bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloma Is Characterized by Stage-Specific Alterations in DNA Methylation That Occur Early during Myelomagenesis
Authors: Heuck Christoph J. , Mehta Jayesh , Bhagat Tushar , Gundabolu Krishna , Yu Yiting , Khan Shahper , Chrysofakis Grigoris , Schinke Carolina , Tariman Joseph , Vickrey Eric , Pulliam Natalie , Nischal Sangeeta , Zhou Li , Bhattacharyya Sanchari , Meagher Richard , Hu Caroline , Maqbool Shahina , Suzuki Masako , Parekh Samir , Reu Frederic , Steidl Ulrich , Greally John , Verma Amit , Singhal Seema B. 
Published: February 2013

Abstract
Epigenetic changes play important roles in carcinogenesis and influence initial steps in neoplastic transformation by altering genome stability and regulating gene expression. To characterize epigenomic changes during the transformation of normal plasma cells to myeloma, we modified the HpaII tiny fragment enrichment by ligation–mediated PCR assay to work with small numbers of purified primary marrow plasma cells. The nano-HpaII tiny fragment enrichment by ligation–mediated PCR assay was used to analyze the methylome of CD138+ cells from 56 subjects representing premalignant (monoclonal gammopathy of uncertain significance), early, and advanced stages of myeloma, as well as healthy controls. Plasma cells from premalignant and early stages of myeloma were characterized by striking, widespread hypomethylation. Gene-specific hypermethylation was seen to occur in the advanced stages, and cell lines representative of relapsed cases were found to be sensitive to decitabine. Aberrant demethylation in monoclonal gammopathy of uncertain significance occurred primarily in CpG islands, whereas differentially methylated loci in cases of myeloma occurred predominantly outside of CpG islands and affected distinct sets of gene pathways, demonstrating qualitative epigenetic differences between premalignant and malignant stages. Examination of the methylation machinery revealed that the methyltransferase, DNMT3A, was aberrantly hypermethylated and underexpressed, but not mutated in myeloma. DNMT3A underexpression was also associated with adverse overall survival in a large cohort of patients, providing insights into genesis of hypomethylation in myeloma. These results demonstrate widespread, stage-specific epigenetic changes during myelomagenesis and suggest that early demethylation can be a potential contributor to genome instability seen in myeloma. We also identify DNMT3A expression as a novel prognostic biomarker and suggest that relapsed cases can be therapeutically targeted by hypomethylating agents.
Tissue-Derived Hedgehog Proteins Modulate Th Differentiation and Disease
Authors: Furmanski Anna L. , Saldana Jose Ignacio , Ono Masahiro , Sahni Hemant , Paschalidis Nikolaos , D’Acquisto Fulvio , Crompton Tessa 
Published: February 2013

Abstract
Genome-wide association studies of complex immune-mediated diseases have indicated that many genetic factors, each with individual low risk, contribute to overall disease. It is therefore timely and important to characterize how immune responses may be subtly modified by tissue context. In this article, we explore the role of tissue-derived molecules in influencing the function of T cells, which, owing to their migratory nature, come into contact with many different microenvironments through their lifespan. Hedgehog (Hh) proteins act as secreted morphogens, providing concentration-dependent positional and temporal cell-fate specification in solid tissues. Hh signaling is required for embryogenesis and is important in postnatal tissue renewal and in malignancy. However, the function of Hh in dynamic, fluid systems, such as in mammalian immunity, is largely unknown. In this article, we show that Hh-dependent transcription in T cells promoted Th2 transcriptional programs and differentiation, exacerbating allergic disease. Of interest, expression of Sonic Hh increased in lung epithelial cells following the induction of allergic disease, and lung T cells upregulated Hh target gene expression, indicating that T cells respond to locally secreted Hh ligands in vivo. We show that Il4, the key Th2 cytokine, is a novel transcriptional target of Hh signals in T cells, providing one mechanism for the role of Hh in Th differentiation. We propose that Hh, secreted from inflamed, remodeling, or malignant tissue, can modulate local T cell function. Our data present an unexpected and novel role for tissue-derived morphogens in the regulation of fluid immune responses, with implications for allergy and tumor responses, suggesting new uses for anti-Hh therapeutics.
Cutting Edge: Innate Memory CD8+ T Cells Are Distinct from Homeostatic Expanded CD8+ T Cells and Rapidly Respond to Primary Antigenic Stimuli
Authors: Huang Weishan , Hu Jianfang , August Avery 
Published: February 2013

