Miracle-dz/UniFAR-FTUs huggingface dataset:
Reply to ‘Comment on “Experimental verification of ion stopping power prediction from dual energy CT data in tissue surrogates”’

We read the comment by Farace with great interest. We acknowledge the accuracy of their results and the simplification offered by not explicitly taking the Zeff information into account for the SPR prediction. We nevertheless believe that the separation of Z-dependency in photon attenuation and determination of electron density are major benefits of using the dual energy CT (DECT) technology for protonand ion beam treatment planning. Even if the electron density represents the most important tissue parameter with respect to stopping power, we would like to point out that there are tissues having the same electron density but expressing different effective atomic numbers and vice versa (see ‘mammary gland 2’ and ‘urine’ in (Hünemohr et al 2014)). These differences are large enough to be differentiated by DECT (Mahnken et al 2009) and Zeff proved to be a proxy for the I-value (Yang et al 2010) (in contrast of using a Hounsfield unit). Despite the ln I in the Bethe equation, the available information on Zeff represents a step towards higher accuracy in stopping power prediction for these tissues, not to mention its value for Monte Carlo based dose calculation algorithms and related topics (Landry et al 2013), and should not be discarded. Furthermore, we agree the relation between Zeff and I is far from trivial and influenced by at least three factors: (a) the relation of I-value and atomic number itself (ICRU Report 49 1951), (b) the relation of I-value and Zeff for compounds on an atomic level and (c) the relation of I-value and Zeff for tissue mixtures. When a tissue is considered to be a compound consisting of base components, ln I is found to depend linearly on Zeff with the slope being determined by the base components according to (a) and (b). This is especially the case for the soft and bony tissue from (Schneider et al 2000) (figure 1) whose compositions are interpolated using base N Hünemohr et al
Computation of mean and variance of the radiotherapy dose for PCA-modeled random shape and position variations of the target

Radiotherapy dose delivery in the tumor and surrounding healthy tissues is affected by movements and deformations of the corresponding organs between fractions. The random variations may be characterized by non-rigid, anisotropic principal component analysis (PCA) modes. In this article new dynamic dose deposition matrices, based on established PCA modes, are introduced as a tool to evaluate the mean and the variance of the dose at each target point resulting from any given set of fluence profiles. The method is tested for a simple cubic geometry and for a prostate case. The movements spread out the distributions of the mean dose and cause the variance of the dose to be highest near the edges of the beams. The non-rigidity and anisotropy of the movements are reflected in both quantities. The dynamic dose deposition matrices facilitate the inclusion of the mean and the variance of the dose in the existing fluence-profile optimizer for radiotherapy planning, to ensure robust plans with respect to the movements.
CARM1 activates myogenin gene via PCAF in the early differentiation of TPA‐induced rhabdomyosarcoma‐derived cells

CARM1/PRMT4 is a member of the protein arginine methyltransferase (PRMT) family. CARM1 as a transcriptional coactivator plays an active role on mammalian genes. Here, we show that CARM1 can be recruited to the promoter of myogenin gene to enhance its transcriptional activation via PCAF at the early stage of TPA‐induced RD cell differentiation. By adding adenosine dialdehyde, AdOx, to inhibit the PRMT in RD cells, the TPA‐induced recruiting of p300, PCAF and the Brg1 at the myogenin promoter is abolished and myogenic differentiation is blocked. More specifically, the expression of PCAF and its nucleation are prohibited when CARM1 is knockdown by its specific siRNA. We suggest that the physical interaction of CARM1 and PCAF is likely pivotal for the activation of PCAF in the downstream of CARM1 pathway for inducing myogenin under TPA‐induced differentiation. The findings shed lights on novel therapeutic targets in the treatment of rhabdomyosarcoma patients. J. Cell. Biochem. 110: 162–170, 2010. © 2010 Wiley‐Liss, Inc.
Is antibiotic resistance a problem in the treatment of ophthalmic infections?

