bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lay models of self-management: how do people manage knee osteoarthritis in context?
Authors: Morden Andrew , Jinks Clare , Bie Nio Ong  
Published: February 2011

Objective: Current NICE guidelines for Osteoarthritis (OA) identify several core self-management recommendations (exercise and weight loss if overweight/obese) to be supported by Healthcare Professionals. Contemporary research stresses that a patient-centred model of self-management that builds upon existing patient action and belief is essential. The lay beliefs regarding self-management for OA have not been explicitly explored previously. Method: Of the participants, 22 people were recruited to undertake in-depth interviews and a diary study. The constant comparative method and narrative methods were utilized to analyse the data. Results: Making adaptations and using strategies to get on with ‘normal’ daily life is as much a part of caring for OA as easing painful symptoms. Moreover, participants ‘normal’ routines ensured that they were able to stay active and keep the knee joint moving. Thus, maintaining everyday social roles and valued activities parallels recommendations from policy and practice. Engaging in exercise is influenced by biography, preferred lifestyle and contextual need. Conclusion: Practitioners and policy need to embrace the complexities of managing chronic OA conditions, by taking onboard the needs and priorities of patients. The findings highlight the disease specific needs of self-management that may be omitted from programmes like the Expert Patients Programme.
Human induced pluripotent stem cells are capable of B-cell lymphopoiesis
Authors: Carpenter Lee , Malladi Ram , Yang Cheng-Tao , French Anna , Pilkington Katherine J. , Forsey Richard W. , Sloane-Stanley Jackie , Silk Kathryn M. , Davies Timothy J. , Fairchild Paul J. , Enver Tariq , Watt Suzanne M. 
Published: February 2011

Abstract
Induced pluripotent stem (iPS) cells offer a unique potential for understanding the molecular basis of disease and development. Here we have generated several human iPS cell lines, and we describe their pluripotent phenotype and ability to differentiate into erythroid cells, monocytes, and endothelial cells. More significantly, however, when these iPS cells were differentiated under conditions that promote lympho-hematopoiesis from human embryonic stem cells, we observed the formation of pre-B cells. These cells were CD45+CD19+CD10+ and were positive for transcripts Pax5, IL7αR, λ-like, and VpreB receptor. Although they were negative for surface IgM and CD5 expression, iPS-derived CD45+CD19+ cells also exhibited multiple genomic D-JH rearrangements, which supports a pre–B-cell identity. We therefore have been able to demonstrate, for the first time, that human iPS cells are able to undergo hematopoiesis that contributes to the B-cell lymphoid lineage.
miR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27kip1, KPC1, and SOCS-1
Authors: Lu Changming , Huang Xin , Zhang Xiaoxiao , Roensch Kristin , Cao Qing , Nakayama Keiichi I. , Blazar Bruce R. , Zeng Yan , Zhou Xianzheng 
Published: February 2011

Abstract
Dendritic cells (DCs) are potent antigen-presenting cells derived from hematopoietic progenitor cells and circulating monocytes. To investigate the role of microRNAs (miRNAs) during DC differentiation, maturation, and function, we profiled miRNA expression in human monocytes, immature DCs (imDCs), and mature DCs (mDCs). Stage-specific, differential expression of 27 miRNAs was found during monocyte differentiation into imDCs and mDCs. Among them, decreased miR-221 and increased miR-155 expression correlated with p27kip1 accumulation in DCs. Silencing of miR-221 or overexpressing of miR-155 in DCs resulted in p27kip1 protein increase and DC apoptosis. Moreover, mDCs from miR-155−/− mice were less apoptotic than those from wild-type mice. Silencing of miR-155 expression had little effect on DC maturation but reduced IL-12p70 production, whereas miR-155 overexpression in mDCs enhanced IL-12p70 production. Kip1 ubiquitination-promoting complex 1, suppressor of cytokine signaling 1, and CD115 (M-CSFR) were functional targets of miR-155. Furthermore, we provide evidence that miR-155 indirectly regulated p27kip1 protein level by targeting Kip1 ubiquitination-promoting complex 1. Thus, our study uncovered miRNA signatures during monocyte differentiation into DCs and the new regulatory role of miR-221 and miR-155 in DC apoptosis and IL-12p70 production.
Community-acquired pneumonia as an emergency: time for an aggressive intervention to lower mortality
Authors: Ewig S. , Torres A. 
Published: February 2011

