bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human regulatory T cells are selectively activated by low‐dose application of the CD28 superagonist TGN1412/TAB08
Authors: Tabares Paula , Berr Susanne , Römer Paula S. , Chuvpilo Sergej , Matskevich Alexey A. , Tyrsin Dmitry , Fedotov Yury , Einsele Hermann , Tony Hans‐Peter , Hünig Thomas 
Published: December 2013

CD28 superagonists (CD28SAs) are potent T‐cell‐activating monoclonal antibodies (mAbs). In contrast to their benign behavior and marked therapeutic efficacy as activators of regulatory T (Treg) cells in preclinical rodent models, a phase I trial of the human CD28SA TGN1412 (now called TAB08) in 2006 resulted in a life‐threatening cytokine release syndrome (CRS). We studied TAB08‐mediated Treg‐cell activation in a recently developed in vitro system of human PBMCs, which also reproduces the CRS experienced by the healthy volunteers. We show that just as in rodents, CD28SAs are potent activators and expanders of Treg cells from healthy donors and rheumatoid arthritis patients, even under effective blockade of pro‐inflammatory cytokine release by a corticosteroid. Moreover, CD28SA titration identifies a dose range where pro‐inflammatory cytokine secretion from conventional T cells is absent while appreciable Treg‐cell activation is maintained. Finally, we report that low‐dose application of TAB08 to healthy volunteers results in dose‐dependent systemic release of the Treg‐cell signature cytokine IL‐10 in the absence of the pro‐inflammatory factors associated with the CRS of the 2006 TGN1412 study. These results demonstrate the potential of appropriately dosed CD28SA and corticosteroid comedication to mobilize human Treg cells for the treatment of autoimmune and inflammatory conditions.
Accounting for Word‐of‐Mouth Effects in Preference‐Based Market Forecasts
Authors: Pescher Christian , Spann Martin 
Published: December 2013

ABSTRACTConsumers differ in their involvement in new product purchase decisions. Opinion leaders usually show a higher involvement in their purchase decisions than other consumers. This leads to a higher stability in their answers when being asked about their preferences. An important question that previous research has not analyzed yet is whether and how to capture this finding in preference‐based market forecasts. The authors study these aspects for a representative sample of 364 consumers in the mobile phone market of a large European country. They find that assigning higher weights to the preferences of opinion leaders in aggregate market forecasts results in estimates that are more consistent with observed market shares than forecasts in which all consumers are given equal weights. The authors further test different measures of opinion leadership and find that sociometric indicators outperform psychographic constructs to account for the outcome of opinion leadership in preference‐based market forecasts. Copyright © 2013 John Wiley & Sons, Ltd.
A tiered area‐of‐review framework for geologic carbon sequestration
Authors: Birkholzer Jens , Cihan Abdullah , Bandilla Karl 
Published: December 2013

AbstractThis paper discusses the current guidance given by the United States Environmental Protection Agency (EPA) on delineating the so‐called Area of Review (AoR) for the permitting of geologic carbon sequestration (GCS) projects. According to the EPA's regulatory framework for GCS, the AoR refers to the region surrounding the CO2 injection well(s) wherein leakage of CO2 and/or the migration of formation fluids could possibly endanger overlying groundwater resources. Our evaluation of the current framework for delineating the size of this area finds unnecessary conservatism in the definition of the critical pressure, which could lead to a heavy burden on permit applicants that seek to get regulatory compliance, in particular for very large GCS projects. We propose a risk‐based re‐interpretation of this framework, separating the total Area of Review into different sub‐areas with different regulatory requirements depending on whether the concern is about free‐phase CO2 or pressure‐driven brine migration. This leads to a tiered AoR definition in which the projected region of CO2 plume extent would have the highest regulatory standards regarding site characterization, monitoring, and corrective action. The requirements in the AoR outside this central region would be less burdensome because of a narrower focus on major pathways for brine leakage such as unplugged wellbores and large faults. We expect that this revised framework would allow for a reduction in the cost of regulatory compliance for projects with very large injection volumes, while ensuring that the objective of protecting valuable groundwater resources is preserved.
LIQUIDITY SHOCKS AND THE SUPPLY OF CREDIT AFTER THE 2007–2008 CRISIS
Authors: Kapan Tümer , Minoiu Camelia 
Published: December 2013

