bluuebunny/crossref_metadata_2025_split huggingface dataset:
Universal screening detects two-times more thyroid disorders in early pregnancy than targeted high-risk case finding
Authors: Horacek Jiri , Spitalnikova Sylvie , Dlabalova Blanka , Malirova Eva , Vizda Jaroslav , Svilias Ioannis , Cepkova Jitka , Mc Grath Catherine , Maly Jaroslav 
Published: August 2010

ObjectiveScreening of thyroid disorders in pregnancy has been controversial. Recent recommendations favour targeted high-risk case finding, though this approach may miss a significant number of those affected. We aimed to assess the prevalence of accepted high-risk criteria in women with autoimmune thyroiditis and/or hypothyroidism detected from universal screening in an iodine-sufficient population.DesignIn 400 non-selected women in the 9–11th gestational week, thyroid-related tests were performed, and those with abnormalities were offered consultation.MethodsTSH was determined by IRMA, and the upper cut-off value for screening was set at 3.5 mIU/l. For free thyroxine (FT4) and thyroperoxidase antibodies (TPO-Ab), RIAs were used, with cut-offs of <10 pmol/l and >50 IU/ml respectively. Endocrinological consultation included Doppler ultrasonography and was aimed to confirm autoimmune thyroiditis and/or hypothyroidism. The prevalence of consensus high-risk criteria was assessed.ResultsAmong the 400 women, 65 (16.3%) had ≥1 abnormality: higher TSH was found in 10.3%, lower FT4 in 2% and positive TPO-Ab in 8.3%. Fifty-one women were examined and followed up. Levo-T4 treatment was initiated in 49 women for autoimmune thyroiditis (in 42), hypothyroidism (in 34) or both (in 27). Only 22 (45%) of 49 treated women fulfilled ≥1 high-risk criterion: most commonly family history (31%), history of miscarriage or preterm delivery (14%) and personal history (8%).ConclusionsOver half (55%) of pregnant women with abnormalities suggestive of autoimmune thyroiditis and/or hypothyroidism would be missed if only those with high-risk criteria were examined. A more extensive screening of thyroid autoimmunity and dysfunction seems warranted.
Adjuvant Therapy in Non-Small Cell Lung Cancer: Current and Future Directions
Authors: Sangha Randeep , Price Julie , Butts Charles A. 
Published: August 2010

Abstract
The cornerstone of treatment for early-stage non-small cell lung cancer (NSCLC) has long been surgical resection. Over the past few years, there has been a paradigm shift to provide adjuvant platinum-based chemotherapy for patients with completely resected stage II–IIIA NSCLC founded on large randomized clinical trials demonstrating longer overall survival with this treatment. Reassuringly, the National Cancer Institute of Canada Cancer Therapeutics Group JBR.10 trial recently reported a continued survival advantage for patients treated with adjuvant chemotherapy after &gt;9 years of median follow-up. In contrast, the gains from using this approach for stage IB disease are less clear, although data from an unplanned subgroup analysis suggest benefit for patients with tumors ≥4 cm. Herein, we review the evidence supporting adjuvant therapy in early-stage NSCLC patients before discussing key mitigating factors in providing treatment, such as stage of disease and the impact of the new seventh edition of the tumor–node–metastasis classification system. Criteria such as patient age and performance status, as well as the value of appropriate chemotherapy selection, are highlighted as measures to help guide management. The role of postoperative radiotherapy and the future landscape of early-stage NSCLC research are also explored; namely, therapeutic strategies exploiting pharmacogenomic and gene-expression profiling, in an attempt to personalize care, and the integration of novel targeted therapies into adjuvant clinical trials.
Advertising Competition in Retail Markets
Authors: Bagwell Kyle , Lee Gea M 
Published: August 2010

