bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the Optimal Degree of Heparin Anticoagulation for Peripheral Vascular Interventions
Authors: Kasapis Christos , Gurm Hitinder S. , Chetcuti Stanley J. , Munir Khan , Luciano Ann , Smith Dean , Aronow Herbert D. , Kassab Elias H. , Knox Michael F. , Moscucci Mauro , Share David , Grossman P. Michael 
Published: November 2010

Background—
The optimal degree of heparin anticoagulation for peripheral vascular interventions (PVIs) has not been defined. We sought to correlate total heparin dose and peak procedural activated clotting time (ACT) with postprocedural outcomes in patients undergoing PVI.

Methods and Results—

We studied 4743 patients who received heparin during PVIs in a regional, multicenter registry. From those, 1246 had recorded peak procedural ACT with the same point-of-care device. Periprocedural and in-hospital outcomes were compared between patients who received a total heparin dose <60 U/kg (n=2161) and ≥60 U/kg (n=2582). Similarly, outcomes were evaluated between groups with a peak procedural ACT <250 seconds (n=855) and ≥250 seconds (n=391). Technical and procedural success as well as intraprocedural thrombotic events did not differ between groups. Patients with heparin dose ≥60 U/kg had a higher rate of postprocedural hemoglobin drop ≥3 g/dL (7.09% versus 5.09%, respectively,
P
=0.004) and a higher transfusion rate compared with those with heparin dose <60 U/kg (4.92% versus 3.15%, respectively,
P
=0.002). In multivariate analysis, independent predictors of bleeding requiring transfusion were total heparin dose ≥60 U/kg, ACT ≥250 seconds, female sex, age ≥70 years, prior anemia, prior heart failure, low creatinine clearance, hybrid vascular surgery, rest pain, and below-knee intervention. In propensity-matched, risk-adjusted models and after hierarchical modeling, total heparin dose ≥60 U/kg and ACT ≥250 seconds remained strong predictors of post-PVI drop in hemoglobin ≥3 g/dL or transfusion.

Conclusions—
During PVI, higher total heparin dose (≥60 U/kg) and peak ACT ≥250 seconds were predictors of postprocedural transfusion. The high technical and procedural success in all groups suggests that use of weight-based heparin dosing with a target ACT <250 seconds in PVI may minimize the bleeding risk without compromising procedural success or increasing thromboembolic complications.
The Postcolonial in Motion: Hijra ila ardi al-ahlam and the Construction of Postcolonial Counterdiscourse
Authors: Simour Lhoussain 
Published: November 2010

AbstractThis paper examines the poetics and politics of representing cultural otherness in Sellam Chahidi's travel-inspired narrative Hijra ila ardi al-ahlam. Since Western cultural encounters have developed an overall epistemological outline in which Moroccan cultural identities are framed and often preconditioned to express western perspectives, Chahidi's narrative foregrounds new ways whereby the existing paradigm of interpretation and power relations are disturbed and subverted. Hijra ila ardi al-ahlam shows an inquisitive mode of cross-cultural negotiation in which various ideological and cross-cultural appropriations are dislocated to take on new twists. It is motivated by a strong desire to forge a new space capable of transcending the sociopolitical reality of the motherland but also capable of challenging the unilateral constructions of identity dictated by the ideologies of an Orientalist mindset.
Hashish and the 'Carnivalesque' in Egyptian Cinema
Authors: Al-Zobaidi Sobhi 
Published: November 2010

AbstractThis paper focuses on the ever-growing popularity of scenes depicting and referring to hashish and marijuana use in Egyptian cinema. It argues that a shift in attitude and in the overall depiction of these substances has emerged in more recent films, those produced in the 1990s and after. It suggests that whereas in older cinema these substances were always associated with social and political ills, almost all negative connotations and associations have disappeared in favor of an acceptable and playful depiction. Drawing on the theoretical framework of the carnivalesque developed by Bakhtin, and the work of other scholars such as Gilles Deleuze and Walter Benjamin, this paper suggests that the depictions of smoking hashish and marijuana are subversive moments that ultimately aim at escaping rigid social structures and power hierarchies while providing commentaries on repressive social and political realities.
Bare Singular NPs in Argument Positions: Restrictions on Indefiniteness
Authors: Geist Ljudmila 
Published: November 2010

