bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Hepatitis C Treatment on Cd4+ T-C El L Counts And The Risk Of Death In HIV–HCV-Coinfected Patients: The Cohere Collaboration
Authors:   The HCV working group of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord, Smit Colette , Sterne Jonathan AC , d'Arminio Monforte Antonella , Puotti Massimo , de Wolf Frank , Peters Lars , Ledergerber Bruno , de Wit Stephane , Sambatakou Hellen , Rauch Andri , Dabis Francois 
Published: August 2012

Background The short- and long-term effects of anti-hepatitis C treatment on mortality in the HIV–HCV-coinfected population have not been evaluated in observational cohorts. Such evaluations must use methods that allow for time-varying prognostic factors that both predict treatment and are affected by prior treatment. We aimed to study immunological changes in HIV–HCV-coinfected individuals during HCV treatment and to estimate the effect of HCV-treatment on mortality. Methods Patients were included if they were aged ≥16 years, were HIV–HCV-coinfected and were enrolled in the COHERE cohort. Data were pooled within COHERE in December 2009 in EuroCoord. Random-effects models were used to model immunological changes during HCV treatment. Marginal structural models were used to estimate the effect of HCV treatment on mortality, allowing for time-dependent confounders affected by prior treatment. Results In total, 780/6,433 (12%) HIV–HCV-coinfected patients initiated HCV treatment (interferon [IFN] and ribavirin n=692, IFN alone n=88). CD4+ T-cell counts decreased during the first 12 weeks of treatment ( P<0.0001) and stabilized from week 24 onwards. The estimated mortality hazard ratio for comparing HCV-treated with -untreated individuals was 0.72 (95% CI 0.43, 1.21). The estimated hazard ratio for liver-related death was 0.57 (95% CI 0.21, 1.55). Conclusions Despite its effect in reducing CD4+ T-cell counts, the effect of HCV treatment on mortality was in the direction of benefit and our results excluded a substantial increase in mortality. Such benefit may be related to a lower risk of liver-related death. New HCV treatment strategies might contribute to a further reduction in mortality.
Vitamin D Deficiency and Its Relation to Bone Mineral Density and Liver Fibrosis in HIV–HCV Coinfection
Authors: El-Maouche Diala , Mehta Shruti H , Sutcliffe Catherine G , Higgins Yvonne , Torbenson Michael S , Moore Richard D , Thomas David L , Sulkowski Mark S , Brown Todd T 
Published: August 2012

Background Fractures and cirrhosis are major causes of morbidity and mortality among HIV–HCV-coinfected individuals. It is not known whether vitamin D deficiency is associated with these outcomes. Methods Between 2005 and 2007, 116 HIV–HCV-coinfected individuals underwent dual-energy X-ray absorptiometry within 1 year of a liver biopsy. 25-Hydroxyvitamin D (25OHD) and parathyroid hormone were measured from archived samples. Low bone mineral density (BMD) was defined as BMD≥2 standard deviations lower than age-, sex- and race-matched controls (Z-score ≤-2.0) at the total hip, femoral neck or lumbar spine. Histological fibrosis staging was assessed according to the METAVIR system (0 [no fibrosis] to 4 [cirrhosis]). Results The cohort was 87% African-American and 63% male. The median age (IQR) was 49.9 years (46.5–53.3). A total of 89% had a CD4+ T-cell count >200 cells/mm3 and 64% were receiving HAART. The median 25OHD was 19 ng/ ml (IQR 11.0-26.0). Hypovitaminosis D (25OHD≤15 ng/ml) was present in 41% and secondary hyperparathyroidism, defined by parathyroid hormone >65 pg/ml, was present in 24%. In total, 27% had low BMD (Z-score ≤-2) at the spine, femoral neck or total hip, and 39% had significant hepatic fibrosis (METAVIR≥2). In multivariate analysis, vitamin D deficiency was not associated with significant fibrosis or with BMD at any site. Conclusions Vitamin D deficiency was highly prevalent in this mostly African-American HIV-HCV-coinfected population, but was not related to BMD or liver disease severity. These data suggest that efforts to increase vitamin D levels in this population may not improve bone or liver outcomes.
Clinical and Virological Response to Entecavir in HBV-Related Chronic Hepatitis or Cirrhosis: Data from the Clinical Practice in a Single-Centre Cohort
Authors: Marengo Andrea , Bitetto Davide , D'Avolio Antonio , Ciancio Alessia , Fabris Carlo , Marietti Milena , Toniutto Pierluigi , Perri Giovanni Di , Rizzetto Mario , Marzano Alfredo 
Published: August 2012

