Miracle-dz/UniFAR-FTUs huggingface dataset:
Diffusion Tensor Imaging (DTI) of the Kidney at 3 Tesla–Feasibility, Protocol Evaluation and Comparison to 1.5 Tesla

Purpose:The purpose of this study was to evaluate the feasibility of diffusion tensor imaging of the kidney at a field strength of 3T. We assessed fractional anisotropy (FA) and apparent diffusion coefficients (ADC) of various acquisition protocols and determined the reproducibility of these measurements. FA, ADC, signal-to-noise ratios (SNR), and contrast-to-noise ratios (CNR) were compared with those acquired at 1.5T. Material and Methods:Ten healthy volunteers were examined with a respiratory-triggered echo-planar imaging sequence (TR: 1800 ms, TE: 58 ms, b = 0, 300 s/mm2) on a 3-Tesla whole-body MR scanner. Protocol variations included diffusion measurements during free-breathing, in 6 or 12 directions, and an additional b-value of 50 s/mm2. A breath-hold protocol was also integrated (TR: 820 ms, TE: 58 ms, b = 0, 300 s/mm2). Measurements with 2 b-values and 6 diffusion directions were also acquired at 1.5 T. SNR was calculated with the difference-image method. Statistical analysis was performed with Wilcoxon signed-rank tests. Intrareader correlation was assessed with weighted kappa coefficients and reproducibility with the root-mean-square-average and the Bland-Altman-method. Results:At 3T, SNR of cortex and medulla and CNR of cortex/medulla were significantly higher than at 1.5T, leading to improved corticomedullary discrimination. There were no significant FA- and ADC differences with 2 b-values and 6 diffusion directions between measurements at 1.5T and 3T. FA of the medulla was significantly higher than that of the cortex in all measurements. Tractography visualized a typical radial diffusion direction in the medulla. Best image quality was achieved with a respiratory triggered protocol with 12 acquisition directions. Measurements with 3 b-values led to decreased ADCs. Acquisition in 12 directions resulted in decreased cortical FA. FA and ADC of breath-hold and free-breathing acquisitions were significantly higher than that of the respiratory-triggered protocol. Intrareader correlation ranged from kappa 0.60 to 0.96. Variance of the respiratory-triggered protocol was smaller than that of breath-hold and free-breathing protocols. Variance was highest for medullary FA in all protocols with reproducibility coefficients ranging from 0.36 to 0.46. Conclusion:Diffusion tensor imaging of the kidney at 3T is feasible and yields significantly higher SNR and CNR. FA and ADCs do not significantly differ from 1.5T. Number of b-values influences ADC-values. Acquisitions in 12 directions provide lower cortical FA-values. We recommend a respiratory-triggered protocol because of improved image quality and reproducibility.
Interpolation of tabulated proton Bragg peaks

Treatment planning databases for pencil beam scanning can be large, difficult to manage and problematic for quality assurance when they contain tabulated Bragg peaks at small range resolution. Smaller range resolution, in the absence of an accurate interpolation method, improves the accuracy in dose calculations. In this work, we derive an approximate scaling function to interpolate between tabulated Bragg peaks, and determine the accuracy of this interpolation technique and the minimum number of tabulated peaks in a treatment planning database. With the new interpolation technique, three tabulated mono-energetic Bragg peaks (N = 3) are a suitable lower limit for N to achieve interpolation accuracy better than ±1% of the maximum dose in pristine and spread out Bragg peaks for ranges between 6.8 and 32.1 cm of water.
A delicate balance: TGF‐β and the tumor microenvironment

The activated form of TGF‐β is a known regulator of epithelial cell autonomous tumor initiation, progression, and metastasis. Recent studies have also indicated that TGF‐β mediates interactions between cancer cells and their local tumor microenvironment. Specifically, the loss of TGF‐β signaling in stromal components including fibroblasts and T‐cells can result in an “activated” microenvironment that supports and even initiates transformation of adjacent epithelial cells. TGF‐β signaling in cancer can be regulated through mechanisms involving ligand activation and expression of essential components within the pathway including the receptors and downstream effectors. TGF‐β signaling in the tumor microenvironment significantly impacts carcinoma initiation, progression, and metastasis via epithelial cell autonomous and interdependent stromal–epithelial interactions in vivo. J. Cell. Biochem. 101: 851–861, 2007. © 2007 Wiley‐Liss, Inc.
Comparison Between Nonspecific and Necrosis-avid Gadolinium Contrast Agents in Vascular Disrupting Agent-Induced Necrosis of Rodent Tumors at 3.0T