Abstract
We consider non-price advertising by retail firms that are privately informed as to their respective production costs. We construct an advertising equilibrium in which informed consumers use an advertising search rule whereby they buy from the highest-advertising firm. Consumers are rational in using the advertising search rule since the lowest-cost firm advertises the most and also selects the lowest price. Even though the advertising equilibrium facilitates productive efficiency, we establish conditions under which firms enjoy higher expected profit when advertising is banned. Consumer welfare falls in this case, however. Under free entry, social surplus is higher when advertising is allowed. In addition, we consider a benchmark model of price competition; we provide comparative-statics results with respect to the number of informed consumers, the number of firms and the distribution of costs; and we consider the possibility of sequential search.
INS-1 Cells Undergoing Caspase-Dependent Apoptosis Enhance the Regenerative Capacity of Neighboring Cells
Authors: Bonner Caroline , Bacon Siobhán , Concannon Caoimhín G. , Rizvi Syed R. , Baquié Mathurin , Farrelly Angela M. , Kilbride Seán M. , Dussmann Heiko , Ward Manus W. , Boulanger Chantal M. , Wollheim Claes B. , Graf Rolf , Byrne Maria M. , Prehn Jochen H.M. 
Published: August 2010

OBJECTIVE
In diabetes, β-cell mass is not static but in a constant process of cell death and renewal. Inactivating mutations in transcription factor 1 (tcf-1)/hepatocyte nuclear factor1a (hnf1a) result in decreased β-cell mass and HNF1A–maturity onset diabetes of the young (HNF1A-MODY). Here, we investigated the effect of a dominant-negative HNF1A mutant (DN-HNF1A) induced apoptosis on the regenerative capacity of INS-1 cells.

RESEARCH DESIGN AND METHODS
DN-HNF1A was expressed in INS-1 cells using a reverse tetracycline-dependent transactivator system. Gene(s)/protein(s) involved in β-cell regeneration were investigated by real-time quantitative RT-PCR, Western blotting, and immunohistochemistry. Pancreatic stone protein/regenerating protein (PSP/reg) serum levels in human subjects were detected by enzyme-linked immunosorbent assay.

RESULTS
We detected a prominent induction of PSP/reg at the gene and protein level during DN-HNF1A–induced apoptosis. Elevated PSP/reg levels were also detected in islets of transgenic HNF1A-MODY mice and in the serum of HNF1A-MODY patients. The induction of PSP/reg was glucose dependent and mediated by caspase activation during apoptosis. Interestingly, the supernatant from DN-HNF1A–expressing cells, but not DN-HNF1A–expressing cells treated with zVAD.fmk, was sufficient to induce PSP/reg gene expression and increase cell proliferation in naïve, untreated INS-1 cells. Further experiments demonstrated that annexin-V–positive microparticles originating from apoptosing INS-1 cells mediated the induction of PSP/reg. Treatment with recombinant PSP/reg reversed the phenotype of DN-HNF1A–induced cells by stimulating cell proliferation and increasing insulin gene expression.

CONCLUSIONS
Our results suggest that apoptosing INS-1 cells shed microparticles that may stimulate PSP/reg induction in neighboring cells, a mechanism that may facilitate the recovery of β-cell mass in HNF1A-MODY.
Antiobesity Effect of Eicosapentaenoic Acid in High-Fat/High-Sucrose Diet–Induced Obesity
Authors: Sato Ayumi , Kawano Hiroyuki , Notsu Tatsuto , Ohta Masahiko , Nakakuki Masanori , Mizuguchi Kiyoshi , Itoh Michiko , Suganami Takayoshi , Ogawa Yoshihiro 
Published: August 2010

OBJECTIVE
Given the pleiotropic effect of eicosapentaenoic acid (EPA), it is interesting to know whether EPA is capable of improving obesity. Here we examined the anti-obesity effect of EPA in mice with two distinct models of obesity.

RESEARCH DESIGN AND METHODS
Male C57BL/6J mice were fed a high-fat/high-sucrose diet (25.0% [w/w] fat, 32.5% [w/w] sucrose) (HF/HS group) or a high-fat diet (38.1% [w/w] fat, 8.5% [w/w] sucrose) (HF group) for 4–20 weeks. A total of 5% EPA was administered by partially substituting EPA for fat in the HF/HS + EPA and HF + EPA groups.

