bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Routes to Targeted Therapy of Intrahepatic Cholangiocarcinomas Revealed by Next-Generation Sequencing
Authors: Ross Jeffrey S. , Wang Kai , Gay Laurie , Al-Rohil Rami , Rand Janne V. , Jones David M. , Lee Hwa J. , Sheehan Christine E. , Otto Geoff A. , Palmer Gary , Yelensky Roman , Lipson Doron , Morosini Deborah , Hawryluk Matthew , Catenacci Daniel V. T. , Miller Vincent A. , Churi Chaitanya , Ali Siraj , Stephens Philip J. 
Published: February 2014

Abstract

Background.
Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer that is rarely curable by surgery and is rapidly increasing in incidence. Relapsed ICC has a poor prognosis, and current systemic nontargeted therapies are commonly extrapolated from those used in other gastrointestinal malignancies. We hypothesized that genomic profiling of clinical ICC samples would identify genomic alterations that are linked to targeted therapies and that could facilitate a personalized approach to therapy.

Methods.
DNA sequencing of hybridization-captured libraries was performed for 3,320 exons of 182 cancer-related genes and 36 introns of 14 genes frequently rearranged in cancer. Sample DNA was isolated from 40 μm of 28 formalin-fixed paraffin-embedded ICC specimens and sequenced to high coverage.

Results.
The most commonly observed alterations were within ARID1A (36%), IDH1/2 (36%), and TP53 (36%) as well as amplification of MCL1 (21%). Twenty cases (71%) harbored at least one potentially actionable alteration, including FGFR2 (14%), KRAS (11%), PTEN (11%), CDKN2A (7%), CDK6 (7%), ERBB3 (7%), MET (7%), NRAS (7%), BRCA1 (4%), BRCA2 (4%), NF1 (4%), PIK3CA (4%), PTCH1 (4%), and TSC1 (4%). Four (14%) of the ICC cases featured novel gene fusions involving the tyrosine kinases FGFR2 and NTRK1 (FGFR2-KIAA1598, FGFR2-BICC1, FGFR2-TACC3, and RABGAP1L-NTRK1).

Conclusion.
Two thirds of patients in this study harbored genomic alterations that are associated with targeted therapies and that have the potential to personalize therapy selection for to individual patients.
Polymorphisms in MicroRNA-Related Genes Are Associated With Survival of Patients With T-Cell Lymphoma
Authors: Li Xi , Tian Xiaobo , Zhang Bo , Chen Jieping 
Published: February 2014

Abstract

Objective
Elaborate evaluation of prognosis of T-cell lymphoma (TCL) is vital for current therapy and future stratified and individualized therapy. MicroRNAs (miRNAs) play important roles in cancer development and prognosis. We aimed to assess the effects of single nucleotide polymorphisms (SNPs) in miRNA-related genes on the survival of patients with TCL.

Patients and Methods
We genotyped 13 SNPs selected from 12 miRNA-related genes in 220 TCL patients and explored the association of SNPs with survival.

Results
Among the 13 SNPs, four (DROSHA rs6877842, DICER rs3742330, mir149 rs2292832, and mir499 rs3746444) were significantly associated with TCL survival after adjusting for subtype and International Prognostic Index score. In stratified analyses, all four SNPs remained significantly associated with survival in patients with mature T type. Of the four SNPs, only mir149 rs2292832 was not significantly associated with survival in patients with an International Prognostic Index score of 0–1. Furthermore, a dose-dependent cumulative effect of the four SNPs on TCL survival was observed by counting the number of unfavorable genotypes. Survival tree analysis also showed higher order interactions between these SNPs.

Conclusion
The results suggested that miRNA-related polymorphisms are associated with survival of TCL patients; thus, they may be used individually and jointly to predict survival of patients with TCL.
Continuous-Infusion Topotecan and Erlotinib: A Study in Topotecan-Pretreated Ovarian Cancer Assessing Shed Collagen Epitopes as a Marker of Invasiveness
Authors: Warner Eiran , Liebes Leonard , Levinson Benjamin , Downey Andrea , Tiersten Amy , Muggia Franco 
Published: February 2014

Abstract

Background.
Continuous-infusion topotecan with erlotinib has the potential to reverse topotecan resistance due to drug efflux mechanisms. We assessed the activity of such a regimen in ovarian cancer patients previously failing bolus topotecan. Assay for shed collagen epitopes recognized by antibody HU177 during treatment explored its ability to reflect tumor invasion.

