bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic evaluation of the methodology of randomized controlled trials of anticoagulation in patients with cancer
Authors: Rada Gabriel , Schünemann Holger J , Labedi Nawman , El-Hachem Pierre , Kairouz Victor F , Akl Elie A 
Published: February 2013

Abstract

Background
Randomized controlled trials (RCTs) that are inappropriately designed or executed may provide biased findings and mislead clinical practice. In view of recent interest in the treatment and prevention of thrombotic complications in cancer patients we evaluated the characteristics, risk of bias and their time trends in RCTs of anticoagulation in patients with cancer.

Methods
We conducted a comprehensive search, including a search of four electronic databases (MEDLINE, EMBASE, ISI the Web of Science, and CENTRAL) up to February 2010. We included RCTs in which the intervention and/or comparison consisted of: vitamin K antagonists, unfractionated heparin (UFH), low molecular weight heparin (LMWH), direct thrombin inhibitors or fondaparinux. We performed descriptive analyses and assessed the association between the variables of interest and the year of publication.

Results
We included 67 RCTs with 24,071 participants. In twenty one trials (31%) DVT diagnosis was triggered by clinical suspicion; the remaining trials either screened for DVT or were unclear about their approach. 41 (61%), 22 (33%), and 11 (16%) trials respectively reported on major bleeding, minor bleeding, and thrombocytopenia. The percentages of trials satisfying risk of bias criteria were: adequate sequence generation (85%), adequate allocation concealment (61%), participants’ blinding (39%), data collectors’ blinding (44%), providers’ blinding (41%), outcome assessors’ blinding (75%), data analysts’ blinding (15%), intention to treat analysis (57%), no selective outcome reporting (12%), no stopping early for benefit (97%). The mean follow-up rate was 96%. Adequate allocation concealment and the reporting of intention to treat analysis were the only two quality criteria that improved over time.

Conclusions
Many RCTs of anticoagulation in patients with cancer appear to use insufficiently rigorous outcome assessment methods and to have deficiencies in key methodological features. It is not clear whether this reflects a problem in the design, conduct or the reporting of these trials, or both. Future trials should avoid the shortcomings described in this article.
Effect of Mukitake mushroom (Panellus serotinus) on the pathogenesis of lipid abnormalities in obese, diabetic ob/ob mice
Authors: Inoue Nao , Inafuku Masashi , Shirouchi Bungo , Nagao Koji , Yanagita Teruyoshi 
Published: February 2013

Abstract

Background
Various mushrooms have been used in folk medicine for the treatment of lifestyle diseases in eastern countries, and several compounds that modulate the immune system, lower blood lipid levels, and inhibit tumor and viral action have been isolated. The fruiting body of Panellus serotinus (Mukitake) is recognized in Japan as one of the most delicious edible mushrooms, and previous studies have demonstrated that the dietary intake of powdered whole Mukitake or Mukitake extracts prevents the development of non-alcoholic fatty liver disease (NAFLD) in leptin-resistant db/db mice. In the present study, we evaluated the effect of the Mukitake diet on the pathogenesis of metabolic disorders in leptin-deficient ob/ob mice.

Results
After 4 weeks of feeding, hepatomegaly, hepatic lipid accumulation, and elevated hepatic injury markers in the serum were markedly alleviated in Mukitake-fed ob/ob mice compared with control mice. Moreover, the mild hyperlipidemia in control ob/ob mice was attenuated and the elevated atherogenic index was reduced in Mukitake-fed ob/ob mice. These effects were partly attributable to the suppression of hepatic lipogenic enzyme activity due to the Mukitake diet.

Conclusion
The current results showed that Mukitake supplementation is beneficial for the alleviation of NAFLD and dyslipidemia in obese, diabetic ob/ob mice.
Approximation of fixed points for nonexpansive semigroups in Hilbert spaces
Authors: Yao Yonghong , Kang Jung Im , Cho Yeol Je , Liou Yeong-Cheng 
Published: February 2013

Abstract
In this paper, we propose two new algorithms for finding a common fixed point of a nonexpansive semigroup in Hilbert spaces and prove some strong convergence theorems for nonexpansive semigroups. Our results improve and generalize the corresponding results given by Shimizu and Takahashi (J. Math. Anal. Appl. 211:71-83, 1997), Shioji and Takahashi (Nonlinear Anal. TMA 34:87-99, 1998), Lau et al. (Nonlinear Anal. TMA 67:1211-1225, 2007) and many others.