ABSTRACTWe examine the impact of heightened liquidity risk in bank funding markets during the 2007–2008 subprime crisis on the supply of credit to firms internationally. Our sample comprises almost 800 banks lending in the syndicated loan market to borrowers from 48 advanced and emerging market economies. To control for simultaneous changes in demand, we relate within‐borrower changes in bank credit from multiple banks to banks' exposure to liquidity risk. To capture banks' vulnerability to the liquidity shocks that occurred during 2007–2008, we use measures of pre‐crisis reliance on wholesale funding. Our results suggest that banks that were more exposed to liquidity risk during the crisis reduced syndicated lending more than other banks. Our results are robust to alternate measures of vulnerability to liquidity risk, choice of sample period and simultaneous movements in exchange rates. Copyright © 2013 John Wiley & Sons, Ltd.
MANAGING THE FRAGILITY OF THE EUROZONE BY PAUL De GRAUWE
Authors: Borgy Vladimir , Bouthevillain Carine , Dufrénot Gilles 
Published: December 2013

ABSTRACTThis paper discusses sources of self‐fulfilling equilibria in the Eurozone when some governments are highly susceptible to movements of distrust by investors who fear some payment difficulty. Self‐fulfilling prophecies occur when countries become insolvent only because investors fear insolvency. They induce multiple equilibria, some of which correspond to bad equilibria and others to good equilibria. An important issue then is to solve this problem, notably to eliminate the bad equilibria. In the short‐run, the role of the central bank as a lender of last resort is key. But this raises issues about the risk inherent to its intervention (inflation, solvency). In the medium run, macroeconomic policies in the euro are central (structural reforms and the reduction of external imbalances). In the long run, it may be worth proceeding to the consolidation of national budgets and debts, which would protect the countries of being forced with default by the financial markets. Copyright © 2013 John Wiley & Sons, Ltd.
GLOBAL IMBALANCES AND FINANCIAL SECTOR INSTABILITIES: INTRODUCTION
Authors: Borgy Vladimir , Bouthevillain Carine , Dufrénot Gilles 
Published: December 2013

ABSTRACTThis special issue provides several views about the sources of the current crisis and policy solutions to cope with it. It brings together papers from academic institutions, international organizations and central banks. The first three papers argue that the crisis was triggered by the lack of confidence of the investors in the markets. This was reflected, for instance, in the pricing of the public debt (with an increase in the sovereign debt spreads) and in the reduced syndicated lending in wholesale lending markets. The other three papers focus on policy aspects by analyzing indicators that could serve as early warning signals of increasing stress and vulnerability. The authors propose three set of indicators: policy‐based indicators, some variables used in the macro‐prudential literature and financial indexes. The papers are a selection of papers presented at a Conference on Macroeconomic and financial vulnerability indicators in advanced economies co‐organizes by the Banque de France and the University of Strasbourg on 13–14 September 2013. Copyright © 2013 John Wiley & Sons, Ltd.
PRICING SOVEREIGN BOND RISK IN THE EUROPEAN MONETARY UNION AREA: AN EMPIRICAL INVESTIGATION
Authors: Afonso António , Arghyrou Michael G. , Kontonikas Alexandros 
Published: December 2013

ABSTRACTWe use a panel of 10 euro area countries to assess the determinants of long‐term sovereign bond yield spreads over the period 1999.01–2010.11. We find that government bond yield spreads are well explained by fiscal fundamentals over the crisis period. We also find that the menu of risk factors priced by markets has been significantly enriched since March 2009, including international risk, liquidity risk and the risk of the crisis' transmission among European Monetary Union member states. Finally, we find that transmission risk has increased considerably since spring 2009 because of rapidly increasing risk of investing in periphery bonds relative to core ones. Copyright © 2013 John Wiley & Sons, Ltd.
Osteoblasts Protect AML Cells From SDF‐1‐Induced Apoptosis
Authors: Kremer Kimberly N. , Dudakovic Amel , McGee‐Lawrence Meghan E. , Philips Rachael L. , Hess Allan D. , Smith B. Douglas , van Wijnen Andre J. , Karp Judith E. , Kaufmann Scott H. , Westendorf Jennifer J. , Hedin Karen E. 
Published: December 2013

