarian oocytes arrested at metphase I in the starfish body cavity, but phosphorylation of CPEB was not sufficient for elongation of cyclin B poly(A) tails. Immediately after spawning, however, mRNA was polyadenylated, suggesting that an increase in intracellular pH (pHi) upon spawning triggers the elongation of poly(A) tails. Using a cell‐free system made from maturing oocytes at metaphase I, we demonstrated that polyadenylation was indeed suppressed at pH below 7.0. These results suggest that a pH‐sensitive process, functioning after CPEB phosphorylation, is blocked under physiologically low pHi (<7.0) in metaphase‐I‐arrested oocytes. The increase in pHi (>7.0) that occurs after spawning triggers polyadenylation of cyclin B mRNA and progression into meiosis II. Mol. Reprod. Dev. 83: 79–87, 2016. © 2015 Wiley Periodicals, Inc.
Nop2 is required for mammalian preimplantation development
Authors: Cui Wei , Pizzollo Jason , Han Zhengbin , Marcho Chelsea , Zhang Kun , Mager Jesse 
Published: December 2015

SUMMARYNucleolar protein 2 (NOP2) is evolutionarily conserved from yeast to human, and has been found to play an important role in accelerating cell proliferation, cell‐cycle progression, and tumor aggressiveness. The expression pattern and function of Nop2 during early mammalian embryo development, however, has not been investigated. We identified Nop2 as an essential gene for development to the blastocyst stage while performing an RNA interference (RNAi)‐based screen in mouse preimplantation embryos. Nop2 is expressed throughout preimplantation development, with highest mRNA and protein accumulation at the 8‐cell and morula stages, respectively. RNAi‐mediated knockdown of Nop2 results in embryos that arrest as morula. NOP2‐deficient embryos exhibit reduced blastomere numbers, greatly increased apoptosis, and impaired cell‐lineage specification. Furthermore, knockdown of Nop2 results in global reduction of all RNA species, including rRNA, small nuclear RNA, small nucleolar RNA, and mRNA. Taken together, our results demonstrate that Nop2 is an essential gene for blastocyst formation, and is required for RNA processing and/or stability in vivo during preimplantation embryo development in the mouse. Mol. Reprod. Dev. 83: 124–131, 2016. © 2015 Wiley Periodicals, Inc.
Further evidence of the involvement of the Wnt signaling pathway in Dupuytren’s disease
Authors: ten Dam Evert-Jan P. M. , van Beuge Marike M. , Bank Ruud A. , Werker Paul M. N. 
Published: December 2015

AbstractGenetic background plays an important role in the development of Dupuytren’s disease. A genome-wide association study (GWAS) showed that nine loci are associated with the disease, six of which contain genes that are involved in Wnt signaling (WNT2, WNT4, WNT7B, RSPO2, SFRP4, SULF1). To obtain insight in the role of these genes, we performed expression studies on affected and unaffected patient’s tissues. Surgically obtained nodules and cords from eight Dupuytren’s patients were compared to patient-matched control tissue (unaffected transverse palmar fascia). The Wnt-related genes found in the GWAS, the classical Wnt-downstream protein β-catenin, as well as (myo)fibroblast markers were analyzed using real-time qPCR and immunohistochemical stainings for mRNA levels and protein levels, respectively. The collagen-coding genes COL1A1 and COL3A1 were highly upregulated on mRNA level, both in cords and nodules. Three Wnt-related genes were found to be differently regulated compared to control tissue: WNT2 was downregulated in nodules, WNT7B was upregulated in nodules, and SFRP4 was upregulated in nodules and cords. Immunohistochemistry revealed significantly less staining of Wnt2 in cords, but significantly more staining for Wnt7b in nodules. There was significantly more staining of α-SMA in nodules and cord and β-catenin in nodules than in control tissue. We found differences in expression, both at mRNA and protein level, in several Wnt-related genes found earlier to be associated with Dupuytren’s disease. Of these, Wnt7b was upregulated and found in close association with both α-SMA and β-catenin expressing cells, making it a candidate pro-fibrotic mediator in Dupuytren’s disease.
1,25‐Dihydroxyvitamin D3 exerts neuroprotective effects in an ex vivo model of mild hyperhomocysteinemia
Authors: Longoni Aline , Kolling Janaina , dos Santos Tiago M. , dos Santos João Paulo , da Silva Jussemara Souza , Pettenuzzo Letícia , Gonçalves Carlos‐Alberto , de Assis Adriano M. , Quincozes‐Santos André , Wyse Angela T.S. 
Published: December 2015

