bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enterococcus faecalis Produces Abundant Extracellular Structures Containing DNA in the Absence of Cell Lysis during Early Biofilm Formation
Authors: Barnes Aaron M. T. , Ballering Katie S. , Leibman Rachel S. , Wells Carol L. , Dunny Gary M. 
Published: July 2012

ABSTRACT

Enterococcus faecalis
is a common Gram-positive commensal bacterium of the metazoan gastrointestinal tract capable of biofilm formation and an opportunistic pathogen of increasing clinical concern. Dogma has held that biofilms are slow-growing structures, often taking days to form mature microcolonies. Here we report that extracellular DNA (eDNA) is an integral structural component of early
E. faecalis
biofilms (≤4 h postinoculation). Combining cationic dye-based biofilm matrix stabilization techniques with correlative immuno-scanning electron microscopy (SEM) and fluorescent techniques, we demonstrate that—in early
E. faecalis
biofilms—eDNA localizes to previously undescribed intercellular filamentous structures, as well as to thick mats of extruded extracellular matrix material. Both of these results are consistent with previous reports that early biofilms are exquisitely sensitive to exogenous DNase treatment. High-resolution SEM demonstrates a punctate labeling pattern in both structures, suggesting the presence of an additional, non-DNA constituent. Notably, the previously described fratricidal or lytic mechanism reported as the source of eDNA in older (≥24 h)
E. faecalis
biofilms does not appear to be at work under these conditions; extensive visual examination by SEM revealed a striking lack of lysed cells, and bulk biochemical assays also support an absence of significant lysis at these early time points. In addition, some cells demonstrated eDNA labeling localized at the septum, suggesting the possibility of DNA secretion from metabolically active cells. Overall, these data are consistent with a model in which a subpopulation of viable
E. faecalis
cells secrete or extrude DNA into the extracellular matrix.

IMPORTANCE
This paper reports the production of extracellular DNA during early biofilm formation in
Enterococcus faecalis
. The work is significant because the mechanism of eDNA (extracellular DNA) production is independent of cell lysis and the DNA is confined to well-defined structures, suggesting a novel form of DNA secretion by viable cells. Previous models of biofilm formation in enterococci and related species propose cell lysis as the mechanism of DNA release.
Health Impact Assessment of increased cycling to place of work or education in Copenhagen
Authors: Holm Astrid Ledgaard , Glümer Charlotte , Diderichsen Finn 
Published: July 2012

ObjectiveTo quantify the effects of increased cycling on both mortality and morbidity.DesignHealth Impact Assessment.SettingCycling to place of work or education in Copenhagen, Denmark.PopulationEffects were calculated based on the working-age population of Copenhagen.Main outcome measuresThe primary outcome measure was change in burden of disease (measured as disability-adjusted life years (DALY)) due to changed exposure to the health determinants physical inactivity, air pollution (particulate matter <2.5 μm) and traffic accidents.ResultsObtainment of the proposed increase in cycling could reduce the burden of disease in the study population by 19.5 DALY annually. This overall effect comprised a reduction in the burden of disease from health outcomes associated with physical inactivity (76.0 DALY) and an increase in the burden of disease from outcomes associated with air pollution and traffic accidents (5.4 and 51.2 DALY, respectively).ConclusionThis study illustrates how quantitative Health Impact Assessment can help clarify potential effects of policies: increased cycling involves opposing effects from different outcomes but with the overall health effect being positive. This result illustrates the importance of designing policies that promote the health benefits and minimise the health risks related to cycling.
Perineal resuturing versus expectant management following vaginal delivery complicated by a dehisced wound (PREVIEW): protocol for a pilot and feasibility randomised controlled trial
Authors: Dudley Lynn , Kettle Christine , Carter Pamela , Thomas Peter , Ismail Khaled M 
Published: July 2012

