bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-reported outcomes of cancer survivors in England 1–5 years after diagnosis: a cross-sectional survey
Authors: Glaser Adam W , Fraser Lorna K , Corner Jessica , Feltbower Richard , Morris Eva J A , Hartwell Greg , Richards Mike 
Published: April 2013

ObjectivesTo determine the feasibility of collecting population-based patient-reported outcome measures (PROMs) in assessing quality of life (QoL) to inform the development of a national PROMs programme for cancer and to begin to describe outcomes in a UK cohort of survivors.DesignCross-sectional postal survey of cancer survivors using a population-based sampling approach.SettingEnglish National Health Service.Participants4992 breast, colorectal, prostate and non-Hodgkin's lymphoma (NHL) survivors 1–5 years from diagnosis.Primary and secondary outcome measuresImplementation issues, response rates, cancer-specific morbidities utilising items including the EQ5D, tumour-specific subscales of the Functional Assessment of Cancer Therapy and Social Difficulties Inventory.Results3300 (66%) survivors returned completed questionnaires. The majority aged 85+ years did not respond and the response rates were lower for those from more deprived area. Response rates did not differ by gender, time since diagnosis or cancer type. The presence of one or more long-term conditions was associated with significantly lower QoL scores. Individuals from most deprived areas reported lower QoL scores and poorer outcomes on other measures, as did those self-reporting recurrent disease or uncertainty about disease status. QoL scores were comparable at all time points for all cancers except NHL. QoL scores were lower than those from the general population in Health Survey for England (2008) and General Practice Patient Survey (2012). 47% of patients reported fear of recurrence, while 20% reported moderate or severe difficulties with mobility or usual activities. Bowel and urinary problems were common among colorectal and prostate patients. Poor bowel and bladder control were significantly associated with lower QoL.ConclusionsThis method of assessing QoL of cancer survivors is feasible and acceptable to most survivors. Routine collection of national population-based PROMs will enable the identification of, and the support for, the specific needs of survivors while allowing for comparison of outcome by service provider.
The new oral anticoagulants: practical management for patients attending for endoscopic procedures
Authors: Woodhouse C , Evans G , Muller A F 
Published: April 2013

Guidelines published by the British Society of Gastroenterology have standardised the care of patients attending for endoscopy procedures, taking aspirin, clopidogrel and warfarin.Two new oral anticoagulant drugs, Rivaroxaban and Dabigatran, are licensed and National Institute of Clinical Excellence (NICE) approved for use in the UK. Unlike warfarin, these drugs do not require regular monitoring, and are at least as effective in preventing stroke in non-valvular atrial fibrillation. As such, they are likely to become popular among patients and clinicians alike. This paper summarises the practical management of patients taking these drugs attending for endoscopic procedures.
SRC Signaling Is Crucial in the Growth of Synovial Sarcoma Cells
Authors: Michels Sebastian , Trautmann Marcel , Sievers Elisabeth , Kindler Dagmar , Huss Sebastian , Renner Marcus , Friedrichs Nicolaus , Kirfel Jutta , Steiner Susanne , Endl Elmar , Wurst Peter , Heukamp Lukas , Penzel Roland , Larsson Olle , Kawai Akira , Tanaka Shinya , Sonobe Hiroshi , Schirmacher Peter , Mechtersheimer Gunhild , Wardelmann Eva , Büttner Reinhard , Hartmann Wolfgang 
Published: April 2013