Antibiotic resistance is a world-wide problem of systemic medicine, but it appears to be less problematic in the treatment of ophthalmic infections. The use of topical administration and intraocular injection of antibiotics provides very high antibiotic concentrations in the ocular tissues. These high concentrations are effective in treating bacteria that are deemed resistant using standard interpretations of susceptibility. Although in vitro bacterial resistance, based on serum standard interpretation, is reported for ocular bacteria, these isolates are generally not spread from patient-to-patient and there are antibiotics available to effectively treat and overcome the false resistance.
Reducing patient delay in Acute Coronary Syndrome (RAPiD): research protocol for a web‐based randomized controlled trial examining the effect of a behaviour change intervention

AIMS To evaluate the efficacy of a behaviour change technique-based intervention and compare two possible modes of delivery (text + visual and text-only) with usual care. BACKGROUND Patient delay prevents many people from achieving optimal benefit of time-dependent treatments for acute coronary syndrome. Reducing delay would reduce mortality and morbidity, but interventions to change behaviour have had mixed results. Systematic inclusion of behaviour change techniques or a visual mode of delivery might improve the efficacy of interventions. DESIGN A three-arm web-based, parallel randomized controlled trial of a theory-based intervention. METHODS The intervention comprises 12 behaviour change techniques systematically identified following systematic review and a consensus exercise undertaken with behaviour change experts. We aim to recruit n = 177 participants who have experienced acute coronary syndrome in the previous 6 months from a National Health Service Hospital. Consenting participants will be randomly allocated in equal numbers to one of three study groups: i) usual care, ii) usual care plus text-only behaviour change technique-based intervention or iii) usual care plus text + visual behaviour change technique-based intervention. The primary outcome will be the change in intention to phone an ambulance immediately with symptoms of acute coronary syndrome ≥15-minute duration, assessed using two randomized series of eight scenarios representing varied symptoms before and after delivery of the interventions or control condition (usual care). Funding granted January 2014. DISCUSSION Positive results changing intentions would lead to a randomized controlled trial of the behaviour change intervention in clinical practice, assessing patient delay in the event of actual symptoms. TRIAL REGISTRATION Registered at ClinicalTrials.gov: NCT02820103.
A systematic review: effectiveness of pediatric peripheral intravenous catheterization strategies

AIM The aim of this study was to identify interventions associated with peripheral intravenous catheterization first attempt success in pediatric inpatients and emergency department patients who require vascular access for therapeutic interventions. BACKGROUND Unsuccessful peripheral intravenous catheterization puts children at risk for increased pain and treatment delays. Effective interventions to increase peripheral intravenous catheterization first attempt success are unclear. DESIGN Systematic review of randomized controlled trials according to the Cochrane Handbook for the Systematic Review of Interventions. DATA SOURCES Through November and December 2014, we searched 10 databases including MEDLINE (OVID), EMBASE (OVID) and CINAHL (EBSCO) without date limits. The references of articles were also reviewed. We included full text reports of randomized controlled trials testing intervention first attempt success rates vs. standard of care. REVIEW METHODS According to inclusion and exclusion criteria set a priori, data were extracted using a standardized tool. We assessed for risk of bias with the Cochrane Collaboration Risk of Bias Tool. Due to unclear reporting narrative synthesis was used to report results. RESULTS Four cluster randomized control trials and ten randomized control trials involving 4539 participants ranging from 15·6 days to 16 years of age met our inclusion criteria. We excluded the four cluster trials from meta-analysis due to unclear reporting. Interventions did not increase first attempt success rate compared with standard of care. CONCLUSIONS There was insufficient evidence to support the use of ultrasound, infrared light or transillumination. Interventions to reduce children's pain did not decrease first attempt success. Research examining between-clinician proficiency and persistence differences is absent.
PTEN‐ and p53‐mediated apoptosis and cell cycle arrest by FTY720 in gastric cancer cells and nude mice

