bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bridging the gaps among research, policy and practice in ten low- and middle-income countries: Development and testing of a questionnaire for health-care providers
Authors: Guindon G Emmanuel , Lavis John N , Boupha Boungnong , Shi Guang , Sidibe Mintou , Turdaliyeva Botagoz ,   Research to Policy and Practice Study Team (RPPST)
Published: May 2012

AbstractBackgroundThe reliability and validity of instruments used to survey health-care providers' views about and experiences with research evidence have seldom been examined.MethodsCountry teams from ten low- and middle-income countries (China, Ghana, India, Iran, Kazakhstan, Laos, Mexico, Pakistan, Senegal and Tanzania) participated in the development, translation, pilot-testing and administration of a questionnaire designed to measure health-care providers' views and activities related to improving their clinical practice and their awareness of, access to and use of research evidence, as well as changes in their clinical practice that they attribute to particular sources of research evidence that they have used. We use internal consistency as a measure of the questionnaire's reliability and, whenever possible, we use explanatory factor analyses to assess the degree to which questions that pertain to a single domain actually address common themes. We assess the questionnaire's face validity and content validity and, to a lesser extent, we also explore its criterion validity.ResultsThe questionnaire has high internal consistency, with Cronbach's alphas between 0.7 and 0.9 for 16 of 20 domains and sub-domains (identified by factor analyses). Cronbach's alphas are greater than 0.9 for two domains, suggesting some item redundancy. Pre- and post-field work assessments indicate the questionnaire has good face validity and content validity. Our limited assessment of criterion validity shows weak but statistically significant associations between the general influence of research evidence among providers and more specific measures of providers' change in approach to preventing or treating a clinical condition.ConclusionOur analysis points to a number of strengths of the questionnaire - high internal consistency (reliability) and good face and content validity - but also to areas where it can be shortened without losing important conceptual domains.
Bridging the gaps among research, policy and practice in ten low- and middle-income countries: Development and testing of a questionnaire for researchers
Authors: Cameron David , Lavis John N , Guindon G Emmanuel , Akhtar Tasleem , Becerra Posada Francisco , Ndossi Godwin D , Boupha Boungnong ,   Research to Policy and Practice Study Team
Published: May 2012

Abstract

Background
A questionnaire could assist researchers, policymakers, and healthcare providers to describe and monitor changes in efforts to bridge the gaps among research, policy and practice. No questionnaire focused on researchers' engagement in bridging activities related to high-priority topics (or the potential correlates of their engagement) has been developed and tested in a range of low- and middle-income countries (LMICs).

Methods
Country teams from ten LMICs (China, Ghana, India, Iran, Kazakhstan, Laos, Mexico, Pakistan, Senegal, and Tanzania) participated in the development and testing of a questionnaire. To assess reliability we calculated the internal consistency of items within each of the ten conceptual domains related to bridging activities (specifically Cronbach's alpha). To assess face and content validity we convened several teleconferences and a workshop. To assess construct validity we calculated the correlation between scales and counts (i.e., criterion measures) for the three countries that employed both and we calculated the correlation between different but theoretically related (i.e., convergent) measures for all countries.

Results
Internal consistency (Cronbach's alpha) for sets of related items was very high, ranging from 0.89 (0.86-0.91) to 0.96 (0.95-0.97), suggesting some item redundancy. Both face and content validity were determined to be high. Assessments of construct validity using criterion-related measures showed statistically significant associations for related measures (with gammas ranging from 0.36 to 0.73). Assessments using convergent measures also showed significant associations (with gammas ranging from 0.30 to 0.50).