Abstract
Synovial sarcoma is a soft-tissue malignancy characterized by a reciprocal t(X;18) translocation encoding a chimeric transcriptional modifier. Several receptor tyrosine kinases have been found activated in synovial sarcoma; however, no convincing therapeutic concept has emerged from these findings. On the basis of the results of phosphokinase screening arrays, we here investigate the functional and therapeutic relevance of the SRC kinase in synovial sarcoma. Immunohistochemistry of phosphorylated SRC and its regulators CSK and PTP1B (PTPN1) was conducted in 30 synovial sarcomas. Functional aspects of SRC, including dependence of SRC activation on the SS18/SSX fusion proteins, were analyzed in vitro. Eventually, synovial sarcoma xenografts were treated with the SRC inhibitor dasatinib in vivo. Activated phospho (p)-(Tyr416)-SRC was detected in the majority of tumors; dysregulation of CSK or PTP1B was excluded as the reason for the activation of the kinase. Expression of the SS18/SSX fusion proteins in T-REx-293 cells was associated with increased p-(Tyr416)-SRC levels, linked with an induction of the insulin-like growth factor pathway. Treatment of synovial sarcoma cells with dasatinib led to apoptosis and inhibition of cellular proliferation, associated with reduced phosphorylation of FAK (PTK2), STAT3, IGF-IR, and AKT. Concurrent exposure of cells to dasatinib and chemotherapeutic agents resulted in additive effects. Cellular migration and invasion were dependent on signals transmitted by SRC involving regulation of the Rho GTPases Rac and RhoA. Treatment of nude mice with SYO-1 xenografts with dasatinib significantly inhibited tumor growth in vivo. In summary, SRC is of crucial biologic importance and represents a promising therapeutic target in synovial sarcoma. Cancer Res; 73(8); 2518–28. ©2013 AACR.
Bevacizumab-Induced Normalization of Blood Vessels in Tumors Hampers Antibody Uptake
Authors: Arjaans Marlous , Oude Munnink Thijs H. , Oosting Sjoukje F. , Terwisscha van Scheltinga Anton G.T. , Gietema Jourik A. , Garbacik Erik T. , Timmer-Bosscha Hetty , Lub-de Hooge Marjolijn N. , Schröder Carolina P. , de Vries Elisabeth G.E. 
Published: April 2013

Abstract
In solid tumors, angiogenesis occurs in the setting of a defective vasculature and impaired lymphatic drainage that is associated with increased vascular permeability and enhanced tumor permeability. These universal aspects of the tumor microenvironment can have a marked influence on intratumoral drug delivery that may often be underappreciated. In this study, we investigated the effect of blood vessel normalization in tumors by the antiangiogenic drug bevacizumab on antibody uptake by tumors. In mouse xenograft models of human ovarian and esophageal cancer (SKOV-3 and OE19), we evaluated antibody uptake in tumors by positron emission tomographic imaging 24 and 144 hours after injection of 89Zr-trastuzumab (SKOV-3 and OE19), 89Zr-bevacizumab (SKOV-3), or 89Zr-IgG (SKOV-3) before or after treatment with bevacizumab. Intratumor distribution was assessed by fluorescence microscopy along with mean vessel density (MVD) and vessel normalization. Notably, bevacizumab treatment decreased tumor uptake and intratumoral accumulation compared with baseline in the tumor models relative to controls. Bevacizumab treatment also reduced MVD in tumors and increased vessel pericyte coverage. These findings are clinically important, suggesting caution in designing combinatorial trials with therapeutic antibodies due to a possible reduction in tumoral accumulation that may be caused by bevacizumab cotreatment. Cancer Res; 73(11); 3347–55. ©2013 AACR.
Interdecadal Amplitude Modulation of El Niño–Southern Oscillation and Its Impact on Tropical Pacific Decadal Variability*
Authors: Ogata Tomomichi , Xie Shang-Ping , Wittenberg Andrew , Sun De-Zheng 
Published: April 2013

Abstract
The amplitude of El Niño–Southern Oscillation (ENSO) displays pronounced interdecadal modulations in observations. The mechanisms for the amplitude modulation are investigated using a 2000-yr preindustrial control integration from the Geophysical Fluid Dynamics Laboratory Climate Model, version 2.1 (GFDL CM2.1). ENSO amplitude modulation is highly correlated with the second empirical orthogonal function (EOF) mode of tropical Pacific decadal variability (TPDV), which features equatorial zonal dipoles in sea surface temperature (SST) and subsurface temperature along the thermocline. Experiments with an ocean general circulation model indicate that both interannual and decadal-scale wind variability are required to generate decadal-scale tropical Pacific temperature anomalies at the sea surface and along the thermocline. Even a purely interannual and sinusoidal wind forcing can produce substantial decadal-scale effects in the equatorial Pacific, with SST cooling in the west, subsurface warming along the thermocline, and enhanced upper-ocean stratification in the east. A mechanism is proposed by which residual effects of ENSO could serve to alter subsequent ENSO stability, possibly contributing to long-lasting epochs of extreme ENSO behavior via a coupled feedback with TPDV.
Physical Mechanisms Underlying Selected Adaptive Sampling Techniques for Tropical Cyclones
Authors: Hoover Brett T. , Velden Chris S. , Majumdar Sharanya J. 
Published: April 2013

