bluuebunny/crossref_metadata_2025_split huggingface dataset:
The human epidermal growth factor receptor (EGFR) gene in European patients with advanced colorectal cancer harbors infrequent mutations in its tyrosine kinase domain
Authors: Metzger Brigitte , Chambeau Laetitia , Begon Dominique Y , Faber Carlo , Kayser Jacques , Berchem Guy , Pauly Marc , Boniver Jacques , Delvenne Philippe , Dicato Mario , Wenner Thomas 
Published: November 2011

Abstract

Background
The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptors, is a transmembrane tyrosine kinase (TK) activated by the binding of extracellular ligands of the EGF-family and involved in triggering the MAPK signaling pathway, which leads to cell proliferation. Mutations in the EGFR tyrosine kinase domain are frequent in non-small-cell lung cancer (NSCLC). However, to date, only very few, mainly non-European, studies have reported rare EGFR mutations in colorectal cancer (CRC).

Methods
We screened 236 clinical tumor samples from European patients with advanced CRC by direct DNA sequencing to detect potential, as yet unknown mutations, in the EGFR gene exons 18 to 21, mainly covering the EGFR TK catalytic domain.

Results
EGFR sequences showed somatic missense mutations in exons 18 and 20 at a frequency of 2.1% and 0.4% respectively. Somatic SNPs were also found in exons 20 and 21 at a frequency of about 3.1% and 0.4% respectively. Of these mutations, four have not yet been described elsewhere.

Conclusions
These mutation frequencies are higher than in a similarly sized population characterized by Barber and colleagues, but still too low to account for a major role played by the EGFR gene in CRC.
The effect of a new direct Factor Xa inhibitor on human osteoblasts: an in-vitro study comparing the effect of rivaroxaban with enoxaparin
Authors: Solayar Gandhi N , Walsh Pauline M , Mulhall Kevin J 
Published: November 2011

Abstract

Background
Current treatments for the prevention of thromboembolism include heparin and low-molecular weight heparins (LMWHs). A number of studies have suggested that long term administration of these drugs may adversely affect osteoblasts and therefore, bone metabolism. Xarelto™ (Rivaroxaban) is a new anti-thrombotic drug for the prevention of venous thromboembolism in adult patients undergoing elective hip and knee replacement surgery. The aim of this in vitro study was to investigate the possible effects of rivaroxaban on osteoblast viability, function and gene expression compared to enoxaparin, a commonly used LMWH.

Methods
Primary human osteoblast cultures were treated with varying concentrations of rivaroxaban (0.013, 0.13, 1.3 and 13 μg/ml) or enoxaparin (1, 10 and 100 μg/ml). The effect of each drug on osteoblast function was evaluated by measuring alkaline phosphatase activity. The MTS assay was used to assess the effect of drug treatments on cell proliferation. Changes in osteocalcin, Runx2 and BMP-2 messenger RNA (mRNA) expression following drug treatments were measured by real-time polymerase chain reaction (PCR).

Results
Rivaroxaban and enoxaparin treatment did not adversely affect osteoblast viability. However, both drugs caused a significant reduction in osteoblast function, as measured by alkaline phosphatase activity. This reduction in osteoblast function was associated with a reduction in the mRNA expression of the bone marker, osteocalcin, the transcription factor, Runx2, and the osteogenic factor, BMP-2.

Conclusions
These data show that rivaroxaban treatment may negatively affect bone through a reduction in osteoblast function.
Assessment of the knowledge of graphical symbols labelled on malaria rapid diagnostic tests in four international settings
Authors: Hermans Veerle , Monzote Lianet , Van den Sande Björn , Mukadi Pierre , Sopheak Thai , Gillet Philippe , Jacobs Jan 
Published: November 2011

Abstract

Background
Graphical symbols on in vitro diagnostics (IVD symbols) replace the need for text in different languages and are used on malaria rapid diagnostic tests (RDTs) marketed worldwide. The present study assessed the comprehension of IVD symbols labelled on malaria RDT kits among laboratory staff in four different countries.

Methods
Participants (n = 293) in Belgium (n = 96), the Democratic Republic of the Congo (DRC, n = 87), Cambodia (n = 59) and Cuba (n = 51) were presented with an anonymous questionnaire with IVD symbols extracted from ISO 15223 and EN 980 presented as stand-alone symbols (n = 18) and in context (affixed on RDT packages, n = 16). Responses were open-ended and scored for correctness by local professionals.

