bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1–related Hodgkin lymphoma in the era of combination antiretroviral therapy: incidence and evolution of CD4+ T-cell lymphocytes
Authors: Bohlius Julia , Schmidlin Kurt , Boué François , Fätkenheuer Gerd , May Margaret , Caro-Murillo Ana Maria , Mocroft Amanda , Bonnet Fabrice , Clifford Gary , Paparizos Vassilios , Miro Jose M. , Obel Niels , Prins Maria , Chêne Geneviève , Egger Matthias ,   Collaboration of Observational HIV Epidemiological Research Europe
Published: March 2011

AbstractThe risk of Hodgkin lymphoma (HL) is increased in patients infected with HIV-1. We studied the incidence and outcomes of HL, and compared CD4+ T-cell trajectories in HL patients and controls matched for duration of combination antiretroviral therapy (cART). A total of 40 168 adult HIV-1–infected patients (median age, 36 years; 70% male; median CD4 cell count, 234 cells/μL) from 16 European cohorts were observed during 159 133 person-years; 78 patients developed HL. The incidence was 49.0 (95% confidence interval [CI], 39.3-61.2) per 100 000 person-years, and similar on cART and not on cART (P = .96). The risk of HL declined as the most recent (time-updated) CD4 count increased: the adjusted hazard ratio comparing more than 350 with less than 50 cells/μL was 0.27 (95% CI, 0.08-0.86). Sixty-one HL cases diagnosed on cART were matched to 1652 controls: during the year before diagnosis, cases lost 98 CD4 cells (95% CI, −159 to −36 cells), whereas controls gained 35 cells (95% CI, 24-46 cells; P < .0001). The incidence of HL is not reduced by cART, and patients whose CD4 cell counts decline despite suppression of HIV-1 replication on cART may harbor HL.
Heparin promotes platelet responsiveness by potentiating αIIbβ3-mediated outside-in signaling
Authors: Gao Cunji , Boylan Brian , Fang Juan , Wilcox David A. , Newman Debra K. , Newman Peter J. 
Published: March 2011

AbstractUnfractionated heparin (UFH) is a widely used anticoagulant that has long been known to potentiate platelet responses to subthreshold doses of platelet agonists. UFH has been reported to bind and induce modest conformational changes in the major platelet integrin, αIIbβ3, and induce minor changes in platelet morphology. The mechanism by which UFH elicits these platelet-activating effects, however, is not well understood. We found that both human and murine platelets exposed to UFH, either in solution or immobilized onto artificial surfaces, underwent biochemical and morphologic changes indicative of a potentiated state, including phosphorylation of key cytosolic signaling molecules and cytoskeletal changes leading to cell spreading. Low molecular weight heparin and the synthetic pentasaccharide, fondaparinux, had similar platelet-potentiating effects. Human or mouse platelets lacking functional integrin αIIbβ3 complexes and human platelets pretreated with the fibrinogen receptor antagonists eptifibatide or abciximab failed to become potentiated by heparin, demonstrating that heparin promotes platelet responsiveness via its ability to initiate αIIbβ3-mediated outside-in signaling. Taken together, these data provide novel insights into the mechanism by which platelets become activated after exposure to heparin and heparin-coated surfaces, and suggest that currently used glycoprotein IIb-IIIa inhibitors may be effective inhibitors of nonimmune forms of heparin-induced platelet activation.
Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells
Authors: Weichhart Thomas , Haidinger Michael , Katholnig Karl , Kopecky Chantal , Poglitsch Marko , Lassnig Caroline , Rosner Margit , Zlabinger Gerhard J. , Hengstschläger Markus , Müller Mathias , Hörl Walter H. , Säemann Marcus D. 
Published: March 2011

