bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive factor of re‐bleeding after negative capsule endoscopy for obscure gastrointestinal bleeding: Over 1‐year follow‐up study
Authors: Matsumura Tomoaki , Arai Makoto , Saito Keiko , Okimoto Kenichiro , Saito Masaya , Minemura Shoko , Oyamada Arata , Maruoka Daisuke , Nakagawa Tomoo , Watabe Hirotsugu , Katsuno Tatsuro , Yokosuka Osamu 
Published: March 2014

Background and AimCapsule endoscopy (CE) is now widely accepted as a first‐line diagnostic modality for obscure gastrointestinal bleeding (OGIB), with a high diagnostic yield compared to other modalities. However, even after negative CE examination, re‐bleeding is often known to occur. The aim of the present study was to identify predictive factors of re‐bleeding after negative CE, and to clarify the clinical utility of double‐balloon enteroscopy (DBE) after negative CE for OGIB.MethodsTwo hundred and sixty patients who underwent CE for OGIB between October 2007 and September 2012 were included, and followed up for at least 1 year after CE examination. Demographic and clinical parameters associated with re‐bleeding after negative CE were investigated.ResultsA total of 154 patients (59.2%) had negative findings. Thirteen of those patients (8.4%) had one or more re‐bleeding episodes during the follow‐up period. In comparing patients with and without re‐bleeding, Cox hazard regression analysis revealed that advanced age was a predictive factor for re‐bleeding after negative CE (hazard ratio 1.05 [1.01–1.10], P = 0.03). Subsequent DBE for reasons other than re‐bleeding was carried out in 51 patients (33.1%). Mucosal lesions (ulcer or multiple erosions) were subsequently detected in seven patients (13.7%), and endoscopic therapies were carried out in two patients (3.9%).ConclusionsIn patients of advanced age, more extensive follow up is needed, even if the CE result is negative. In addition, DBE subsequent to negative CE may be useful to detect lesions that were overlooked on CE.
Species richness of associates of ants in the nests of red wood ant Formica polyctena (Hymenoptera, Formicidae)
Authors: Härkönen Salla K. , Sorvari Jouni 
Published: March 2014

Abstract

Ant nests are rich with various other fauna, and they may be seen as resources for these guest species. We studied the species richness and abundance of ant guests in the nests of Formica polyctena by addressing the resource concentration hypothesis, which predicts that nests in high densities would support higher species richness and abundance of specialised guests.

In 12 nests we found 1562 individuals belonging to 70 taxa, of which beetles were the most species rich group. The resource concentration hypothesis was supported, as we found the species richness to be higher in nests with close neighbours. There was no relationship between the abundance of associates and the nearest neighbour distance.

Non‐parametric methods were applied for total species richness estimation. These suggest that additional sampling would yield more associate species.

In addition, we studied the similarity of the species composition in the nests and how the distance between the nests correlates with it. Overall, nests from the same area appeared to be most similar with each other. A significant negative trend between geographical distance and similarity of the species composition was found when all species and non‐myrmecophiles were tested.

For maintaining and conserving high arthropod diversity in temperate and boreal forests, forest management practices preserving dense red wood ant populations should be used if the habitat cannot be protected.
Effectiveness of ProTaper Universal retreatment instruments used with rotary or reciprocating adaptive motion in the removal of root canal filling material
Authors: Capar I. D. , Arslan H. , Ertas H. , Gök T. , Saygılı G. 
Published: March 2014