Abstract
To efficiently and effectively prioritize resources, adaptive observations can be targeted by using some objective criteria to estimate the potential impact an initial condition perturbation (or analysis increment) in a specific region would have on the future forecast. Several objective targeting guidance techniques have been developed, including total-energy singular vectors (TESV), adjoint-derived sensitivity steering vectors (ADSSV), and the ensemble transform Kalman filter (ETKF), all of which were tested during the 2008 The Observing System Research and Predictability Experiment (THORPEX) Pacific Asian Regional Campaign (T-PARC) and the Office of Naval Research Tropical Cyclone Structure-2008 (TCS-08) field experiments. An intercomparison between these techniques is performed in order to find underlying physical mechanisms in the respective guidance products, based on four tropical cyclone (TC) cases from the T-PARC/TCS-08 field campaigns. It is found that the TESV energy norm and the ADSSV response function are largely indirect measures of the TC track divergence that can be produced by an initial condition perturbation, explaining the strong correlation between these products. The downstream targets routinely chosen by the ETKF guidance system are often not found in the TESV and ADSSV guidance products, and it is found that downstream perturbations can affect the steering of a TC through the development of a Rossby wave in the subtropics that modulates the strength of the nearby subtropical ridge. It is hypothesized that the ubiquitousness of these downstream targets in the ETKF is largely due to the existence of large uncertainties downstream of the TC that are not taken into consideration by either the TESV or ADSSV techniques.
Dynamics of a Simulated North American Monsoon Gulf Surge Event
Authors: Newman Andrew J. , Johnson Richard H. 
Published: April 2013

Abstract
Gulf surges are transient disturbances that propagate along the Gulf of California (GoC) from south to north, transporting cool moist air toward the deserts of northwest Mexico and the southwest United States during the North American monsoon. They have been shown to modulate precipitation and have been linked to severe weather and flooding in northern Mexico and the southwest United States. The general features and progression of surge events are well documented but their detailed dynamical evolution is still unclear. In this study, a convection-permitting simulation is performed over the core monsoon region for the 12–14 July 2004 gulf surge event and the dynamics of the simulated surge are examined. Initially, convection associated with the tropical easterly wave precursor to Tropical Cyclone Blas creates a disturbance in the southern GoC on early 12 July. This disturbance is a precursor to the gulf surge on 13 July and is a Kelvin shock (internal bore under the influence of rotation) that dissipates in the central GoC. The surge initiates from inflow from the mouth of the GoC along with convective outflow impinging on the southern GoC. Continued convective outflow along the GoC generates multiple gravity currents and internal bores while intensifying the simulated surge as it propagates up the GoC. As the core of the surge reaches the northern GoC, a Kelvin shock is again the best dynamical fit to the phenomenon. Substantial low-level cooling and moistening are associated with the modeled surge along the northern GoC as is observed.
Tropical Cyclogenesis in the Western North Pacific as Revealed by the 2008–09 YOTC Data*
Authors: Xu Yamei , Li Tim , Peng Melinda 
Published: April 2013

Abstract
The Year of Tropical Convection (YOTC) high-resolution global reanalysis dataset was analyzed to reveal precursor synoptic-scale disturbances related to tropical cyclone (TC) genesis in the western North Pacific (WNP) during the 2008–09 typhoon seasons. A time filtering is applied to the data to isolate synoptic (3–10 day), quasi-biweekly (10–20 day), and intraseasonal (20–90 day) time-scale components. The results show that four types of precursor synoptic disturbances associated with TC genesis can be identified in the YOTC data. They are 1) Rossby wave trains associated with preexisting TC energy dispersion (TCED) (24%), 2) synoptic wave trains (SWTs) unrelated to TCED (32%), 3) easterly waves (EWs) (16%), and 4) a combination of either TCED-EW or SWT-EW (24%). The percentage of identifiable genesis events is higher than has been found in previous analyses.
Most of the genesis events occurred when atmospheric quasi-biweekly and intraseasonal oscillations are in an active phase, suggesting a large-scale control of low-frequency oscillations on TC formation in the WNP. For genesis events associated with SWT and EW, maximum vorticity was confined in the lower troposphere. During the formation of Jangmi (2008), maximum Rossby wave energy dispersion appeared in the middle troposphere. This differs from other TCED cases in which energy dispersion is strongest at low level. As a result, the midlevel vortex from Rossby wave energy dispersion grew faster during the initial development stage of Jangmi.
The Baby-Friendly Hospital Initiative in Switzerland
Authors: Forrester-Knauss Christine , Merten Sonja , Weiss Carine , Ackermann-Liebrich Ursula , Zemp Stutz Elisabeth 
Published: April 2013

