bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum transforming growth factor β1 during diabetes development in non-obese diabetic mice and humans
Authors: Olivieri A , De Angelis S , Dionisi S , D'Annunzio G , Locatelli M , Marinaro M , Bonato V , Amendola A , Songini M , Velluzzi F , Schirru C , Cotichini R , Stazi M A , Dotta F , Lorini R , Bottazzo G F , Boirivant M 
Published: September 2010

Summary
Recent data show that regulatory cells with transforming growth factor (TGF)-β1-dependent activity are able to restore self-tolerance in overtly diabetic non-obese diabetic (NOD) mice. Thus, TGF-β1 seems to have a relevant role in protection from autoimmune diabetes. Our aim was to investigate the possible significance of serum TGF-β1 measurement in the natural history of diabetes in NOD mice, as well as in children positive for at least one islet-related antibody. Serum TGF-β1 (both total and active) was measured by enzyme-linked immunosorbent assay at monthly intervals in 26 NOD mice during the spontaneous development of diabetes and, on a yearly basis, in nine siblings of patients with type 1 diabetes (T1D) with a follow-up of 4 years. Diabetes appeared between the 12th week of age and the end of the study period (36 weeks) in 17 mice. TGF-β1 serum level variations occurred in the prediabetic period in both NOD mice and humans and diabetes diagnosis followed a continuing reduction of active TGF-β1 (aTGF-β1) serum levels. In mice, aTGF-β1 serum levels measured at 4 weeks of age correlated positively with severity of insulitis, and negatively with percentage of insulin-positive cells. Our findings suggest that in NOD mice serum TGF-β1 levels during the natural history of the diabetes reflect the course of islet inflammation. The measurement of aTGF-β1 in islet-related antibody-positive subjects may provide insights into the natural history of prediabetic phase of T1D.
Trace elements in nails as biomarkers in clinical research
Authors: He Ka 
Published: September 2010

Eur J Clin Invest 2010; 41 (1): 98–102AbstractBackground  The importance of trace elements in relation to human health has been increasingly recognized. Accurate and adequate quantification of trace elements are crucial in clinical research.Design  This review was to discuss the rationale of using nail trace elements as biomarkers in clinical studies.Results  For most trace elements, dietary instruments cannot appropriately capture the intakes because of the minimal amounts and wide variations in the same foods grown in different area as well as the nondietary exposures. Therefore, biomarkers may be essential in studying trace elements. Although there are notable differences among trace elements in the availability of biomarkers, increasing evidence supports that nails, particularly toenail concentrations of most trace elements, are useful biomarkers of exposure in which a single sample is assumed to represent long‐term exposure.Conclusions  Compared with other potential biomarkers of trace elements, nail measurement has certain advantages in clinical research.
The impact of smoking on incident type 2 diabetes in a cohort with hepatitis B but not hepatitis C infection
Authors: Wang C.‐S. , Chang T.‐T. , Yao W.‐J. , Wang S.‐T. , Chou P. 
Published: September 2010

SummarySmoking may be a risk factor for diabetes, and it has been suggested that viral hepatitis may predispose to diabetes. We studied diabetes and smoking histories in people with viral hepatitis. From 1997 to 2004, we studied the risk of incident diabetes in a community cohort with hyperendemic HBV and HCV infection in southern Taiwan. The cohort involved 3539 people (40–70 years old) without diabetes. Four hundred and twenty‐three individuals developed diabetes. Those who were ≥65 years old, frequently consumed alcohol, had a BMI ≥25, had <9 years of education, were anti‐HCV+ or smoked ≥1 pack per day were more likely to develop diabetes (P < 0.05). A cumulative hazard function test showed that the higher the smoking levels, the greater the cumulative incidence rate of diabetes in HBsAg+ participants only (P = 0.03 by log‐rank test). A multiple Cox proportional hazards model analysis in different hepatitis statuses showed smoking levels were strong predictors of diabetes with a dose–response relationship for type 2 diabetes in those with HBsAg+: hazard ratio (HR) = 3.8, (95% CI: 1.2, 12.3) for light smokers (<1 pack per day) and HR = 4.4 (95% CI: 1.5, 13.3) for heavy smokers (≥1 pack per day). Increasing BMI was a common predictor in all people. Smoking is a strong predictor for diabetes with a dose–response relationship in HBsAg+ individuals and a mild predictor for seronegative individuals but not significant in anti‐HCV+ individuals.
Cluster Policies in Bulgaria: European Integration, Postsocialist Dynamics and Local Level Initiatives
Authors: SELLAR CHRISTIAN , EMILOVA MAKSIMILIANA , PETKOVA‐TANCHEVA CHRASTINA DIMITROVA , MCNEIL KATHLEEN 
Published: September 2010