AbstractAimTo compare the effectiveness of ProTaper Universal retreatment instruments with continuous rotation and adaptive motion (AM; a modified reciprocating motion that combines rotational and reciprocating motion) in the removal of filling material.MethodologyMesiobuccal root canals in 36 mandibular first molars were instrumented up to size F2 with the ProTaper Universal instrument (Dentsply Maillefer, Ballaigues, Switzerland) and filled using sealer and ProTaper Universal F2 gutta‐percha cones. Gutta‐percha was then down‐packed and the root canal backfilled using the extruder hand‐piece of the Elements Obturation System (SybronEndo, Orange, CA, USA). The teeth were assigned to two groups (n = 18), and removal of the root fillings was performed using one of the following techniques: group 1) ProTaper Universal retreatment files used with rotational motion (RM) and group 2) ProTaper Universal retreatment files used with adaptive motion (AM) (600° clockwise/0° counter‐clockwise to 370° clockwise/50° counter‐clockwise). The teeth were sectioned, and both halves were analysed at 8 × magnification. The percentage of remaining filling material was recorded. The data were analysed statistically using the Student's t‐test at a 95% confidence level (P < 0.05).ResultsThere was no significant difference between the groups with respect to the total time required for retreatment (P = 0.481). The AM technique left significantly less filling material than the RM method (P = 0.013).ConclusionThe use of ProTaper Universal retreatment files with adaptive motion removed more filling materials from root canals than the rotational movement.
Transforming growth factor‐β1 requires NADPH oxidase 4 for angiogenesis in vitro and in vivo
Authors: Peshavariya Hitesh M , Chan Elsa C , Liu Guei Sheung , Jiang Fan , Dusting Gregory J 
Published: March 2014

AbstractAngiogenesis, the formation of new blood vessels, is a key physiological event in organ development and tissue responses to hypoxia but is also involved in pathophysiologies such as tumour growth and retinopathies. Understanding the molecular mechanisms involved is important to design strategies for therapeutic intervention. One important regulator of angiogenesis is transforming growth factor‐β1 (TGF‐β1). In addition, reactive oxygen species (ROS) and the ROS‐forming NADPH oxidase type 4 (Nox4) have been implicated as additional regulators such as during hypoxia. Here, we show that both processes are indeed mechanistically linked. TGF‐β1‐stimulated Nox4 expression and ROS formation in endothelial cells. In cells from Nox4‐deficient mice, TGF‐β1‐induced cell proliferation, migration and tube formation were abolished. In vivo, TGF‐β1 stimulated growth of blood vessels into sponges implanted subcutaneously, and this angiogenesis was markedly reduced in Nox4 knockout mice. Thus, endothelial cells are regulated by a TGF‐β1 signalling pathway involving Nox4‐derived ROS to promote angiogenesis. In order to abrogate pathological angiogenesis triggered by a multitude of factors, such as TGF‐β1 and hypoxia, Nox4 may thus be an ideal therapeutic target.
Contribution of extrahepatic collaterals to liver parenchymal circulation after proper hepatic artery embolization
Authors: Mine Takahiko , Murata Satoru , Ueda Tatsuo , Takeda Minako , Onozawa Shiro , Yamaguchi Hidenori , Kawano Youichi , Kumita Shin‐ichiro 
Published: March 2014

AbstractBackground and AimTo retrospectively evaluate proper hepatic artery embolization, with respect to the development of extrahepatic collaterals.MethodsProper hepatic artery embolization was performed in 18 patients with hemorrhagic arterial lesions in the hepatic hilum. Post‐procedural development of extrahepatic collaterals was evaluated by computed tomography or angiography. Embolization data and liver function tests were assessed. The correlation of outcomes with portal venous stenosis, hepatic failure prior to embolization, elevation of prothrombin time, and insufficient collateral development were analyzed.ResultsPostoperative bleeding occurred in 17/18 patients, and one was treated for an idiopathic aneurysm of the proper hepatic artery; all treatments achieved technical success. Extrahepatic collaterals were confirmed in 13 patients. Elevations of liver function test values were transient and returned to baseline within 14 days in patients with collateral development (n = 13), but were unimproved in patients without collaterals (n = 5) (P < 0.001). Portal venous stenosis; prior hepatic failure; unrecovered, elevation of prothrombin time; and insufficient collateral development were significantly correlated with poor outcomes (P < 0.05, respectively).ConclusionsProper hepatic artery embolization is effective for hemostasis, and extrahepatic collateral development is expected. Therefore, this is a safe treatment without prolonged hepatic ischemic damage, especially in patients without severe portal venous stenosis or prior hepatic failure.
Minority nations and attitudes towards immigration: the case of Quebec
Authors: Turgeon Luc , Bilodeau Antoine 
Published: March 2014