Objective:To compare a commercial contrast agent (CA) Dotarem and a necrosis-avid CA (NACA) for their ability to evaluate the therapeutic necrosis with a vascular disrupting agent (VDA) on magnetic resonance imaging in rodent liver tumors to determine which could better correlate with the histopathologic outcome. Methods:After the VDA treatment, 16 rats with 32 liver rhabdomyosarcomas were randomized into Dotarem and NACA groups (n = 8 per group) for both interindividual and intraindividual comparisons. T2-weighted imaging, T1-weighted imaging (T1WI), contrast-enhanced T1-weighted imaging (CE-T1WI), and diffusion-weighted imaging were performed at baseline, after VDA treatment and CA injections. The enhancing efficacy of CAs at immediate and delayed enhancement on CE-T1WI in viable tumor and necrosis was compared. Tumor necrosis ratios calculated from NACA and Dotarem were compared and correlated with gold-standard histopathology. Results:On the immediate CE-T1WI, viable tumor was enhanced by either CA. On the delayed CE-T1WI at 30 minutes, both CAs failed to demarcate viable tumor from necrosis. At 24 hours post-NACA, the necrosis was clearly distinguished from viable tumor and thus derived necrosis ratio matched that from histopathology (P = 0.99); necrosis ratio from Dotarem was significantly lower than that from NACA and histopathology (P < 0.05, both), with a higher correlation of NACA than that of Dotarem with histopathology (r = 0.99 vs. r = 0.82). Conclusions:NACA better evaluated VDA-induced tumor necrosis than nonspecific CA on T1WI in tumor models of rat liver. NACA showed a closer correlation with histopathology than nonspecific CA for the delineation of true necrosis. Delayed enhancement on T1WI with nonspecific CA is not suitable for the assessment of VDA-induced tumor necrosis.
Fine mapping and functional activity of the adenosine deaminase origin in murine embryonic fibroblasts

DNA replication initiates at origins within the genome. The late‐firing murine adenosine deaminase (mAdA) origin is located within a 2 kb fragment of DNA, making it difficult to examine by realtime technology. In this study, fine mapping of the mAdA region by measuring the abundance of nascent strand DNA identified two origins, mAdA‐1 and mAdA‐C, located 397 bp apart from each other. Both origins conferred autonomous replication to plasmids transfected in murine embryonic fibroblasts (MEFs), and exhibited similar activities in vivo and in vitro. Furthermore, both were able to recruit the DNA replication initiator proteins Cdc6 and Ku in vitro, similar to other bona fide replication origins. When tested in a murine Ku80−/− cell line, both origins exhibited replication activities comparable to those observed in wildtype cells, as did the hypoxanthine‐guanine phosphoribosyltransferase (HPRT) and c‐myc origins. This contrasts with previously published studies using Ku80‐deficient human cells lines and suggests differences in the mechanism of initiation of DNA replication between the murine and human systems. J. Cell. Biochem. 104: 773–784, 2008. © 2008 Wiley‐Liss, Inc.
Isolation of lesbian, gay, bisexual and transgender youth: a dimensional concept analysis.

AIM To present the findings of a dimensional analysis of isolation in the context, and from the perspective, of lesbian, gay, bisexual and transgender youth. BACKGROUND Lesbian, gay, bisexual and transgender youth are often at greater risk for negative health outcomes compared with heterosexual youth. Isolation is one risk factor cited throughout the literature; however, the concept is complicated and has many uses and thus warrants clarification. DESIGN Concept Analysis. DATA SOURCES Sources comprise 35 English language research articles retrieved from CINAHL and EBSCOHost (1987-2012). METHODS A dimensional concept analysis was undertaken to analyse how the concept, isolation, is socially constructed. RESULTS This dimensional analysis revealed five socially constructed dimensions and four sub-dimensions. These findings indicate that there is substantial variability in the concept of isolation. These differences and variations are most notably observed in the 20 articles (57%) that had more than one dimension. Although some of these articles were explicit with the different meanings and use of the concept, most of the papers had wide variability in the use and meaning of the concept. CONCLUSION The disproportionately greater physical and mental health disparities between lesbian, gay, bisexual and transgender and heterosexual youth are a signal to conduct more research to clarify the concept of isolation, to develop instrumentation to identify at-risk youth and to explore predictors and consequences of isolation. Nurses and others can lead the way in translating this knowledge into strategies that will improve the health and lives of these young people.
Nurses' perception of senior managers at the front line: people working with clipboards.