Community-acquired pneumonia (CAP) is one of the major contemporary acute life-threatening conditions. Short-term mortality reaches 14% (7% if nursing-home residents and bedridden patients are excluded) and long-term mortality reaches 50% within 5 yrs.CAP and acute myocardial infarction (AMI) have a lot in common with regard to acuity, prognosis, need for risk stratification and early intervention, and secondary prevention measures. The obvious success in the treatment of AMI is due to an effective organisation of pre-hospital care and evidence-based interventions in the hospital within defined timescales.Less evidence is available about effective strategies to lower short- and long-term mortality in patients with CAP. Nevertheless, it is estimated that ∼30% of hospitalised patients with CAP could be subject to a management approach in parallel to that of acute coronary syndrome (ACS).Management of patients with severe CAP should be intensified using all elements that have been established in the care for patients with ACS and stroke. One of the main challenges of future research will be to define whether and which additional patients at risk of mortality truly profit from timely and structured interventions. In the meantime, patients at increased risk of death according to clinical prediction tools should also be subject to an aggressive management approach.
Fertilization in C. elegans requires an intact C-terminal RING finger in sperm protein SPE-42
Authors: Wilson Luke D , Sackett Jacqueline M , Mieczkowski Bryce D , Richie Abigail L , Thoemke Kara , Rumbley Jon N , Kroft Tim L 
Published: February 2011

AbstractBackgroundTheC. eleganssperm protein SPE-42, a membrane protein of unknown structure and molecular function, is required for fertilization. Sperm from worms withspe-42mutations appear normal but are unable to fertilize eggs. Sequence analysis revealed the presence of 8 conserved cysteine residues in the C-terminal cytoplasmic domain of this protein suggesting these residues form a zinc-coordinating RING finger structure.ResultsWe made anin silicostructural model of the SPE-42 RING finger domain based on primary sequence analysis and previously reported RING structures. To test the model, we createdspe-42transgenes coding for mutations in each of the 8 cysteine residues predicted to coordinate Zn++ions in the RING finger motif. Transgenes were crossed into aspe-42null background and protein function was measured by counting progeny. We found that all 8 cysteines are required for protein function. We also showed that sequence differences between the C-terminal 29 and 30 amino acids inC. elegansandC. briggsaeSPE-42 following the RING finger domain are not responsible for the failure of theC. briggsaeSPE-42 homolog to rescueC. elegans spe-42mutants.ConclusionsThe results suggest that abona fideRING domain is present at the C-terminus of the SPE-42 protein and that this motif is required for sperm-egg interactions duringC. elegansfertilization. Our structural model of the RING domain provides a starting point for further structure-function analysis of this critical region of the protein. The C-terminal domain swap experiment suggests that the incompatibility between theC. elegansandC. briggsaeSPE-42 proteins is caused by small amino acid differences outside the C-terminal domain.
Epigenetic reprogramming in the porcine germ line
Authors: Hyldig Sara MW , Croxall Nicola , Contreras David A , Thomsen Preben D , Alberio Ramiro 
Published: February 2011

Abstract

Background
Epigenetic reprogramming is critical for genome regulation during germ line development. Genome-wide demethylation in mouse primordial germ cells (PGC) is a unique reprogramming event essential for erasing epigenetic memory and preventing the transmission of epimutations to the next generation. In addition to DNA demethylation, PGC are subject to a major reprogramming of histone marks, and many of these changes are concurrent with a cell cycle arrest in the G2 phase. There is limited information on how well conserved these events are in mammals. Here we report on the dynamic reprogramming of DNA methylation at CpGs of imprinted loci and DNA repeats, and the global changes in H3K27me3 and H3K9me2 in the developing germ line of the domestic pig.

Results
Our results show loss of DNA methylation in PGC colonizing the genital ridges. Analysis of IGF2-H19 regulatory region showed a gradual demethylation between E22-E42. In contrast, DMR2 of IGF2R was already demethylated in male PGC by E22. In females, IGF2R demethylation was delayed until E29-31, and was de novo methylated by E42. DNA repeats were gradually demethylated from E25 to E29-31, and became de novo methylated by E42. Analysis of histone marks showed strong H3K27me3 staining in migratory PGC between E15 and E21. In contrast, H3K9me2 signal was low in PGC by E15 and completely erased by E21. Cell cycle analysis of gonadal PGC (E22-31) showed a typical pattern of cycling cells, however, migrating PGC (E17) showed an increased proportion of cells in G2.