RESULTS
Both the HF/HS and HF groups similarly developed obesity. EPA treatment strongly suppresses body weight gain and obesity-related hyperglycemia and hyperinsulinemia in HF/HS-fed mice (HF/HS + EPA group), where hepatic triglyceride content and lipogenic enzymes are increased. There is no appreciable effect of EPA on body weight in HF-fed mice (HF + EPA group) without enhanced expression of hepatic lipogenic enzymes. Moreover, EPA is capable of reducing hepatic triglyceride secretion and changing VLDL fatty acid composition in the HF/HS group. By indirect calorimetry analysis, we also found that EPA is capable of increasing energy consumption in the HF/HS + EPA group.

CONCLUSIONS
This study is the first demonstration that the anti-obesity effect of EPA in HF/HS-induced obesity is associated with the suppression of hepatic lipogenesis and steatosis. Because the metabolic syndrome is often associated with hepatic lipogenesis and steatosis, the data suggest that EPA is suited for treatment of the metabolic syndrome.
Identification of a Serum-Induced Transcriptional Signature Associated With Type 1 Diabetes in the BioBreeding Rat
Authors: Kaldunski Mary , Jia Shuang , Geoffrey Rhonda , Basken Joel , Prosser Simon , Kansra Sanjay , Mordes John P. , Lernmark Åke , Wang Xujing , Hessner Martin J. 
Published: August 2010

OBJECTIVEInflammatory mediators associated with type 1 diabetes are dilute and difficult to measure in the periphery, necessitating development of more sensitive and informative biomarkers for studying diabetogenic mechanisms, assessing preonset risk, and monitoring therapeutic interventions.RESEARCH DESIGN AND METHODSWe previously utilized a novel bioassay in which human type 1 diabetes sera were used to induce a disease-specific transcriptional signature in unrelated, healthy peripheral blood mononuclear cells (PBMCs). Here, we apply this strategy to investigate the inflammatory state associated with type 1 diabetes in biobreeding (BB) rats.RESULTSConsistent with their common susceptibility, sera of both spontaneously diabetic BB DRlyp/lyp and diabetes inducible BB DR+/+ rats induced transcription of cytokines, immune receptors, and signaling molecules in PBMCs of healthy donor rats compared with control sera. Like the human type 1 diabetes signature, the DRlyp/lyp signature, which is associated with progression to diabetes, was differentiated from that of the DR+/+ by induction of many interleukin (IL)-1–regulated genes. Supplementing cultures with an IL-1 receptor antagonist (IL-1Ra) modulated the DRlyp/lyp signature (P &lt; 10−6), while administration of IL-1Ra to DRlyp/lyp rats delayed onset (P = 0.007), and sera of treated animals did not induce the characteristic signature. Consistent with the presence of immunoregulatory cells in DR+/+ rats was induction of a signature possessing negative regulators of transcription and inflammation.CONCLUSIONSParalleling our human studies, serum signatures in BB rats reflect processes associated with progression to type 1 diabetes. Furthermore, these studies support the potential utility of this approach to detect changes in the inflammatory state during therapeutic intervention.
Femoral Adipose Tissue May Accumulate the Fat That Has Been Recycled as VLDL and Nonesterified Fatty Acids
Authors: McQuaid Siobhán E. , Humphreys Sandy M. , Hodson Leanne , Fielding Barbara A. , Karpe Fredrik , Frayn Keith N. 
Published: August 2010

OBJECTIVE
Gluteo-femoral, in contrast to abdominal, fat accumulation appears protective against diabetes and cardiovascular disease. Our objective was to test the hypothesis that this reflects differences in the ability of the two depots to sequester fatty acids, with gluteo-femoral fat acting as a longer-term “sink.”

RESEARCH DESIGN AND METHODS
A total of 12 healthy volunteers were studied after an overnight fast and after ingestion of a mixed meal. Blood samples were taken from veins draining subcutaneous femoral and abdominal fat and compared with arterialized blood samples. Stable isotope-labeled fatty acids were used to trace specific lipid fractions. In 36 subjects, adipose tissue blood flow in the two depots was monitored with 133Xe.