Results
Presented as stand-alone, three and five IVD symbols were correctly scored for comprehension by 67% and 50% of participants; when contextually presented, five and seven symbols reached the 67% and 50% correct score respectively. 'Batch code' scored best (correctly scored by 71.3% of participants when presented as stand-alone), 'Authorized representative in the European Community' scored worst (1.4% correct). Another six IVD symbols were scored correctly by less than 10% of participants: 'Do not reuse', 'In vitro diagnostic medical device', 'Sufficient for', 'Date of manufacture', 'Authorised representative in EC', and 'Do not use if package is damaged'. Participants in Belgium and Cuba both scored six symbols above the 67% criterion, participants from DRC and Cambodia scored only two and one symbols above this criterion. Low correct scores were observed for safety-related IVD symbols, such as for 'Biological Risk' (42.7%) and 'Do not reuse' (10.9%).

Conclusion
Comprehension of IVD symbols on RDTs among laboratory staff in four international settings was unsatisfactory. Administrative and outreach procedures should be undertaken to assure their acquaintance by end-users.
Endothelial Dysfunction in the Apolipoprotein E-deficient Mouse: insights into the influence of diet, gender and aging
Authors: Meyrelles Silvana S , Peotta Veronica A , Pereira Thiago MC , Vasquez Elisardo C 
Published: November 2011

Abstract
Since the early 1990s, several strains of genetically modified mice have been developed as models for experimental atherosclerosis. Among the available models, the apolipoprotein E-deficient (apoE-/-) mouse is of particular relevance because of its propensity to spontaneously develop hypercholesterolemia and atherosclerotic lesions that are similar to those found in humans, even when the mice are fed a chow diet. The main purpose of this review is to highlight the key achievements that have contributed to elucidating the mechanisms pertaining to vascular dysfunction in the apoE-/- mouse. First, we summarize lipoproteins and atherosclerosis phenotypes in the apoE-/- mouse, and then we briefly discuss controversial evidence relative to the influence of gender on the development of atherosclerosis in this murine model. Second, we discuss the main mechanisms underlying the endothelial dysfunction of conducting vessels and resistance vessels and examine how this vascular defect can be influenced by diet, aging and gender in the apoE-/- mouse.
Optimizing parameters for clinical-scale production of high IL-12 secreting dendritic cells pulsed with oxidized whole tumor cell lysate
Authors: Chiang Cheryl L-L , Maier Dawn A , Kandalaft Lana E , Brennan Andrea L , Lanitis Evripidis , Ye Qunrui , Levine Bruce L , Czerniecki Brian J , Powell Jr Daniel J , Coukos George 
Published: November 2011

AbstractBackgroundDendritic cells (DCs) are the most potent antigen-presenting cell population for activating tumor-specific T cells. Due to the wide range of methods for generating DCs, there is no common protocol or defined set of criteria to validate the immunogenicity and function of DC vaccines.MethodsMonocyte-derived DCs were generated during 4 days of culture with recombinant granulocyte-macrophage colony stimulating factor and interleukin-4, and pulsed with tumor lysate produced by hypochlorous acid oxidation of tumor cells. Different culture parameters for clinical-scale DC preparation were investigated, including: 1) culture media; 2) culture surface; 3) duration of activating DCs with lipopolysaccharide (LPS) and interferon (IFN)-gamma; 4) method of DC harvest; and 5) cryomedia and final DC product formulation.ResultsDCs cultured in CellGenix DC media containing 2% human AB serum expressed higher levels of maturation markers following lysate-loading and maturation compared to culturing with serum-free CellGenix DC media or AIM-V media, or 2% AB serum supplemented AIM-V media. Nunclon™Δ surface, but not Corning®tissue-culture treated surface and Corning®ultra-low attachment surface, were suitable for generating an optimal DC phenotype. Recombinant trypsin resulted in reduced major histocompatibility complex (MHC) Class I and II expression on mature lysate-loaded DCs, however presentation of MHC Class I peptides by DCs was not impaired and cell viability was higher compared to cell scraping. Preservation of DCs with an infusible cryomedia containing Plasma-Lyte A, dextrose, sodium chloride injection, human serum albumin, and DMSO yielded higher cell viability compared to using human AB serum containing 10% DMSO. Finally, activating DCs for 16 hours with LPS and IFN-γ stimulated robust mixed leukocyte reactions (MLRs), and high IL-12p70 productionin vitrothat continued for 24 hours after the cryopreserved DCs were thawed and replated in fresh media.ConclusionsThis study examined criteria including DC phenotype, viability, IL-12p70 production and the ability to stimulate MLR as metrics of whole oxidized tumor lysate-pulsed DC immunogenicity and functionality. Development and optimization of this unique method is now being tested in a clinical trial of autologous oxidized tumor lysate-pulsed DC in clinical-scale in recurrent ovarian, primary peritoneal or fallopian tube cancer (NCT01132014).
A simple route to vertical array of quasi-1D ZnO nanofilms on FTO surfaces: 1D-crystal growth of nanoseeds under ammonia-assisted hydrolysis process
Authors: Ali Umar Akrajas , Abd Rahman Mohd Yusri , Taslim Rika , Mat Salleh Muhamad , Oyama Munetaka 
Published: November 2011