Conclusions
Our study demonstrates that epigenetic reprogramming occurs in pig migratory and gonadal PGC, and establishes the window of time for the occurrence of these events. Reprogramming of histone H3K9me2 and H3K27me3 detected between E15-E21 precedes the dynamic DNA demethylation at imprinted loci and DNA repeats between E22-E42. Our findings demonstrate that major epigenetic reprogramming in the pig germ line follows the overall dynamics shown in mice, suggesting that epigenetic reprogramming of germ cells is conserved in mammals. A better understanding of the sequential reprogramming of PGC in the pig will facilitate the derivation of embryonic germ cells in this species.
Investigation of the human pathogen Acinetobacter baumannii under iron limiting conditions
Authors: Eijkelkamp Bart A , Hassan Karl A , Paulsen Ian T , Brown Melissa H 
Published: February 2011

Abstract

Background
Iron acquisition systems are important virulence factors in pathogenic bacteria. To identify these systems in Acinetobacter baumannii, the transcriptomic response of the completely sequenced strain ATCC 17978 under iron limiting conditions was investigated using a genomic microarray that contained probes for all annotated open reading frames.

Results
Under low iron conditions, transcription levels were more than 2-fold up-regulated for 463 genes, including 95 genes that were up-regulated more than 4-fold. Of particular significance, three siderophore biosynthesis gene clusters, including one novel cluster, were highly up-regulated. Binding sites for the ferric uptake regulator were identified in the promoter regions of many up-regulated genes, suggesting a prominent role for this regulator in the Acinetobacter iron acquisition response. Down-regulation under iron limitation was less dramatic as the transcription of only 202 genes varied more than 2-fold. Various genes involved in motility featured prominently amongst the genes down-regulated when iron was less readily available. Motility assays confirmed that these transcriptional changes are manifested at the phenotypic level. The siderophore biosynthesis gene clusters were further investigated by means of comparative genomic analysis of 10 sequenced Acinetobacter isolates. These analyses revealed important roles for mobile genetic elements in shaping the siderophore meditated iron acquisition mechanisms between different Acinetobacter strains.

Conclusions

A. baumannii grown under iron limited conditions resulted in major transcriptional changes of not only many iron acquisition related genes, but also genes involved in other processes such as motility. Overall, this study showed that A. baumannii is well adaptable to growth in an environment which has limiting iron availability.
Notch signaling contributes to the maintenance of both normal neural stem cells and patient-derived glioma stem cells
Authors: Hu Yi-Yang , Zheng Min-Hua , Cheng Gang , Li Liang , Liang Liang , Gao Fang , Wei Ya-Ning , Fu Luo-An , Han Hua 
Published: February 2011

Abstract

Background
Cancer stem cells (CSCs) play an important role in the development and recurrence of malignant tumors including glioma. Notch signaling, an evolutionarily conserved pathway mediating direct cell-cell interaction, has been shown to regulate neural stem cells (NSCs) and glioma stem cells (GSCs) in normal neurogenesis and pathological carcinogenesis, respectively. However, how Notch signaling regulates the proliferation and differentiation of GSCs has not been well elucidated.

Methods
We isolated and cultivate human GSCs from glioma patient specimens. Then on parallel comparison with NSCs, we inhibited Notch signaling using γ-secretase inhibitors (GSI) and assessed the potential functions of Notch signaling in human GSCs.

Results
Similar to the GSI-treated NSCs, the number of the primary and secondary tumor spheres from GSI-treated GSCs decreased significantly, suggesting that the proliferation and self-renewal ability of GSI-treated GSCs were attenuated. GSI-treated GSCs showed increased differentiation into mature neural cell types in differentiation medium, similar to GSI-treated NSCs. Next, we found that GSI-treated tumor spheres were composed of more intermediate progenitors instead of CSCs, compared with the controls. Interestingly, although inhibition of Notch signaling decreased the ratio of proliferating NSCs in long term culture, we found that the ratio of G2+M phase-GSCs were almost undisturbed on GSI treatment within 72 h.