Conclusions
While no direct comparison can be made to a comparable questionnaire, our findings do suggest a number of strengths of the questionnaire but also the need to reduce item redundancy and to test its capacity to monitor changes over time.
Identification of subpopulations in mesenchymal stem cell-like cultures from human umbilical cord
Authors: Majore Ingrida , Moretti Pierre , Hass Ralf , Kasper Cornelia 
Published: May 2012

Abstract

Background
A variety of cell types can be identified in the adherent fraction of bone marrow mononuclear cells including more primitive and embryonic-like stem cells, mesenchymal stem cells (MSC), lineage-committed progenitors as well as mature cells such as osteoblasts and fibroblasts. Different methods are described for the isolation of single bone marrow stem cell subpopulations – beginning from ordinary size sieving, long term cultivation under specific conditions to FACS-based approaches. Besides bone marrow-derived subpopulations, also other tissues including human umbilical cord (UC) have been recently suggested to provide a potential source for MSC. Although of clinical importance, these UC-derived MSC populations remain to be characterized. It was thus the aim of the present study to identify possible subpopulations in cultures of MSC-like cells obtained from UC. We used counterflow centrifugal elutriation (CCE) as a novel strategy to successfully address this question.

Results
UC-derived primary cells were separated by CCE and revealed differentially-sized populations in the fractions. Thus, a subpopulation with an average diameter of about 11 μm and a small flat cell body was compared to a large sized subpopulation of about 19 μm average diameter. Flow cytometric analysis revealed the expression of certain MSC stem cell markers including CD44, CD73, CD90 and CD105, respectively, although these markers were expressed at higher levels in the small-sized population. Moreover, this small-sized subpopulation exhibited a higher proliferative capacity as compared to the total UC-derived primary cultures and the large-sized cells and demonstrated a reduced amount of aging cells.

Conclusion
Using the CCE technique, we were the first to demonstrate a subpopulation of small-sized UC-derived primary cells carrying MSC-like characteristics according to the presence of various mesenchymal stem cell markers. This is also supported by the high proliferative capacity of these MSC-like cells as compared to whole primary culture or other UC-derived subpopulations. The accumulation of a self-renewing MSC-like subpopulation by CCE with low expression levels of the aging marker senescence-associated β-galactosidase provides a valuable tool in the regenerative medicine and an alternative to bone-marrow-derived MSC.
A decentralized spectrum allocation and partitioning scheme for a two-tier macro-femtocell network with downlink beamforming
Authors: Ryoo Sunheui , Joo Changhee , Bahk Saewoong 
Published: May 2012

Abstract
This article examines spectrum allocation and partitioning schemes to mitigate cross-tier interference under downlink beamforming environments. The enhanced SIR owing to beamforming allows more femtocells to share their spectrum with the macrocell and accordingly improves overall spectrum efficiency. We first design a simplified centralized scheme as the optimum and then propose a practical decentralized algorithm that determines which femtocells to use the full or partitioned spectrum with acceptable control overhead. To exploit limited information of the received signal strength efficiently, we consider two types of probabilistic femtocell base station (HeNB) selection policies. They are equal selection and interference weighted selection policies, and we drive their outage probabilities for a macrocell user. Through performance evaluation, we demonstrate that the outage probability and the cell capacity in our decentralized scheme are significantly better than those in a conventional cochannel deployment scheme. Furthermore, we show that the cell utility in our proposed scheme is close to that in the centralized scheme and better than that in the spectrum partitioning scheme with a fixed ratio.
MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency
Authors: Grupping Katrijn , Selhorst Philippe , Michiels Johan , Vereecken Katleen , Heyndrickx Leo , Kessler Pascal , Vanham Guido , Martin Loïc , Ariën Kevin K 
Published: May 2012

Abstract

Background
Binding of the viral envelope protein (Env), and particularly of its gp120 subunit, to the cellular CD4 receptor is the first essential step of the HIV-1 entry process. The CD4 binding site (CD4bs) of gp120, and especially a recessed cavity occupied by the CD4 Phe43 residue, are known to be highly conserved among the different circulating subtypes and therefore constitute particularly interesting targets for vaccine and drug design. The miniCD4 proteins are a promising class of CD4bs inhibitors. Studying virus evolution under pressure of CD4bs inhibitors could provide insight on the gp120-CD4 interaction and viral entry.