AbstractIt has been assumed that in articleless languages such as Russian, bare singular NPs in argument positions can receive a definite or an indefinite interpretation. While the definite interpretation depends on the broader discourse and may freely arise if the referent is familiar, the option of an indefinite interpretation for bare NPs introducing new discourse referents is more restricted. This paper investigates conditions on the indefinite interpretation of bare singular NPs in Russian. It shows that this interpretation is restricted by the topic-comment structure: the indefinite interpretation may arise only if the NP belongs to the comment part of the sentence and is excluded for NPs which are aboutness topics. This restriction can be explained by the requirement that indefinite aboutness topics must be specific. Bare indefinite NPs however can only receive a non-specific existential interpretation, and hence do not qualify as topics. The paper contributes to the elucidation of the interaction between the semantic and pragmatic components of an overall theory of NP interpretation and argues that weak existential NPs should be distinguished from cases of noun incorporation.
Investigating the Consequences of Focus on the Production and Comprehension of Referring Expressions
Authors: Kaiser Elsi 
Published: November 2010

AbstractThis paper investigates issues related to referent tracking in discourse, in particular whether and how contrastive focus interacts with other factors – in particular pronominalization and subjecthood – to influence comprehenders' and speakers' expectations about what entities will be referred to/mentioned in upcoming discourse. On the basis of data from two psycholinguistic experiments, I argue that to better understand the discourse-structuring effects of contrastive focus, we need to consider not only pronoun interpretation but also production-based questions having to do with choice of upcoming referent and choice of referential form. I suggest that looking at the discourse-level consequences of contrastive focus from the perspective of the comprehender as well as the perspective of the speaker (i) allows us to gain new insights about the effects of focus and the discourse-status of focus-induced alternatives, and (ii) highlights (potentially unexpected) asymmetries between likelihood of upcoming mention and likelihood of pronominalization.
Regulation of vascular endothelial growth factor receptor 2 trafficking and angiogenesis by Golgi localized t-SNARE syntaxin 6
Authors: Manickam Venkatraman , Tiwari Ajit , Jung Jae-Joon , Bhattacharya Resham , Goel Apollina , Mukhopadhyay Debabrata , Choudhury Amit 
Published: November 2010

AbstractVascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in physiologic and pathologic angiogenesis. Plasma membrane (PM) levels of VEGFR2 are regulated by endocytosis and secretory transport through the Golgi apparatus. To date, the mechanism whereby the VEGFR2 traffics through the Golgi apparatus remains incompletely characterized. We show in human endothelial cells that binding of VEGF to the cell surface localized VEGFR2 stimulates exit of intracellular VEGFR2 from the Golgi apparatus. Brefeldin A treatment reduced the level of surface VEGFR2, confirming that VEGFR2 traffics through the Golgi apparatus en route to the PM. Mechanistically, we show that inhibition of syntaxin 6, a Golgi-localized target membrane-soluble N-ethylmaleimide attachment protein receptor (t-SNARE) protein, interferes with VEGFR2 trafficking to the PM and facilitates lysosomal degradation of the VEGFR2. In cell culture, inhibition of syntaxin 6 also reduced VEGF-induced cell proliferation, cell migration, and vascular tube formation. Furthermore, in a mouse ear model of angiogenesis, an inhibitory form of syntaxin 6 reduced VEGF-induced neovascularization and permeability. Our data demonstrate the importance of syntaxin 6 in the maintenance of cellular VEGFR2 levels, and suggest that the inhibitory form of syntaxin 6 has good potential as an antiangiogenic agent.
Significant differences in B-cell subpopulations characterize patients with chronic graft-versus-host disease–associated dysgammaglobulinemia
Authors: Kuzmina Zoya , Greinix Hildegard T. , Weigl Roman , Körmöczi Ulrike , Rottal Arno , Frantal Sophie , Eder Sandra , Pickl Winfried F. 
Published: November 2010