RESULTS
Blood flow increased in response to the meal in both depots, and these responses were correlated (rs = 0.44, P &lt; 0.01). Nonesterified fatty acid (NEFA) release was suppressed after the meal in both depots; it was lower in femoral fat than in abdominal fat (P &lt; 0.01). Plasma triacylglycerol (TG) extraction by femoral fat was also lower than that by abdominal fat (P = 0.05). Isotopic tracers showed that the difference was in chylomicron-TG extraction. VLDL-TG extraction and direct NEFA uptake were similar in the two depots.

CONCLUSIONS
Femoral fat shows lower metabolic fluxes than subcutaneous abdominal fat, but differs in its relative preference for extracting fatty acids directly from the plasma NEFA and VLDL-TG pools compared with chylomicron-TG.
A 1-Year Lifestyle Intervention for Weight Loss in Individuals With Type 2 Diabetes Reduces High C-Reactive Protein Levels and Identifies Metabolic Predictors of Change
Authors: Belalcazar L. Maria , Reboussin David M. , Haffner Steven M. , Hoogeveen Ron C. , Kriska Andrea M. , Schwenke Dawn C. , Tracy Russell P. , Pi-Sunyer F. Xavier , Ballantyne Christie M. ,   for the Look AHEAD Research Group
Published: August 2010

OBJECTIVE
We examined whether a 1-year intensive lifestyle intervention (ILI) for weight loss reduced elevated high-sensitivity C-reactive protein (hs-CRP) levels in obese individuals with diabetes and identified metabolic and fitness predictors of hs-CRP change.

RESEARCH DESIGN AND METHODS
Look AHEAD (Action for Health in Diabetes) is an ongoing multicenter clinical trial examining the effects of weight loss achieved through ILI on cardiovascular events and overall mortality in obese/overweight adults with type 2 diabetes. We report on 1,759 Look AHEAD participants who had hs-CRP and fitness data at baseline and 1 year. Subjects were randomly assigned to ILI or to usual care (diabetes support and education [DSE]). ILI involved frequent counseling to increase moderate-intensity exercise to 175 min/week, reduce caloric and saturated fat intake, and change macronutrient composition to improve glycemic control.

RESULTS
ILI reduced median hs-CRP by 43.6% from baseline to 1 year, compared with a 16.7% reduction with DSE (P &lt; 0.001). ILI decreased weight (8.8%), A1C (0.7%), and triglycerides (17%) and increased fitness (19%) and HDL cholesterol (7.5%) (P &lt; 0.0001 vs. changes with DSE). Changes in adiposity and glucose control with ILI remained independent predictors of hs-CRP change at 1 year (P &lt; 0.0001 for each) after adjustment for demographics, smoking, cardiovascular history, statin and thiazolidinedione use, and changes in fitness and lipid control. Neither statin nor insulin therapy modified the association between ILI and hs-CRP.

CONCLUSIONS
A 1-year lifestyle intervention for weight loss in obese individuals with diabetes was associated with substantial reductions in hs-CRP. Improved glycemic control and reduced adiposity had comparable effects on hs-CRP change.
Synthesis and Biological Evaluation of Heat-Shock Protein 90 Inhibitors: Geldanamycin Derivatives with Broad Antiviral Activities
Authors: Li Yan-Ping , Shan Guang-Zhi , Peng Zong-Gen , Zhu Jian-Hua , Meng Shuai , Zhang Tian , Gao Lin-Yan , Tao Pei-Zhen , Gao Rong-Mei , Li Yu-Huan , Jiang Jian-Dong , Li Zhuo-Rong 
Published: August 2010