Results
The present study reports on the resistance induction of two subtype B HIV-1 against the most active miniCD4, M48U1, and its ancestor, M48, and how these mutated positions affect CD4bs recognition, entry efficiency, and sensitivity to other CD4bs inhibitors. Resistance against M48U1 was always associated with S375R/N substitution in both BaL and SF162; M48 resistance was associated with D474N substitution in SF162 and with H105Y substitution in BaL. In addition, some other mutations at position V255 and G471 were of importance for SF162 resistant viruses. Except for 474, all of these mutated positions are conserved, and introducing them into an SF162 Env expressing infectious molecular clone (pBRNL4.3 SF162) resulted in decreased entry efficiency. Furthermore, resistant mutants showed at least some cross-resistance towards other CD4bs inhibitors, the V3 monoclonal antibody 447-52D and some even against the monoclonal antibody 17b, of which the epitope overlaps the co-receptor binding site.

Conclusions
The mutations H105Y, V255M, S375R/N, G471R/E, and D474N are found to be involved in resistance towards M48 and M48U1. All mutated positions are part of, or in close proximity to, the CD4bs; most are highly conserved, and all have an impact on the entry efficiency, suggesting their importance for optimal virus infectivity.
Interaction between Serotonin Transporter and Serotonin Receptor 1 B genes polymorphisms may be associated with antisocial alcoholism
Authors: Wang Tzu-Yun , Lee Sheng-Yu , Chen Shiou-Lan , Chang Yun-Hsuan , Chen Shih-Heng , Chu Chun-Hsien , Huang San-Yuan , Tzeng Nian-Sheng , Wang Chen-Lin , Lee I Hui , Yeh Tzung Lieh , Yang Yen Kuang , Lu Ru-Band 
Published: May 2012

AbstractBackgroundSeveral studies have hypothesized that genes regulating the components of the serotonin system, includingserotonin transporter(5-HTTLPR) andserotonin 1 B receptor (5-HT1B),may be associated with alcoholism, but their results are contradictory because of alcoholism’s heterogeneity. Therefore, we examined whether the5-HTTLPRgene and5-HT1BgeneG861Cpolymorphism are susceptibility factors for a specific subtype of alcoholism, antisocial alcoholism in Han Chinese in Taiwan.MethodsWe recruited 273 Han Chinese male inmates with antisocial personality disorder (ASPD) [antisocial alcoholism (AS-ALC) group (n = 120) and antisocial non-alcoholism (AS-N-ALC) group (n = 153)] and 191 healthy male controls from the community. Genotyping was done using PCR-RFLP.ResultsThere were no significant differences in the genotypic frequency of the5-HT1B G861Cpolymorphism between the 3 groups. Although AS-ALC group members more frequently carried the5-HTTLPR S/S, S/LG,andLG/LGgenotypes than controls, the difference became non-significant after controlling for the covarying effects of age. However, the5-HTTLPR S/S, S/LG,andLG/LGgenotypes may have interacted with the5-HT1B G861C C/Cpolymorphism and increased the risk of becoming antisocial alcoholism.ConclusionOur study suggests that neither the5-HTTLPRgene nor the5-HT1B G861Cpolymorphism alone is a risk factor for antisocial alcoholism in Taiwan’s Han Chinese population, but that the interaction between both genes may increase susceptibility to antisocial alcoholism.
Research into practice: Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Nottinghamshire, Derbyshire, Lincolnshire (NDL)
Authors: Rowley Emma , Morriss Richard , Currie Graeme , Schneider Justine 
Published: May 2012

Abstract

Background
To address the problem of translation from research-based evidence to routine healthcare practice, the Collaboration for Leadership in Applied Health Research and Care for Nottinghamshire, Derbyshire, and Lincolnshire (CLAHRC-NDL) was funded by the National Institute for Health Research as one of nine CLAHRCs across England. This paper outlines the underlying theory and its application that CLAHRC-NDL has adopted, as a case example that might be generalised to practice outside the CLAHRC, in comparison to alternative models of implementation.