Abstract
Manifestations of chronic graft-versus-host disease (cGVHD) can resemble those seen in immunodeficiency states and autoimmune disorders. Reports by us and others suggest an involvement of B cells in the pathogenesis of cGVHD. We investigated B-lymphocyte subpopulations in cGVHD cohorts defined by serum immunoglobulin G (IgG) levels to characterize novel biomarkers for impairment of humoral immunity after allogeneic hematopoietic stem cell transplantation. Seventy-six patients were enrolled a median of 46 months after hematopoietic stem cell transplantation. The hypogammaglobulinemia group had significantly diminished CD19+ B cells (165 vs 454 vs 417 × 106/L) with elevated CD19+CD21low immature (16.5%, 7.7%, and 9.1%) and CD19+CD21int-highCD38highIgMhigh transitional (10.5% vs 4.2% vs 6.3%) B-cell proportions compared with the normogammaglobulinemia and hypergammaglobulinemia groups. CD19+CD10−CD27−CD21high naive B cells were highly elevated in all patients with cGVHD. CD19+CD27+IgD+ non–class-switched (4 vs 12 vs 11 × 106/L) and class-switched (7 vs 35 vs 42 × 106/L) memory B cells were significantly lower in the hypogammaglobulinemia group compared with the others. Besides significantly higher B-cell activation factor/B-cell ratios, significantly more cGVHD patients with hypergammaglobulinemia had autoantibodies compared with the hypogammaglobulinemia subgroup (68% vs 24%, P = .024). In conclusion, B-cell subpopulations can serve as novel cellular biomarkers for immunodeficiency and autoimmunity indicating different pathogenetic mechanisms of cGVHD and encouraging future prospective longitudinal studies.
Improving academic leadership and oversight in large industry-sponsored clinical trials: the ARO-CRO model
Authors: Goldenberg Neil A. , Spyropoulos Alex C. , Halperin Jonathan L. , Kessler Craig M. , Schulman Sam , Turpie Alexander G. G. , Skene Allan M. , Cutler Neal R. , Hiatt William R. ,   for the Antithrombotic Trials Leadership and Steering Group
Published: November 2010

Abstract
Standards for clinical trial design, execution, and publication have increased in recent years. However, the current structure for interaction among the pharmaceutical sponsor funding a drug or device development program, the contract research organization (CRO) that typically assists in executing the trial, regulatory agencies, and academicians, provides inadequate leadership and oversight of the development process. Conventional academic steering committees are not provided with the independent infrastructure by which to verify statistical analyses and conclusions regarding safety and efficacy. We propose an alternative approach centered on partnerships between CROs and university-based academic research organizations (AROs). In this model, the ARO takes responsibility for processes that address journal requirements and regulatory expectations for independent academic oversight (including oversight of Steering Committee and Data and Safety Monitoring Board activities), whereas the CRO provides infrastructure for efficient trial execution, site monitoring, and data management. The ARO engages academic experts throughout the trial process and minimizes conflicts of interest in individual industry relationships via diversification of sponsors, agents, and therapeutic areas. Although numerous models can be entertained, the ARO-CRO model is uniquely structured to meet the demand for greater assurance of integrity in clinical trials and the needs of each stakeholder in the process.
PathEx: a novel multi factors based datasets selector web tool
Authors: Bareke Eric , Pierre Michael , Gaigneaux Anthoula , Meulder Bertrand De , Depiereux Sophie , Habra Naji , Depiereux Eric 
Published: November 2010

Abstract
Background
Microarray experiments have become very popular in life science research. However, if such experiments are only considered independently, the possibilities for analysis and interpretation of many life science phenomena are reduced. The accumulation of publicly available data provides biomedical researchers with a valuable opportunity to either discover new phenomena or improve the interpretation and validation of other phenomena that partially understood or well known. This can only be achieved by intelligently exploiting this rich mine of information.