AbstractGrowing international migration constitutes a tremendous challenge for contemporary democracies, no more so than for minority nations. An important challenge for the latter is one of acceptance of immigration from the native‐born population, in a context in which immigrant can be seen as both a cultural and a political threat. In this article we ask what explains attitudes towards immigration in minority nations. More specifically, we seek to provide answers to these questions: What is the impact of cultural insecurity on attitudes towards immigration in minority nations? Is strong attachment to a minority nation associated with less positive attitudes towards immigration? And finally, are proponents of independence for minority nations more likely to favour a reduction in the level of immigration than those who oppose it? The article seeks to answer these questions by exploring the case of Quebec.
Genome rearrangements derived from homoeologous recombination following allopolyploidy speciation in coffee
Authors: Lashermes Philippe , Combes Marie‐Christine , Hueber Yann , Severac Dany , Dereeper Alexis 
Published: March 2014

SummaryAllopolyploidization is widespread and has played a major role in flowering plant diversification. Genomic changes are common consequences of allopolyploidization, but their mechanisms of occurrence and dynamics over time are still poorly understood. Coffea arabica, a recently formed allotetraploid, was chosen as a model to investigate genetic changes in allopolyploid using an approach that exploits next‐generation sequencing technologies. Genes affected by putative homoeolog loss were inferred by comparing the numbers of single‐nucleotide polymorphisms detected using RNA‐seq in individual accessions of C. arabica, and between accessions of its two diploid progenitor species for common sequence positions. Their physical locations were investigated and clusters of genes exhibiting homoeolog loss were identified. To validate these results, genome sequencing data were generated from one accession of C. arabica and further analyzed. Genomic rearrangements involving homoeologous exchanges appear to occur in C. arabica and to be a major source of genetic diversity. At least 5% of the C. arabica genes were inferred to have undergone homoeolog loss. The detection of a large number of homoeologous exchange events (HEEs) shared by all accessions of C. arabica strongly reinforces the assumption of a single allopolyploidization event. Furthermore, HEEs were specific to one or a few accessions, suggesting that HEE accumulates gradually. Our results provide evidence for the important role of HEE in allopolyploid genome evolution.
Genome Sequence of Pseudomonas aeruginosa Strain LCT-PA220, Which Was Selected after Space Flight by Using Biolog's Powerful Carbon Source Utilization Technology
Authors: Xu Guogang , Hu Juan , Fang Xiangqun , Zhang Xuelin , Wang Junfeng , Guo Yinghua , Li Tianzhi , Chen Zhenghong , Dai Wenkui , Liu Changting 
Published: March 2014

ABSTRACT

To explore the changes of
Pseudomonas aeruginosa
in space flight, we present the draft genome sequence of
P. aeruginosa
strain LCT-PA220, which originated from a
P. aeruginosa
strain, ATCC 27853, that traveled on the Shenzhou-VIII spacecraft.
Draft Genome Sequence of Bacillus thuringiensis Serovar Tolworthi Strain Na205-3, an Isolate Toxic for Helicoverpa armigera
Authors: Palma Leopoldo , Muñoz Delia , Murillo Jesús , Caballero Primitivo 
Published: March 2014

ABSTRACT

We report here the complete annotated 6,510,053-bp draft genome sequence of
Bacillus thuringiensis
serovar tolworthi strain Na205-3, which is toxic for
Helicoverpa armigera
. This strain potentially contains nine insecticidal toxin genes homologous to
cry1Aa12
,
cry1Ab1
,
cry1Ab8
,
cry1Ba1
,
cry1Af1
,
cry1Ia10
,
vip1Bb1
,
vip2Ba2
, and
vip3Aa6
.
The Nedd8-Activating Enzyme Inhibitor MLN4924 Thwarts Microenvironment-Driven NF-κB Activation and Induces Apoptosis in Chronic Lymphocytic Leukemia B Cells
Authors: Godbersen J. Claire , Humphries Leigh Ann , Danilova Olga V. , Kebbekus Peter E. , Brown Jennifer R. , Eastman Alan , Danilov Alexey V. 
Published: March 2014