MSC:47H05, 47H10, 47H17.
An application on the second-order generalized difference equations
Authors: Manuel Mariasebastin Maria Susai , Kılıçman Adem , Xavier Gnanadhass Britto Antony , Pugalarasu Rajan , Dilip Devadanam Suseela 
Published: February 2013

Abstract
In this paper, we study the solutions of the second-order generalized difference equation having the form of

Δ
ℓ
2

u
(
k
)
+
f

(
k
,
u
(
k
)
)

=
0
,

k
∈
[
a
,
∞
)
,
a
>
0
,
ℓ
∈
(
0
,
∞
)
,

where

Δ
ℓ

u
(
k
)
=
u
(
k
+
ℓ
)
−
u
(
k
)

. Then we provide applications on

ℓ

2
(
ℓ
)

and

c

0
(
ℓ
)

.

AMS Subject Classification:39A12, 39A70, 47B39, 39B60.
Dynamics of resistance mutations to NS3 protease inhibitors in a cohort of Brazilian patients chronically infected with hepatitis C virus (genotype 1) treated with pegylated interferon and ribavirin: a prospective longitudinal study
Authors: Hoffmann Luísa , Ramos Juliene Antonio , de Souza Elizabeth Valentin , de Araújo Ramos Ana Lucia , Villela-Nogueira Cristiane Alves , Ürményi Turán Péter , Tanuri Amilcar , Rondinelli Edson , Silva Rosane 
Published: February 2013

Abstract
About sixty thousand new cases of Hepatitis C virus (HCV) infection are recorded in Brazil each year. These cases are currently treated with pegylated interferon (PEG-IFN) and ribavirin (RBV) with an overall success rate of 50%. New compounds for anti-HCV therapy targeted to the HCV NS3 protease are being developed and some already form the components of licensed therapies. Mapping NS3 protease resistance mutations to protease inhibitors or anti-viral drug candidates is important to direct anti-HCV drug treatment.

Methods

Sequence analysis of the HCV NS3 protease was conducted in a group of 68 chronically infected patients harboring the HCV genotype 1. The patients were sampled before, during and after a course of PEG-IFN-RBV treatment.

Results

Resistance mutations to the protease inhibitors, Boceprevir and Telaprevir were identified in HCV isolated from three patients (4.4%); the viral sequences contained at least one of the following mutations: V36L, T54S and V55A. In one sustained virological responder, the T54S mutation appeared during the course of PEG-IFN and RBV therapy. In contrast, V36L and V55A mutations were identified in virus isolated from one relapsing patient before, during, and after treatment, whereas the T54S mutation was identified in virus isolated from one non-responding patient, before and during the treatment course.

Conclusions

The incidence and persistence of protease resistance mutations occurring in HCV from chronically infected patients in Brazil should be considered when using protease inhibitors to treat HCV disease. In addition, patients treated with the current therapy (PEG-IFN and RBV) that are relapsing or are non-responders should be considered candidates for protease inhibitor therapy.
Synthesis and characteristics of (Hydrogenated) ferulic acid derivatives as potential antiviral agents with insecticidal activity
Authors: Huang Guang-Ying , Cui Can , Wang Zhi-Peng , Li Yong-Qiang , Xiong Li-Xia , Wang Li-Zhong , Yu Shu-Jing , Li Zheng-Ming , Zhao Wei-Guang 
Published: February 2013

Abstract

Background
Plant viruses cause many serious plant diseases and are currently suppressed with the simultaneous use of virucides and insecticides. The use of such materials, however, increases the amounts of pollutants in the environment. To reduce environmental contaminants, virucides with insecticidal activity is an attractive option.

Results
A series of substituted ferulic acid amide derivatives 7 and the corresponding hydrogenated ferulic acid amide derivatives 13 were synthesized and evaluated for their antiviral and insecticidal activities. The majority of the synthesized compounds exhibited good levels of antiviral activity against the tobacco mosaic virus (TMW), with compounds 7a, 7b and 7d in particular providing higher levels of protective and curative activities against TMV at 500 μg/mL than the control compound ribavirin. Furthermore, these compounds displayed good insecticidal activities against insects with piercing-sucking mouthparts, which can spread plant viruses between and within crops.