Methods.
Topotecan 0.4 mg/m2 per day was administered by continuous infusion for 9–10 days every 3 weeks. Erlotinib, 150 mg orally, was administered on days 1–10 of each cycle. Cycles were repeated until progression or toxicity. Serum for shed HU177 collagen epitopes was collected weekly. This was a two-stage design to detect a CA-125 response rate of at least 20% in 30 patients after completing two treatment cycles. The trial would be terminated early if there were less than two CA-125 responses in 16 patients. Four or more CA-125 responses in 30 patients would justify further study of this regimen in prior topotecan treatment failures.

Results.
Six patients were enrolled, with four receiving three or more cycles and one achieving a partial response by cancer antigen 125 (CA-125) criteria. Shed epitope levels became undetectable on at least one measurement in all patients who received three or more cycles (Fig. 1A) and reappeared concomitantly with rises in CA-125 and clinical progression (Fig. 1B). After logistical delays, the trial was closed by the sponsor's decision to stop developing erlotinib in ovarian cancer.

Conclusion.
Continuous-infusion topotecan with erlotinib was found safe in six pretreated ovarian cancer patients; one met CA-125 criteria for partial response. Serial shed epitope levels to reflect invasiveness deserve further study.
Novel estradiol analogue induces apoptosis and autophagy in esophageal carcinoma cells
Authors: Wolmarans Elize , Mqoco Thandi , Stander Andre , Nkandeu Sandra , Sippel Katherine , McKenna Robert , Joubert Annie 
Published: February 2014

AbstractCancer is the second leading cause of death in South Africa. The critical role that microtubules play in cell division makes them an ideal target for the development of chemotherapeutic drugs that prevent the hyperproliferation of cancer cells. The new in silico-designed estradiol analogue 2-ethyl-3-O-sulfamoylestra-1,3,5(10)16-tetraene (ESE-16) was investigated in terms of its in vitro antiproliferative effects on the esophageal carcinoma SNO cell line at a concentration of 0.18 μM and an exposure time of 24 h. Polarization-optical differential interference contrast and triple fluorescent staining (propidium iodide, Hoechst 33342 and acridine orange) revealed a decrease in cell density, metaphase arrest, and the occurrence of apoptotic bodies in the ESE-16-treated cells when compared to relevant controls. Treated cells also showed an increase in the presence of acidic vacuoles and lysosomes, suggesting the occurrence of autophagic processes. Cell death via autophagy was confirmed using the Cyto-ID autophagy detection kit and the aggresome detection assay. Results showed an increase in autophagic vacuole and aggresome formation in ESE-16 treated cells, confirming the induction of cell death via autophagy. Cell cycle progression demonstrated an increase in the sub-G1 fraction (indicative of the presence of apoptosis). In addition, a reduction in mitochondrial membrane potential was also observed, which suggests the involvement of apoptotic cell death induced by ESE-16 via the intrinsic apoptotic pathway. In this study, it was demonstrated that ESE-16 induces cell death via both autophagy and apoptosis in esophageal carcinoma cells. This study paves the way for future investigation into the role of ESE-16 in ex vivo and in vivo studies as a possible anticancer agent.
Through the looking glass: a trip inside the L2 reader’s head
Authors: Taillefer Gail 
Published: February 2014

Alors qu’il existe une « Mission lecture » pour évaluer la performance de lecture des élèves et étudiants dans leur langue maternelle, le besoin se fait sentir d’un outil semblable pour la langue 2. En anglais de spécialité, il convenait de mettre en place des formations destinées à développer la compétence de lecture. L’auteur présente ici une évaluation quantitative et qualitative du travail mené en ce sens à partir de l’ouvrage de J. Billant et P. Fade Compréhension écrite en anglais pour les sciences humaines (1992).
Fonction des équivalences dans un dictionnaire bilingue
Authors: Schuwer Martine 
Published: February 2014

Dans un dictionnaire bilingue, on conçoit bien l’objectif explicite du lexicographe qui propose, pour un terme, plusieurs équivalences dans la langue cible. Il rend ainsi compte de la non-isomorphie bien établie des champs sémantiques. Mais au-delà de ces informations, quelle fonction ces équivalences jouent-elles pour le lecteur ?
Complexité tarifaire et choix de consommation
Authors: Rebaï Lilia , Flacher David 
Published: February 2014