Abstract
Background: Stromal-mediated signaling enhances NF-κB pathway activity in chronic lymphocytic leukemia (CLL) B cells, leading to cell survival and chemoresistance. Ubiquitination of IκBα may partially account for constitutive activation of NF-κB. MLN4924 is an investigational agent that inhibits the Nedd8-activating enzyme, thereby neutralizing Cullin-RING ubiquitin ligases and preventing degradation of their substrates.
Experimental Design: We conducted a preclinical assessment of MLN4924 in CLL. Primary CLL cells were cocultured in vitro with CD40L-expressing stroma to mimic the prosurvival conditions present in lymphoid tissue. The effect of MLN4924 on CLL cell apoptosis, NF-κB pathway activity, Bcl-2 family members, and cell cycle was assessed by flow cytometry, Western blotting, PCR, and immunocytochemistry.
Results: CD40L-expressing stroma protected CLL cells from spontaneous apoptosis and induced resistance to multiple drugs, accompanied by NF-κB activation and Bim repression. Treatment with MLN4924 induced CLL cell apoptosis and circumvented stroma-mediated resistance. This was accompanied by accumulation of phospho-IκBα, decreased nuclear translocation of p65 and p52 leading to inhibition of both the canonical and noncanonical NF-κB pathways, and reduced transcription of their target genes, notably chemokines. MLN4924 promoted induction of Bim and Noxa in the CLL cells leading to rebalancing of Bcl-2 family members toward the proapoptotic BH3-only proteins. siRNA-mediated knockdown of Bim or Noxa decreased sensitivity to MLN4924. MLN4924 enhanced the antitumor activity of the inhibitors of B-cell receptor (BCR)–associated kinases.
Conclusions: MLN4924 disrupts NF-κB activation and induces Bim expression in CLL cells, thereby preventing stroma-mediated resistance. Our data provide rationale for further evaluation of MLN4924 in CLL. Clin Cancer Res; 20(6); 1576–89. ©2014 AACR.
Cancer Drug Development and the Evolving Regulatory Framework for Companion Diagnostics in the European Union
Authors: Pignatti Francesco , Ehmann Falk , Hemmings Robert , Jonsson Bertil , Nuebling Micha , Papaluca-Amati Marisa , Posch Martin , Rasi Guido 
Published: March 2014

Abstract
The European Union (EU) legal framework for medical device regulation is currently under revision. The European Commission has proposed a new framework to ensure that medical devices serve the needs and ensure the safety of European citizens, aiming for a framework that is fit for purpose, more transparent, and better adapted to scientific and technological progress. The proposed new framework is described as an evolution of the current regime keeping the same legal approach. An important proposed change is that companion diagnostics will no longer be considered as low risk and subject to self-certification by the manufacturer. According to the new proposal, companion diagnostics will be classified as high individual risk or moderate public health risk (category C) and require conformity assessment by a notified body. It has also been proposed that evidence of the clinical utility of the device for the intended purpose should be required for companion diagnostics. In this article, we review the EU legal framework relevant for companion diagnostics, describe the proposed changes, and summarize the available scientific guidance from the European Medicines Agency and its regulatory experience with cancer drug development including companion diagnostics.
See all articles in this CCR Focus section, “The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development.”
Clin Cancer Res; 20(6); 1458–68. ©2014 AACR.
Activating mTOR Mutations in a Patient with an Extraordinary Response on a Phase I Trial of Everolimus and Pazopanib
Authors: Wagle Nikhil , Grabiner Brian C. , Van Allen Eliezer M. , Hodis Eran , Jacobus Susanna , Supko Jeffrey G. , Stewart Michelle , Choueiri Toni K. , Gandhi Leena , Cleary James M. , Elfiky Aymen A. , Taplin Mary Ellen , Stack Edward C. , Signoretti Sabina , Loda Massimo , Shapiro Geoffrey I. , Sabatini David M. , Lander Eric S. , Gabriel Stacey B. , Kantoff Philip W. , Garraway Levi A. , Rosenberg Jonathan E. 
Published: March 2014