Background: Previous studies have suggested that geldanamycin (GA) inhibits the replication of several viruses in vitro. Here, we aimed to synthesize and evaluate the antiviral activity of 17-amino-17-demethoxygeldanamycin derivatives. Methods: A series of 17-substituted and 17-,19-disubstituted GA derivatives were screened for antiviral activities against eight different viral strains, including herpesvirus, hepatitis virus, retrovirus and picornavirus. Results: Most of the tested compounds showed inhibitory activity against the viruses and showed reduced cytotoxicity in vitro as compared with the parent compound GA. In vivo efficacy evaluation results showed that compound 6 noticeably inhibited duckling hepatitis B virus DNA replication in duckling serum after oral administration. Viral rebound did not occur after termination of the treatment. The modified GA derivatives also showed median lethal dose values that were higher than that of the parent GA in mice intraperitoneally treated with the study compounds. Conclusions: Targeting heat-shock protein 90 could be a new antiviral approach that is not prone to the development of drug resistance. The 17-amino-17-demethoxygeldanamycin derivatives could be novel agents with potential antiviral activity.
The Relation of Interleukin 17 (IL-17) and IL-23 to Th1/Th2 Cytokines and Disease Activity in Systemic Lupus Erythematosus
Authors: MOK MO YIN , WU HAI JING , LO YI , LAU CHAK SING 
Published: August 2010

Objective.Interleukin 17 (IL-17) was recently linked to pathogenesis of systemic lupus erythematosus (SLE), but its relation to disease activity has not been well characterized. We examined the relation between serum levels of Th17 (IL-17, IL-23), Th1 (IL-12, interferon-γ), Th2 (IL-10, IL-6, IL-4) cytokines and disease activity in patients with SLE.Methods.Serum cytokines were measured by enzyme linked immunosorbent assays. Disease activity was determined by SLE disease activity index (SLEDAI), anti-dsDNA antibody, and C3 and C4 levels.Results.Serum levels of IL-17 (p < 0.001), IL-6 (p = 0.006) and IL-10 (p < 0.001) were higher in SLE patients (n = 70) compared to healthy controls (n = 36). Higher serum IL-23 level was found in patients with active disease with cutaneous manifestations (p = 0.004) and serositis (p = 0.04) compared to those without. Serum IL-17 level above the detection limit was more frequently found in patients who had active lupus nephritis (11/23, 47.8%) (p = 0.002), nonrenal active disease (9/15, 60%) (p = 0.001), and inactive lupus (21/32, 65.6%) (p < 0.001) compared to healthy controls (0%). Serum IL-17 levels were otherwise comparable between these 3 groups of patients and were not related to SLEDAI, glomerular filtration rate, activity or chronicity score and ISN/RPS criteria class among patients with active lupus nephritis. There was no significant correlation between serum IL-17/IL-23 and Th1 or Th2 cytokine levels.Conclusion.SLE patients had higher serum IL-17 levels than healthy controls. Elevated serum IL-23 was found in patients with inflammatory manifestations including cutaneous involvement and serositis. The lack of correlation between Th17, Th1, and Th2 cytokines suggested independent regulatory mechanisms for these cytokines.
De la mesure de l'intelligence au développement mental : la mobilité épistémologique d'Alfred Binet
Authors: Andrieu Bernard 
Published: August 2010

RÉSUMÉ La science pédagogique était-elle le projet d’Alfred Binet ou seulement un terrain de circonstance pour une théorie cognitive plus holistique ? Le défaut de la pédagogie expérimentale, même si elle ne consiste pas en un exercice séparé, est de présenter une théorie analytique du fonctionnement de l’esprit. Les différents examens pédagogiques et mesures de la croissance physique, de la vision, de l’audition, de l’écriture, de la lecture ou de l’orthographe s’avèrent pertinents en eux-mêmes mais ils séparent l’intelligence des phénomènes de sensibilité, d’émotion et de volonté. A. Binet 1, celui qui collabore avec Th. Simon, Vaney ou encore Belot, étudie le développement mental à partir du modèle anthropométrique de manière partielle, précise et discontinue. La coupe est ici synchronique produisant d’instantanées et légitimant la pédagogie comparée. Un A. Binet 2, pour autant que ce soit un second Binet dans le temps, à moins que ce ne soit un dédoublement A. Binet 1 pratique A. Binet théorie, est le résultat d’une mobilité épistémologique : celle de rechercher une théorie synthétique du développement mental sans modèle biologique.
Compréhension de la dissimulation des émotions chez l'enfant d'âge scolaire
Authors: Perron Mélanie , Gosselin Pierre 
Published: August 2010