AbstractThis article investigates public policies aimed at developing industrial clusters in Bulgaria by looking at initiatives at supranational, national and local levels. It argues that cluster policies have functioned as paths directing actions in the postsocialist transformation of Bulgaria. In doing so, it seeks answers to the following research questions: what are the connections between policy implementation, institutional changes and economic transformation at the national and local levels in Bulgaria; what is the role of the European Union in shaping these changes; and what is the role of local actors in shaping the policies and development trends within one specific cluster? Through an analysis of government policies, data and empirical research, the article shows how different groups (foreign consultants, local elites and national administrators) have understood the concepts of ‘clusters’ and ‘industrial districts’ in different ways, then used these concepts as a tool to access foreign resources. The analysis highlights both similarities and differences in cluster policies at the three levels considered.RésuméCet examen des politiques publiques de développement de pôles industriels en Bulgarie s’intéresse aux initiatives de niveaux supranational, national et local. Il affirme qu’au cours de la phase de transformation postsocialiste, ces politiques ont servi de mesures d’orientation de trajectoires. Parallèlement, l’étude cherche à répondre aux questions suivantes: quels sont les rapports entre mise en œuvre des politiques publiques, évolutions institutionnelles et transformations économiques tant au plan national que local? quel rôle l’Union européenne a‐t‐elle dans la configuration de ces changements, et quel poids les acteurs locaux ont‐ils dans la détermination des politiques et des axes de développement concernant un pôle particulier? En analysant les politiques gouvernementales, les faits et l’étude empirique, l’article montre que différents groupes (experts étrangers, élites locales et représentants de l’administration nationale) n’ont pas appréhendé de la même manière les concepts de ‘pôles’ (clusters) et de ‘districts industriels’, et qu’ils les ont ensuite utilisés afin d’accéder à des ressources d’origine étrangère. Ainsi, il est possible d’établir similitudes et divergences entre les politiques relatives aux pôles industriels, et ce, à chacun des trois niveaux étudiés.
Access to Primary and Preventive Care among Foreign‐Born Adults in Canada and the United States
Authors: Lebrun Lydie A. , Dubay Lisa C. 
Published: September 2010

Objective. To conduct cross‐country comparisons and assess the effect of foreign birth on access to primary and preventive care in Canada and the United States.Data Sources. Secondary data from the 2002 to 2003 Joint Canada–United States Survey of Health.Study Design. Descriptive and comparative analyses were conducted, and logistic regression models were used to assess the effect of immigrant status and country of residence on access to care. Outcomes included measures of health care systems and processes, utilization, and patient perceptions.Principal Findings. In adjusted analyses, immigrants in Canada fared worse than nonimmigrants regarding having timely Pap tests; in the United States, immigrants fared worse for having a regular doctor and an annual consultation with a health professional. Immigrants in Canada had better access to care than immigrants in the United States; most of these differences were explained by differences in socioeconomic status and insurance coverage across the two countries. However, U.S. immigrants were more likely to have timely Pap tests than Canadian immigrants, even after adjusting for potential confounders.Conclusions. In both countries, foreign‐born populations had worse access to care than their native‐born counterparts for some indicators but not others. However, few differences in access to care were found when direct cross‐country comparisons were made between immigrants in Canada versus the United States, after accounting for sociodemographic differences.
Who Mobilizes? Participatory Democracy in Chávez's Bolivarian Revolution
Authors: Hawkins Kirk A. 
Published: September 2010

AbstractThis article assesses popular mobilization under the Chávez government's participatory initiatives in Venezuela using data from the AmericasBarometer survey of 2007. This is the first study of the so-called Bolivarian initiatives using nationally representative, individual-level data. The results provide a mixed assessment. Most of the government's programs invite participation from less active segments of society, such as women, the poor, and the less educated, and participation in some programs is quite high. However, much of this participation clusters within a narrow group of activists, and a disproportionate number of participants are Chávez supporters. This partisan bias probably reflects self-screening by Venezuelans who accept Chávez's radical populist discourse and leftist ideology, rather than vote buying or other forms of open conditionality. Thus, the Venezuelan case suggests some optimism for proponents of participatory democracy, but also the need to be more attuned to its practical political limits.
The 3‐ureidopropionase ofCaenorhabditis elegans, an enzyme involved in pyrimidine degradation
Authors: Janowitz Tim , Ajonina Irene , Perbandt Markus , Woltersdorf Christian , Hertel Patrick , Liebau Eva , Gigengack Ulrike 
Published: September 2010