Abstract
Understanding the genetic mechanisms of sensitivity to targeted anticancer therapies may improve patient selection, response to therapy, and rational treatment designs. One approach to increase this understanding involves detailed studies of exceptional responders: rare patients with unexpected exquisite sensitivity or durable responses to therapy. We identified an exceptional responder in a phase I study of pazopanib and everolimus in advanced solid tumors. Whole-exome sequencing of a patient with a 14-month complete response on this trial revealed two concurrent mutations in mTOR, the target of everolimus. In vitro experiments demonstrate that both mutations are activating, suggesting a biologic mechanism for exquisite sensitivity to everolimus in this patient. The use of precision (or “personalized”) medicine approaches to screen patients with cancer for alterations in the mTOR pathway may help to identify subsets of patients who may benefit from targeted therapies directed against mTOR.
Significance: The study of exceptional responders represents a promising approach to better understanding the mechanisms that underlie sensitivity to targeted anticancer therapies. Here, we identify two activating mTOR mutations in a patient with exquisite sensitivity to everolimus and pazopanib, suggesting an approach to identifying patients who might benefit most from mTOR inhibitors. Cancer Discov; 4(5); 546–53. ©2014 AACR.
See related commentary by Rejto and Abraham, p. 513
This article is highlighted in the In This Issue feature, p. 495
Probiotic Administration Attenuates Myocardial Hypertrophy and Heart Failure After Myocardial Infarction in the Rat
Authors: Gan Xiaohong Tracey , Ettinger Grace , Huang Cathy X. , Burton Jeremy P. , Haist James V. , Rajapurohitam Venkatesh , Sidaway James E. , Martin Glynn , Gloor Gregory B. , Swann Jonathan R. , Reid Gregor , Karmazyn Morris 
Published: March 2014

Background—
Probiotics are extensively used to promote gastrointestinal health, and emerging evidence suggests that their beneficial properties can extend beyond the local environment of the gut. Here, we determined whether oral probiotic administration can alter the progression of postinfarction heart failure.

Methods and Results—

Rats were subjected to 6 weeks of sustained coronary artery occlusion and administered the probiotic
Lactobacillus rhamnosus
GR-1 or placebo in the drinking water ad libitum. Culture and 16s rRNA sequencing showed no evidence of GR-1 colonization or a significant shift in the composition of the cecal microbiome. However, animals administered GR-1 exhibited a significant attenuation of left ventricular hypertrophy based on tissue weight assessment and gene expression of atrial natriuretic peptide. Moreover, these animals demonstrated improved hemodynamic parameters reflecting both improved systolic and diastolic left ventricular function. Serial echocardiography revealed significantly improved left ventricular parameters throughout the 6-week follow-up period including a marked preservation of left ventricular ejection fraction and fractional shortening. Beneficial effects of GR-1 were still evident in those animals in which GR-1 was withdrawn at 4 weeks, suggesting persistence of the GR-1 effects after cessation of therapy. Investigation of mechanisms showed a significant increase in the leptin:adiponectin plasma concentration ratio in rats subjected to coronary ligation, which was abrogated by GR-1. Metabonomic analysis showed differences between sham control and coronary artery ligated hearts particularly with respect to preservation of myocardial taurine levels.

Conclusions—
The study suggests that probiotics offer promise as a potential therapy for the attenuation of heart failure.
Optimal Perfusion Computed Tomographic Thresholds for Ischemic Core and Penumbra Are Not Time Dependent in the Clinically Relevant Time Window
Authors: Qiao Yujie , Zhu Guangming , Patrie James , Xin Wenjun , Michel Patrik , Eskandari Ashraf , Jovin Tudor , Wintermark Max 
Published: March 2014

Background and Purpose—
This study aims to determine whether perfusion computed tomographic (PCT) thresholds for delineating the ischemic core and penumbra are time dependent or time independent in patients presenting with symptoms of acute stroke.

Methods—
Two hundred seventeen patients were evaluated in a retrospective, multicenter study. Patients were divided into those with either persistent occlusion or recanalization. All patients received admission PCT and follow-up imaging to determine the final ischemic core, which was then retrospectively matched to the PCT images to identify optimal thresholds for the different PCT parameters. These thresholds were assessed for significant variation over time since symptom onset.

Results—
In the persistent occlusion group, optimal PCT parameters that did not significantly change with time included absolute mean transit time, relative mean transit time, relative cerebral blood flow, and relative cerebral blood volume when time was restricted to 15 hours after symptom onset. Conversely, the recanalization group showed no significant time variation for any PCT parameter at any time interval. In the persistent occlusion group, the optimal threshold to delineate the total ischemic area was the relative mean transit time at a threshold of 180%. In patients with recanalization, the optimal parameter to predict the ischemic core was relative cerebral blood volume at a threshold of 66%.

Conclusions—
Time does not influence the optimal PCT thresholds to delineate the ischemic core and penumbra in the first 15 hours after symptom onset for relative mean transit time and relative cerebral blood volume, the optimal parameters to delineate ischemic core and penumbra.