AIM To provide an original perspective on front-line nurses' perception of senior managers who are not nurses. BACKGROUND A key element of new public management had been the drive for 'hands-on' professional management within the UK National Health Service, meaning the employment of mangers with managerial experience but little or no healthcare experience. DESIGN An interpretive qualitative study, based on a single case study design with semi-structured interviews. METHODS Semi-structured interviews were carried out with 31 front-line Scottish National Health Service nurses exploring their perceptions of the role of managers between July-September 2010. RESULTS/FINDINGS Nursing staff were often unsure of the responsibilities of managers and perceived that there were an unnecessarily high number of managers within the National Health Service. Nursing staff raised concerns over the non-clinical background of managers, including their ability to understand the pressures faced at the front line. CONCLUSIONS The main reason for conflict between managers and nursing staff was their differing foci. Managers were seen to concentrate on decisions surrounding targets, audits and budgets with little consideration given to the impact of these decisions on patient care.
Varying kVp as a means of reducing CT breast dose to pediatric patients

We investigated the possibility of reducing radiation dose to the breast tissue of pediatric females by using multiple tube voltages within a single CT examination. The peak kilovoltage (kVp) was adjusted when the x-ray beam was directly exposing the representative breast tissue of a 5-year-old, 10-year-old, and an adult female anthropomorphic phantom; this strategy was called kVp splitting and was emulated by using a different kVp over the anterior and posterior tube angles. Dose savings from kVp splitting were calculated relative to using a fixed kVp over all tube angles and the results indicated savings in all three phantoms when using 80 kVp over the posterior tube angles regardless of the anterior kVp. Monte Carlo (MC) simulations with and without kVp splitting were performed to estimate absorbed breast dose in voxelized models constructed from the CT images of pediatric female patients; 80 kVp was used over the posterior tube angles. The MC simulations revealed breast dose savings of between 9.8% and 33% from using kVp splitting compared to simulations using a fixed kVp protocol with the anterior technique. Before this strategy could be implemented clinically, the development of suitable image reconstruction algorithms and the image quality of scans with kVp splitting would need further study.
A quantitative systematic review of the efficacy of mobile phone interventions to improve medication adherence.

AIMS To evaluate the characteristics and efficacy of mobile phone interventions to improve medication adherence. Secondary aims are to explore participants' acceptability and satisfaction with mobile phone interventions and to evaluate the selected studies in terms of study rigour, impact, cost and resource feasibility, generalizability and implications for nursing practice and research. BACKGROUND Medication non-adherence is a major global challenge. Mobile phones are the most commonly used form of technology worldwide and have the potential to promote medication adherence. DESIGN Guidelines from the Centre for Reviews and Dissemination were followed for this systematic review. DATA SOURCES A comprehensive search of databases (PubMed, Web of Science, CINAHL, PsycInfo, Google Chrome and Cochrane) and bibliographies from related articles was performed from January 2002-January 2013 to identify the included studies. REVIEW METHODS A quantitative systematic review without meta-analysis was conducted and the selected studies were critically evaluated to extract and summarize pertinent characteristics and outcomes. RESULTS The literature search produced 29 quantitative research studies related to mobile phones and medication adherence. The studies were conducted for prevention purposes as well as management of acute and chronic illnesses. All of the studies used text messaging. Eighteen studies found significant improvement in medication adherence. CONCLUSION While the majority of investigators found improvement in medication adherence, long-term studies characterized by rigorous research methodologies, appropriate statistical and economic analyses and the test of theory-based interventions are needed to determine the efficacy of mobile phones to influence medication adherence.
3D‐model of adult cardiac stem cells promotes cardiac differentiation and resistance to oxidative stress