Background Limited data are available on entecavir in Caucasian patients with HBV cirrhosis or chronic hepatitis B who are treated in the clinical practice. The aim was to evaluate the efficacy of entecavir in an Italian cohort of unselected patients with different stages of liver fibrosis, comparing the virological and clinical results obtained between patients with and without liver cirrhosis. Methods Efficacy and safety of entecavir were retrospectively evaluated in 100 patients recruited in the Gastro-Hepatology Unit, San Giovanni Battista Hospital (Turin, Italy). A pharmacokinetic analysis was performed in 34 participants to assess whether cirrhosis may affect entecavir metabolism. Participants were followed-up for a median (range) duration of 21 months (2–108). Results Rates of virological response (negative viraemia by PCR for ≥2 consecutive determinations) after 12, 24 and 36 months were 91.7%, 97.5% and 93.7%, respectively. In the 84 patients who were treated for ≥12 months, presence of cirrhosis (OR 1.730, 95% CI 1.082, 2.766; P=0.022) and absence of hepatitis B e antigen (OR 0.479, 95% CI 0.273, 0.842; P=0.011) were independent predictors of earlier clearance of serum HBV DNA. There were no differences between the serum concentrations in the steady-state level of entecavir between patients with or without cirrhosis. No significant differences were detected between the average area under the curve in the means of the two groups ( P=0.55). Conclusions Entecavir represents an excellent therapy in patients with HBV-related liver disease and particularly with cirrhosis where it showed a good profile of tolerability, higher efficacy and an earlier virological response.
Grandir avec une rectocolite (commentaire de l'article de Claire Rojas)
Authors: Szwec Gérard 
Published: August 2012

Résumé Dans la discussion du cas, présenté par C. Rojas, d’un enfant en période de latence atteint d’une rectocolite hémorragique, l’auteur considère que les jeux de cet enfant sont révélateurs d’un état traumatique. Il discute de la sortie progressive de cet état à travers l’évolution de ces jeux vers une conflictualité œdipienne plus classique.
Les psychothérapies conjointes parent(s)/enfant d'inspiration psychanalytique
Authors: Golse Bernard 
Published: August 2012

Résumé La psychanalyse des enfants a été longtemps contestée dans sa légitimité, et plus récemment les psychothérapies conjointes parents/bébé qui se trouvent pourtant en plein essor depuis quelques années. S’agit-il d’une récente et authentique conquête de la psychanalyse, ou s’agit-il seulement d’une dérive ? Les axes de réflexion que nous proposons ici sont ceux du cadre tout d’abord, de l’analyse des résistances, du transfert et du contre-transfert ensuite, de la topique, et enfin de la place de la verbalisation au regard de celle de l’interprétation.
Les bébés-bulles
Authors: Weil-Halpern Françoise 
Published: August 2012