Pyrimidines are important metabolites in all cells. Levels of cellular pyrimidines are controlled by multiple mechanisms, with one of these comprising the reductive degradation pathway. In the model invertebrateCaenorhabditis elegans, two of the three enzymes of reductive pyrimidine degradation have previously been characterized. The enzyme catalysing the final step of pyrimidine breakdown, 3‐ureidopropionase (β‐alanine synthase), had only been identified based on homology. We therefore cloned and functionally expressed the 3‐ureidopropionase ofC. elegansas hexahistidine fusion protein. The purified recombinant enzyme readily converted the two pyrimidine degradation products: 3‐ureidopropionate and 2‐methyl‐3‐ureidopropionate. The enzyme showed a broad pH optimum between pH 7.0 and 8.0. Activity was highest at approximately 40 °C, although the half‐life of activity was only 65 s at that temperature. The enzyme showed clear Michaelis–Menten kinetics, with aKmof 147 ± 26 μmand aVmaxof 1.1 ± 0.1 U·mg protein−1. The quaternary structure of the recombinant enzyme was shown to correspond to a dodecamer by ‘blue native’ gel electrophoresis and gel filtration. The organ specific and subcellular localization of the enzyme was determined using a translational fusion to green fluorescent protein and high expression was observed in striated muscle cells. With the characterization of the 3‐ureidopropionase, the reductive pyrimidine degradation pathway inC. eleganshas been functionally characterized.Structured digital abstract MINT‐7986015:3‐ureidopropionase(uniprotkb:Q19437) and3‐ureidopropionase(uniprotkb:Q19437)bind(MI:0407) byblue native page(MI:0276)
Differential Mechanisms of Acquired Resistance to Insulin-like Growth Factor-I Receptor Antibody Therapy or to a Small-Molecule Inhibitor, BMS-754807, in a Human Rhabdomyosarcoma Model
Authors: Huang Fei , Hurlburt Warren , Greer Ann , Reeves Karen A. , Hillerman Stephen , Chang Han , Fargnoli Joseph , Graf Finckenstein Friedrich , Gottardis Marco M. , Carboni Joan M. 
Published: September 2010

Abstract
Agents targeting insulin-like growth factor-I receptor (IGF-IR), including antibodies and small-molecule inhibitors, are currently in clinical development for the treatment of cancers including sarcoma. However, development of resistance is a common phenomenon resulting in failures of anticancer therapies. In light of this problem, we developed two resistant models from the rhabdomyosarcoma cell line Rh41: Rh41-807R, with acquired resistance to BMS-754807, a small-molecule dual-kinase inhibitor targeting IGF-IR and insulin receptor (IR), and Rh41-MAB391R, with resistance to MAB391, an IGF-IR–blocking antibody. In addition, tumor xenograft models were established from Rh41 and Rh41-807R cell lines. Gene expression and DNA copy number analyses of these models revealed shared as well as unique acquired resistance mechanisms for the two types of IGF-IR inhibitors. Each resistant model used different signaling pathways as a mechanism for proliferation. Platelet-derived growth factor receptor α (PDGFRα) was amplified, overexpressed, and constitutively activated in Rh41-807R cells and tumors. Knockdown of PDGFRα by small interfering RNA in Rh41-807R resensitized the cells to BMS-754807. Synergistic activities were observed when BMS-754807 was combined with PDGFRα inhibitors in the Rh41-807R model in vitro. In contrast, AXL expression was highly elevated in Rh41-MAB391R but downregulated in Rh41-807R. Notably, BMS-754807 was active in Rh41-MAB391R cells and able to overcome resistance to MAB391, but MAB391 was not active in Rh41-807R cells, suggesting potentially broader clinical activity of BMS-754807. This is the first study to define and compare acquired resistance mechanisms for IGF-IR–targeted therapies. It provides insights into the differential acquired resistance mechanisms for IGF-IR/IR small-molecule inhibitor versus anti–IGF-IR antibody. Cancer Res; 70(18); 7221–31. ©2010 AACR.
hnRNP A2/B1 Modulates Epithelial-Mesenchymal Transition in Lung Cancer Cell Lines
Authors: Tauler Jordi , Zudaire Enrique , Liu Huaitian , Shih Joanna , Mulshine James L. 
Published: September 2010