Description
Considering that technologies like microarrays remain prohibitively expensive for researchers with limited means to order their own experimental chips, it would be beneficial to re-use previously published microarray data. For certain researchers interested in finding gene groups (requiring many replicates), there is a great need for tools to help them to select appropriate datasets for analysis. These tools may be effective, if and only if, they are able to re-use previously deposited experiments or to create new experiments not initially envisioned by the depositors. However, the generation of new experiments requires that all published microarray data be completely annotated, which is not currently the case. Thus, we propose the PathEx approach.

Conclusion
This paper presents PathEx, a human-focused web solution built around a two-component system: one database component, enriched with relevant biological information (expression array, omics data, literature) from different sources, and another component comprising sophisticated web interfaces that allow users to perform complex dataset building queries on the contents integrated into the PathEx database.
Spontaneously immortalised bovine mammary epithelial cells exhibit a distinct gene expression pattern from the breast cancer cells
Authors: Zhao Chenfu , Meng Lu , Hu Hongyu , Wang Xudong , Shi Fangyu , Wang Yajuan , Li Qianqian , Lin Aixing 
Published: November 2010

Abstract

Background
Spontaneous immortalisation of cultured mammary epithelial cells (MECs) is an extremely rare event, and the molecular mechanism behind spontaneous immortalisation of MECs is unclear. Here, we report the establishment of a spontaneously immortalised bovine mammary epithelial cell line (BME65Cs) and the changes in gene expression associated with BME65Cs cells.

Results
BME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous bTERT (bovine Telomerase Reverse Transcriptase) and stabilisation of the telomere. Currently, BME65Cs cells have been passed for more than 220 generations, and these cells exhibit non-malignant transformation. The expression of multiple genes was investigated in BME65Cs cells, senescent BMECs (bovine MECs) cells, early passage BMECs cells and MCF-7 cells (a human breast cancer cell line). In comparison with early passage BMECs cells, the expression of senescence-relevant apoptosis-related gene were significantly changed in BME65Cs cells. P16INK4a was downregulated, p53 was low expressed and Bax/Bcl-2 ratio was reversed. Moreover, a slight upregulation of the oncogene c-Myc, along with an undetectable level of breast tumor-related gene Bag-1 and TRPS-1, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7. In addition, DNMT1 is upregulated in BME65Cs. These results suggest that the inhibition of both senescence and mitochondrial apoptosis signalling pathways contribute to the immortality of BME65Cs cells. The expression of p53 and p16

INK4a
in BME65Cs was altered in the pattern of down-regulation but not "loss", suggesting that this spontaneous immortalization is possibly initiated by other mechanism rather than gene mutation of p53 or p16

INK4a
.

Conclusions
Spontaneously immortalised BME65Cs cells maintain many characteristics of normal BMEC cells and exhibit non-malignant transformation. Although this cell line displays altered patterns of gene expression, it is clearly distinct from malignant breast cancer cell line. It showed that co-inhibition of cellular senescence and mitochondrial apoptosis pathways coordinates BME65Cs cells immortalisation. Additionally, mechanisms other than gene mutation are likely to be involved in regulation of cellular functions. This study provides an insight into the relationship between cell senescence and immortalisation. BME65Cs cells will be useful in future studies of cellular senescence and tumorigenesis.
Maternal effects, flight versus fecundity trade-offs, and offspring immune defence in the Speckled Wood butterfly, Pararge aegeria
Authors: Gibbs Melanie , Breuker Casper J , Hesketh Helen , Hails Rosemary S , Van Dyck Hans 
Published: November 2010