Abstract
Innate memory phenotype (IMP) CD8+ T cells are nonconventional αβ T cells exhibiting features of innate immune cells and are significantly increased in the absence of ITK. Their developmental path and function are not clear. In this study, we show hematopoietic MHC class I (MHCI)-dependent generation of Ag-specific IMP CD8+ T cells using bone marrow chimeras. Wild-type bone marrow gives rise to IMP CD8+ T cells in MHCI−/− recipients, resembling those in Itk−/− mice, but distinct from those derived via homeostatic proliferation, and independent of recipient thymus. In contrast, MHCI−/− bone marrow does not lead to IMP CD8+ T cells in wild-type recipients. OTI IMP CD8+ T cells generated via this method exhibited enhanced early response to Ag without prior primary stimulation. Our findings suggest a method to generate Ag-specific “naive” CD8+ IMP T cells, as well as demonstrate that they are not homeostatic proliferation cells and can respond promptly in an Ag-specific fashion.
Que penser de l’embourgeoisement rural au Québec ? Visions différenciées d’acteurs locaux
Authors: Simard Myriam , Guimond Laurie 
Published: February 2013

L’embourgeoisement rural, lié notamment à la migration de la ville vers la campagne d’urbains de classes sociales moyennes ou aisées, touche de plus en plus les milieux ruraux au Québec. Or, contrairement aux recherches foisonnantes sur le concept derural gentrificationau Royaume-Uni, ce phénomène n’a que peu retenu l’attention dans la production scientifique québécoise. Cet article propose donc d’explorer les représentations contrastées de divers acteurs locaux à propos de l’embourgeoisement et de ses incidences dans deux municipalités régionales de comté (MRC) : Brome-Missisquoi et Arthabaska. Il s’appuie sur les résultats d’entrevues réalisées auprès de quatre types d’acteurs : néo-ruraux, ruraux de longue date, dirigeants d’organismes locaux et régionaux, élus municipaux. Il montre la complexité de ce phénomène sur divers plans de la vie rurale, soit sociodémographique, économique, résidentiel, communautaire, culturel, environnemental et politique. Les résultats révèlent la nécessité de dépasser les seules représentations des « gentrifieurs », en l’enrichissant de celles d’autres acteurs concernés par l’embourgeoisement rural. Ils montrent l’importance de scruter les effets globaux de ce phénomène pour en arriver à une meilleure compréhension.
La classe moyenne se met en scène : la publicité des quotidiens montréalais comme discours de classe, 1920-1970
Authors: Couvrette Sébastien 
Published: February 2013

Peu étudiées jusqu’à présent, les publicités des grands quotidiens d’information rendent compte de la complexité d’un phénomène majeur du 20esiècle : la formation et la définition de la classe moyenne. À partir de l’analyse de publicités parues dans deux quotidiens montréalais de 1920 à 1970, cet article met en évidence les caractéristiques identitaires et les aspirations attribuées à la classe moyenne dans le discours publicitaire. Dans les réclames, le modèle de la réussite sociale passe du mode de vie de la bourgeoisie, dans l’entre-deux-guerres, à celui du salarié de la banlieue aisée, dans l’après-guerre. Tout au long de la période étudiée, la classe moyenne se définit par la présence des femmes dans l’espace domestique et par celle des hommes dans l’espace public. En outre, certains annonceurs locaux mettent en place des stratégies de marketing tenant compte du contexte socioculturel montréalais.
High‐risk human papillomavirus infection in HIV‐positive African women living in Europe
Authors: Konopnicki Deborah , Manigart Yannick , Gilles Christine , Barlow Patricia , de Marchin Jérome , Feoli Francesco , Larsimont Denis , Delforge Marc , De Wit Stéphane , Clumeck Nathan 
Published: February 2013