The regenerative inadequacy of the injured myocardium leads to adverse remodeling, cardiac dysfunction, and heart disease. Stem cell‐replacement of damaged myocardium faces major challenges such as inappropriate differentiation, cellular uncoupling, scar formation, and accelerated apoptosis of transplanted cells. These challenges can be met by engineering an in vitro system for delivering stem cells capable of cardiac differentiation, tissue integration, and resistance to oxidative stress. In this study, we describe the formation of three‐dimensional (3D) cell aggregates (“cardiospheres”) by putative stem cells isolated from adult dog myocardium using poly‐L‐ornithine. De novo formation of cardiospheres in growth factor‐containing medium occurred over a period of 2–3 weeks, but accelerated to 2–3 days when seeded on poly‐L‐ornithine. Older cardiospheres developed foci of “beating” cells upon co‐culture with rat neonatal cardiomyocytes. Cardiospheres contained cells that exhibited characteristics of undifferentiated cells; differentiating cardiomyocytes with organized contractile machinery; and vascular cells capable of forming “vessel‐like” networks. They exhibited strong resistance to elevated concentrations of hydrogen peroxide in culture and survived subcutaneous injections without undergoing neoplastic transformation up to 3 weeks post‐transplantation. These findings suggest that cardiospheres are potentially useful for delivering functional stem cells to the damaged heart. J. Cell. Biochem. 105: 612–623, 2008. © 2008 Wiley‐Liss, Inc.
'Keep fit' exercise interventions to improve health, fitness and well-being of children and young people who use wheelchairs: mixed-method systematic review protocol.

AIM This mixed-method systematic review aims to establish the current evidence base for 'keep fit', exercise or physical activity interventions for children and young people who use wheelchairs. BACKGROUND Nurses have a vital health promotion, motivational and monitoring role in optimizing the health and well-being of disabled children. Children with mobility impairments are prone to have low participation levels in physical activity, which reduces fitness and well-being. Effective physical activity interventions that are fun and engaging for children are required to promote habitual participation as part of a healthy lifestyle. Previous intervention programmes have been trialled, but little is known about the most effective types of exercise to improve the fitness of young wheelchair users. DESIGN Mixed-method design using Cochrane systematic processes. Evidence regarding physiological and psychological effectiveness, health economics, user perspectives and service evaluations will be included and analysed under distinct streams. METHODS The project was funded from October 2012. Multiple databases will be searched using search strings combining relevant medical subheadings and intervention-specific terms. Articles will also be identified from ancestral references and by approaching authors to identify unpublished work. Only studies or reports evaluating the effectiveness, participation experiences or cost of a physical activity programme will be included. Separate analyses will be performed for each data stream, including a meta-analysis if sufficient homogeneity exists and thematic analyses. Findings across streams will be synthesized in an overarching narrative summary. DISCUSSION Evidence from the first systematic review of this type will inform development of effective child-centred physical activity interventions and their evaluation.
Mammary epithelial cell transformation is associated with deregulation of the vitamin D pathway

The vitamin D endocrine system mediates anti‐proliferative and pro‐differentiating signaling in multiple epithelial tissues, including mammary gland and breast tumors. The vitamin D metabolite 1α,25(OH)2D3 mediates growth inhibitory signaling via activation of the vitamin D receptor (VDR), a ligand dependent transcription factor. 1α,25(OH)2D3 is synthesized from 25(OH)D3 (the major circulating form of the vitamin) by the mitochondrial enzyme CYP27b1 in renal and other tissues. Human mammary epithelial (HME) cells express VDR and CYP27b1 and undergo growth inhibition when exposed to physiological concentrations of 25(OH)D3, suggesting that autocrine or paracrine vitamin D signaling contributes to maintenance of differentiation and quiescence in the mammary epithelium. In the current studies we tested the hypothesis that cancer cells would exhibit reduced sensitivity to vitamin D mediated negative growth regulation. We used a series of progressively transformed HME cell lines expressing known oncogenic manipulations to study the effects of transformation per se on the vitamin D pathway. We report that mRNA and protein levels of VDR and CYP27b1 were reduced greater than 70% upon stable introduction of known oncogenes (SV40 T antigens and H‐rasV12) into HME cells. Oncogenic transformation was also associated with reduced 1α,25(OH)2D3 synthesis, and cellular sensitivity to growth inhibition by 1α,25(OH)2D3 and 25(OH)D3 was decreased approximately 100‐fold in transformed cells. These studies provide evidence that disruption of the vitamin D signaling pathway occurs early in the cancer development process. J. Cell. Biochem. 105: 980–988, 2008. © 2008 Wiley‐Liss, Inc.
E‐cadherin dis‐engagement activates the Rap1 GTPase