AbstractA simple method for the synthesis of ZnO nanofilms composed of vertical array of quasi-1D ZnO nanostructures (quasi-NRs) on the surface was demonstrated via a 1D crystal growth of the attached nanoseeds under a rapid hydrolysis process of zinc salts in the presence of ammonia at room temperature. In a typical procedure, by simply controlling the concentration of zinc acetate and ammonia in the reaction, a high density of vertically oriented nanorod-like morphology could be successfully obtained in a relatively short growth period (approximately 4 to 5 min) and at a room-temperature process. The average diameter and the length of the nanostructures are approximately 30 and 110 nm, respectively. The as-prepared quasi-NRs products were pure ZnO phase in nature without the presence of any zinc complexes as confirmed by the XRD characterisation. Room-temperature optical absorption spectroscopy exhibits the presence of two separate excitonic characters inferring that the as-prepared ZnO quasi-NRs are high-crystallinity properties in nature. The mechanism of growth for the ZnO quasi-NRs will be proposed. Due to their simplicity, the method should become a potential alternative for a rapid and cost-effective preparation of high-quality ZnO quasi-NRs nanofilms for use in photovoltaic or photocatalytics applications.PACS: 81.07.Bc; 81.16.-c; 81.07.Gf.
One-step fabrication of biocompatible chitosan-coated ZnS and ZnS:Mn2+ quantum dots via a γ-radiation route
Authors: Chang Shu-quan , Kang Bin , Dai Yao-dong , Zhang Hong-xu , Chen Da 
Published: November 2011

AbstractBiocompatible chitosan-coated ZnS quantum dots [CS-ZnS QDs] and chitosan-coated ZnS:Mn2+ quantum dots [CS-ZnS:Mn2+ QDs] were successfully fabricated via a convenient one-step γ-radiation route. The as-obtained QDs were around 5 nm in diameter with excellent water-solubility. These QDs emitting strong visible blue or orange light under UV excitation were successfully used as labels for PANC-1 cells. The cell experiments revealed that CS-ZnS and CS-ZnS:Mn2+ QDs showed low cytotoxicity and good biocompatibility, which offered possibilities for further biomedical applications. Moreover, this convenient synthesis strategy could be extended to fabricate other nanoparticles coated with chitosan.PACS: 81.07.Ta; 78.67.Hc; 82.35.Np; 87.85.Rs.
Inhibition of highly pathogenic PRRSV replication in MARC-145 cells by artificial microRNAs
Authors: Xiao Shuqi , Wang Qiwei , Gao Jintao , Wang Liangliang , He Zuyong , Mo Delin , Liu Xiaohong , Chen Yaosheng 
Published: November 2011

Abstract

Background
Highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS) has caused large economic losses in swine industry in recent years. However, current antiviral strategy could not effectively prevent and control this disease. In this research, five artificial microRNAs (amiRNAs) respectively targeted towards ORF5 (amirGP5-243, -370) and ORF6 (amirM-82, -217,-263) were designed and incorporated into a miRNA-based vector that mimics the backbone of murine miR-155 and permits high expression of amiRNAs in a GFP fused form mediated by RNA Pol II promoter CMV.

Results
It was found that amirGP5-370 could effectively inhibit H-PRRSV replication. The amirM-263-M-263, which was a dual pre-amiRNA expression cassette where two amirM-263s were chained, showed stronger virus inhibitory effects than single amirM-263. H-PRRSV replication was inhibited up to 120 hours in the MARC-145 cells which were stably transduced by recombinant lentiviruses (Lenti-amirGP5-370, -amirM-263-M-263). Additionally, efficacious dose of amirGP5-370 and amirM-263 expression did not trigger the innate interferon response.