Abstract
A central role for the mammalian target of rapamycin (mTOR) in innate immunity has been recently defined by its ability to limit proinflammatory mediators. Although glucocorticoids (GCs) exert potent anti-inflammatory effects in innate immune cells, it is currently unknown whether the mTOR pathway interferes with GC signaling. Here we show that inhibition of mTOR with rapamycin or Torin1 prevented the anti-inflammatory potency of GC both in human monocytes and myeloid dendritic cells. GCs could not suppress nuclear factor-κB and JNK activation, the expression of proinflammatory cytokines, and the promotion of Th1 responses when mTOR was inhibited. Interestingly, long-term activation of monocytes with lipopolysaccharide enhanced the expression of TSC2, the principle negative regulator of mTOR, whereas dexamethasone blocked TSC2 expression and reestablished mTOR activation. Renal transplant patients receiving rapamycin but not those receiving calcineurin inhibitors displayed a state of innate immune cell hyper-responsiveness despite the concurrent use of GC. Finally, mTOR inhibition was able to override the healing phenotype of dexamethasone in a murine lipopolysaccharide shock model. Collectively, these data identify a novel link between the glucocorticoid receptor and mTOR in innate immune cells, which is of considerable clinical importance in a variety of disorders, including allogeneic transplantation, autoimmune diseases, and cancer.
Accumulation and transport of microbial-size particles in a pressure protected model burn unit: CFD simulations and experimental evidence
Authors: Beauchêne Christian , Laudinet Nicolas , Choukri Firas , Rousset Jean-Luc , Benhamadouche Sofiane , Larbre Juliette , Chaouat Marc , Benbunan Marc , Mimoun Maurice , Lajonchère Jean-Patrick , Bergeron Vance , Derouin Francis 
Published: March 2011

Abstract

Background
Controlling airborne contamination is of major importance in burn units because of the high susceptibility of burned patients to infections and the unique environmental conditions that can accentuate the infection risk. In particular the required elevated temperatures in the patient room can create thermal convection flows which can transport airborne contaminates throughout the unit. In order to estimate this risk and optimize the design of an intensive care room intended to host severely burned patients, we have relied on a computational fluid dynamic methodology (CFD).

Methods
The study was carried out in 4 steps: i) patient room design, ii) CFD simulations of patient room design to model air flows throughout the patient room, adjacent anterooms and the corridor, iii) construction of a prototype room and subsequent experimental studies to characterize its performance iv) qualitative comparison of the tendencies between CFD prediction and experimental results. The Electricité De France (EDF) open-source software Code_Saturne
® (http://www.code-saturne.org) was used and CFD simulations were conducted with an hexahedral mesh containing about 300 000 computational cells. The computational domain included the treatment room and two anterooms including equipment, staff and patient. Experiments with inert aerosol particles followed by time-resolved particle counting were conducted in the prototype room for comparison with the CFD observations.

Results
We found that thermal convection can create contaminated zones near the ceiling of the room, which can subsequently lead to contaminate transfer in adjacent rooms. Experimental confirmation of these phenomena agreed well with CFD predictions and showed that particles greater than one micron (i.e. bacterial or fungal spore sizes) can be influenced by these thermally induced flows. When the temperature difference between rooms was 7°C, a significant contamination transfer was observed to enter into the positive pressure room when the access door was opened, while 2°C had little effect. Based on these findings the constructed burn unit was outfitted with supplemental air exhaust ducts over the doors to compensate for the thermal convective flows.

Conclusions
CFD simulations proved to be a particularly useful tool for the design and optimization of a burn unit treatment room. Our results, which have been confirmed qualitatively by experimental investigation, stressed that airborne transfer of microbial size particles via thermal convection flows are able to bypass the protective overpressure in the patient room, which can represent a potential risk of cross contamination between rooms in protected environments.
Structural analysis of heme proteins: implications for design and prediction
Authors: Li Ting , Bonkovsky Herbert L , Guo Jun-tao 
Published: March 2011

Abstract

Background
Heme is an essential molecule and plays vital roles in many biological processes. The structural determination of a large number of heme proteins has made it possible to study the detailed chemical and structural properties of heme binding environment. Knowledge of these characteristics can provide valuable guidelines in the design of novel heme proteins and help us predict unknown heme binding proteins.

Results
In this paper, we constructed a non-redundant dataset of 125 heme-binding protein chains and found that these heme proteins encompass at least 31 different structural folds with all-α class as the dominating scaffold. Heme binding pockets are enriched in aromatic and non-polar amino acids with fewer charged residues. The differences between apo and holo forms of heme proteins in terms of the structure and the binding pockets have been investigated. In most cases the proteins undergo small conformational changes upon heme binding. We also examined the CP (cysteine-proline) heme regulatory motifs and demonstrated that the conserved dipeptide has structural implications in protein-heme interactions.