Conclusions
These data indicate that like NSCs, Notch signaling maintains the patient-derived GSCs by promoting their self-renewal and inhibiting their differentiation, and support that Notch signal inhibitor GSI might be a prosperous candidate of the treatment targeting CSCs for gliomas, however, with GSI-resistance at the early stage of GSCs cell cycle.
Reactive strategies for containing developing outbreaks of pandemic influenza
Authors: Andradóttir Sigrún , Chiu Wenchi , Goldsman David , Lee Mi Lim , Tsui Kwok-Leung , Sander Beate , Fisman David N , Nizam Azhar 
Published: February 2011

Abstract

Background
In 2009 and the early part of 2010, the northern hemisphere had to cope with the first waves of the new influenza A (H1N1) pandemic. Despite high-profile vaccination campaigns in many countries, delays in administration of vaccination programs were common, and high vaccination coverage levels were not achieved. This experience suggests the need to explore the epidemiological and economic effectiveness of additional, reactive strategies for combating pandemic influenza.

Methods
We use a stochastic model of pandemic influenza to investigate realistic strategies that can be used in reaction to developing outbreaks. The model is calibrated to documented illness attack rates and basic reproductive number (R0) estimates, and constructed to represent a typical mid-sized North American city.

Results
Our model predicts an average illness attack rate of 34.1% in the absence of intervention, with total costs associated with morbidity and mortality of US$81 million for such a city. Attack rates and economic costs can be reduced to 5.4% and US$37 million, respectively, when low-coverage reactive vaccination and limited antiviral use are combined with practical, minimally disruptive social distancing strategies, including short-term, as-needed closure of individual schools, even when vaccine supply-chain-related delays occur. Results improve with increasing vaccination coverage and higher vaccine efficacy.

Conclusions
Such combination strategies can be substantially more effective than vaccination alone from epidemiological and economic standpoints, and warrant strong consideration by public health authorities when reacting to future outbreaks of pandemic influenza.
Rationale and development of a survey tool for describing and auditing the composition of, and flows between, specialist and community clinical services for sexually transmitted infections
Authors: Aicken Catherine RH , Cassell Jackie A , Estcourt Claudia S , Keane Frances , Brook Gary , Rait Greta , White Peter J , Mercer Catherine H 
Published: February 2011

AbstractBackgroundNational health strategies have called for an expansion of the role of primary care in England to increase access to sexual health services. However, there is little guidance for service planners and commissioners as to the public health impact of different combinations of specialist genitourinary medicine (GUM) clinics and primary care based services for local populations. Service planning for infectious diseases like sexually transmitted infections (STI) is further complicated because the goal of early detection and treatment is not only to improve the health of the individual, but to benefit the wider population and reduce future treatment costs by preventing onward transmission. Therefore, we are developing a survey tool that will enable service planners to better understand the needs of their local STI care-seeking population and which will help inform evidence-based decision-making about current and future service configurations. Here we describe the rationale and development of this survey tool.Methods/DesignA pen-and-paper questionnaire asking about sociodemographics, reasons for attendance, care pathways, and recent sexual risk behaviours, is being developed for patients to complete in waiting rooms of diverse clinical services, including GUM clinics and primary-care based services in sociodemographically- and geographically-contrasting populations in England. The questionnaire was cognitively tested before being piloted. In the pilot, 67% of patients participated, of whom 84% consented to our linking their questionnaire to data on STI testing and diagnosis and partner notification outcomes from their clinical records.DiscussionThe pilot study suggests that both the questionnaire and its linkage to routinely-collected clinical data are likely to be acceptable to patients. By supplementing existing surveillance, data gathered by the survey tool will inform service planners' and providers' understanding of the needs and care-pathways of their patients, facilitating improved services and greater public health benefit.
How should we assess knowledge translation in research organizations; designing a knowledge translation self-assessment tool for research institutes (SATORI)
Authors: Gholami Jaleh , Majdzadeh Reza , Nedjat Saharnaz , Nedjat Sima , Maleki Katayoun , Ashoorkhani Mahnaz , Yazdizadeh Bahareh 
Published: February 2011

Abstract

Background
The knowledge translation self-assessment tool for research institutes (SATORI) was designed to assess the status of knowledge translation in research institutes. The objective was, to identify the weaknesses and strengths of knowledge translation in research centres and faculties associated with Tehran University of Medical Sciences (TUMS).