AbstractElevated plasma homocysteine (Hcy) levels have been detected in patients with various neurodegenerative conditions. Studies of brain tissue have revealed that hyperhomocysteinemia may impair energy metabolism, resulting in neuronal damage. In addition, new evidence has indicated that vitamin D plays crucial roles in brain development, brain metabolism and neuroprotection. The aim of this study was to investigate the neuroprotective effects of 1,25‐dihydroxivitamin D3 (calcitriol) in cerebral cortex slices that were incubated with a mild concentration of Hcy. Cerebral cortex slices from adult rats were first pre‐treated for 30 min with one of three different concentrations of calcitriol (50 nM, 100 nM and 250 nM), followed by Hcy for 1 h to promote cellular dysfunction. Hcy caused changes in bioenergetics parameters (e.g., respiratory chain enzymes) and mitochondrial functions by inducing changes in mitochondrial mass and swelling. Here, we used flow cytometry to analyze neurons that were double‐labelled with Propidium Iodide (PI) and found that Hcy induced an increase in NeuN+/PI cells but did not affect GFAP+/Pi cells. Hcy also induced oxidative stress by increasing reactive oxygen species generation, lipid peroxidation and protein damage and reducing the activity of antioxidant enzymes (e.g., SOD, CAT and GPx). Calcitriol (50 nM) prevented these alterations by increasing the level of the vitamin D receptor. Our findings suggest that using calcitriol may be a therapeutic strategy for treating the cerebral complications caused by Hcy.
The black and the red: Shanks & Tilley's programme for a radical archaeology
Authors: Kristiansen Kristian 
Published: December 2015

Prominent in the new literature of a ‘post-processual’, ‘critical’ or ‘radical’ archaeology are a pair of books, conveniently colour-coded as one black and one red, written by Michael Shanks 6. Christopher Tilley, and both published in 1987. The ‘black book’, from Cambridge University Press, has a stark cover mostly of solid black; the cover of the ‘red book’, from Polity Press, is a more cheerful crimson, though its picture, a 19th-century Comedy of death, is a despairing image of dismal decay.Kristian Kristiansen, of the Center for Research in the Humanities, University of Copenhagen, reviews here the black and the red, and the post-modern vision of archaeology they amount to.
Imposed magnetic field and hot electron propagation in inertial fusion hohlraums
Authors: Strozzi David J. , Perkins L. J. , Marinak M. M. , Larson D. J. , Koning J. M. , Logan B. G. 
Published: December 2015

The effects of an imposed, axial magnetic field $B_{z0}$ on hydrodynamics and energetic electrons in inertial confinement fusion indirect-drive hohlraums are studied. We present simulations from the radiation-hydrodynamics code HYDRA of a low-adiabat ignition design for the National Ignition Facility, with and without $B_{z0}=70~\text{T}$. The field’s main hydrodynamic effect is to significantly reduce electron thermal conduction perpendicular to the field. This results in hotter and less dense plasma on the equator between the capsule and hohlraum wall. The inner laser beams experience less inverse bremsstrahlung absorption before reaching the wall. The X-ray drive is thus stronger from the equator with the imposed field. We study superthermal, or ‘hot’, electron dynamics with the particle-in-cell code ZUMA, using plasma conditions from HYDRA. During the early-time laser picket, hot electrons based on two-plasmon decay in the laser entrance hole (Regan et al., Phys. Plasmas, vol. 17(2), 2010, 020703) are guided to the capsule by a 70 T field. Twelve times more energy deposits in the deuterium–tritium fuel. For plasma conditions early in peak laser power, we present mono-energetic test-case studies with ZUMA as well as sources based on inner-beam stimulated Raman scattering. The effect of the field on deuterium–tritium deposition depends strongly on the source location, namely whether hot electrons are generated on field lines that connect to the capsule.
The cost and utilization of psychotherapy in Community-bases Mental Health Services. A multicentre study in five Italian areas
Authors: Chiappelli Marco , Grigoletti Laura , Albanese Paolo , Taras Maria Antonietta , Tulli Paola , Grassi Aldrigo ,   Gruppo I-Psycost
Published: December 2015

SUMMARYAims— To investigate the prevalence of psychotherapy intervention in five Italian Centres for Mental Health. Analysing sociodemographic characteristics, geographical differences, frequencies of psychotherapy interventions, and the costs of these interventions.Methods— Five Italian Community—based Psychiatric Services collected data from 1250 patients during October 2002. Socio—demographic and clinical characteristics and GAF scores were collected at baseline. All psychiatric contacts during the following six months were recorded and categorised into 24 service contact categories. A comparison between patients who received or did not receive psychotherapy was made.Results— The socio—demographic characteristics of patients are very similar to those found in previous studies; there is a great difference in the number of psychotherapy treatments between the five areas. Psychotherapy patients use different services compared to the other patients, and their care cost less.Conclusions— This study provides a description of the provision of psychotherapy by Italian Mental Health Services. Further research is required into this topic.Declaration of Interest:None.
The role of social responsibility, philanthropy and entrepreneurship in the sport industry
Authors: Ratten Vanessa , Babiak Kathy 
Published: December 2015