Conclusions
Our analysis revealed that heme binding pockets show special features and that most of the heme proteins undergo small conformational changes after heme binding, suggesting the apo structures can be used for structure-based heme protein prediction and as scaffolds for future heme protein design.
Time-course of sFlt-1 and VEGF-A release in neutropenic patients with sepsis and septic shock: a prospective study
Authors: Alves Brunna E , Montalvao Silmara AL , Aranha Francisco JP , Lorand-Metze Irene , De Souza Carmino A , Annichino-Bizzacchi Joyce M , De Paula Erich V 
Published: March 2011

Abstract

Background
Septic shock is the most feared complication of chemotherapy-induced febrile neutropenia. So far, there are no robust biomarkers that can stratify patients to the risk of sepsis complications. The VEGF-A axis is involved in the control of microvascular permeability and has been involved in the pathogenesis of conditions associated with endothelial barrier disruption such as sepsis. sFlt-1 is a soluble variant of the VEGF-A receptor VEGFR-1 that acts as a decoy receptor down-regulating the effects of VEGF-A. In animal models of sepsis, sFlt-1 was capable to block the barrier-breaking negative effects of VEGF-A and to significantly decrease mortality. In non-neutropenic patients, sFlt-1 has been shown to be a promising biomarker for sepsis severity.

Methods
We prospectively evaluated concentrations of sFlt-1 and VEGF-A at different time-points during febrile neutropenia, and evaluated the association of these levels with sepsis severity and septic shock development.

Results
Neutropenic patients that evolved with septic shock (n = 10) presented higher levels of sFlt-1 and VEGF-A measured 48 hours after fever onset than patients with non-complicated sepsis (n = 31) and levels of these biomarkers correlated with sepsis severity scores. Estimation of the diagnostic accuracy of sFlt-1 levels for the discrimination of patients that evolved to septic shock yielded promising results in our study population.

Discussion
Our data suggest that sFlt-1 and VEGF-A could be useful biomarkers for sepsis severity in patients with febrile neutropenia. In addition, the kinetics of sFlt-1 release in patients that evolve to septic shock suggest that the sFlt-1 could be a salvage compensatory mechanism in patients with septic shock, but that the magnitude of the sFlt-1 release observed in human sepsis is not sufficient to reproduce the beneficial anti-VEGF-A effects observed in animal models of sepsis.
Chemical characterization of extra layers at the interfaces in MOCVD InGaP/GaAs junctions by electron beam methods
Authors: Frigeri Cesare , Shakhmin Alexey Aleksandrovich , Vinokurov Dmitry Anatolievich , Zamoryanskaya Maria Vladimirovna 
Published: March 2011

AbstractElectron beam methods, such as cathodoluminescence (CL) that is based on an electron-probe microanalyser, and (200) dark field and high angle annular dark field (HAADF) in a scanning transmission electron microscope, are used to study the deterioration of interfaces in InGaP/GaAs system with the GaAs QW on top of InGaP. A CL emission peak different from that of the QW was detected. By using HAADF, it is found that the GaAs QW does not exist any longer, being replaced by extra interlayer(s) that are different from GaAs and InGaP because of atomic rearrangements at the interface. The nature and composition of the interlayer(s) are determined by HAADF. Such changes of the nominal GaAs QW can account for the emission observed by CL.
Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide
Authors: Bellini Maria J , Hereñú Claudia B , Goya Rodolfo G , Garcia-Segura Luis M 
Published: March 2011

AbstractBackgroundInsulin-like growth factor-I (IGF-I) exerts neuroprotective actions in the central nervous system that are mediated at least in part by control of activation of astrocytes. In this study we have assessed the efficacy of exogenous IGF-I and IGF-I gene therapy in reducing the inflammatory response of astrocytes from cerebral cortex.MethodsAn adenoviral vector harboring the rat IGF-I gene and a control adenoviral vector harboring a hybrid gene encoding the herpes simplex virus type 1 thymidine kinase fused toAequorea victoriaenhanced green fluorescent protein were used in this study. Primary astrocytes from mice cerebral cortex were incubated for 24 h or 72 h with vehicle, IGF-I, the IGF-I adenoviral vector, or control vector; and exposed to bacterial lipopolysaccharide to induce an inflammatory response. IGF-I levels were measured by radioimmunoassay. Levels of interleukin 6, tumor necrosis factor-α, interleukin-1β and toll-like receptor 4 mRNA were assessed by quantitative real-time polymerase chain reaction. Levels of IGF-I receptor and IGF binding proteins 2 and 3 were assessed by western blotting. The subcellular distribution of nuclear factor κB (p65) was assessed by immunocytochemistry. Statistical significance was assessed by one way analysis of variance followed by the Bonferroni pot hoc test.ResultsIGF-I gene therapy increased IGF-I levels without affecting IGF-I receptors or IGF binding proteins. Exogenous IGF-I, and IGF-I gene therapy, decreased expression of toll-like receptor 4 and counteracted the lipopolysaccharide-induced inflammatory response of astrocytes. In addition, IGF-I gene therapy decreased lipopolysaccharide-induced translocation of nuclear factor κB (p65) to the cell nucleus.ConclusionThese findings demonstrate efficacy of exogenous IGF-I and of IGF-I gene therapy in reducing the inflammatory response of astrocytes. IGF-I gene therapy may represent a new approach to reduce inflammatory reactions in glial cells.
Newly recognized mosquito-associated viruses in mainland China, in the last two decades
Authors: Liu Hong , Gao Xiaoyan , Liang Guodong 
Published: March 2011