Background: This article reports the trends over a 9-year period for 4 steps of the Baby-Friendly Hospital Initiative (BFHI) (exclusive breastfeeding, uninterrupted rooming-in, no use of pacifiers, and initiation of breastfeeding within the first 2 hours after birth) during hospital stays in Switzerland. Methods: Data were collected annually over a period of 9 years from a monitoring survey of all BFHI-accredited hospitals in Switzerland (between 41 and 65 hospitals). The number of participants included in the study per year ranged between 15 627 and 31 141 healthy mother–newborn pairs. Results: Significant improvements were found for 3 of the 4 steps of the BFHI between 2000 and 2008: rates of exclusive breastfeeding during postpartum stay (35.9%-57.6%, P < .001), uninterrupted rooming-in (48.2%-73.1%, P < .001), and no use of pacifiers (33.6%-48.1%, P < .001). Initiation of breastfeeding within the first 2 hours after birth was always > 90% and did not change significantly over the 9 years. Exclusive breastfeeding during hospital stay was significantly related to no use of pacifiers ( P < .001) and to uninterrupted rooming-in ( P < .001) in the years when exclusive breastfeeding particularly increased (2003, 2004, and 2008). Conclusion: Rates of exclusive breastfeeding during hospital stay and uninterrupted rooming-in increased significantly over the 9 years. Continued promotion of the BFHI may be needed to maintain or further improve the breastfeeding rates and to find ways to deal with difficulties that hospitals face when applying the 10 steps of the BFHI.
MicroRNAs activate natural killer cells through Toll-like receptor signaling
Authors: He Shun , Chu Jianhong , Wu Lai-Chu , Mao Hsiaoyin , Peng Yong , Alvarez-Breckenridge Christopher A. , Hughes Tiffany , Wei Min , Zhang Jianying , Yuan Shunzong , Sandhu Sumeet , Vasu Sumithira , Benson Don M. , C. Hofmeister Craig , He Xiaoming , Ghoshal Kalpana , Devine Steven M. , Caligiuri Michael A. , Yu Jianhua 
Published: April 2013

Key Points
miRNAs activate NK cells through a TLR–NF-κB signaling pathway and may have therapeutic applications in cancer.
Fluorescence in situ Hybridization method using Peptide Nucleic Acid probes for rapid detection of Lactobacillus and Gardnerella spp.
Authors: Machado António , Almeida Carina , Salgueiro Débora , Henriques Ana , Vaneechoutte Mario , Haesebrouck Freddy , Vieira Maria João , Rodrigues Ligia , Azevedo Nuno Filipe , Cerca Nuno 
Published: April 2013

Abstract

Background
Bacterial vaginosis (BV) is a common vaginal infection occurring in women of reproductive age. It is widely accepted that the microbial switch from normal microflora to BV is characterized by a decrease in vaginal colonization by Lactobacillus species together with an increase of Gardnerella vaginalis and other anaerobes. Our goal was to develop and optimize a novel Peptide Nucleic Acid (PNA) Fluorescence in situ Hybridization assay (PNA FISH) for the detection of Lactobacillus spp. and G. vaginalis in mixed samples.

Results
Therefore, we evaluated and validated two specific PNA probes by using 36 representative Lactobacillus strains, 22 representative G. vaginalis strains and 27 other taxonomically related or pathogenic bacterial strains commonly found in vaginal samples. The probes were also tested at different concentrations of G. vaginalis and Lactobacillus species in vitro, in the presence of a HeLa cell line. Specificity and sensitivity of the PNA probes were found to be 98.0% (95% confidence interval (CI), from 87.8 to 99.9%) and 100% (95% CI, from 88.0 to 100.0%), for Lactobacillus spp.; and 100% (95% CI, from 92.8 to 100%) and 100% (95% CI, from 81.5 to 100.0%) for G. vaginalis. Moreover, the probes were evaluated in mixed samples mimicking women with BV or normal vaginal microflora, demonstrating efficiency and applicability of our PNA FISH.

Conclusions
This quick method accurately detects Lactobacillus spp. and G. vaginalis species in mixed samples, thus enabling efficient evaluation of the two bacterial groups, most frequently encountered in the vagina.
Comparative proteomics study on liver mitochondria of primary biliary cirrhosis mouse model
Authors: Song Guang , Hu Chaojun , Zhu Huishan , Li Xi , Zhao Liying , Zhou Renfang , Zhang Xuan , Zhang Fengchun , Wu Lin , Li Yongzhe 
Published: April 2013

Abstract

Background
Primary biliary cirrhosis (PBC) is a liver specific chronic disease with unclear pathogenesis, especially for the early stage molecular events. The mitochondrion is a multi-functional organelle associated with various diseases including PBC. The purpose of this study was to discover the alterations in the mitochondria proteome using an early stage PBC mouse model for revealing the possible pathogenesis mechanisms in the early stages of PBC.