ABSTRACTThe bone marrow provides a protective environment for acute myeloid leukemia (AML) cells that often allows leukemic stem cells to survive standard chemotherapeutic regimens. Targeting these leukemic stem cells within the bone marrow is critical for preventing relapse. We recently demonstrated that SDF‐1, a chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in patient samples expressing high levels of its receptor, CXCR4. Here we show that a subset of osteoblast lineage cells within the bone marrow can protect AML cells from undergoing apoptosis in response to the SDF‐1 naturally present in that location. In co‐culture systems, osteoblasts at various stages of differentiation protected AML cell lines and patient isolates from SDF‐1‐induced apoptosis. The differentiation of the osteoblast cell lines, MC3T3 and W‐20‐17, mediated this protection via a cell contact‐independent mechanism. In contrast, bone marrow‐derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in AML cells via a CXCR4‐dependent mechanism and failed to protect AML cells from exogenously added SDF‐1. These results indicate that osteoblasts in the process of differentiation potently inhibit the SDF‐1‐driven apoptotic pathway of CXCR4‐expressing AML cells residing in the bone marrow. Drugs targeting this protective mechanism could potentially provide a new approach to treating AML by enhancing the SDF‐1‐induced apoptosis of AML cells residing within the bone marrow microenvironment. J. Cell. Biochem. 115: 1128–1137, 2014. © 2013 Wiley Periodicals, Inc.
Expression of P2X7 ATP Receptor Mediating the IL8 and CCL20 Release in Human Periodontal Ligament Stem Cells
Authors: Trubiani Oriana , Horenstein Alberto L. , Caciagli Francesco , Caputi Sergio , Malavasi Fabio , Ballerini Patrizia 
Published: December 2013

ABSTRACTATP is released by human periodontal ligament cells (hPDLCs) and has been shown to regulate PDL regeneration and responses to mechanical stress through activation of P2Y receptors. This nucleotide, however, has also been reported to trigger the pro‐inflammatory cascade by inducing the maturation and/or release of chemokines/cytokines from various cell types mainly via P2X7 receptors. Much less is known on the possible role of ATP in stem cells deriving from PDL (hPDLSCs) which are considered to be a promising tool for cell‐based therapy to restore lesions. Given the role played by P2X7 in pathophysiological conditions, in this study we investigated the expression of P2X7 ATP receptors in hPDLSCs. The results obtained showed that hPDLSCs express P2X7 receptors evaluated by means of cytofluorimetric, immunohistochemistry, reverse transcriptase‐PCR, and Western blot analyses. P2X7 ligation by 2′,3′‐(benzoyl‐4‐benzoyl)‐ATP (BzATP), a specific receptor agonist, was followed by an increase in intracellular Ca2+ and in the uptake of ethidium bromide. These effects were dramatically reduced by oxidized ATP (oATP), the P2X7 irreversible inhibitor, suggesting that the P2X7 is the functional receptor involved. At 24 h treatment of hPDLSCs with BzATP it enhanced the release of the pro‐inflammatory agents IL8 and CCL20, without influencing cell viability. These effects were counteracted by pre‐treating the cells with oATP or with A‐740003, a selective and potent P2X7 competitive antagonist. Collectively, these results indicated that extracellular ATP mediate a pro‐inflammatory response via P2X7 receptors in hPDLSCs opening a further approach to control hPDLSCs behavior in their possible application as therapeutic tool. J. Cell. Biochem. 115: 1138–1146, 2014. © 2013 Wiley Periodicals, Inc.
Age‐Specific 99th Percentile Cutoff of High‐Sensitivity Cardiac Troponin T for Early Prediction of Non‐ST‐Segment Elevation Myocardial Infarction (NSTEMI) in Middle‐Aged Patients
Authors: Fan Lie Ying , Yu Ping , Yu Shan Shan , Gu Yu Ying , Zong Ming , Cai Ying , Liu Zhong Min 
Published: December 2013