AbstractThere are four principal arboviruses in mainland China. Two kinds of them are mosquito-borne viruses, namely Japanese encephalitis virus and dengue virus, which lead to Japanese encephalitis, and dengue fever/dengue hemorrhagic fever respectively; the other two are tick-borne viruses, namely tick-borne encephalitis virus and Crimean-Congo hemorrhagic fever virus (also known as Xinjiang hemorrhagic fever virus), which contribute to tick-borne encephalitis and Xinjiang hemorrhagic fever respectively. With exception of these four main arboviruses, many other mosquito-associated viruses have been isolated and identified in recent years. These newly isolated and identified mosquito-associated viruses are probably responsible for human and animal infections and diseases. The purpose of this review is to describe the newly isolated mosquito-associated viruses in mainland China which belong to five viral families, including their virological properties, phylogenetic relationships, serological evidence, as well as to appeal the public health concentration worldwide.
Intravaginal cytomegalovirus (CMV) challenge elicits maternal viremia and results in congenital transmission in a guinea pig model
Authors: Olejniczak Megan J , Choi K Yeon , McVoy Michael A , Cui Xiaohong , Schleiss Mark R 
Published: March 2011

Abstract

Background
The objective of this study was to compare intravaginal (ivg) and subcutaneous (sc) administration of the guinea pig cytomegalovirus (GPCMV) in pregnant and non-pregnant guinea pigs. These studies tested the hypotheses that ivg infection would elicit immune responses, produce maternal viremia, and lead to vertical transmission, with an efficiency similar to the traditionally employed sc route.

Results
Four groups of age- and size-matched guinea pigs were studied. Two groups were pregnant, and two groups were not pregnant. Animals received 5x105 plaque-forming units (PFU) of a GPCMV reconstituted from an infectious bacterial artificial chromosome (BAC) construct containing the full-length GPCMV genome. Seroconversion was compared by IgG ELISA, and viremia (DNAemia) was monitored by PCR. In both pregnant and non-pregnant animals, sc inoculation resulted in significantly higher serum ELISA titers than ivg inoculation at 8 and 12 weeks post-infection. Patterns of viremia (DNAemia) were similar in animals inoculated by either sc or ivg route. However, in pregnant guinea pigs, animals inoculated by both routes experienced an earlier onset of DNAemia than did non-pregnant animals. Neither the percentage of dead pups nor the percentage of GPCMV positive placentas differed by inoculation route.

Conclusions
In the guinea pig model of congenital CMV infection, the ivg route is as efficient at causing congenital infection as the conventional but non-physiologic sc route. This finding could facilitate future experimental evaluation of vaccines and antiviral interventions in this highly relevant animal model.
Occult HBV infection among Egyptian hepatocellular carcinoma patients
Authors: Hassan Zeinab K , Hafez Mohamed M , Mansor Tarek M , Zekri Abdel N Rahman 
Published: March 2011

Abstract

Background
Occult HBV infection accelerates the progression of liver fibrosis, cirrhosis, and finally leading to hepatocellular carcinoma (HCC). This study analyzed the occult HBV-genotypes in HCC patients.

Methods
To achieve our objective, matched serum and tissue samples were collected from 40 HCC patients. Three sets of primers were used for the HBV-DNA detection by nested-PCR, which cover the HBV-genome; Core, Surface and X genes. Genotyping system based on PCR using type-specific primers was applied on HBV-DNA positive samples.