Nous introduisons la notion de « complexité tarifaire » en tant que structure (ou présentation) tarifaire entraînant une méconnaissance des prix par les consommateurs ou des difficultés particulières à comparer les prix ou à les interpréter. Une enquête originale menée auprès de 1 500 consommateurs représentatifs de la population tunisienne en 2007-2008 permet de montrer l’existence de cette complexité dans le secteur des services de télécommunications : les consommateurs interrogés se révèlent effectivement mal informés sur les prix et leur comportement apparaît plus rationnel (en termes de minimisation des coûts) lorsque les prix sont clairement communiqués. L’ensemble de ces résultats témoignent de la nécessité d’envisager les fondements d’une nouvelle forme de régulation sectorielle : celle de la complexité tarifaire. Des pistes sont proposées pour tenir compte à la fois de la complexité d’origine stratégique et de la complexité liée à l’innovation.
Role of Mouse and Human Autophagy Proteins in IFN-γ–Induced Cell-Autonomous Responses against Toxoplasma gondii
Authors: Ohshima Jun , Lee Youngae , Sasai Miwa , Saitoh Tatsuya , Su Ma Ji , Kamiyama Naganori , Matsuura Yoshiharu , Pann-Ghill Suh , Hayashi Mikako , Ebisu Shigeyuki , Takeda Kiyoshi , Akira Shizuo , Yamamoto Masahiro 
Published: February 2014

Abstract
IFN-γ mediates cellular innate immunity against an intracellular parasite, Toxoplasma gondii, by inducing immunity-related GTPases such as p47 IFN-γ–regulated GTPases (IRGs) and p65 guanylate-binding proteins (GBPs), which also participate in antibacterial responses via autophagy. An essential autophagy protein, Atg5, was previously shown to play a critical role in anti–T. gondii cell-autonomous immunity. However, the involvement of other autophagy proteins remains unknown. In this study, we show that essential autophagy proteins differentially participate in anti–T. gondii cellular immunity by recruiting IFN-γ–inducible GTPases. IFN-γ–induced suppression of T. gondii proliferation and recruitment of an IRG Irgb6 and GBPs are profoundly impaired in Atg7- or Atg16L1-deficient cells. In contrast, cells lacking other essential autophagy proteins, Atg9a and Atg14, are capable of mediating the anti–T. gondii response and recruiting Irgb6 and GBPs to the parasites. Although IFN-γ also stimulates anti–T. gondii cellular immunity in humans, whether this response requires GBPs and human autophagy proteins remains to be seen. To analyze the role of human ATG16L1 and GBPs in IFN-γ–mediated anti–T. gondii responses, human cells lacking ATG16L1 or GBPs were generated by the Cas9/CRISPR genome-editing technique. Although both ATG16L1 and GBPs are dispensable for IFN-γ–induced inhibition of T. gondii proliferation in the human cells, human ATG16L1 is also required for the recruitment of GBPs. Taken together, human ATG16L1 and mouse autophagy components Atg7 and Atg16L1, but not Atg9a and Atg14, participate in the IFN-γ–induced recruitment of the immunity-related GTPases to the intracellular pathogen.
Inhibitory Fcγ Receptor Is Required for the Maintenance of Tolerance through Distinct Mechanisms
Authors: Li Fubin , Smith Patrick , Ravetch Jeffrey V. 
Published: February 2014

Abstract
The inhibitory FcγR FcγRIIB is widely expressed on B cells, dendritic cells (DCs), and myeloid effector cells and modulates a variety of Ab-driven in vivo functions. Although it has been established that FcγRIIB plays an important role in the maintenance of peripheral tolerance, the responsible cell-specific FcγRIIB expression remains to be determined. In this study, we generated mice with selective deletion of FcγRIIB in B cells, DCs, and myeloid effector cells and evaluated these novel strains in models of tolerance and autoimmune diseases. Our results demonstrate that mice with selective deletion of FcγRIIB expression in B cells and DCs have increased Ab and T cell responses, respectively, and display enhanced susceptibility to disease in distinct models, suggesting that FcγRIIB expression in distinct cellular populations contributes to the maintenance of peripheral tolerance through different mechanisms.
Influenza Infection Suppresses NADPH Oxidase–Dependent Phagocytic Bacterial Clearance and Enhances Susceptibility to Secondary Methicillin-Resistant Staphylococcus aureus Infection
Authors: Sun Keer , Metzger Dennis W. 
Published: February 2014

Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a leading contributor to mortality during recent influenza pandemics. The mechanism for this influenza-induced susceptibility to secondary S. aureus infection is poorly understood. In this study, we show that innate antibacterial immunity was significantly suppressed during the recovery stage of influenza infection, even though MRSA superinfection had no significant effect on viral burdens. Compared with mice infected with bacteria alone, postinfluenza MRSA–infected mice exhibited impaired bacterial clearance, which was not due to defective phagocyte recruitment, but rather coincided with reduced intracellular reactive oxygen species levels in alveolar macrophages and neutrophils. NADPH oxidase is responsible for reactive oxygen species production during phagocytic bacterial killing, a process also known as oxidative burst. We found that gp91phox-containing NADPH oxidase activity in macrophages and neutrophils was essential for optimal bacterial clearance during respiratory MRSA infections. In contrast to wild-type animals, gp91phox−/− mice exhibited similar defects in MRSA clearance before and after influenza infection. Using gp91phox+/− mosaic mice, we further demonstrate that influenza infection inhibits a cell-intrinsic contribution of NADPH oxidase to phagocyte bactericidal activity. Taken together, our results establish that influenza infection suppresses NADPH oxidase–dependent bacterial clearance and leads to susceptibility to secondary MRSA infection.
Effect of type of secondary task on cued gait on people with idiopathic Parkinson′s disease
Authors: Chawla Harsha , Walia Shefali , Behari Madhuri , Noohu Majumi M. 
Published: February 2014

ABSTRACT
Introduction: The purpose of this study was to find out the effect of the secondary cognitive and motor task on cued gait in people with Idiopathic Parkinson′s disease (PD). Design and Setting: A repeated measure same subject design carried out at All India Institute of Medical Sciences, Neurology Department, New Delhi. Materials and Methods: The subjects were made to walk in random order on a paper walkway under three conditions: Free walking with cues at preferred walking speed, coin transference while walking with cues at preferred walking speed and digit subtraction while walking with cues at preferred walking speed. Outcome: The stride length, cadence, walking speed and stops were recorded. Results: There was a significant reduction in their walking speed and stride length, but increase in the cadence and the number of stops was seen, when they had to perform dual tasks along with the cued gait, but the changes were more pronounced when secondary cognitive task was added to the cued gait in people with idiopathic PD. Conclusion: The results of this study demonstrated that there is a significant difference in the effect of secondary motor task when compared with secondary cognitive task on cued gait parameters in people with Idiopathic PD.
The seasonal variation of the CO2 flux over Tropical Asia estimated from GOSAT, CONTRAIL, and IASI
Authors: Basu S. , Krol M. , Butz A. , Clerbaux C. , Sawa Y. , Machida T. , Matsueda H. , Frankenberg C. , Hasekamp O. P. , Aben I. 
Published: February 2014

AbstractWe estimate the CO2 flux over Tropical Asia in 2009, 2010, and 2011 using Greenhouse Gases Observing Satellite (GOSAT) total column CO2(XCO2) and in situ measurements of CO2. Compared to flux estimates from assimilating surface measurements of CO2, GOSAT XCO2 estimates a more dynamic seasonal cycle and a large source in March–May 2010. The more dynamic seasonal cycle is consistent with earlier work by Patra et al. (2011), and the enhanced 2010 source is supported by independent upper air CO2 measurements from the Comprehensive Observation Network for Trace gases by Airliner (CONTRAIL) project. Using Infrared Atmospheric Sounding Interferometer (IASI) measurements of total column CO (XCO), we show that biomass burning CO2 can explain neither the dynamic seasonal cycle nor the 2010 source. We conclude that both features must come from the terrestrial biosphere. In particular, the 2010 source points to biosphere response to above‐average temperatures that year.
A climatology of medium‐scale gravity wave activity in the midlatitude/low‐latitude daytime upper thermosphere as observed by CHAMP
Authors: Park J. , Lühr H. , Lee C. , Kim Y. H. , Jee G. , Kim J.‐H. 
Published: February 2014