Abstract
Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) has been reported to be overexpressed in lung cancer and in other cancers such as breast, pancreas, and liver. However, a mechanism linking hnRNP A2/B1 overexpression and progression to cancer has not yet been definitively established. To elucidate this mechanism, we have silenced hnRNPA2/B1 mRNA in non–small-cell lung cancer cell lines A549, H1703, and H358. These cell lines present different levels of expression of epithelial-to-mesenchymal transition (EMT) markers such as E-cadherin, fibronectin, and vimentin. Microarray expression analysis was performed to evaluate the effect of silencing hnRNP A2/B1 in A549 cells. We identified a list of target genes, affected by silencing of hnRNP A2/B1, that are involved in regulation of migration, proliferation, survival, and apoptosis. Silencing hnRNP A2/B1 induced formation of cell clusters and increased proliferation. In the anchorage-independent assay, silencing hnRNP A2/B1 increased colony formation by 794% in A549 and 174% in H1703 compared with a 25% increase in proliferation, in both cell lines, in a two-dimensional proliferation assay. Silencing hnRNP A2/B1 decreased migration in intermediate cell line A549 and mesenchymal cell line H1703; however, no changes in proliferation were observed in epithelial cell line H358. Silencing hnRNP A2/B1 in A549 and H1703 cells correlated with an increase of E-cadherin expression and downregulation of the E-cadherin inhibitors Twist1 and Snai1. These data suggest that expression of hnRNP A2/B1 may play a role in EMT, in nonepithelial lung cancer cell lines A549 and H1703, through the regulation of E-cadherin expression. Cancer Res; 70(18); 7137–47. ©2010 AACR.
Modulation of Gene Expression and Tumor Cell Growth by Redox Modification of STAT3
Authors: Li Li , Cheung Shing-hu , Evans Emma L. , Shaw Peter E. 
Published: September 2010

Abstract
Reactive oxygen species (ROS) promote tumor cell proliferation and survival by directly modulating growth-regulatory molecules and key transcription factors. The signal transducer and activator of transcription 3 (STAT3) is constitutively active in a variety of tumor cell types, where the effect of ROS on the Janus kinase/STAT pathway has been examined. We report here that STAT3 is directly sensitive to intracellular oxidants. Oxidation of conserved cysteines by peroxide decreased STAT3 binding to consensus serum-inducible elements (SIE) in vitro and in vivo and diminished interleukin (IL)-6–mediated reporter expression. Inhibitory effects produced by cysteine oxidation in STAT3 were negated in redox-insensitive STAT3 mutants. In contrast, ROS had no effect on IL-6–induced STAT3 recruitment to the c-myc P2 promoter. Expression of a redox-insensitive STAT3 in breast carcinoma cells accelerated their proliferation while reducing resistance to oxidative stress. Our results implicate STAT3 in coupling intracellular redox homeostasis to cell proliferation and survival. Cancer Res; 70(20); 8222–32. ©2010 AACR.
Detailed Distribution of NK012, an SN-38–Incorporating Micelle, in the Liver and Its Potent Antitumor Effects in Mice Bearing Liver Metastases
Authors: Takahashi Amane , Ohkohchi Nobuhiro , Yasunaga Masahiro , Kuroda Jun-ichiro , Koga Yoshikatsu , Kenmotsu Hirotsugu , Kinoshita Taira , Matsumura Yasuhiro 
Published: September 2010

AbstractPurpose: To clarify and compare the antitumor effects and specific biodistribution of NK012, an SN-38–incorporating polymeric micelle, in mice bearing multiple liver metastases of human colon cancer HT-29 cells with irinotecan hydrochloride (CPT-11).Experimental Design: The maximum tolerable dose of NK012 (30 mg/kg) or CPT-11 (66.7 mg/kg) was i.v. administered three times every 4 days to mice bearing metastases to the liver colonized 7 days after the portal administration of HT-29 cells (n = 6). In vivo antitumor effects were evaluated by bioluminescence imaging and histopathologic examination. Drug biodistribution was analyzed by high-performance liquid chromatography and fluorescence microscopy (n = 3).Results: NK012 eradicated the liver metastases and produced a significant longer survival rate than CPT-11 (P = 0.0006). High-performance liquid chromatography showed the prolonged distribution of NK012 and free SN-38 released from NK012 in the tumors, liver, and spleen for weeks after NK012 administration. On the other hand, the accumulation levels of CPT-11 and free SN-38 converted from CPT-11 rapidly decreased within 1 day after CPT-11 administration. In the liver metastases, fluorescence microscopy and immunohistochemistry showed that administered NK012 was distributed mainly adjacent to tumor vessels after 1 day. As for the normal liver, NK012 was distributed in Kupffer cells instead of hepatocytes for at least 7 days after administration.Conclusion: This study suggests that NK012 is strongly effective against liver metastases and does not damage the liver despite the long retention time of NK012 in Kupffer cells. Clin Cancer Res; 16(19); 4822–31. ©2010 AACR.
Molecular Therapy Targeting Sonic Hedgehog and Hepatocyte Growth Factor Signaling in a Mouse Model of Medulloblastoma
Authors: Coon Valerie , Laukert Tamara , Pedone Carolyn A. , Laterra John , Kim K. Jin , Fults Daniel W. 
Published: September 2010