FTY720, a new immunosuppressant, derived from ISP‐1, has been studied for its putative anti‐cancer properties in the recent years. In this study, we have reported that FTY720 greatly inhibited gastric cancer cell proliferation for the first time, and found this effect was associated with G1 phase cell cycle arrest and apoptosis. Results from our Western blotting and Real‐time PCR showed that FTY720 induced obvious PTEN expression in a p53‐independent way, consistent with a substantial decrease in p‐Akt and MDM2. FTY720 dramatically increased the expression of Cip1/p21, p27, and BH3‐only proteins through the accumulation of p53 by PTEN‐mediated inhibition of the PI3K/Akt/MDM2 signaling. Suppression of PTEN expression with siRNA significantly reduced the p53 and p21 levels and activated Akt, resulting in decreased apoptosis and increased cell survival. Furthermore, we have observed an additive effect of FTY720 in killing gastric cancer cells when in combination with Cisplatin, partly through PTEN‐mediated Akt/MDM2 inhibition. In vivo study has also shown that tumor growth was significantly suppressed after FTY720 treatment. In conclusion, our results suggest that FTY720 induces a significant increase of PTEN, which inhibits p‐Akt and MDM2, and then increases the level of p53, thereby inducing G1 phase arrest and apoptosis. We have characterized a novel immunosuppressant, for the first time, which shows potential anti‐tumor effects on gastric cancer by PTEN activation through p53‐independent mechanism, especially in combination with Cisplatin. This PTEN target‐based therapy is worth further investigation and warrants clinical evaluation. J. Cell. Biochem. 111: 218–228, 2010. © 2010 Wiley‐Liss, Inc.
Work climate and the mediating role of workplace bullying related to job performance, job satisfaction, and work ability: A study among hospital nurses

AIM To increase understanding of workplace bullying and its relation to work climate and different outcomes among nurses. Examine a proposed bullying model including both job resource and job demands, as well as nurse outcomes reflected in job performance, job satisfaction, and work ability. BACKGROUND Workplace bullying has been identified as some of the most damaging mechanisms in workplace settings. It is important to increase understanding of workplace bullying in relation to work climate and different outcomes among nurses. DESIGN This study adopted a cross-sectional web based survey design. METHOD A sample of 2946 Registered Nurses from four public Norwegian hospitals were collected during October 2014. We analysed data using descriptive statistics, correlations, Cronbach's alpa, confirmatory factor analyses, and structural equation modelling. RESULTS The majority of work climate characteristics confirmed to influence workplace bullying, and additionally had direct influence on nurse outcomes; job performance, job satisfaction, and work ability. Bullying had a mediational role between most of the work climate dimensions and nurse outcomes. CONCLUSION This study increases our understanding of organizational antecedent of bullying among nurses. Workplace bullying among nurses functions as a mediator between the majority of work climate dimensions and outcomes related to job satisfaction and work ability. Strategies to reduce bullying should look at the study finding and specifically job resources and job demands that influence bullying and nurse outcomes.
Cytokine Stimulation Promotes Increased Glucose Uptake Via Translocation at the Plasma Membrane of GLUT1 in HEK293 Cells

Interleukin‐3 (IL‐3) and granulocyte/macrophage colony‐stimulating factor (GM‐CSF) are two of the best‐characterized cell survival factors in hematopoietic cells; these factors induce an increase in Akt activity in multiple cell lines, a process thought to be involved in cellular survival. It is known that growth factors require sustained glucose metabolism to promote cell survival. It has been determined that IL‐3 and GM‐CSF signal for increased glucose uptake in hematopoietic cells. Interestingly, receptors for IL‐3 and GM‐CSF are present in several non‐hematopoietic cell types but their roles in these cells have been poorly described. In this study, we demonstrated the expression of IL‐3 and GM‐CSF receptors in HEK293 cells and analyzed their effect on glucose uptake. In these cells, both IL‐3 and GM‐CSF, increased glucose uptake. The results indicated that this increase involves the subcellular redistribution of GLUT1, affecting glucose transporter levels at the cell surface in HEK293 cells. Also the data directly demonstrates that the PI 3‐kinase/Akt pathway is an important mediator of this process. Altogether these results show a role for non‐insulin growth factors in the regulation of GLUT1 trafficking that has not yet been directly determined in non‐hematopoietic cells. J. Cell. Biochem. 110: 1471–1480, 2010. © 2010 Wiley‐Liss, Inc.
Recombinant vascular basement membrane derived multifunctional peptide blocks endothelial cell angiogenesis and neovascularization