AbstractWe report on a detailed global climatology of medium‐scale (150–600 km) thermospheric gravity wave (GW) activity using mass density observations onboard the CHAMP satellite from 2001 to 2010. Our study focuses mainly on daytime (09–18 h in local time) and midlatitude/low‐latitude upper thermosphere between 300 km and 400 km altitudes. Midlatitude GW activity is strongest in the winter hemisphere. GW activity during June solstice adjacent to the Andes and Antarctic Peninsula is stronger than in any other season or location. GW activity in the low‐latitude summer hemisphere is stronger above continents than above oceans: especially during December solstice and equinoxes. In terms of relative density variation, GW activity is stronger during solar minimum than solar maximum. These results agree well with the characteristics of stratospheric GWs, implying that the CHAMP GWs are mainly caused by GWs from tropospheric/stratospheric processes. Using mesosphere/lower thermosphere wind observations at a Korean Antarctic station, we investigated at which altitudes the upper thermospheric GW climatology becomes visible. While the correlation is insignificant at z=82–88 km, it becomes significant for most cases at z=90–98 km, suggesting that the upper thermospheric GW climatology may start to emerge at z≥90 km.
Dynamic streambed fluxes during rainfall‐runoff events
Authors: Karan Sachin , Engesgaard Peter , Rasmussen Jørn 
Published: February 2014

AbstractObserved 3‐D temperature distributions within a streambed were used to analyze the effects on exchange fluxes between groundwater and the stream during rainfall‐runoff events. By combining a dense vertical and lateral monitoring network of streambed temperatures with coupled surface/subsurface 3‐D flow and heat transport modeling, we demonstrate how temperature can be used directly as a calibration target. Three model setups with different hydraulic conductivity distributions were evaluated in an optimization approach using temperature and hydraulic head data. The hydraulic conductivity distributions were based on slug test surveys within the streambed and aquifer. A detailed characterization of the hydraulic conductivity of the streambed and aquifer is needed to accurately simulate observed temperatures. Hence, the most sensitive parameters, the vertical hydraulic conductivity and the thermal conductivity, were calibrated within different conductivity zones of the heterogeneous model. Simulated exchange fluxes across the streambed showed variations up to a factor of four within just a meter. Such differences may not have been correctly predicted using 1‐D heat transport models due to lateral conduction amongst the different flow paths. During the rainfall‐runoff event, fluxes decreased substantially (−50%) due to a decrease in the hydraulic gradient with increased stream stage. Although no flow reversals were observed during the studied conditions, it is possible that these can occur during larger rainfall‐runoff events. We show that with the current sampling and modeling techniques, 3‐D temperature data can be used to estimate dynamic exchange in heterogeneous flow fields encountered in the field.
Accurate vertical profiles of turbulent flow in z‐layer models
Authors: Platzek F. W. , Stelling G. S. , Jankowski J. A. , Pietrzak J. D. 
Published: February 2014

AbstractThree‐dimensional hydrodynamic z‐layer models, which are used for simulating the flow in rivers, estuaries, and oceans, suffer from an inaccurate and often discontinuous bottom shear stress representation, due to the staircase bottom. We analyze the governing equations and clearly show the cause of the inaccuracies. Based on the analysis, we present a new method that significantly reduces the errors and the grid dependency of the results. The method consists of a near‐bed layer‐remapping and a modified near‐bed discretization of the k − ε turbulence model. We demonstrate the applicability of the approach for uniform channel flow, using a schematized two‐dimensional vertical model and for the flow over a bottom sill using the Delft3D modeling system.
Health and Culture
Authors: Quah Stella R. 
Published: February 2014

Abstract
practically all social science research on health and illness in the twenty‐first century acknowledges the influence of culture on health‐related behavior and attitudes. We have advanced from the early assumption that culture was one of several predictors of health behavior. Today we know that culture is not just one of many factors associated with health, but is the context within which health‐related behavior unfolds. This entry discusses in three sections why culture is significant in health‐related behavior: the definition of culture, the link between culture and health behavior, and the link between culture and healing systems.
Professions, Organized
Authors: Martin Graham P. 
Published: February 2014

Abstract
Traditional conceptualizations of “profession” have emphasized, among other things, their autonomy and independence from organizational bureaucracies as one of the defining features of professions. However, empirical study has emphasized the variety of ways in which professions coexist with wider organizational structures, sometimes in conflict, and sometimes in reconciliation. Beyond the “professional bureaucracy,” recent developments in the health care context have given rise to novel ways in which professions and organizations interact, some of which are considered in this entry.