IntroductionCervical infection with high‐risk human papillomavirus (HRHPV) induces cervical cancer and is present in 14% of women in Europe. We assessed the prevalence and incidence of cervical HRHPV in a cohort of HIV‐positive women living in Belgium.MethodsProspective observational program of screening and follow up of HRHPV cervical infection performed by Hybrid Capture in 825 HIV‐positive women between 2002 and 2011. Women without normal cervix at baseline were excluded.ResultsThe final analysis included 652 women: median age 38 years, African origin (81%), median HIV follow‐up (66 months), median CD4 count (426 cells/μL) and 79% on antiretroviral therapy (cART). At baseline, HRHPV prevalence was 43% and decreased significantly as both age and CD4 cell count increased: highest prevalence (100%) in women <30 years and <200 CD4/μL and lowest (19%) in women >40 years and >500 CD4/μL (p<0.0001, multivariate analysis). The relative risk (RR) to carry HRHPV at baseline decreases proportionally by 11% for each 5 years‐age increase and by 11% for each 100 CD4 cells/μL rise (RR=0.89, 95% CI: 0.85‐0.93; p<0.0001, Poisson regression for both). During follow‐up, incidence rate of HRHPV was 13.4 per 100 women‐years.ConclusionsWe found a high HRHPV prevalence of 43% and an incidence rate of 13 per 100 women‐years in this cohort of HIV‐positive women living in Europe and on cART. Women under 40 years‐age had the highest prevalence even with CD4 count >350 cells/μL. The magnitude of HRHPV epidemiology should prompt to evaluate the clinical efficacy of vaccines against HPV in HIV‐infected women.
Analyzing Arthropods for the Presence of Bacteria
Authors: Andrews Elizabeth S. 
Published: February 2013

AbstractBacteria within arthropods can be identified using culture‐independent methods. This unit describes protocols for surface sterilization of arthropods, DNA extraction of whole bodies and tissues, touchdown PCR amplification using 16S rDNA general bacteria primers, and profiling the bacterial community using denaturing gradient gel electrophoresis. Curr. Protoc. Microbiol. 28:1E.6.1‐1E.6.14. © 2013 by John Wiley & Sons, Inc.
Growth and Laboratory Maintenance of Staphylococcus aureus
Authors: Missiakas Dominique M. , Schneewind Olaf 
Published: February 2013

AbstractStaphylococcus aureus is a facultative anaerobic Gram‐positive coccus and a member of the normal skin flora as well as the nasal passages of humans. S. aureus is also the etiological agent of suppurative abscesses, as first described by Sir Alexander Ogston in 1880. Ever since, studies on S. aureus have focused on the complex battery of virulence factors and regulators that allow for its swift transition between commensalism and pathogenic states and escape from host immune defenses. The success of this pathogen is further evidenced by its ability to acquire antibiotic resistance traits through mechanisms that often remain poorly understood. Curr. Protoc. Microbiol. 28:9C.1.1‐9C.1.9. © 2013 by John Wiley & Sons, Inc.
Retinal Gene Delivery by rAAV and DNA Electroporation
Authors: Venkatesh Aditya , Ma Shan , Langellotto Fernanda , Gao Guangping , Punzo Claudio 
Published: February 2013

AbstractOcular gene therapy is a fast‐growing area of research. The eye is an ideal organ for gene therapy since it is immune privileged and easily accessible, and direct viral delivery results primarily in local infection. Because the eye is not a vital organ, mutations in eye‐specific genes tend to be more common. To date, over 40 eye‐specific genes have been identified harboring mutations that lead to blindness. Gene therapy with recombinant adeno‐associated virus (rAAV) holds the promise to treat patients with such mutations. However, proof‐of‐concept and safety evaluation for gene therapy remains to be established for most of these diseases. This unit describes the in vivo delivery of genes to the mouse eye by rAAV‐mediated gene transfer and plasmid DNA electroporation. Advantages and limitations of these methods are discussed, and detailed protocols for gene delivery, required materials, and subsequent tissue processing methods are described. Curr. Protoc. Microbiol. 28:14D.4.1‐14D.4.32. © 2013 by John Wiley & Sons, Inc.
The Eunuch Steward: A Trans‐Asiatic Tale of Seduction and Castration
Authors: Propp William H. C. 
Published: February 2013