AbstractThis introduction to the special issue of the Journal of Management & Organization on social responsibility, philanthropy and entrepreneurship in the sport industry frames the key issues sport businesses, corporate partners, and related nonprofit organizations grapple with to ensure that both the organizations and the social causes which are being addressed benefit in some way. The importance of social responsibility is first examined in the context of corporations and sports. The increasing importance of social issues to sport-related industries and the role of strategic philanthropy is discussed. Next, the connection between social responsibility and philanthropic endeavors is addressed in terms of social entrepreneurship. Finally, the article concludes by highlighting the increased significance of sport in society and how the articles in this special issue contribute to a better understanding of the role of social responsibility, philanthropy and entrepreneurship in sport.
Molecular mechanism by which acyclic retinoid induces nuclear localization of transglutaminase 2 in human hepatocellular carcinoma cells
Authors: Shrestha R , Tatsukawa H , Shrestha R , Ishibashi N , Matsuura T , Kagechika H , Kose S , Hitomi K , Imamoto N , Kojima S 
Published: December 2015

AbstractNuclear accumulation of transglutaminase 2 (TG2) is an important step in TG2-dependent cell death. However, the underlying molecular mechanisms for nuclear translocation of TG2 are still poorly understood. In this study, we demonstrated that acyclic retinoid (ACR) induced nuclear accumulation of TG2 in JHH-7 cells, a hepatocellular carcinoma (HCC) leading to their apoptosis. We further demonstrated molecular mechanism in nuclear-cytoplasmic trafficking of TG2 and an effect of ACR on it. We identified a novel 14-amino acid nuclear localization signal (NLS) 466AEKEETGMAMRIRV479 in the ‘C’ domain and a leucine-rich nuclear export signal (NES) 657LHMGLHKL664 in the ‘D’ domain that allowed TG2 to shuttle between the nuclear and cytosolic milieu. Increased nuclear import of GAPDH myc-HIS fused with the identified NLS was observed, confirming its nuclear import ability. Leptomycin B, an inhibitor of exportin-1 as well as point mutation of all leucine residues to glutamine residues in the NES of TG2 demolished its nuclear export. TG2 formed a trimeric complex with importin-α and importin-β independently from transamidase activity which strongly suggested the involvement of a NLS-based translocation of TG2 to the nucleus. ACR accelerated the formation of the trimeric complex and that may be at least in part responsible for enhanced nuclear localization of TG2 in HCC cells treated with ACR.
Loss of serum response factor induces microRNA-mediated apoptosis in intestinal smooth muscle cells
Authors: Park C , Lee M Y , Slivano O J , Park P J , Ha S , Berent R M , Fuchs R , Collins N C , Yu T J , Syn H , Park J K , Horiguchi K , Miano J M , Sanders K M , Ro S 
Published: December 2015

AbstractSerum response factor (SRF) is a transcription factor known to mediate phenotypic plasticity in smooth muscle cells (SMCs). Despite the critical role of this protein in mediating intestinal injury response, little is known about the mechanism through which SRF alters SMC behavior. Here, we provide compelling evidence for the involvement of SRF-dependent microRNAs (miRNAs) in the regulation of SMC apoptosis. We generated SMC-restricted Srf inducible knockout (KO) mice and observed both severe degeneration of SMCs and a significant decrease in the expression of apoptosis-associated miRNAs. The absence of these miRNAs was associated with overexpression of apoptotic proteins, and we observed a high level of SMC death and myopathy in the intestinal muscle layers. These data provide a compelling new model that implicates SMC degeneration via anti-apoptotic miRNA deficiency caused by lack of SRF in gastrointestinal motility disorders.
Target engagement and drug residence time can be observed in living cells with BRET
Authors: Robers Matthew B. , Dart Melanie L. , Woodroofe Carolyn C. , Zimprich Chad A. , Kirkland Thomas A. , Machleidt Thomas , Kupcho Kevin R. , Levin Sergiy , Hartnett James R. , Zimmerman Kristopher , Niles Andrew L. , Ohana Rachel Friedman , Daniels Danette L. , Slater Michael , Wood Monika G. , Cong Mei , Cheng Yi-Qiang , Wood Keith V. 
Published: December 2015

AbstractThe therapeutic action of drugs is predicated on their physical engagement with cellular targets. Here we describe a broadly applicable method using bioluminescence resonance energy transfer (BRET) to reveal the binding characteristics of a drug with selected targets within intact cells. Cell-permeable fluorescent tracers are used in a competitive binding format to quantify drug engagement with the target proteins fused to Nanoluc luciferase. The approach enabled us to profile isozyme-specific engagement and binding kinetics for a panel of histone deacetylase (HDAC) inhibitors. Our analysis was directed particularly to the clinically approved prodrug FK228 (Istodax/Romidepsin) because of its unique and largely unexplained mechanism of sustained intracellular action. Analysis of the binding kinetics by BRET revealed remarkably long intracellular residence times for FK228 at HDAC1, explaining the protracted intracellular behaviour of this prodrug. Our results demonstrate a novel application of BRET for assessing target engagement within the complex milieu of the intracellular environment.