Discussion
Conventional approaches to health research frequently generate evidence in isolation from the environment in which it is intended for use. The premise of the CLAHRC-NDL model is that barriers to implementation can be overcome if knowledge is co-produced by academic and clinical service staff, taking account of the organisational context in which it is to be applied. This approach is founded on organisational learning theory, recognising that change is a social and political phenomenon. Evidence is produced in real time, taking full account of the environment in which it is to be implemented. To support this process, senior health service staff are seconded to the CLAHRC as ‘diffusion fellows’ (DFs) to actively bridge the research to practice gap by being a full member of both the research team and their area of clinical practice. To facilitate innovation and embed change in the local health community, existing communities of practice are enhanced and new ones are fostered around specific themes. Our approach has been adopted by 16 clinical research studies in the areas of mental health, children and young people, primary care, and stroke rehabilitation.

Summary
The CLAHRC-NDL model of implementation applies organisational learning theory by addressing the social and situational barriers and enablers to implementation, and adopting a philosophy of co-production. Two key mechanisms for translation of innovation have been utilised: DFs, to actively bridge the research to practice gap, and communities of practice, to underpin and sustain improvements in healthcare. The model shows promising results in putting research into practice, which may be transferable to other healthcare contexts.
Lysosomal Membrane Permeabilization is an Early Event in Sigma-2 Receptor Ligand Mediated Cell Death in Pancreatic Cancer
Authors: Hornick John R , Vangveravong Suwanna , Spitzer Dirk , Abate Carmen , Berardi Francesco , Goedegebuure Peter , Mach Robert H , Hawkins William G 
Published: May 2012

Abstract

Background
Sigma-2 receptor ligands have been studied for treatment of pancreatic cancer because they are preferentially internalized by proliferating cells and induce apoptosis. This mechanism of apoptosis is poorly understood, with varying reports of caspase-3 dependence. We evaluated multiple sigma-2 receptor ligands in this study, each shown to decrease tumor burden in preclinical models of human pancreatic cancer.

Results
Fluorescently labeled sigma-2 receptor ligands of two classes (derivatives of SW43 and PB282) localize to cell membrane components in Bxpc3 and Aspc1 pancreatic cancer cells and accumulate in lysosomes. We found that interactions in the lysosome are critical for cell death following sigma-2 ligand treatment because selective inhibition of a protective lysosomal membrane glycoprotein, LAMP1, with shRNA greatly reduced the viability of cells following treatment. Sigma-2 ligands induced lysosomal membrane permeabilization (LMP) and protease translocation triggering downstream effectors of apoptosis. Subsequently, cellular oxidative stress was greatly increased following treatment with SW43, and the hydrophilic antioxidant N-acetylcysteine (NAC) gave greater protection against this than a lipophilic antioxidant, α-tocopherol (α-toco). Conversely, PB282-mediated cytotoxicity relied less on cellular oxidation, even though α-toco did provide protection from this ligand. In addition, we found that caspase-3 induction was not as significantly inhibited by cathepsin inhibitors as by antioxidants. Both NAC and α-toco protected against caspase-3 induction following PB282 treatment, while only NAC offered protection following SW43 treatment. The caspase-3 inhibitor DEVD-FMK offered significant protection from PB282, but not SW43.

Conclusions
Sigma-2 ligand SW43 commits pancreatic cancer cells to death by a caspase-independent process involving LMP and oxidative stress which is protected from by NAC. PB282 however undergoes a caspase-dependent death following LMP protected by DEVD-FMK and α-toco, which is also known to stabilize the mitochondrial membrane during apoptotic stimuli. These differences in mechanism are likely dependent on the structural class of the compounds versus the inherent sigma-2 binding affinity. As resistance of pancreatic cancers to specific apoptotic stimuli from chemotherapy is better appreciated, and patient-tailored treatments become more available, ligands with high sigma-2 receptor affinity should be chosen based on sensitivities to apoptotic pathways.
A new vision of definition, commentary, and understanding in clinical and translational medicine
Authors: Wang Xiangdong 
Published: May 2012