Angiogenesis is an innovative target in the therapy of cancer and other diseases, but the effects of anti‐angiogenic drugs have been rather modest in clinical trials. We have developed a small peptide, recombinant vascular basement membrane derived multifunctional peptide (rVBMDMP), which significantly inhibits endothelial cells in vitro. Here we test the mechanisms of rVBMDMP in angiogenesis balance in assays of tubule formation, colony formation, and apoptosis in HUVE‐12 endothelial cells. We also analyzed the differential expression of phosphorylation proteins and related genes in a protein phosphorylation chip and extracellular matrix adhesion molecule cDNA microarray, and validated changes with Western blot or real‐time quantitative PCR, respectively. rVBMDMP dose‐dependently inhibited colony formation, induced apoptosis, and inhibited in vitro tubule formation. rVBMDMP increased the phosphorylation of 88 signal proteins, including caspase‐3, death receptor 3, 4, and 5, and integrin αV, β1, and β3, and down‐regulated 41 signal proteins, including EGFR, pEGFR, VEGFR‐1, and survivin versus control. rVBMDMP upregulated 14 genes, including collagen 4, 7, and 27, and down‐regulated 21 genes, including integrin αVβ3, MMP10, and MMP12. Our study suggests that rVBMDMP inhibits angiogenesis and may be a viable drug candidate in anti‐angiogenesis and anticancer therapies. J. Cell. Biochem. 111: 453–460, 2010. © 2010 Wiley‐Liss, Inc.
Co‐chaperone BAG3 and adenovirus penton base protein partnership

The BAG family of Hsp70/Hsc70 co‐chaperones is characterised by the presence of a conserved BAG domain at the carboxyl‐terminus. BAG3 protein is the only member of this family containing also the N‐terminally located WW domain. We describe here the identification of adenovirus (Ad) penton base protein as the first BAG3 partner recognising BAG3 WW domain. Ad penton base is the viral capsid constituent responsible for virus internalisation. It contains in the N‐terminal part two conserved PPxY motifs, known ligands of WW domains. In cells producing Ad penton base protein, cytoplasmic endogenous BAG3 interacts with it and co‐migrates to the nucleus. Preincubation of BAG3 with Ad base protein results in only slight modulation of BAG3 co‐chaperone activity, suggesting that this interaction is not related to the classical BAG3 co‐chaperone function. However, depletion of BAG3 impairs the cell entry of the virus and viral progeny production in Ad‐infected cells, suggesting that the interaction between virus penton base protein and cellular co‐chaperone BAG3 positively influences virus life cycle. These results thus demonstrate a novel host–pathogen interaction, which contributes to the successful infectious life cycle of adenoviruses. In addition, these data enrich our knowledge about the multifunctionality of the BAG3 co‐chaperone. J. Cell. Biochem. 111: 699–708, 2010. © 2010 Wiley‐Liss, Inc.
Commentary: major defects are overestimated

After reclassification of birth defects according to the system used by the Western Australian Birth Defects Registry, Kurinczuk and Bower's reanalysis of our data suggests that the 420 live born infants conceived by intracytoplasmic sperm injection were twice as likely to have a major birth defect as the general population of Western Australia. This result is considered unlikely to be due to chance. For the cardiac malformations in particular, we think that the authors overestimate the number of major malformations. They do not take into account the fact that these malformations were found as part of an ultrasound research screening programme for the infants conceived by intracytoplasmic sperm injection. Kurinczuk and Bower made conservative estimates about the patent ductus arteriosus in six children, since we had given insufficient information to determine whether they should be included as major defects according to Australian criteria. In fact, …
A systematic review of qualitative research into people's experiences of living with venous leg ulcers