Résumé La décision de pratiquer une greffe de moelle et de confiner un nourrisson en enceinte stérile ou « bulle » a provoqué beaucoup de questions en 1970. Nous n’avions aucune idée de la manière dont ces mères, ces parents allaient supporter la séparation dès les premiers jours de vie et la limitation des activités de toucher, des stimulations corporelles, affectives dans un milieu hospitalier. C’était le début d’une grande aventure, jalonnée d’interrogations spécifiques. Il s’agissait de découvrir, de confirmer ou d’infirmer les données concernant le développement du bébé, les interactions entre la mère et son enfant dans un système potentiellement carentiel en regard de toutes les connaissances théoriques et cliniques du moment.
Quel lien entre le bébé prématuré et ses parents en médecine néonatale ?
Authors: Druon Catherine 
Published: August 2012

Résumé La question qui se pose, à la lumière des entretiens psychanalytiques avec les parents durant le séjour de leur bébé hospitalisé pour prématurité en réanimation néonatale, est celle des séquelles dans la relation liées à la souffrance physique de l’enfant et à la souffrance psychique des parents. Comment tout cela s’inscrira-t-il ou non dans la mémoire inconsciente corporelle de l’enfant et dans le mode relationnel parents-enfant ultérieur ?
NK Cells Regulate CD8+ T Cell Priming and Dendritic Cell Migration during Influenza A Infection by IFN-γ and Perforin-Dependent Mechanisms
Authors: Ge Moyar Qing , Ho Adrian W. S. , Tang Yafang , Wong Kenneth H. S. , Chua Benson Y. L. , Gasser Stephan , Kemeny David Michael 
Published: August 2012

Abstract
An effective immune response against influenza A infection depends on the generation of virus-specific T cells. NK cells are one of the first-line defenses against influenza A infection. We set out to delineate the role of NK cells in T cell immunity using a murine model of influenza A infection with A/PR/8/34. We show that early T cell recruitment mainly occurs in the posterior mediastinal lymph node (pMLN). Depletion of NK cells significantly impaired both dendritic cell (DC) and T cell recruitment into the pMLN. A similar reduction of T cell recruitment was observed when migration was blocked by pertussis toxin, suggesting that migration of pulmonary NK cells and DCs regulates cell recruitment to the pMLN. T cell recruitment was dependent on IFN-γ, and transfer of IFN-γ–competent naive NK cells into IFN-γ−/− mice restored T cell recruitment, whereas IFN-γ–deficient NK cells failed to do so. In addition, NK cell depletion reduced the uptake and transport of influenza A virus by DCs, and significantly impaired the virus-specific T cell response. Both IFN-γ−/− and perforin−/− mice showed reduced viral Ag transport by DCs, suggesting that the ability of NK cells to influence virus transport depends on IFN-γ and perforin. In summary, our data suggest that NK cells play a critical role in the initiation and shaping of the T cell response after influenza A infection.
IFN-γ Production by Allogeneic Foxp3+ Regulatory T Cells Is Essential for Preventing Experimental Graft-versus-Host Disease
Authors: Koenecke Christian , Lee Chun-Wei , Thamm Kristina , Föhse Lisa , Schafferus Matthias , Mittrücker Hans-Willi , Floess Stefan , Huehn Jochen , Ganser Arnold , Förster Reinhold , Prinz Immo 
Published: August 2012