BackgroundEach year, approximately 350 000 women in the UK experience perineal suturing following childbirth. For those women whose perineal wound dehisces, the management will vary according to individual practitioner's preferences. For most women, the wound will be managed expectantly (healing by secondary intention), whereas others may be offered resuturing. However, there is limited scientific evidence and no clear guidelines to inform best practice. PREVIEW is a two-part study aiming to identify the best management strategy for dehisced perineal wounds, in terms of clinical effectiveness and women's preferences.Methods/designThe main part of this study is a pilot and feasibility randomised controlled trial designed to provide preliminary evidence of the effectiveness of resuturing versus expectant management for dehisced perineal wounds following childbirth and to feed into the design and feasibility of a larger definitive trial. 144 participants will be randomly allocated to either intervention. The primary outcome is the proportion of women with a healed perineal wound at 6–8 weeks from the trial entry. Secondary outcomes include perineal pain, breast feeding rates, dyspareunia and women's satisfaction with the aesthetic results of the wound healing at 6 weeks, 3 months and 6 months post randomisation. Information will be collected using validated questionnaires. The second part of this study will be to conduct semistructured interviews with 12 study participants, aiming to capture information relating to their physical and psychological experiences following perineal wound dehiscence, assess the acceptability of the research plan and ensure that all outcomes relevant to women are included in the definitive trial.DisseminationThe results of this study will inform a definitive randomised controlled trial that will provide conclusive evidence of what is the best management of perineal wound dehiscence. This will potentially lead to significant improvements in perineal care and will help to reduce the short- and long-term morbidity experienced by women.Clinical trials registrationPREVIEW is registered with the International Standard Research for Clinical Trials (no:ISRCTN05754020) and adopted as a National Institute for Health Research (NIHR) Reproductive Health and Childbirth specialty group portfolio study UKCRN ID 9098.
Characterization of highly fractured basement, Say'un Masila Basin, Yemen
Authors: Murray Ann , Montgomery David W. 
Published: July 2012

Abstract
This case study of ten oil wells drilled into highly fractured and heterogeneous crystalline basement rocks of the Bayoot Field, Say'un Masila Basin, Yemen, brings together the findings from a wealth of oil field data and shows that a multidisciplinary approach is required for full characterization. An improved method for targeting hydrocarbons has been established for the study area. This has been achieved by drilling highly deviated wellbores into the upper basement reaches and optimally orienting them to intersect a maximum number of stress-sensitive fractures together with major seismic-scale fault damage zones that are not in direct connection to the local Bayoot Fault.
The patient’s use of metaphor within a palliative care setting: Theory, function and efficacy. A narrative literature review
Authors: Southall David 
Published: July 2012

Background: The modes of communication which patients use are seen as important within the sphere of palliative care and have been the focus of much research. Aim: This literature review aims to identify and analyse one particular mode of patient expression, namely that of the figure of speech (trope) ‘metaphor’, and ask questions regarding metaphor’s therapeutic usefulness when engaging with the life-limited patient. Data Sources: The investigation revolves around a literature review of academic papers which focus on the metaphorical ways in which patients speak of their condition. Results: This paper provides the theoretical foundations for the patient’s metaphoric utterances. It also delineates the variety and diversity of metaphors used by patients and categorises them into broad groupings which encompass metaphors of war, journeying, personhood, the natural world and existential concepts. Conclusions: The papers reviewed suggest that metaphoric communication allows sensitive subjects to be dealt with and provides benefits for patients. The results suggest that engaging with patients at the metaphoric level enables them to create new ways of viewing their situation and opens up the possibilities of new coping strategies. Finally, some developmental trajectories emanating from the reviewed papers are suggested, which will allow the efficacy of metaphor to be explored further within a palliative care setting.
Evaluation of HLA matching in unrelated hematopoietic stem cell transplantation for nonmalignant disorders
Authors: Horan John , Wang Tao , Haagenson Michael , Spellman Stephen R. , Dehn Jason , Eapen Mary , Frangoul Haydar , Gupta Vikas , Hale Gregory A. , Hurley Carolyn K. , Marino Susana , Oudshoorn Machteld , Reddy Vijay , Shaw Peter , Lee Stephanie J. , Woolfrey Ann 
Published: July 2012