BackgroundHigh‐sensitivity cardiac troponin T (hs‐cTnT) assay is used in the diagnosis and risk assessment of patients with symptoms of myocardial infarction. This study was undertaken to establish an age‐specific 99th percentile cutoff value for hs‐cTnT in Chinese population, and to evaluate its potential for early prediction of non‐ST‐segment elevation myocardial infarction (NSTEMI) in middle‐aged patients.MethodsTroponin T levels in blood obtained from healthy Chinese adults were assayed using hs‐cTnT. The distribution was plotted and 99th percentiles were determined by nonparametric statistics. Prediction performance at the conventional cutoff (14 ng/L) recommended by the Roche company was compared with the age‐specific cutoff for NSTEMI in 100 middle‐aged patients (40–60 years of age) with acute chest pain.ResultsThe 99th percentile for hs‐cTnT was 14 ng/L for patients ≥60 years of age and 11 ng/L for those <60. Fifty of the 100 patients were finally diagnosed with NSTEMI. The age‐specific 99th percentile cutoff value of 11 ng/L identified a higher number of patients with NSTEMI than the conventional 14 ng/L cutoff (46 vs. 40 patients), although the difference was not statistically significant (P = 0.084). In addition, the sensitivity of hs‐cTnT increased from 80 to 92% and the negative predictive values increased from 82.4 to 91.8%.ConclusionUsing 11 ng/L as a decision‐making cutoff point for hs‐cTnT facilitated earlier prediction of NSTEMI in middle‐aged patients than the conventional 14 ng/L cutoff. Further studies are needed to confirm this finding in larger group of patients.
Significant Increase of Prostaglandin E‐Major Urinary Metabolite in Male Smokers: A Screening Study of Age and Gender Differences Using a Simple Radioimmunoassay
Authors: Okayasu Isao , Ohnishi Hiromitsu , Sarandi Istvan , Shojima Junko , Komatsu Junko , Oritsu Masae , Sasabe Masataka , Nanami Kaori Okayasu , Matsuura Masaaki , Azumi Jun‐ichi , Ito Satoru , Fujiwara Mutsunori 
Published: December 2013

BackgroundFor the assessment of inflammatory status, we have developed a simple, reliable radioimmunoassay (RIA) of prostaglandin E‐major urinary metabolite (PGE‐MUM), which remains stable in urine after it is metabolized. Using this method, we conducted a screening study to compare standard values of PGE‐MUM to serum C‐reactive protein (CRP) levels in health check volunteers.MethodsPGE‐MUM (micrograms per gram creatinine) was measured in normal urine samples obtained from 797 samples in volunteers for health check, using a newly developed RIA, and analyzed in relation to age, gender, smoking, and drinking habits. Results were compared to serum CRP.ResultsPGE‐MUM was significantly higher in males than in females. It was significantly higher in smoking males, compared to males who had never smoked (nonsmokers), particularly in those above 40 years of age. In nonsmokers, PGE‐MUM declined in males with advancing age, while it rose in females. Although PGE‐MUM reflected current smoking status, independent of smoking index (SI), serum CRP indicated both current and former smoking condition, rather dependent upon SI.ConclusionsPGE‐MUM increases in smokers, as suggested by possible inflammatory injury of pulmonary tissue. This RIA method for PGE‐MUM may be thus a sensitive and reliable biomarker for current inflammation, different from serum CRP.
Serum 25‐Hydroxyvitamin D Level and Extent and Complexity of Coronary Artery Disease
Authors: Şeker Taner , Gür Mustafa , Yüksel Kalkan Gülhan , Kuloğlu Osman , Yıldız Koyunsever Nermin , Yıldıray Şahin Durmuş , Türkoğlu Caner , Akyol Selahattin , Elbasan Zafer , Harbalıoğlu Hazar , Çaylı Murat 
Published: December 2013

BackgroundThere are limited number of studies about relationship between serum vitamin D level and presence and severity of coronary artery disease (CAD). We assessed the relationship between the extent and complexity of CAD assessed by SYNTAX score and 25‐hydroxyvitamin D level in patients with stable CAD.MethodsIn the study, 209 consecutive patients with stable CAD (age: 63.1 ± 10.0 years) and 102 healthy control subjects (age 61.3 ± 13.7 years) were included. Serum 25‐hydroxyvitamin D was measured using a direct competitive chemiluminescent immunoassay and other biochemical markers were measured in all subjects. All subjects underwent coronary angiography and SS was calculated.ResultsThe mean serum 25‐hydroxyvitamin D level of CAD group was lower than the control group (P < 0,001). Multivariate regression analysis showed that serum 25‐hydroxyvitamin D level was independently associated with SYNTAX score (β = −0.396, P < 0.001), hypertension (β = −0.183, P = 0.003), high sensitive C‐reactive protein (β = −0.141, P = 0.014), and body mass index (β = −0.135, P = 0.023) in patient group.Conclusion25‐Hydroxyvitamin D level was associated with extent and complexity of CAD. 25‐Hydroxyvitamin D may play a role in pathogenesis and severity of coronary atherosclerosis.
Antiadenohypophysis Autoantibodies in Patients with Nongluten‐related Gastroenteropathies
Authors: Aguado Rocío , Fernández Silvia , Estévez Orlando A. , Santamaría Manuel , Ortega Consuelo 
Published: December 2013