Conclusions
Two series of ferulic acid derivatives have been synthesized efficiently. The bioassay showed title compounds not only inhibit the plant viral infection, but also prevented the spread of plant virus by insect vectors. These findings therefore demonstrate that the ferulic acid amides represent a new template for future antiviral studies.
Epigenetic inactivation of the MIR129-2 in hematological malignancies
Authors: Wong Kwan-Yeung , Yim Rita Lok-Hay , Kwong Yok-Lam , Leung Chung-Ying , Hui Pak-Kwan , Cheung Florence , Liang Raymond , Jin Dong-Yan , Chim Chor-Sang 
Published: February 2013

Abstract

Background

MIR129-2 has been shown to be a tumor suppressor microRNA hypermethylated in epithelial cancers.

Patients and methods
Epigenetic inactivation of MIR129-2 was studied by methylation-specific PCR (MSP) in 13 cell lines (eight myeloma and five lymphoma), 15 normal controls and 344 primary samples including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM) at diagnosis, MM at relapse/progression, and monoclonal gammopathy of undetermined significance (MGUS). Expression of MIR129 and its target, SOX4, in cell lines was measured before and after hypomethylating treatment and MIR129 overexpression. MIR129 expression was correlated with MIR129-2 methylation status in primary lymphoma samples. Tumor suppressor function of MIR129 was demonstrated by MTT and trypan blue exclusion assay after MIR129 overexpression.

Results
The sensitivity of the methylated-MSP was one in 103. Different MSP statuses, including complete methylation, partial methylation, and complete unmethylation, were verified by quantitative bisulfite pyrosequencing. All five lymphoma and seven of eight myeloma cell lines showed complete and partial MIR129-2 methylation. In primary samples, MIR129-2 methylation was absent in AML and CML, but detected in 5% ALL, 45.9% CLL, 49.5% MM at diagnosis, and 59.1% NHL. In CLL, MIR129-2 methylation adversely impacted on survival (p=0.004). In MM, MIR129-2 methylation increased from 27.5% MGUS to 49.5% MM at diagnosis and 41.5% at relapse/progression (p=0.023). In NHL, MIR129-2 methylation was associated with MIR124-1 and MIR203 methylation (p<0.001), and lower MIR129 expression (p=0.009). Hypomethylation treatment of JEKO-1, homozygously methylated for MIR129-2, led to MIR129-2 demethylation and MIR129 re-expression, with downregulation of SOX4 mRNA. Moreover, MIR129 overexpression in both mantle cell lines, JEKO-1 and GRANTA-519, inhibited cellular proliferation and enhanced cell death, with concomitant SOX4 mRNA downregulation.

Conclusions

MIR129-2 is a tumor suppressive microRNA frequently methylated in lymphoid but not myeloid malignancies, leading to reversible MIR129-2 silencing. In CLL, MIR129-2 methylation was associated with an inferior survival. In MM, MIR129-2 methylation might be acquired during progression from MGUS to symptomatic MM. In NHL, MIR129-2 methylation might collaborate with MIR124-1 and MIR203 methylation in lymphomagenesis.
High gravity and high cell density mitigate some of the fermentation inhibitory effects of softwood hydrolysates
Authors: Kapu Nuwan Sella , Piddocke Maya , Saddler Jack N 
Published: February 2013

AbstractAfter steam pretreatment of lignocellulosic substrates the fermentation of the biomass derived sugars to ethanol is typically problematic because of both the generally low sugar concentrations that can be supplied and the presence of naturally occurring and process derived inhibitors. As the majority of the inhibitory materials are usually associated with the hemicellulose rich, water soluble component, this fraction was supplemented with glucose to simulate high solids, un-detoxified substrate to see if a high gravity/high cell consistency approach might better cope with inhibition. Several yeast strains were assessed, with the Tembec T1, T2 and Lallemand LYCC 6469 strains showing the greatest ethanol productivity and yield. The addition of supplemental glucose enabled the faster and quantitatively higher removal of hydroxymethylfurfural (HMF). High cell density could provide effective fermentation at high sugar concentrations while enhancing inhibitor reduction. A 77% ethanol yield could be achieved using strain LYCC 6469 after 48 h at high cell density. It was apparent that a high cell density approach improved ethanol production by all of the evaluated yeast strains.
Osteocalcin Reverses Endoplasmic Reticulum Stress and Improves Impaired Insulin Sensitivity Secondary to Diet-Induced Obesity Through Nuclear Factor-κB Signaling Pathway
Authors: Zhou Bo , Li Huixia , Xu Lin , Zang Weijin , Wu Shufang , Sun Hongzhi 
Published: February 2013