Methods
Mouse model of early stage of PBC was constructed by consecutive administration of poly I:C. Mitochondria of mouse models and controls were purified and comparative proteomics was performed by iTRAQ technology. Then, differentially expressed proteins were validated by western blotting.

Results
In total 354 proteins that satisfied the criteria for comparative proteomics study were identified. Of them, nine proteins were downregulated and 20 were up-regulated in liver mitochondria of PBC mouse model. Most differentially expressed proteins are associated with oxidation-reduction and lipid metabolism, and some are involved in the biosynthesis of steroid hormone and primary bile acid. Interestingly, four proteins (HCDH, CPT I, DECR, ECHDC2) involved in the fatty acid beta-oxidation were all upregulated.

Conclusions
iTRAQ is a powerful tool for comparative proteomics study of PBC mouse model and differentially expressed proteins in mitochondria proteome of PBC mouse model provide insights for the pathogenesis mechanism at early stage of PBC.
Synthesis and cytotoxic properties of novel (E)-3-benzylidene-7-methoxychroman-4-one derivatives
Authors: Noushini Saeedeh , Alipour Eskandar , Emami Saeed , Safavi Maliheh , Ardestani Sussan Kabudanian , Gohari Ahmad Reza , Shafiee Abbas , Foroumadi Alireza 
Published: April 2013

AbstractBackground and the purpose of the studyThere has been increscent interest in the field of cancer chemotherapy by discovery and development of novel agents with high efficacy, low toxicity, and minimum side effects. In order to find new anticancer agents, we replaced the pyrazolone part of well-known cytotoxic agent SJ-172550 with 7-methoxychroman-4-one. Thus, a novel series of 3-benzylidene-4-chromanones were synthesized and tested in vitro against human cancer cell lines.MethodsThe title compounds were prepared by condensation of 7-methoxychroman-4-one with suitable aldehydes in appropriate alcohol in the presence of gaseous HCl. The antiproliferative activity of target compounds were evaluated against MDA-MB-231 (breast cancer), KB (nasopharyngeal epidermoid carcinoma) and SK-N-MC (human neuroblastoma) cell lines using MTT assay.ResultsAlthough the direct analog of SJ-172550 (compound5d) did not show any cytotoxic activity against tested cell lines, but 2-(2-chloro-6-methoxyphenoxy)acetic acid methyl ester analog5cshowed some activity against MDA-MB-231 and SK-N-MC cells. Further modification of compound5cresulted in the 3-chloro-4,5-dimethoxybenzylidene derivative5bwhich demonstrated better cytotoxic profile against all tested cell lines (IC50values = 7.56–25.04 μg/ml).ConclusionThe results demonstrated that the cytotoxic activity of compound5bagainst MDA-MB-231 and SK-N-MC cells is more than etoposide. Therefore, compound5bprototype could be considered as novel cytotoxic agent for further developing new anticancer chemotherapeutics.
Comparative meta-RNA-seq of the vaginal microbiota and differential expression by Lactobacillus iners in health and dysbiosis
Authors: Macklaim Jean M , Fernandes Andrew D , Di Bella Julia M , Hammond Jo-Anne , Reid Gregor , Gloor Gregory B 
Published: April 2013

Abstract

Background
Bacterial vaginosis (BV), the most common vaginal condition of reproductive-aged women, is associated with a highly diverse and heterogeneous microbiota. Here we present a proof-of-principle analysis to uncover the function of the microbiota using meta-RNA-seq to uncover genes and pathways that potentially differentiate healthy vaginal microbial communities from those in the dysbiotic state of bacterial vaginosis (BV).

Results
The predominant organism, Lactobacillus iners, was present in both conditions and showed a differing expression profile in BV compared to healthy. Despite its minimal genome, L. iners differentially expressed over 10% of its gene complement. Notably, in a BV environment L. iners increased expression of a cholesterol-dependent cytolysin, and of mucin and glycerol transport and related metabolic enzymes. Genes belonging to a CRISPR system were greatly upregulated suggesting that bacteriophage influence the community. Reflective of L. iners, the bacterial community as a whole demonstrated a preference for glycogen and glycerol as carbon sources under BV conditions. The predicted end-products of metabolism under BV conditions include an abundance of succinate and other short-chain fatty-acids, while healthy conditions are predicted to largely contain lactic acid.

Conclusions
Our study underscores the importance of understanding the functional activity of the bacterial community in addition to characterizing the population structure when investigating the human microbiome.