AimTo investigate the presence of antipituitary antibodies (APA) in the serum of patients undergoing gastroenteropathies (GEP) other than celiac disease (CD).MethodsAPA were analyzed in GEP patients (n = 103), CD patients (n = 94), idiopathic growth hormone (GH) deficiency patients (n = 21), and 98 age‐ and sex‐matched controls. Indirect immunofluorescence was performed in cryostat sections of baboon pituitary gland.ResultsAPA were detected in 30% of GEP patients, 38% of them showed failure to thrive. No significant differences were found when we compared thrive impairment in negative and positive APA GEP patients. Indeed, normal values of insulin‐like growth factor 1 were found in 93% of positive APA GEP patients. APA were detected in 52% of the CD patients. Ninety‐one percent of them, in contrast to GEP group, showed significant growth impairment (P < 0.05) when compared to APA negative CD individuals. GH‐deficient non‐CD patients did not show APA.ConclusionsWe have shown the presence of APA in patients with nongluten‐related enteropathies. The presence of antipituitary autoantibodies in GEP patients does not seem to be associated with failure to thrive as it occurs in CD.
The Development and Organization of Newborn Screening Programs in Turkey
Authors: Tezel Başak , Dilli Dilek , Bolat Hilal , Şahman Hatice , Özbaş Sema , Acıcan Deniz , Ertek Mustafa , Köse Mehmet Rıfat , Dilmen Uğur 
Published: December 2013

BackgroundNewborn screening tests have been designed to identify infants with severe disorders that are relatively prevalent and treatable or controllable. Comparing to other countries, the incidence of these diseases are very high in Turkey where the rate of consanguineous marriage is high.MethodsIn this article, it is aimed to evaluate the development and organization of newborn screening programs in Turkey which include phenylketonuria, congenital hypothyroidism and biotinidase deficiency screenings. The point reached today, limitations of the program, expectations and projects for the future are discussed.ResultsToday, the point reached in screening programs of the country is appreciable. While the screening rate of the live born babies was 4,7% in 1987, this rate reached to 95% by 2008. Predicted target for newborn screening program at the strategic plan of Ministry of Health for 2010–2014 was to enhance this rate above 95% by the end of 2012. It seems that the envisaged goal has been reached.ConclusionNational newborn screening program appears to be conducted successfully and extensively as a result of political determination and performance of health care workers who are in charge of this program. Nevertheless, limited numbers of the nutrition and metabolism clinics and specialists on these branches have caused some access difficulties, waste of time, and financial loss. Therefore, special planning to improve quality and the number of the clinics would be useful.
Evaluation of Antigen Detection Test (Chromatographic Immunoassay): Potential to Replace the Antibody Assay Using Purified 45‐kDa Protein for Rapid Diagnosis of Tuberculosis
Authors: Tasbiti Alireza Hadizadeh , Bahrmand Ahmadreza , Shokrgozar Mohammad Ali , Ghanaie Mostafa , Fateh Abolfazl , Karimi Ali , Yari Shamsi 
Published: December 2013

BackgroundThe current strategy for combating tuberculosis (TB) is based on the early detection and treatment of patients to halt transmission. The present study was conducted to evaluate the diagnostic potential of three Mycobacterium tuberculosis antigens, 45‐kDa, A60, and sonicated MTB antigen (SmTB‐Ag), as antibody/antigen detection methods for the rapid and accurate diagnosis of TB.MethodsThe SmTB‐Ag and 45‐kDa antigens were purified and A60 antigen was supplied by Anda‐Biologicals, France. The 45‐kDa and A60 antigens (for antibody detection procedures) and SmTB‐Ag (for antigen detection test) were tested in the same study subjects. ELISA and immunochromatographic (rapid) test were performed on 201 sputum and serum samples. Ninety‐eight samples from TB patients and 103 samples from control individuals were studied.ResultsThe mean absorbance value of antibodies against 45‐kDa antigen in the TB patients were (1.17 ± 0.44, CI 1.09–1.26), significantly higher than in the non‐TB group, (0.8 ± 0.28, CI 0.74–0.85, P < 0.05). The sensitivities of tests using two antigens, 84% for the 45‐kDa antigen and 65% for the A60 antigen, were lower than SmTB‐Ag(93%). The rapid test yielded 93% sensitivity and 92% specificity.ConclusionFindings highlighted the importance of antigen detection as a diagnostic tool. The rapid test evaluated in this study may be useful for diagnosis of TB.