E‐cadherin based adherens junctions are finely regulated by multiple cellular signaling events. Here we show that the Ras‐related Rap1 GTPase is enriched in regions of nascent cell–cell contacts and strengthens E‐cadherin junctions: constitutively active Rap1 expressing MDCK cells exhibit increased junctional contact and resisted calcium depletion‐induced cell–cell junction disruption. E‐cadherin disengagement activated Rap1 and this correlated with E‐cadherin association with the Rap GEFs, C3G and PDZ‐GEF I. PDZ‐GEF I associated with E‐cadherin and β‐catenin whereas C3G interaction with E‐cadherin did not involve β‐catenin. Knockdown of PDZ‐GEF I in MDCK cells decreased Rap1 activity following E‐cadherin junction disruption. We hereby show that Rap1 plays a role in the maintenance and repair of E‐cadherin junctions and is activated via an “outside‐in” signaling pathway initiated by E‐cadherin and mediated at least in part by PDZ‐GEF I. J. Cell. Biochem. 105: 1027–1037, 2008. © 2008 Wiley‐Liss, Inc.
Roscovitine up‐regulates p53 protein and induces apoptosis in human HeLaS3 cervix carcinoma cells

Exposure of human HeLaS3 cervix carcinoma cells to high doses of conventional cytostatic drugs, e.g. cisplatin (CP) strongly inhibits their proliferation. However, most cytostatic agents are genotoxic and may generate a secondary malignancy. Therefore, therapeutic strategy using alternative, not cytotoxic drugs would be beneficial. Inhibition of cyclin‐dependent kinases (CDKs) by pharmacological inhibitors became recently a promising therapeutic option. Roscovitine (ROSC), a selective CDK inhibitor, efficiently targets human malignant cells. ROSC induces cell cycle arrest and apoptosis in human MCF‐7 breast cancer cells. ROSC also activates p53 protein. Activation of p53 tumor suppressor protein is essential for induction of apoptosis in MCF‐7 cells. Considering the fact that in HeLaS3 cells wt p53 is inactivated by the action of HPV‐encoded E6 oncoprotein, we addressed the question whether ROSC would be able to reactivate p53 protein in them. Their exposure to ROSC for 24 h induced cell cycle arrest at G2/M and reduced the number of viable cells. Unlike CP, ROSC in the used doses did not induce DNA damage and was not directly cytotoxic. Despite lack of detectable DNA lesions, ROSC activated wt p53 protein. The increase of p53 levels was attributable to the ROSC‐mediated protein stabilization. Further analyses revealed that ROSC induced site‐specific phosphorylation of p53 protein at Ser46. After longer exposure, ROSC induced apoptosis in HeLaS3 cells. These results indicate that therapy of HeLaS3 cells by ROSC could offer an advantage over that by CP due to its increased selectivity and markedly reduced risk of generation of a secondary cancer. J. Cell. Biochem. 105: 1161–1171, 2008. © 2008 Wiley‐Liss, Inc.
Oncoprotein BMI‐1 induces the malignant transformation of HaCaT cells

BMI‐1 (B‐cell‐specific Moloney murine leukemia virus integration site 1), a novel oncogene, has attracted much attention in recent years for its involvement in the initiation of a variety of tumors. Recent evidence showed that BMI‐1 was highly expressed in neoplastic skin lesions. However, whether dysregulated BMI‐1 expression is causal for the transformation of skin cells remains unknown. In this study, we stably expressed BMI‐1 in a human keratinocyte cell line, HaCaT. The expression of wild‐type BMI‐1 induced the malignant transformation of HaCaT cells in vitro. More importantly, we found that expression of BMI‐1 promoted formation of squamous cell carcinomas in vivo. Furthermore, we showed that BMI‐1 expression led to the downregulation of tumore suppressors, such as p16INK4a and p14ARF, cell adhesion molecules, such as E‐Cadherin, and differentiation related factor, such as KRT6. Therefore, our findings demonstrated that dysregulated BMI‐1 could indeed lead to keratinocytes transformation and tumorigenesis, potentially through promoting cell cycle progression and increasing cell mobility. J. Cell. Biochem. 106: 16–24, 2009. © 2008 Wiley‐Liss, Inc.