Abstract
The use of genetically engineered mice has provided insights into the molecular pathogenesis of the pediatric brain tumor medulloblastoma and revealed promising therapeutic targets. Ectopic expression of Sonic hedgehog (Shh) in cerebellar neural progenitor cells induces medulloblastomas in mice, and coexpression of hepatocyte growth factor (HGF) enhances Shh-induced tumor formation. To determine whether Shh + HGF–driven medulloblastomas were responsive to Shh signaling blockade and whether treatment response could be enhanced by combination therapy targeting both HGF and Shh signaling pathways, we carried out a survival study in mice. We induced medulloblastomas by retrovirus-mediated expression of Shh and HGF, after which we treated the mice systemically with (a) HGF-neutralizing monoclonal antibody L2G7, (b) Shh signaling inhibitor cyclopamine, (c) Shh-neutralizing monoclonal antibody 5E1, (d) L2G7 + cyclopamine, or (e) L2G7 + 5E1. We report that monotherapy targeting either HGF signaling or Shh signaling prolonged survival and that anti-HGF therapy had a more durable response than Shh-targeted therapy. The effect of L2G7 + 5E1 combination therapy on cumulative survival was equivalent to that of L2G7 monotherapy and that of L2G7 + cyclopamine therapy was worse. The principal mechanism by which Shh- and HGF-targeted therapies inhibited tumor growth was a potent apoptotic death response in tumor cells, supplemented by a weaker suppressive effect on proliferation. Our observation that combination therapy either failed to improve or even reduced survival in mice bearing Shh + HGF–induced medulloblastomas compared with monotherapy underscores the importance of preclinical testing of molecular-targeted therapies in animal models of tumors in which the targeted pathways are known to be active. Mol Cancer Ther; 9(9); 2627–36. ©2010 AACR.
Passive Ranges of Motion of the Hips and Their Relationship with Pitching Biomechanics and Ball Velocity in Professional Baseball Pitchers
Authors: Robb Andrew J. , Fleisig Glenn , Wilk Kevin , Macrina Leonard , Bolt Becky , Pajaczkowski Jason 
Published: September 2010

Background Pelvis and trunk motions during baseball pitching are associated with ball velocity. Thus, limits in hip flexibility may adversely affect pitching biomechanics and the ability to generate ball velocity. Hypotheses Professional baseball pitchers will have less passive range of motion in the nondominant hip and the measured ranges of motion of both the nondominant and dominant hips will correlate with biomechanical parameters of the lower extremity among professional pitchers. Study Design Cross-sectional study; Level of evidence, 3. Methods Nineteen healthy professional baseball pitchers volunteered for testing. Fluid goniometry was used to measure passive range of motion of adduction (ADD), abduction (ABD), internal rotation, external rotation, total arc of rotation, and total arc of ADD + ABD. Pitching biomechanical data were collected using an automated 3-dimensional motion analysis system while participants threw fastballs. Results Pitchers possessed significantly less passive range of motion in the nondominant hip when compared with the dominant hip for all ranges. Total arc of rotation of the nondominant hip correlated with ball velocity (r = .50). Total arc of ADD + ABD in the nondominant hip and ABD in the nondominant hip were correlated with stride length (r = —.72 and. 70, respectively). Dominant hip ABD (r = .63), total arc of rotation in the nondominant hip (r = —.45), and total arc of ADD + ABD of the dominant hip (r = .44) were correlated with trunk separation. Total arc of ADD + ABD of the nondominant hip (r = —.52) and total arc of rotation of the dominant hip (r = —.44) were correlated with pelvic orientation. Conclusion Passive range of motion is smaller in the nondominant hip than the dominant hip among professional pitchers. The measured disparity between the hips is significantly correlated with various pitching biomechanical parameters of the trunk and pelvis. Future research is required to investigate a causal relationship between less hip passive range of motion and both ball velocity and pitching biomechanics.