AbstractBackgroundMaternal condition can generate resource-related maternal effects through differential egg provisioning, and can greatly affect offspring performance. In the present study, the speckled wood butterflyPararge aegeria(L.) was used to investigate whether (after controlling for egg size) maternal age, and increased flight during the oviposition period, resulted in changes in egg provisioning and whether this contributed to variation in offspring performance, i) early in development (egg stage and early post-hatching development), and ii) later in larval development after being exposed to the model viral pathogen system; the baculovirusAutographa californicamultinucleocapsid nucleopolyhedrovirus (AcMNPV).ResultsAge-related changes in maternal egg provisioning were observed to influence egg stage development only. Flight-induced changes in maternal egg provisioning had direct consequences for offspring growth and survival across each life stage from egg to adulthood; offspring from forced flight mothers had lower larval masses and longer development times. Offspring with lower larval masses also had reduced survival after exposure to the viral pathogen.ConclusionThe present study demonstrates that a change in maternal provisioning as a result of increased flight during the oviposition period has the potential to exert non-genetic cross-generational fitness effects inP. aegeria. This could have important consequences for population dynamics, particularly in fragmented anthropogenic landscapes.
Phospholipase D promotes Arcanobacterium haemolyticum adhesion via lipid raft remodeling and host cell death following bacterial invasion
Authors: Lucas Erynn A , Billington Stephen J , Carlson Petteri , McGee David J , Jost B Helen 
Published: November 2010

AbstractBackgroundArcanobacterium haemolyticumis an emerging bacterial pathogen, causing pharyngitis and more invasive infections. This organism expresses an unusual phospholipase D (PLD), which we propose promotes bacterial pathogenesis through its action on host cell membranes. Thepldgene is found on a genomic region of reduced %G + C, suggesting recent horizontal acquisition.ResultsRecombinant PLD rearranged HeLa cell lipid rafts in a dose-dependent manner and this was inhibited by cholesterol sequestration. PLD also promoted host cell adhesion, as apldmutant had a 60.3% reduction in its ability to adhere to HeLa cells as compared to the wild type. Conversely, thepldmutant appeared to invade HeLa cells approximately two-fold more efficiently as the wild type. This finding was attributable to a significant loss of host cell viability following secretion of PLD from intracellular bacteria. As determined by viability assay, only 15.6% and 82.3% of HeLa cells remained viable following invasion by the wild type orpldmutant, respectively, as compared to untreated HeLa cells. Transmission electron microscopy of HeLa cells inoculated withA. haemolyticumstrains revealed that thepldmutant was contained within intracellular vacuoles, as compared to the wild type, which escaped the vacuole. Wild type-infected HeLa cells also displayed the hallmarks of necrosis. Similarly inoculated HeLa cells displayed no signs of apoptosis, as measured by induction of caspase 3/7, 8 or 9 activities.ConclusionsThese data indicate that PLD enhances bacterial adhesion and promotes host cell necrosis following invasion, and therefore, may be important in the disease pathogenesis ofA. haemolyticuminfections.
Polymorphism of SERPINE2 gene is associated with pulmonary emphysema in consecutive autopsy cases
Authors: Fujimoto Koichi , Ikeda Shinobu , Arai Tomio , Tanaka Noriko , Kumasaka Toshio , Ishii Takeo , Kida Kozui , Muramatsu Masaaki , Sawabe Motoji 
Published: November 2010

Abstract

Background
The SERPINA1, SERPINA3, and SERPINE2 genes, which encode antiproteases, have been proposed to be susceptible genes for of chronic obstructive pulmonary disease (COPD) and related phenotypes. Whether they are associated with emphysema is not known.

Methods
Twelve previously reported single nucleotide polymorphisms (SNPs) in SERPINA1 (rs8004738, rs17751769, rs709932, rs11832, rs1303, rs28929474, and rs17580), SERPINA3 (rs4934, rs17473, and rs1800463), and SERPINE2 (rs840088 and rs975278) were genotyped in samples obtained from 1,335 consecutive autopsies of elderly Japanese people. The association between these SNPs and the severity of emphysema, as assessed using macroscopic scores, was determined.

Results
Emphysema of more than moderate degree was detected in 189 subjects (14.1%) and showed a significant gender difference (males, 20.5% and females, 7.0%; p < 0.0001). Among the 12 examined SNPs, only rs975278 in the SERPINE2 gene was positively associated with emphysema. Unlike the major alleles, homozygous minor alleles of rs975278 were associated with emphysema (odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.02-2.30; p = 0.037) and the association was very prominent in smokers (OR = 2.02; 95% CI = 1.29-3.15; p = 0.002).

Conclusions

SERPINE2 may be a risk factor for the development of emphysema and its association with emphysema may be stronger in smokers.