Conclusions
Our study is the first attempt to suppress H-PRRSV replication in MARC-145 cells through vector-based and lentiviral mediated amiRNAs targeting GP5 or M proteins coding sequences of PRRSV, which indicated that artificial microRNAs and recombinant lentiviruses might be applied to be a new potent anti-PRRSV strategy.
How many lobes do you see?
Authors: Karangelis Dimos , Tagarakis Georgios I , Chlapoutakis Serapheim , Papadopoulos Dimitrios , Roubelakis Apostolos , Hevas Athanasios , Daskalopoulos Marios E , Tsantsaridou Angeliki , Lampoura Stefania , Tsilimingas Nikolaos B 
Published: November 2011

Abstract
Accessory fissures represent a variation of the normal lung anatomy. Incomplete development or even the absence of the major or minor fissures can lead to confusion in distinguishing adjacent lobes. This report aims to present a rare intraoperative finding of an anatomic malformation of the right lung in a 19-year old male patient with recurrent pneumothorax who underwent a surgical repair. An accessory fissure which was separating the superior segment of the lower lobe from the basal segments gave to the whole lung the unique image of a four-lobed one. A profound knowledge of the accessory fissures, even if they are incidentally discovered, is of pivotal importance for the thoracic surgeon and leads to optimal operative assessment and strategic planning.
Time-resolved in silico modeling of fine-tuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulation
Authors: Wangorsch Gaby , Butt Elke , Mark Regina , Hubertus Katharina , Geiger Jörg , Dandekar Thomas , Dittrich Marcus 
Published: November 2011

Abstract

Background
Hemostasis is a critical and active function of the blood mediated by platelets. Therefore, the prevention of pathological platelet aggregation is of great importance as well as of pharmaceutical and medical interest. Endogenous platelet inhibition is predominantly based on cyclic nucleotides (cAMP, cGMP) elevation and subsequent cyclic nucleotide-dependent protein kinase (PKA, PKG) activation. In turn, platelet phosphodiesterases (PDEs) and protein phosphatases counterbalance their activity. This main inhibitory pathway in human platelets is crucial for countervailing unwanted platelet activation. Consequently, the regulators of cyclic nucleotide signaling are of particular interest to pharmacology and therapeutics of atherothrombosis. Modeling of pharmacodynamics allows understanding this intricate signaling and supports the precise description of these pivotal targets for pharmacological modulation.

Results
We modeled dynamically concentration-dependent responses of pathway effectors (inhibitors, activators, drug combinations) to cyclic nucleotide signaling as well as to downstream signaling events and verified resulting model predictions by experimental data. Experiments with various cAMP affecting compounds including anti-platelet drugs and their combinations revealed a high fidelity, fine-tuned cAMP signaling in platelets without cross-talk to the cGMP pathway. The model and the data provide evidence for two independent feedback loops: PKA, which is activated by elevated cAMP levels in the platelet, subsequently inhibits adenylyl cyclase (AC) but as well activates PDE3. By multi-experiment fitting, we established a comprehensive dynamic model with one predictive, optimized and validated set of parameters. Different pharmacological conditions (inhibition, activation, drug combinations, permanent and transient perturbations) are successfully tested and simulated, including statistical validation and sensitivity analysis. Downstream cyclic nucleotide signaling events target different phosphorylation sites for cAMP- and cGMP-dependent protein kinases (PKA, PKG) in the vasodilator-stimulated phosphoprotein (VASP). VASP phosphorylation as well as cAMP levels resulting from different drug strengths and combined stimulants were quantitatively modeled. These predictions were again experimentally validated. High sensitivity of the signaling pathway at low concentrations is involved in a fine-tuned balance as well as stable activation of this inhibitory cyclic nucleotide pathway.

Conclusions
On the basis of experimental data, literature mining and database screening we established a dynamic in silico model of cyclic nucleotide signaling and probed its signaling sensitivity. Thoroughly validated, it successfully predicts drug combination effects on platelet function, including synergism, antagonism and regulatory loops.
Lulo cell line derived from Lutzomyia longipalpis (Diptera: Psychodidae): a novel model to assay Leishmania spp. and vector interaction
Authors: Côrtes Luzia MC , Silva Roger MM , Pereira Bernardo AS , Guerra Camila , Zapata Angela C , Bello Felio J , Finkelstein Léa C , Madeira Maria F , Brazil Reginaldo P , Côrte-Real Suzana , Alves Carlos R 
Published: November 2011