Abstract
Osteocalcin, a synthetic osteoblast-specific protein, has recently emerged as an important regulator of energy metabolism, but the underlying mechanisms are not fully understood. In the present study, mice fed a high-fat diet and receiving osteocalcin showed reduced body weight gain, less fat pad gain, and improved insulin sensitivity as well as increased energy expenditure compared with mice fed a high-fat diet and receiving vehicle. Meanwhile, increased endoplasmic reticulum (ER) stress, defective insulin signaling, and mitochondrial dysfunction induced by obesity were also effectively alleviated by treatment with osteocalcin. Consistent with these findings, the addition of osteocalcin to the culture medium of 3T3-L1 adipocytes, Fao liver cells, and L6 muscle cells markedly reduced ER stress and restored insulin sensitivity. These effects were nullified by blockade of nuclear factor–κB (NF-κB) or phosphatidylinositol 3-kinase but not by U0126, a mitogen-activated protein kinase inhibitor, indicating the causative role of phosphatidylinositol 3-kinase/NF-κB in action of osteocalcin. In addition, the reversal effects of osteocalcin in cells deficient in X-box–binding protein-1, a transcription factor that modulates ER stress response, further confirmed its protective role against ER stress and insulin resistance. Our findings suggest that osteocalcin attenuates ER stress and rescues impaired insulin sensitivity in insulin resistance via the NF-κB signaling pathway, which may offer novel opportunities for treatment of obesity and diabetes.
Vaginal vault brachytherapy in endometrial cancer: verifying target coverage with image-guided applicator placement
Authors: Humphrey P , Cornes P , Al-Booz H 
Published: February 2013

Objective:
This quality assurance study assesses whether CT image-guided verification has led to improvements in the technique when compared with previous studies.

Methods:
The CT images were studied from a cohort of 105 consecutive patients with endometrial cancer having adjuvant brachytherapy to the vaginal vault in 2010. Images were taken at first insertion, checked for air gaps and treatment delivered. Images were later transferred to the planning system and air gaps between vaginal mucosa and vaginal cylinder were measured. Comparisons were made with the 2008 results from this centre and the literature series.

Results:
Images from two patients were not assessable owing to artefacts from hip replacements. Air gaps &gt;2 mm were seen in 11/103 patients. Repositioning or use of a larger cylinder reduced air gaps to 7/103 patients. In total, 96/103 patients (over 93%) were able to achieve good vaginal contact throughout the treatment volume. This shows a significant improvement in applicator positioning in our centre since 2008 and also a significant improvement over the total data published in 2010 (Pearson χ 2 test=46.19; p&lt;0.0001).

Conclusion:
The vaginal cylinder technique with CT imaging was proven to be effective for 96/103 patients. It is necessary to consider whether there is a better technique for the few patients with air gaps &gt;2 mm.

Advances in knowledge:
For the vast majority of patients, this technique is well tolerated, without the need for analgesia, and will continue to be the first choice technique in this centre.
Gaming und Bibliotheken
Authors: Deeg Christoph 
Published: February 2013

Zusammenfassung:
Das Thema Gaming ist neben Social-Media die nächste große Herausforderung für Bibliotheken. In diesem Beitrag geht es zum einen um die Frage warum sich Bibliotheken dem Thema Gaming erneut nähern sollten und zum anderen was die Deutsch-Amerikanischen Gaming-Liga des Vereins Zukunftswerkstatt Kultur- und Wissensvermittlung e. V. leistet.
Computerspiele in der Kultur- und Wissensvermittlung
Authors: Nötzelmann Cordula 
Published: February 2013

Zusammenfassung:
Der Artikel beleuchtet die Potenziale von Computerspielen in erster Linie für Öffentliche, aber auch für Wissenschaftliche Bibliotheken, Archive und Museen. Am Beispiel der Stadtbibliothek Köln wird illustriert, wie es gelingt, eine heterogene Community durch Computerspielthemen an die Bibliothek zu binden. Neben den Möglichkeiten in der Programmarbeit von Bibliotheken und anderen Kultur- und Bildungseinrichtungen spielen zunehmend auch Aspekte der Medienpädagogik, Kulturvermittlung und Technikdokumentation eine Rolle.
Numerical Simulations of Electromigration and Stress-Driven Diffusion in Polycrystalline Interconnects
Authors: Povirk G. L. 
Published: February 2013