AbstractThe importance of human leukocyte antigen (HLA) matching in unrelated donor transplantation for nonmalignant diseases (NMD) has yet to be defined. We analyzed data from 663 unrelated marrow and peripheral blood stem cell transplants performed from 1995 to 2007 for treatment of NMD. Transplantation from a donor mismatched at the HLA-A, -B, -C, or -DRB1, but not -DQB1 or -DPB1, loci was associated with higher mortality in multivariate analyses (P = .002). The hazard ratio for mortality for single (7/8) and double mismatched (6/8) transplants was 1.29 (0.97-1.72; P = .079) and 1.82 (1.30-2.55; P = .0004), respectively, compared with 8/8 matched transplants. HLA mismatches were not associated with acute or chronic GVHD, but were strongly associated with graft failure. After adjustment for other factors, the odds ratio for graft failure for 7/8 and 6/8 (allele and/or antigen) matched pairs compared with 8/8 matched transplants was 2.81 (1.74-4.54; P < .0001) and 2.22 (1.26-3.97; P = .006), respectively. Patients with NMD should receive transplants from allele matched (8/8) donors if possible. Unlike the case with malignancies, HLA mismatching in NMD is associated with graft failure rather than GVHD.
The gene therapy journey for hemophilia: are we there yet?
Authors: High Katherine A. 
Published: July 2012

AbstractSince the isolation and characterization of the genes for FVIII and FIX some 30 years ago, a longstanding goal of the field has been development of successful gene therapy for the hemophilias. In a landmark study published in 2011, Nathwani et al demonstrated successful conversion of severe hemophilia B to mild or moderate disease in 6 adult males who underwent intravenous infusion of an adeno-associated viral (AAV) vector expressing factor IX. These 6 subjects have now exhibited expression of FIX at levels ranging from 1% to 6% of normal for periods of > 2 years. This review discusses obstacles that were overcome to reach this goal and the next steps in clinical investigation. Safety issues that will need to be addressed before more widespread use of this approach are discussed. Efforts to extend AAV-mediated gene therapy to hemophilia A, and alternate approaches that may be useful for persons with severe liver disease, who may not be candidates for gene transfer to liver, are also discussed.
The effect of PTZ-induced epileptic seizures on hippocampal expression of PSA-NCAM in offspring born to kindled rats
Authors: Rajabzadeh Aliakbar , Bideskan Alireza Ebrahimzadeh , Fazel Alireza , Sankian Mojtaba , Rafatpanah Houshang , Haghir Hossein 
Published: July 2012

Abstract

Background
Maternal epileptic seizures during pregnancy can affect the hippocampal neurons in the offspring. The polysialylated neural cell adhesion molecule (PSA-NCAM), which is expressed in the developing central nervous system, may play important roles in neuronal migration, synaptogenesis, and axonal outgrowth. This study was designed to assess the effects of kindling either with or without maternal seizures on hippocampal PSA-NCAM expression in rat offspring.

Methods
Forty timed-pregnant Wistar rats were divided into four groups: A) Kind+/Seiz+, pregnant kindled (induced two weeks prior to pregnancy) rats that received repeated intraperitoneal (i.p.) pentylenetetrazol, PTZ injections on gestational days (GD) 14-19; B) Kind-/Seiz+, pregnant non-kindled rats that received PTZ injections on GD14-GD19; C) Kind+/Seiz-, pregnant kindled rats that did not receive any PTZ injections; and D) Kind-/Seiz-, the sham controls. Following birth, the pups were sacrificed on PD1 and PD14, and PSA-NCAM expression and localization in neonates’ hippocampi were analyzed by Western blots and immunohistochemistry.

Results
Our data show a significant down regulation of hippocampal PSA-NCAM expression in the offspring of Kind+/Seiz+ (p = 0.001) and Kind-/Seiz+ (p = 0.001) groups compared to the sham control group. The PSA-NCAM immunoreactivity was markedly decreased in all parts of the hippocampus, especially in the CA3 region, in Kind+/Seiz+ (p = 0.007) and Kind-/Seiz+ (p = 0.007) group’s newborns on both PD1 and 14.