AbstractBackgroundLeishmania (Vianna) braziliensis,Leishmania (Leishmania) amazonensis and Leishmania (Leishmania) chagasiare important parasites in the scenario of leishmaniasis in Brazil. During the life cycle of these parasites, the promastigote forms adhere to the midgut epithelial microvillii of phlebotomine insects to avoid being secreted along with digestive products. Lulo cells are a potential model that will help to understand the features of this adhesion phenomenon. Here, we analyze the interaction betweenLeishmaniaspp. promastigotes and Lulo cellsin vitro, specifically focusing on adhesion events occurring between threeLeishmaniaspecies and this cell line.MethodsConfluent monolayers of Lulo cells were incubated with promastigotes and adhesion was assessed using both light microscopy and scanning electron microscopy.FindingsThe results indicate that species from the subgeneraLeishmaniaandVianniahave great potential to adhere to Lulo cells. The highest adherence rate was observed forL. (L.) chagasiafter 24 h of incubation with Lulo cells (27.3 ± 1.8% of cells with adhered promastigotes), followed byL. (L.) amazonensis(16.0 ± 0.7%) andL. (V.) braziliensis(3.0 ± 0.7%), both after 48 h. In the ultrastructural analysis, promastigote adherence was also assessed by scanning electron microscopy, showing that, for parasites from both subgenera, adhesion occurs by both the body and the flagellum. The interaction of Lulo cells withLeishmania (L.) chagasishowed the participation of cytoplasmic projections from the former closely associating the parasites with the cells.ConclusionsWe present evidence that Lulo cells can be useful in studies of insect-parasite interactions forLeishmaniaspecies.
Find-and-Fetch Search on a Tree
Authors: Alpern Steve 
Published: November 2011

We introduce a new type of search game called the “find-and-fetch” game F(Q, O). The Hider simply picks any point H in the network Q. The Searcher starts at time zero at a given point O of Q, moving at unit speed until he reaches H (finds the Hider). Then he returns at a given speed ρ along the shortest path back to O, arriving at time R, the payoff.This models the problem faced in many types of search, including search-and-rescue problems and foraging problems of animals (where food must be found and returned to the lair). When Q is a binary tree, we derive optimal probabilities for the Searcher to branch at the nodes. These probabilities give a positive bias towards searching longer branches first. We show that the minimax value of the return time R (the game value of F(Q, O)) is μ + D/ρ, where μ is the total length of Q and D is the mean distance from the root O to the leaves (terminal nodes) of Q, where the mean is taken with respect to what is known as the equal branch density distribution. As ρ goes to infinity, our problem reduces to the search game model where the payoff is simply the time to reach the Hider, and our results tend to those obtained by Gal [Gal, S. 1979. Search games with mobile and immobile hider. SIAM J. Control Optim. 17(1) 99–122] and Anderson and Gal [Anderson, E. J., S. Gal. 1990. Search in a maze. Probab. Engrg. Inform. Sci. 4(3) 311–318] for that model. We also apply our return time formula μ + D/ρ to determine the ideal location for the root (lair or rescue center) O, assuming it can be moved. In the traditional “find only” model, the location of O does not matter.
A Comparative Study of Interventions for Delaying The Initiation of Sexual Intercourse Among Latino And Black Youth
Authors: Guilamo‐Ramos Vincent , Jaccard James , Dittus Patricia , Bouris Alida , Gonzalez Bernardo , Casillas Eileen , Banspach Stephen 
Published: November 2011

CONTEXT: Latino and black adolescents are disproportionately affected by STDs, including HIV, and unintended pregnancies. Few parent‐based interventions have targeted these youth, focused on early adolescence and had high participation rates.
METHODS: Between 2003 and 2009, a randomized clinical trial was conducted with 2,016 Latino and black mother‐adolescent dyads in New York City. Adolescents were eligible if they were in grade 6 or 7. Dyads were assigned to one of three conditions: a parent‐based intervention, Families Talking Together (FTT); an adolescent‐only intervention, Making a Difference! (MAD); or a combined FTT+MAD intervention. Respondents completed questionnaires at baseline and 12 months later. Single‐degree‐of‐freedom contrasts and logistic regression analysis were used to evaluate differences in outcomes by intervention.
RESULTS: The proportion of youth who reported ever having engaged in vaginal intercourse increased over the study period by eight percentage points among those in the MAD group, five points in the FTT group and three points in the combined group; the differences among these increases were not statistically significant. Adolescents in the two FTT groups were significantly more likely than those in the MAD group to indicate that their mother had talked to them about not having intercourse (79% vs. 68%). They also scored higher than youth in the MAD group on measures of communication and perceived maternal attributes, and lower on activities that might lead to risky behaviors.
CONCLUSIONS: The proportions of adolescents who initiated intercourse during the study period were not significantly different across groups, implying that the interventions were comparable. Findings suggest that FTT may have led to improved parenting behaviors.