ABSTRACTFinite element solutions to problems of electromigration and stress-driven diffusion in polycrystalline films are presented. The numerical formulation accounts for diffusion along grain boundaries and through the bulk. The procedures are validated by comparing the finite element solutions to an existing analytic solution of an idealized, isolated grain boundary lying parallel to current flow. A simple polycrystalline interconnect is then considered and the effects of diffusion along each grain boundary and through the bulk are each added separately to the analysis so that the importance of each mechanism can be ascertained. In some cases, the inclusion of additional diffusion paths result in significant reductions in predicted stress levels.
Reliability Improvement of Passivated Power Line in Memory Devices
Authors: Lee Seong-Min , Jang Y. K. , Chung Y. W. , Sim S. M. , Lee K. W. , Hwang B. K. 
Published: February 2013

ABSTRACTIn the present study, several different types of amorphous passivation layers such as PECVD-SiN and PECVD-TEOS were tested to learn how effectively they protect underlying Al interconnection lines. According to the experimental results, a thick monolithic passivation layer composing of PECVD-SiN was found to be highly susceptible to stress-related migration because it did not have sufficient elasticity. Moreover, since silicon nitride also has a high dielectric-breakdown strength, it exhibits an increased impedance to electric current due to parasitic resistance that exists in the path between the two passivated metal lines. On the other hand, passivation thickening through the use of PECVD-TEOS as an initial layer was estimated to be a more effective way to improve device reliability because of its better step coverage and smaller dielectric constant. The FEM simulation explains why the thick multilayer compromising an alternating sequence of mechanically dissimilar layers is an effective way to suppress stress-induced passivation damage during thermal cycling without having a significant effect on the IC pattern.
Finite Element Calculations of Strains in Passivated Metal Lines
Authors: Eppler I. , Schroeder H. , Schilling W. 
Published: February 2013

ABSTRACTPassivated metal lines, commonly used in integrated circuits, show thermally induced strains and stresses due to the mismatch of the thermal expansion coefficients of the lines and their surroundings. These strains depend on the geometry and the elastic constants of both, line and surroundings (i.e. substrate and passivation) and - for the case of an array of parallel lines - on the repetition distance of the lines. For a given set of these parameters the strains and stresses can be obtained from finite element calculations using a model with plane strain conditions.In order to obtain the dependences of the strains from these parameters systematic finite element calculations have been made for an infinite array of parallel lines with variations of the geometries and the elastic constants.Since only the volume mean values of the metal strains can be measured easily (X-ray, wafer curvature method (metal stress)), the dependences of these mean values on the different parameters are presented.
Analyses of Radiation and Mesothelioma in the US Transuranium and Uranium Registries
Authors: Gibb Herman , Fulcher Keri , Nagarajan Sumitha , McCord Stacey , Fallahian Naz Afarin , Hoffman Heather J. , Haver Cary , Tolmachev Sergei 
Published: February 2013

Objectives. We examined the relationship between radiation and excess deaths from mesothelioma among deceased nuclear workers who were part of the US Transuranium and Uranium Registries. Methods. We performed univariate analysis with SAS Version 9.1 software. We conducted proportionate mortality ratio (PMR) and proportionate cancer mortality ratio (PCMR) analyses using the National Institute for Occupational Safety and Health Life Table Analysis System with the referent group being all deaths in the United States. Results. We found a PMR of 62.40 (P < .05) and a PCMR of 46.92 (P < .05) for mesothelioma. PMRs for the 4 cumulative external radiation dose quartiles were 61.83, 57.43, 74.46, and 83.31. PCMRs were 36.16, 47.07, 51.35, and 67.73. The PMR and PCMR for trachea, bronchus, and lung cancer were not significantly elevated. Conclusions. The relationship between cumulative external radiation dose and the PMR and PCMR for mesothelioma suggests that external radiation at nuclear facilities is associated with an increased risk of mesothelioma. The lack of a significantly elevated PMR and PCMR for trachea, bronchus, and lung cancer suggests that asbestos did not confound this relationship.