ABSTRACTThe Eunuch Steward is a fable attested across the expanse of northeast Africa and Asia, from Late Bronze Age Egypt to China some time after 1424ce. In the story, a subordinate young man, accused of invading his master's sexual prerogative, offers a radical act of submission, namely self‐emasculation. The popularity of the tale across many cultures is best explained by citing its Oedipal themes: intergenerational male rivalry over a maternal figure, and the castration of the younger male. Copyright © 2013 John Wiley & Sons, Ltd.
Current Obstacles in Replicating Risk Assessment Findings: A Systematic Review of Commonly Used Actuarial Instruments
Authors: Rossegger Astrid , Gerth Juliane , Seewald Katharina , Urbaniok Frank , Singh Jay P. , Endrass Jérôme 
Published: February 2013

An actuarial risk assessment instrument can be considered valid if independent investigations using novel samples can replicate the findings of the instrument's development study. In order for a study to qualify as a replication, it has to adhere to the methodological protocol of the development study with respect to key design characteristics, as well as ensuring that manual‐recommended guidelines of test administration have been followed.A systematic search was conducted to identify predictive validity studies (N = 84) on three commonly used actuarial instruments: the Violence Risk Appraisal Guide (VRAG), the Sex Offender Risk Appraisal Guide (SORAG), and the Static‐99. Sample (sex, age, criminal history) and design (follow‐up, attrition, recidivism) characteristics, as well as markers of assessment integrity (scoring reliability, item omissions, prorating procedure), were extracted from 84 studies comprising 108 samples.None of the replications matched the development study of the instrument they were attempting to cross‐validate with respect to key sample and design characteristics. Furthermore none of the replications strictly followed the manual‐recommended guidelines for the instruments’ administration.Additional replication studies that follow the methodological protocols outlined in actuarial instruments’ development studies are needed before claims of generalizability can be made. Copyright © 2013 John Wiley & Sons, Ltd.
Effects of percutaneous revascularization of chronic total occlusions on clinical outcomes: A meta‐analysis comparing successful versus failed percutaneous intervention for chronic total occlusion
Authors: Khan Muhammad F. , Wendel Christopher S. , Thai Hoang M. , Movahed Mohammad R. 
Published: February 2013

BackgroundChronic total occlusions (CTOs) represent the most complex and challenging coronary lesions for percutaneous coronary intervention (PCI). PCI for a CTO is a high‐risk procedure and the long‐term benefits of a successful percutaneous CTO recanalization over the medical management (as a result of failed PCI) are not clear, as the studies have shown conflicting results in the past. The goal of this analysis was to clarify this issue by performing a meta‐analysis of the available literature.MethodsUsing major electronic databases, we searched for studies (randomized or observational) comparing death, major adverse cardiovascular events (MACE), myocardial infarction (MI), and target vessel revascularization (TVR) between patients who underwent PCI recanalization of CTOs versus those treated with medical management as a result of failed PCI attempts.ResultsWe identified 23 observational studies comparing the desired clinical parameters between patients with successful CTO recanalization and those managed conservatively as a result of attempted but failed PCI. The total number of patients observed in all of the studies was 12,970 and the mean time of follow up was 3.7 ± 2.1 years. Our results indicated that successful recanalization of a CTO results in improved all‐cause mortality (relative risk [RR] of 0.54, 95% confidence interval [CI] (0.45‐0.65), P‐value < 0.001), lower rates of MACE (RR of 0.70, 95% CI 0.60‐0.83, P‐value < 0.001) and reduced needs for subsequent bypass surgery (RR of 0.25, 95% CI (0.21–0.30), P‐value < 0.001). The difference in long‐term mortality remained statistically significant even after the adjustment for procedure related complications and in‐hospital deaths.ConclusionAs compared to conservative management (as a result of failed intervention), successful PCI recanalization of a CTO appears to be associated with improved long‐term clinical outcomes; however, randomized controlled trials (RCTs) are needed to further confirm these results. © 2013 Wiley Periodicals, Inc.
Hybrid perventricular device closure of doubly committed subarterial ventricular septal defects: Mid‐term results
Authors: Lin Ke , Zhu Da , Tao Kaiyu , Gan Changping , Tang Hong , Feng Yuan , An Qi 
Published: February 2013