Results
Intrahepatic occult HBV-DNA was detected in 62.5%, whereas; Serum occult HBV-DNA were detected in only 22.5% of HCC patients. In patients' positive for both anti-HBs and anti-HBc, 10% had occult HBV in serum. In serologically negative HCV patients, 63% had intrahepatic HBV-DNA, and 21% had HBV-DNA in serum samples. HBV-genotype D (32%) and B (24%) attributed predominantly to intrahepatic HBV infections in HCC patients, whereas HBV-genotype A (4%) and C (8%) infections were the least observed.

Conclusion
This is the first study to show the genotypes of occult HBV infection in HCC Patients. We suggest that B or D may influence the outcome of HBV infection which may lead to the development of HCC.
Cytotoxicity and oxidative stress induced by different metallic nanoparticles on human kidney cells
Authors: Pujalté Igor , Passagne Isabelle , Brouillaud Brigitte , Tréguer Mona , Durand Etienne , Ohayon-Courtès Céline , L'Azou Béatrice 
Published: March 2011

Abstract

Background
Some manufactured nanoparticles are metal-based and have a wide variety of applications in electronic, engineering and medicine. Until now, many studies have described the potential toxicity of NPs on pulmonary target, while little attention has been paid to kidney which is considered to be a secondary target organ. The objective of this study, on human renal culture cells, was to assess the toxicity profile of metallic nanoparticles (TiO2, ZnO and CdS) usable in industrial production. Comparative studies were conducted, to identify whether particle properties impact cytotoxicity by altering the intracellular oxidative status.

Results
Nanoparticles were first characterized by size, surface charge, dispersion and solubility. Cytotoxicity of NPs was then evaluated in IP15 (glomerular mesangial) and HK-2 (epithelial proximal) cell lines. ZnO and CdS NPs significantly increased the cell mortality, in a dose-dependent manner. Cytotoxic effects were correlated with the physicochemical properties of NPs tested and the cell type used. Analysis of reactive oxygen species and intracellular levels of reduced and oxidized glutathione revealed that particles induced stress according to their composition, size and solubility. Protein involved in oxidative stress such as NF-κb was activated with ZnO and CdS nanoparticles. Such effects were not observed with TiO2 nanoparticles.

Conclusion
On glomerular and tubular human renal cells, ZnO and CdS nanoparticles exerted cytotoxic effects that were correlated with metal composition, particle scale and metal solubility. ROS production and oxidative stress induction clearly indicated their nephrotoxic potential.
Reliable transgene-independent method for determining Sleeping Beauty transposon copy numbers
Authors: Kolacsek Orsolya , Krízsik Virág , Schamberger Anita , Erdei Zsuzsa , Apáti Ágota , Várady György , Mátés Lajos , Izsvák Zsuzsanna , Ivics Zoltán , Sarkadi Balázs , Orbán Tamás I 
Published: March 2011

Abstract

Background
The transposon-based gene delivery technique is emerging as a method of choice for gene therapy. The Sleeping Beauty (SB) system has become one of the most favored methods, because of its efficiency and its random integration profile. Copy-number determination of the delivered transgene is a crucial task, but a universal method for measuring this is lacking. In this paper, we show that a real-time quantitative PCR-based, transgene-independent (qPCR-TI) method is able to determine SB transposon copy numbers regardless of the genetic cargo.

Results
We designed a specific PCR assay to amplify the left inverted repeat-direct repeat region of SB, and used it together with the single-copy control gene RPPH1 and a reference genomic DNA of known copy number. The qPCR-TI method allowed rapid and accurate determination of SB transposon copy numbers in various cell types, including human embryonic stem cells. We also found that this sensitive, rapid, highly reproducible and non-radioactive method is just as accurate and reliable as the widely used blotting techniques or the transposon display method. Because the assay is specific for the inverted repeat region of the transposon, it could be used in any system where the SB transposon is the genetic vehicle.

Conclusions
We have developed a transgene-independent method to determine copy numbers of transgenes delivered by the SB transposon system. The technique is based on a quantitative real-time PCR detection method, offering a sensitive, non-radioactive, rapid and accurate approach, which has a potential to be used for gene therapy.
New horizons in Biophysics
Authors: Moylan Elizabeth C 
Published: March 2011

Abstract
This editorial celebrates the re-launch of PMC Biophysics previously published by PhysMath Central, in its new format as BMC Biophysics published by BioMed Central with an expanded scope and Editorial Board. BMC Biophysics will fill its own niche in the BMC series alongside complementary companion journals including BMC Bioinformatics, BMC Medical Physics, BMC Structural Biology and BMC Systems Biology.