Conclusion
Our findings demonstrate that maternal seizures but not kindling influence the expression of PSA-NCAM in the offspring’s hippocampi, which may be considered as a factor for learning/memory and cognitive impairments reported in children born to epileptic mothers.
Finding minimum gene subsets with heuristic breadth-first search algorithm for robust tumor classification
Authors: Wang Shu-Lin , Li Xue-Ling , Fang Jianwen 
Published: July 2012

AbstractBackgroundPrevious studies on tumor classification based on gene expression profiles suggest that gene selection plays a key role in improving the classification performance. Moreover, finding important tumor-related genes with the highest accuracy is a very important task because these genes might serve as tumor biomarkers, which is of great benefit to not only tumor molecular diagnosis but also drug development.ResultsThis paper proposes a novel gene selection method with rich biomedical meaning based on Heuristic Breadth-first Search Algorithm (HBSA) to find as many optimal gene subsets as possible. Due to the curse of dimensionality, this type of method could suffer from over-fitting and selection bias problems. To address these potential problems, a HBSA-based ensemble classifier is constructed using majority voting strategy from individual classifiers constructed by the selected gene subsets, and a novel HBSA-based gene ranking method is designed to find important tumor-related genes by measuring the significance of genes using their occurrence frequencies in the selected gene subsets. The experimental results on nine tumor datasets including three pairs of cross-platform datasets indicate that the proposed method can not only obtain better generalization performance but also find many important tumor-related genes.ConclusionsIt is found that the frequencies of the selected genes follow a power-law distribution, indicating that only a few top-ranked genes can be used as potential diagnosis biomarkers. Moreover, the top-ranked genes leading to very high prediction accuracy are closely related to specific tumor subtype and even hub genes. Compared with other related methods, the proposed method can achieve higher prediction accuracy with fewer genes. Moreover, they are further justified by analyzing the top-ranked genes in the context of individual gene function, biological pathway, and protein-protein interaction network.
Experiences of care planning in England: interviews with patients with long term conditions
Authors: Newbould Jenny , Burt Jenni , Bower Peter , Blakeman Tom , Kennedy Anne , Rogers Anne , Roland Martin 
Published: July 2012

Abstract

Background
The prevalence and impact of long term conditions continues to rise. Care planning for people with long term conditions has been a policy priority in England for chronic disease management. However, it is not clear how care planning is currently understood, translated and implemented in primary care. This study explores experience of care planning in patients with long term conditions in three areas in England.

Methods
We conducted semi-structured interviews with 23 predominantly elderly patients with multiple long term conditions. The interviews were designed to explore variations in and emergent experiences of care planning. Qualitative analysis of interview transcripts involved reflexively coding and re-coding data into categories and themes.

Results
No participants reported experiencing explicit care planning discussions or receiving written documentation setting out a negotiated care plan and they were unfamiliar with the term ‘care planning’. However, most described some components of care planning which occurred over a number of contacts with health care professionals which we term”reactive” care planning. Here, key elements of care planning including goal setting and action planning were rare. Additionally, poor continuity and coordination of care, lack of time in consultations, and patient concerns about what was legitimate to discuss with the doctor were described.

Conclusions
Amongst this population, elements of care planning were present in their accounts, but a structured, comprehensive process and consequent written record (as outlined in English Department of Health policy) was not evident. Further research needs to explore the advantages and disadvantages of different approaches to care planning for different patient groups.
Analysis of the Status of Chinese clinical practice guidelines development
Authors: Zheng Zhi-hong , Cui Shu-qi , Lu Xiao-qin , Zakus David , Liang Wan-nian , Huang Fang , Cao Xiao-na , Zhao Ya-li , Peng Xiao-xia , Rao Ke-qin , Wu Jing 
Published: July 2012

Abstract

Background
The work of developing clinical practice guidelines began just a little more than ten years ago in China. Up to now, there have been few studies about them.