BackgroundDoubly committed Subarterial ventricular septal defect (VSD) is a specific anatomic type of VSD located just beneath the aortic valve. The purpose of this study was to evaluate the safety and feasibility of using minimal invasive perventricular device closure in managing this type of VSD.MethodsDuring Dec 2008 and Aug 2010, 34 Pediatric patients with doubly committed subarterial VSD who met the inclusion criteria for device closure were enrolled in this study. Perventricular closure was attempted using a unique design eccentric device under the guidance of real‐time transesophageal echocardiography. Complications such as residual shunt, valve regurgitation, arrhythmias were all recorded in postoperative period and during follow‐up.ResultPerventricular device closure was successfully done in 28 patients (82%). 6 patients converted to open surgical repair due to residual shunt >3mm (1 patient), more than mild degree aortic regurgitation (3 patients) and device mal‐position (2 patients). Complete closure rate was achieved in 93% at discharge and 100% during 20 months follow‐up. No severe complications such as device embolism, significant arrhythmias and noticeable valve regurgitation were noted during follow‐up. Procedure induced trivial grade aortic valve regurgitation was noted in five (18%) patients after procedure while only one (4%) persisted during midterm follow‐up.ConclusionPerventricular closure of doubly committed subarterial VSDs appears to be a safe and effective minimally invasive technique with good mid‐term outcomes. © 2013 Wiley Periodicals, Inc.
RA and DA satellite access schemes: a survey and some research results and challenges
Authors: Celandroni N. , Ferro E. , Gotta A. 
Published: February 2013

SUMMARYThis paper surveys the most popular random access (RA), demand assignment (DA), and hybrids schemes for satellite broadband access networks. In addition, we present some recent research results that we obtained when a reliable transmission control protocol, that is, TCP, is coupled with the most promising RA methods foreseen in the second generation of Digital Video Broadcasting–Return Channel via Satellite standard. In fact, the necessity to support a wider range of IP‐based traffic, as in the case of either Supervisory Control And Data Acquisition systems or Machine‐to‐Machine communications, fosters the introduction of RA schemes for information transport able to cope with large network sizes and low duty cycle bursty traffic with frequent inactivity periods on the return link. As an indication of future research aspects, we also offer, in the Conclusions section, a list of items to be investigated so that the satellite can become an integral part of the Future Internet. Copyright © 2013 John Wiley & Sons, Ltd.
Cryptanalysis of some user identification schemes for distributed computer networks
Authors: Chen Yu‐Chi , Liu Chao‐Liang , Horng Gwoboa 
Published: February 2013

SUMMARYUser identification plays an important role for access control in networks. Recently, Hsu and Chuang proposed a user identification scheme for distributed computer networks, which can also provide key agreement and user anonymity. However, Tsai pointed out the weakness of Hsu–Chuang's scheme and proposed an improved scheme. In this paper, we present two attacks to examine that some user identification schemes have a serious security loophole. Finally, we propose a new user identification scheme, which is more secure than the existing schemes.Copyright © 2013 John Wiley & Sons, Ltd.
Congestion control with dynamic threshold adaptation and cross‐layer response for TCP Vegas over IEEE 802.11 wireless networks
Authors: Cheng Rung‐Shiang , Deng Der‐Jiunn 
Published: February 2013

SUMMARYWireless technologies provide mobile access and enable rapid andcost‐effective network deployment. But a wireless link is generally accompanied by high interference, transmission errors and a varying latency. The erratic packet losses usually lead to a curbing of the flow of segments on the TCP connection, and thus limit TCP performance. This paper presents a threshold control mechanism with cross‐layer response approach for improving TCP Vegas performance in IEEE 802.11 wireless networks. By making slight modifications to the legacy IEEE 802.11 MAC and TCP, the numerical results reveal that the proposed scheme provides a significant improvement in TCP performance under IEEE 802.11 wireless environments. Copyright © 2013 John Wiley & Sons, Ltd.