Abstract
It is emerging that CD4+Foxp3+ regulatory T (Treg) cells can produce the proinflammatory cytokine IFN-γ when stimulated in a Th1 cytokine environment. In this study, we report that Foxp3+ Treg cells readily produced IFN-γ in vivo in a highly inflammatory model of graft-versus-host disease (GVHD) and during a Th1-dominated immune response to intracellular bacteria. Moreover, stimulation in vitro via TCR in the presence of IL-12 alone was sufficient to induce IFN-γ production by Treg cells in a dose-dependent manner. Transfer of donor Treg cells can prevent lethal GVHD; therefore, we used this model as a robust readout for in vivo Treg function. Interestingly, &gt;50% of allogeneic donor, but not residual recipient Foxp3+ Treg cells produced IFN-γ after transplantation, suggesting that this cytokine production was alloantigen specific. These IFN-γ producers were stable Foxp3+ Treg cells because methylation analysis of the Foxp3 gene locus of transferred and reisolated Treg cells during GVHD showed a fully demethylated Treg-specific–demethylated region. Next, we addressed whether IFN-γ production was supporting or rather impairing the immunosuppressive function of Treg cells during GVHD. Blocking of IFN-γ with specific mAb completely abolished the beneficial effect of donor Treg cells. We could further show that only wild-type Treg cells, but not Treg cells from IFN-γ–deficient donor mice, prevented GVHD. This indicated that Treg cell-intrinsic IFN-γ production was required for their protective function. In conclusion, our data show that IFN-γ produced by Foxp3+ Treg cells has essential immune-regulatory functions that are required for prevention of experimental GVHD.
Dietary Folic Acid Promotes Survival of Foxp3+ Regulatory T Cells in the Colon
Authors: Kinoshita Makoto , Kayama Hisako , Kusu Takashi , Yamaguchi Tomoyuki , Kunisawa Jun , Kiyono Hiroshi , Sakaguchi Shimon , Takeda Kiyoshi 
Published: August 2012

Abstract
Dietary compounds as well as commensal microbiota contribute to the generation of a unique gut environment. In this study, we report that dietary folic acid (FA) is required for the maintenance of Foxp3+ regulatory T cells (Tregs) in the colon. Deficiency of FA in the diet resulted in marked reduction of Foxp3+ Tregs selectively in the colon. Blockade of folate receptor 4 and treatment with methotrexate, which inhibits folate metabolic pathways, decreased colonic Foxp3+ Tregs. Compared with splenic Tregs, colonic Tregs were more activated to proliferate vigorously and were highly sensitive to apoptosis. In colonic Tregs derived from mice fed with a FA-deficient diet, expression of anti-apoptotic molecules Bcl-2 and Bcl-xL was severely decreased. A general reduction of peripheral Tregs was induced by a neutralizing Ab against IL-2, but a further decrease by additional FA deficiency was observed exclusively in the colon. Mice fed with an FA-deficient diet exhibited higher susceptibility to intestinal inflammation. These findings reveal the previously unappreciated role of dietary FA in promotion of survival of Foxp3+ Tregs that are in a highly activated state in the colon.
Role of Mincle in Alveolar Macrophage-Dependent Innate Immunity against Mycobacterial Infections in Mice
Authors: Behler Friederike , Steinwede Kathrin , Balboa Luciana , Ueberberg Bianca , Maus Regina , Kirchhof Gabriele , Yamasaki Sho , Welte Tobias , Maus Ulrich A. 
Published: August 2012

Abstract
The role of macrophage-inducible C-type lectin Mincle in lung innate immunity against mycobacterial infection is incompletely defined. In this study, we show that wild-type (WT) mice responded with a delayed Mincle induction on resident alveolar macrophages and newly immigrating exudate macrophages to infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG), peaking by days 14–21 posttreatment. As compared with WT mice, Mincle knockout (KO) mice exhibited decreased proinflammatory mediator responses and leukocyte recruitment upon M. bovis BCG challenge, and they demonstrated increased mycobacterial loads in pulmonary and extrapulmonary organ systems. Secondary mycobacterial infection on day 14 after primary BCG challenge led to increased cytokine gene expression in sorted alveolar macrophages of WT mice, but not Mincle KO mice, resulting in substantially reduced alveolar neutrophil recruitment and increased mycobacterial loads in the lungs of Mincle KO mice. Collectively, these data show that WT mice respond with a relatively late Mincle expression on lung sentinel cells to M. bovis BCG infection. Moreover, M. bovis BCG-induced upregulation of C-type lectin Mincle on professional phagocytes critically shapes antimycobacterial responses in both pulmonary and extrapulmonary organ systems of mice, which may be important for elucidating the role of Mincle in the control of mycobacterial dissemination in mice.
CD133+, CD166+CD44+, and CD24+CD44+ Phenotypes Fail to Reliably Identify Cell Populations with Cancer Stem Cell Functional Features in Established Human Colorectal Cancer Cell Lines
Authors: Muraro Manuele Giuseppe , Mele Valentina , Däster Silvio , Han Junyi , Heberer Michael , Cesare Spagnoli Giulio , Iezzi Giandomenica 
Published: August 2012