Objectives
To review and analyze the status of Chinese clinical practice guidelines in 1997–2007.

Methods
All Chinese guidelines from 1997–2007 were collected, and made a regression analysis, and a citation analysis for evaluating the impact of guidelines. To analyze the developing quality, the most influential guidelines were evaluated with AGREE instrument, and each guideline was evaluated to check for any updating. In order to analyze the objective and target population, all guidelines were classified and counted separately according to disease/symptom center, and whether towards specialists or general practitioners.

Results
143 guidelines were collected. An exponential function equation was established for the trend in the number of guidelines. The immediacy index in every year was very low while the average citation rate was not. Both the percentages of highly cited and never cited were high. For the evaluation with AGREE, only the average score of clarity and presentation was high (89.9%); the remaining were much lower. Editorial independence scored 0. Only 27 (18.9%) of 143 guidelines, were found to be evidence-based. Only a few had ever been updated, with an average updating interval of 5.2 years. Only 2.1% were symptom-centered, and only 4.2% were aimed at general practitioners.

Conclusion
Much progress has been obtained for Chinese guidelines development. However, there were still defects, and greater efforts should be made in the future.
Microalgal biofactories: a promising approach towards sustainable omega-3 fatty acid production
Authors: Adarme-Vega T Catalina , Lim David K Y , Timmins Matthew , Vernen Felicitas , Li Yan , Schenk Peer M 
Published: July 2012

Abstract
Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) provide significant health benefits and this has led to an increased consumption as dietary supplements. Omega-3 fatty acids EPA and DHA are found in animals, transgenic plants, fungi and many microorganisms but are typically extracted from fatty fish, putting additional pressures on global fish stocks. As primary producers, many marine microalgae are rich in EPA (C20:5) and DHA (C22:6) and present a promising source of omega-3 fatty acids. Several heterotrophic microalgae have been used as biofactories for omega-3 fatty acids commercially, but a strong interest in autotrophic microalgae has emerged in recent years as microalgae are being developed as biofuel crops. This paper provides an overview of microalgal biotechnology and production platforms for the development of omega-3 fatty acids EPA and DHA. It refers to implications in current biotechnological uses of microalgae as aquaculture feed and future biofuel crops and explores potential applications of metabolic engineering and selective breeding to accumulate large amounts of omega-3 fatty acids in autotrophic microalgae.
Tumor penetration and epidermal growth factor receptor saturation by panitumumab correlate with antitumor activity in a preclinical model of human cancer
Authors: Freeman Daniel J , McDorman Kevin , Ogbagabriel Selam , Kozlosky Carl , Yang Bing-Bing , Doshi Sameer , Perez-Ruxio Juan Jose , Fanslow William , Starnes Charlie , Radinsky Robert 
Published: July 2012

Abstract

Background
Successful treatment of solid tumors relies on the ability of drugs to penetrate into the tumor tissue.

Methods
We examined the correlation of panitumumab (an anti-epidermal growth factor [EGFR] antibody) tumor penetration and EGFR saturation, a potential obstacle in large molecule drug delivery, using pharmacokinetics, pharmacodynamics, and tumor growth rate in an A431 epidermoid carcinoma xenograft model of human cancer. To determine receptor saturation, receptor occupancy, and levels of proliferation markers, immunohistochemical and flow cytometric methods were used. Pharmacokinetic data and modeling were used to calculate growth characteristics of panitumumab-treated tumors.

Results
Treatment with panitumumab in vivo inhibited pEGFR, Ki67 and pMAPK levels vs control. Tumor penetration and receptor saturation were dose- and time-dependent, reaching 100% and 78%, respectively. Significant tumor inhibition and eradication (p < 0.05) were observed; plasma concentration associated with tumor eradication was estimated to be 0.2 μg/ml. The tumor inhibition model was able to describe the mean tumor growth and death rates.

Conclusions
These data demonstrate that the antitumor activity of panitumumab correlates with its ability to penetrate into tumor tissue, occupy and inhibit activation of EGFR, and inhibit markers of proliferation and MAPK signaling.