AIM To systematically identify, evaluate and synthesize qualitative research that examined the symptoms and health-related quality of life themes that are important from the perspective of patients with venous leg ulceration. BACKGROUND Venous leg ulceration is a common chronic condition; the symptoms and associated treatments have a negative effect on health-related quality of life. Qualitative research methods can provide insight into the personal experiences of patients with venous leg ulceration. DESIGN Qualitative evidence synthesis (using framework synthesis). DATA SOURCES Multiple electronic databases including MEDLINE, EMBASE, PsycINFO and CINAHL were comprehensively searched from inception to November 2015. REVIEW METHODS Systematic identification, quality assessment and synthesis of existing qualitative research were performed; framework synthesis was conducted on included studies. An inductive approach was used and emergent themes were identified. The final stage in the synthesis involved the development of new interpretations. RESULTS Thirteen studies met the inclusion criteria; the overall quality of the included studies was good. Four overarching themes were identified; physical impact, psychological impact, social impact and treatment and, in these, further subthemes were identified. Ulcer and treatment-related pain, as well as odour and exudate appeared to have significant and direct negative effects on quality of life, with additional and cumulative effects on sleep, mobility and mood. CONCLUSION The themes identified in this review should be considered by professionals providing services, care and treatment for venous leg ulcer patients and in the selection, or development, of patient-reported outcome measures for use with this population.
Association of IFN-γ and IFN regulatory factor 1 polymorphisms with childhood atopic asthma

Abstract Background: IFN-γ and related molecules play important roles in the differentiation and function of T H 2 cells. Objective: We sought to determine whether IFNG and related genes contribute to any susceptibility to atopic asthma, a representative T H 2-dominant disorder. Methods: We investigated the association of IFNG (CA repeat polymorphism within the first intron), IRF1 (GT repeat polymorphism within the intron 7), IFNGR1 (Val 14 Met), and IFNGR2 (Gln 64 Arg) gene polymorphisms with atopic asthma in the Japanese child population. Results: A significant association ( P = .0018) was observed between IFNG gene polymorphism and atopic asthma. The tendency was more prominent in patients with age of onset of 3 years or younger ( P = .0004) or patients with a family history of allergic diseases ( P = .0038). Furthermore, there was a significant association between IRF1 gene whole-allele distribution and atopic asthma ( P = .044). The tendency was more prominent in patients with onset at 3 years of age or less ( P = .0058). On the other hand, IFNGR1 and IFNGR2 gene polymorphisms showed no association with atopic asthma. Conclusion: These results suggested that among IFNG and related genes, IFNG and IRF1 genes confer genetic susceptibility to atopic asthma in Japanese children. (J Allergy Clin Immunol 2001;107:499-504.)
A case study of nurse practitioner care compared with general practitioner care for children with respiratory tract infections

AIM To compare quality of care provided by nurse practitioners (NP) with care provided by general practitioners (GP) for children with respiratory tract infections (RTI) in the Netherlands. BACKGROUND Nurse practitioners increasingly manage acute conditions in general practice, with opportunities for more protocolled care. Studies on quality of NPs' care for children with RTIs are limited to the US healthcare system and do not take into account baseline differences in illness severity. DESIGN Retrospective observational cohort study. METHODS Data were extracted from electronic healthcare records of children 0-6 years presenting with RTI between January-December 2013. Primary outcomes were antibiotic prescriptions and early return visits. Generalized estimating equations were used to correct for potential confounders. RESULTS A total of 899 RTI consultations were assessed (168 seen by NP; 731 by GP). Baseline characteristics differed between these groups. Overall antibiotic prescription and early return visit rates were 21% and 24%, respectively. Adjusted odds ratio for antibiotic prescription after NP vs. GP delivered care was 1.40 (95% confidence interval 0.89-2.22) and for early return visits 1.53 (95% confidence interval 1.01-2.31). Important confounder for antibiotic prescription was illness severity. Presence of wheezing was a confounder for return visits. Complication and referral rates did not differ. CONCLUSION Antibiotic prescription, complication and referral rates for paediatric RTI consultations did not differ significantly between NP and GP consultations, after correction for potential confounders. General practitioners, however, see more severely ill children and have a lower return visit rate. A randomised controlled study is needed to determine whether NP care quality is truly noninferior.