Abstract
Increasing evidence that cancers originate from small populations of so-called cancer stem cells (CSCs), capable of surviving conventional chemotherapies and regenerating the original tumor, urges the development of novel CSC-targeted treatments. Screening of new anticancer compounds is conventionally conducted on established tumor cell lines, providing sufficient material for high-throughput studies. Whether tumor cell lines might comprise CSC populations resembling those of primary tumors, however, remains highly debated. We have analyzed the expression of defined phenotypic profiles, including CD133+, CD166+CD44+, and CD24+CD44+, reported as CSC-specific in human primary colorectal cancer (CRC), on a panel of 10 established CRC cell lines and evaluated their correlation with CSC properties. None of the putative CSC phenotypes consistently correlated with stem cell-like features, including spheroid formation ability, clonogenicity, aldehyde dehydrogenase-1 activity, and side population phenotype. Importantly, CRC cells expressing putative CSC markers did not exhibit increased survival when treated with chemotherapeutic drugs in vitro or display higher tumorigenicity in vivo. Thus, the expression of CD133 or the coexpression of CD166/CD44 or CD24/CD44 did not appear to reliably identify CSC populations in established CRC cell lines. Our findings question the suitability of cell lines for the screening of CSC-specific therapies and underline the urgency of developing novel platforms for anticancer drug discovery.
Serum- and Stromal Cell-Free Hypoxic Generation of Embryonic Stem Cell-Derived Hematopoietic Cells In Vitro, Capable of Multilineage Repopulation of Immunocompetent Mice
Authors: Lesinski Dietrich Armin , Heinz Niels , Pilat-Carotta Sandra , Rudolph Cornelia , Jacobs Roland , Schlegelberger Brigitte , Klump Hannes , Schiedlmeier Bernhard 
Published: August 2012

Abstract
Induced pluripotent stem cells (iPSCs) may become a promising source for the generation of patient-specific hematopoietic stem cells (HSCs) in vitro. A crucial prerequisite will be the availability of reliable protocols for the directed and efficient differentiation toward HSCs. So far, the most robust strategy for generating HSCs from pluripotent cells in vitro has been established in the mouse model involving ectopic expression of the human transcription factor HOXB4. However, most differentiation protocols include coculture on a xenogenic stroma cell line and the use of animal serum. Involvement of any of both would pose a major barrier to the translation of those protocols to human autologous iPSCs intended for clinical use. Therefore, we asked whether long-term repopulating HSCs can, in principle, be generated from embryonic stem cells without stroma cells or serum. Here, we showed that long-term multilineage engraftment could be accomplished in immunocompetent mice when HSCs were generated in serum-free medium without stroma cell support and when hypoxic conditions were used. Under those conditions, HOXB4+ embryonic stem cell-derived hematopoietic stem and progenitor cells were immunophenotypically similar to definitive bone marrow resident E-SLAM+ (CD150+CD48−CD45+CD201+) HSCs. Thus, our findings may ease the development of definitive, adult-type HSCs from pluripotent stem cells, entirely in vitro.
Numerical modeling of seasonal and mesoscale hydrography and circulation in the Mexican Central Pacific
Authors: Pantoja DA , Marinone SG , Parés-Sierra A , Gómez-Valdivia F 
Published: August 2012