Methods
The tool, consisting of 50 statements in four main domains, was used in 20 TUMS-affiliated research centres and departments after its reliability was established. It was completed in a group discussion by the members of the research council, researchers and research users' representatives from each centre and/or department.

Results
The mean score obtained in the four domains of 'The question of research', 'Knowledge production', 'Knowledge transfer' and 'Promoting the use of evidence' were 2.26, 2.92, 2 and 1.89 (out of 5) respectively.
Nine out of 12 interventional priorities with the lowest quartile score were related to knowledge transfer resources and strategies, whereas eight of them were in the highest quartile and related to 'The question of research' and 'Knowledge production'.

Conclusions
The self-assessment tool identifies the gaps in capacity and infrastructure of knowledge translation support within research organizations. Assessment of research institutes using SATORI pointed out that strengthening knowledge translation through provision of financial support for knowledge translation activities, creating supportive and facilitating infrastructures, and facilitating interactions between researchers and target audiences to exchange questions and research findings are among the priorities of research centres and/or departments.
Alpha-1 antitrypsin protein and gene therapies decrease autoimmunity and delay arthritis development in mouse model
Authors: Grimstein Christian , Choi Young-Kook , Wasserfall Clive H , Satoh Minoru , Atkinson Mark A , Brantly Mark L , Campbell-Thompson Martha , Song Sihong 
Published: February 2011

AbstractBackgroundAlpha-1 antitrypsin (AAT) is a multi-functional protein that has anti-inflammatory and tissue protective properties. We previously reported that human AAT (hAAT) gene therapy prevented autoimmune diabetes in non-obese diabetic (NOD) mice and suppressed arthritis development in combination with doxycycline in mice. In the present study we investigated the feasibility of hAAT monotherapy for the treatment of chronic arthritis in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA).MethodsDBA/1 mice were immunized with bovine type II collagen (bCII) to induce arthritis. These mice were pretreated either with hAAT protein or with recombinant adeno-associated virus vector expressing hAAT (rAAV-hAAT). Control groups received saline injections. Arthritis development was evaluated by prevalence of arthritis and arthritic index. Serum levels of B-cell activating factor of the TNF-α family (BAFF), antibodies against both bovine (bCII) and mouse collagen II (mCII) were tested by ELISA.ResultsHuman AAT protein therapy as well as recombinant adeno-associated virus (rAAV8)-mediated hAAT gene therapy significantly delayed onset and ameliorated disease development of arthritis in CIA mouse model. Importantly, hAAT therapies significantly reduced serum levels of BAFF and autoantibodies against bCII and mCII, suggesting that the effects are mediated via B-cells, at least partially.ConclusionThese results present a new drug for arthritis therapy. Human AAT protein and gene therapies are able to ameliorate and delay arthritis development and reduce autoimmunity, indicating promising potential of these therapies as a new treatment strategy for RA.
Atomic characterization of Si nanoclusters embedded in SiO2 by atom probe tomography
Authors: Roussel Manuel , Talbot Etienne , Gourbilleau Fabrice , Pareige Philippe 
Published: February 2011

AbstractSilicon nanoclusters are of prime interest for new generation of optoelectronic and microelectronics components. Physical properties (light emission, carrier storage...) of systems using such nanoclusters are strongly dependent on nanostructural characteristics. These characteristics (size, composition, distribution, and interface nature) are until now obtained using conventional high-resolution analytic methods, such as high-resolution transmission electron microscopy, EFTEM, or EELS. In this article, a complementary technique, the atom probe tomography, was used for studying a multilayer (ML) system containing silicon clusters. Such a technique and its analysis give information on the structure at the atomic level and allow obtaining complementary information with respect to other techniques. A description of the different steps for such analysis: sample preparation, atom probe analysis, and data treatment are detailed. An atomic scale description of the Si nanoclusters/SiO2 ML will be fully described. This system is composed of 3.8-nm-thick SiO layers and 4-nm-thick SiO2 layers annealed 1 h at 900°C.