AbstractThere is growing evidence to the importance of translational science and medicine in the improvement of patient outcome, even though the definitions of translational science, translational medicine, and clinical and translational medicine need to be further clarified. In the present perspective, we collected commentaries and descriptions about clinical and translational medicine from some members of Clinical and Translational Medicine editorial board to stimulate the discussion and help the understanding better.
ATP-binding cassette transporters in immortalised human brain microvascular endothelial cells in normal and hypoxic conditions
Authors: Lindner Christian , Sigrüner Alexander , Walther Franziska , Bogdahn Ulrich , Couraud Pierre O , Schmitz Gert , Schlachetzki Felix 
Published: May 2012

Abstract

Background
Rapid reperfusion following ischemia is the most effective therapy in stroke therapy. However, the success may be compromised by ischemia & reperfusion (I/R) injury and at the human blood–brain barrier (BBB), therefore the effects on transendothelial transport are of special interest. Current studies suggest the ATP-binding cassette (ABC) transporters to be regulated upon ischemic stroke in a way that impedes the effects of drug therapy. The immortalised human brain microvascular endothelial cell line hCMEC/D3 provides most of the unique properties of the BBB with respect to transport and might be a reliable in vitro model to study transendothelial transport after I/R.

Methods
We exposed hCMEC/D3 cells to 24 hours of hypoxia alone and to hypoxia followed by 60 min of reoxygenisation as an in vitro model for I/R. Western blot showed mild upregulation of hypoxia inducible factor (HIF-1α) after hypoxia alone and RNA lysates were analysed with a well-established real-time RT-PCR-based TaqMan low-density array detecting 47 of 48 known human ABC transporters.

Results
No significant increases of ABC mRNA expression levels were detected neither in hypoxic nor in I/R samples. However, slight decrease of ABCC1 in hypoxic and I/R samples and of ABCA10 and ABCD3 in I/R samples was observed.

Conclusion
Our data suggests that hCMEC/D3 cell line and – at the moment – in vitro models in general are a poor basis for stroke research but may be enhanced by co-culturing more cells of the neurovascular unit inducing an overall ischemic response at the BBB.
The effects of oxygen tension and antiaging factor Klothoon Wnt signaling in nucleus pulposus cells
Authors: Hiyama Akihiko , Arai Fumiyuki , Sakai Daisuke , Yokoyama Katsuya , Mochida Joji 
Published: May 2012

Abstract

Introduction

The goals of this study were to examine the oxemic regulation of Wnt signaling to explore whether Wnt signaling accelerates the age-related degeneration of nucleus pulposus cells, and if so, to define the mechanism underlying this effect. We investigated the expression of Klotho, a newly identified antiaging gene, and whether its regulation is attributable to the suppression of Wnt signaling.

Methods

Rat nucleus pulposus cells were cultured under normoxic (21% O2) or hypoxic (2% O2) conditions, and the expression and promoter activity of Wnt signaling and Klotho were evaluated. The effect of Klotho protein was examined with transfection experiments, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, senescence-associated β-galactosidase staining, and cell-cycle analysis. To determine the methylation status of the Klotho promoter region, bisulfite genomic sequencing analysis was performed. Its relation with the activation of Wnt signaling was assessed. We also examined whether the expression of Klotho could block the effects of pathological Wnt expression in nucleus pulposus cells.

Results

Nucleus pulposus cells exhibited increased β-catenin mRNA and protein under the hypoxic condition. Klotho protein was expressed in vivo, and protein and messenger RNA expression decreased under the hypoxic condition. Klotho treatment decreased cell proliferation and induced the quiescence of nucleus pulposus cells. In addition, Klotho treatment inhibited expression of β-catenin gene and protein compared with untreated control cells.

Conclusions

These data indicate that Wnt signaling and Klotho form a negative-feedback loop in nucleus pulposus cells. These results suggest that the expression of Klotho is regulated by the balance between upregulation and downregulation of Wnt signaling.