Based on results from a ROMS numerical model, the dynamics of the Mexican Central Pacific was studied during three years (2003–2005). The model reproduces the mean and seasonal variability of sea surface temperature, as well as mesoscale eddies and meanders from satellite observations. The model adequately represents the main currents in the region: California Current, Mexican Coastal Current, and Gulf of California currents. The Gulf of California currents are linked to the intensificiation of the Mexican Coastal Current and interact in such a way that the lateral shear generates eddies at the entrance to the Gulf of California. The mesoscale eddies were found to have a depth of ~200 m. The eddies generated in the area (internal Rossby radius of deformation, Rd = 40 km) had a diameter L of ~300 km, an orbital speed of 20–30 cm s–1, and a westward translation speed of ~4 cm s–1. Eddies are considered from intermediate to big (L≈ 7.5 Rd, Ro << 1), show geostrophic dynamics, and present a westward drift due to Coriolis variation with latitude (beta effect). The size of the eddies seems to be related to the weakening of the meridional component of wind stress during the North American monsoon.
An In Situ Experimental‐Numerical Approach for Characterization and Prediction of Interface Delamination: Application to CuLF‐MCE Systems
Authors: Kolluri Murthy , Hoefnagels Johan P. M. , Samimi Mohammad , van Dommelen Hans , van der Sluis Olaf , Geers Marc G. D. 
Published: August 2012

AbstractPrevention of delamination failures by improved design calls for accurate characterization and prediction of mixed‐mode interface delamination. In this paper, a combined in situ experimental‐numerical approach is presented to fully characterize the interface behavior for delamination prediction. The approach is demonstrated on two types of industrially‐relevant interface samples – coated copper lead frame‐black molding compound epoxy and uncoated copper lead frame‐white molding compound epoxy, – for which the delamination behavior is characterized in detail using a miniaturized in situ SEM mixed‐mode bending setup and simulated using a newly developed self‐adaptive cohesive zone (CZ) finite element framework. To this end, mixed‐mode load‐displacement responses, fracture toughness versus mode angle trends, and real‐time microscopic observations of the delamination front are analyzed to determine all CZ parameters. The various simulation results are found to be in agreement with experiments for the range of mode mixities accessible, demonstrating the ability of the characterization procedure to accurately obtain the cohesive properties of different interfaces, as well as the stability and efficiency of the self‐adaptive CZ framework.
Following Chemical Charge Trapping in Pentacene Thin Films by Selective Impurity Doping and Wavelength‐Resolved Electric Force Microscopy
Authors: Smieska Louisa M. , Pozdin Vladimir A. , Luria Justin L. , Hennig Richard G. , Hines Melissa A. , Lewis Chad A. , Marohn John A. 
Published: August 2012

AbstractCharge trapping is one of several factors that limit the performance of organic electronic materials, yet even in pentacene, a prototypical small‐molecule semiconductor, the precise chemical nature of charge trapping remains poorly understood. Here the effects of three chemical trap‐precursor candidates are examined by layering thin‐film pentacene transistors with different pentacene defect species. The resulting charge trapping is studied in each device via scanning‐probe electric force microscopy coupled with variable‐wavelength sample illumination. Firstly, it is found that layering with pentacen‐6(13H)‐one (PHO) readily produces uniform charge trapping everywhere in the transistor channel, as expected for an active blanket‐deposited trap‐precursor. However, layering with 6,13‐dihydropentacene (DHP) produces fewer, more‐isolated traps, closely resembling the surface potential distribution in pristine pentacene thin films. Secondly, the rates of trap‐clearing versus illuminating wavelength (trap‐clearing spectra) are measured, revealing enhanced trap‐clearing rates at wavelengths assigned to the absorption of either pentacene or the charged trap species. The trap‐clearing spectrum for the PHO‐layered sample closely resembles the spectrum obtained from pentacene aged in a working transistor, while the trap‐clearing spectrum for the DHP‐layered sample resembles the spectrum observed in pristine pentacene. We conclude that PHO competently creates traps in pentacene that match the expected trap‐clearing spectrum for degraded pentacene, while DHP does not, and that the chemical trap species in aged pentacene is very likely PHO+.