RÉSUMÉ Cette étude examine la compréhension de la notion de dissimulation des émotions au cours de la deuxième moitié de l’enfance. Une attention particulière est prêtée à la justesse et à la complexité du raisonnement des enfants lorsqu’ils doivent expliquer les raisons pour lesquelles une personne dissimule une émotion qu’elle ressent. L’épreuve de compréhension est administrée à 74 enfants âgés entre 5 et 10 ans. Les résultats montrent que les enfants de 9-10 ans comprennent mieux la distinction entre les émotions réelles et apparentes que ceux de 5-6 ans et que leur raisonnement est plus juste et plus complexe. Cependant, une minorité d’enfants de 9-10 ans parviennent à expliquer le phénomène de dissimulation en termes de pensée récursive. Les jeunes enfants ont de la difficulté à expliquer les raisons qui conduisent une personne à dissimuler une émotion. Ils ont tendance à se représenter le phénomène de la dissimulation en termes de changements d’émotions réelles.
Reproduction d'une figure complexe par des enfants d'âge préscolaire
Authors: Lefèvre Cécile , Danis Agnès , Bourdais Cécile , Devouche Emmanuel , Serres Josette , Prudhomme Nathalie , Pêcheux M.-G. , Smina N. 
Published: August 2010

En utilisant un modèle proposé par Rey, on étudie ici comment évoluent, entre 3 et 6 ans, les représentations graphiques d’une figure complexe. Le modèle associe 11 éléments simples (cercle, croix, etc.) en fonction de relations d’inclusion ou d’intersection. Les enfants doivent d’abord copier le modèle, puis le reproduire de mémoire après un délai ; on enregistre par une tablette graphique l’ordre de reproduction des différents éléments. On a distingué différents niveaux de performance : les gribouillis, les éléments principaux séparés, tangents ou sécants. L’évolution avec l’âge se fait dans cet ordre, avec une grande variation interindividuelle. À tous les âges la reproduction est le plus souvent faite de gauche à droite. Les reproductions de mémoire sont de même niveau que les copies. Tous ces résultats concourent à montrer que les jeunes enfants fonctionnent de préférence de proche en proche, sans planification globale de leur activité, bien qu’ils parviennent à se représenter l’ensemble de la figure.
Perception de la maladie chez des enfants asthmatiques et leurs parents
Authors: Chateaux Véronique , Spitz Elisabeth 
Published: August 2010

RÉSUMÉ L’objectif de cette recherche était d’appréhender la perception de l’asthme par l’enfant asthmatique et ses parents. Des enfants asthmatiques (N = 146 ; 8-12 ans) rencontrés en centre de cure et à l’hôpital, et 92 parents ont complété le questionnaire de perception de la maladie : Revised-Illness Perception Questionnaire. Les résultats montrent que la perception de l’asthme i) entre enfants (cure/hôpital) et entre parents (cure/hôpital) ne diffère presque pas, ii) entre enfants et parents diffère. Les enfants disent que leur asthme dépend d’eux, qu’ils peuvent l’influencer, tandis que leurs parents sont plus sensibles à la chronicité de la maladie, et semblent mieux comprendre l’asthme. L’originalité de cette recherche tient à l’utilisation d’un questionnaire de perception de la maladie auprès d’enfants et de leurs parents. Ce travail pourrait être prolongé dans le cadre d’autres maladies chroniques pédiatriques.
Introduction
Authors: Courtin Cyril 
Published: August 2010

RÉSUMÉ Nous souhaitons ici en premier lieu fournir aux parents quelques données leur permettant d’envisager le devenir de leur enfant sourd, et donner aux enseignants des points de repère dans leur pratique quotidienne. Il nous faut donc revenir sur les spécificités linguistiques, cognitives, culturelles de l’enfant sourd, les particularités du système éducatif dans lequel il évolue, etc. On souhaite également déterminer si ces spécificités ne sont pas des clichés entretenus d’un côté et de l’autre du monde gravitant autour de la surdité, deux pôles, pro-signes vs pro-oralisme, qu’il s’agirait de dépasser afin de faire le point sur ce que l’on sait et ce que l’on ne sait pas. C’est un des motifs sous-tendant la publication de ce numéro thématique.