bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Conditional candour’ and ‘knowing me’: an interpretive description study on patient preferences for physician behaviours during end-of-life communication
Authors: Abdul-Razzak Amane , You John , Sherifali Diana , Simon Jessica , Brazil Kevin 
Published: October 2014

ObjectiveTo understand patients’ preferences for physician behaviours during end-of-life communication.MethodsWe used interpretive description methods to analyse data from semistructured, one-on-one interviews with patients admitted to general medical wards at three Canadian tertiary care hospitals. Study recruitment took place from October 2012 to August 2013. We used a purposive, maximum variation sampling approach to recruit hospitalised patients aged ≥55 years with a high risk of mortality within 6–12 months, and with different combinations of the following demographic variables: race (Caucasian vs non-Caucasian), gender and diagnosis (cancer vs non-cancer).ResultsA total of 16 participants were recruited, most of whom (69%) were women and 70% had a non-cancer diagnosis. Two major concepts regarding helpful physician behaviour during end-of-life conversations emerged: (1) ‘knowing me’, which reflects the importance of acknowledging the influence of family roles and life history on values and priorities expressed during end-of-life communication, and (2) ‘conditional candour’, which describes a process of information exchange that includes an assessment of patients’ readiness, being invited to the conversation, and sensitive delivery of information.ConclusionsOur findings suggest that patients prefer a nuanced approach to truth telling when having end-of-life discussions with their physician. This may have important implications for clinical practice and end-of-life communication training initiatives.
Efficacy of dehydroepiandrosterone to overcome the effect of ovarian ageing (DITTO): a proof of principle randomised controlled trial protocol
Authors: Jayaprakasan Kannamannadiar , Narkwichean Amarin , Maalouf Walid E , Campbell Bruce K 
Published: October 2014

IntroductionDehydroepiandrosterone (DHEA) has been proposed to improve pregnancy rates in women with diminished ovarian reserve undergoing in vitro fertilisation (IVF) treatment. However, evidence regarding its efficacy is supported by a limited number of randomised controlled trials (RCTs). This double-blinded RCT aims to measure the effect of DHEA supplementation prior to and during controlled ovarian hyperstimulation on ovarian response prior to IVF treatment in women predicted to have poor ovarian reserve.Methods and analysisSixty women with ovarian antral follicle count ≤10 and serum anti-Mullerian hormone ≤5 pmol/L undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment at the Nurture fertility clinic, Nottingham will be recruited. They will be randomised to either receive DHEA capsule 75 mg/day or placebo for at least 12 weeks before egg collection. All participants will undergo standard long down regulation protocol using human menopausal gonadotropin 300 IU/day. Serum samples and follicular fluids at the time of egg collection will be collected for hormonal immunoassays. For ICSI participants, cumulus cells stripped from oocyte will be collected for cumulus gene expression analyses regarding oocyte competence. Microdrops of oocyte culture media before the time of ICSI will be assessed for glucose, pyruvate and lactate utilisation. Embryo transfer will be performed on day 2, 3 or 5 based on the number and quality of the embryos available. Pregnancy will be defined as urine pregnancy test positive (biochemical pregnancy) and 6–8 weeks ultrasound scan with fetal heart beat (clinical pregnancy) and live birth. It is planned to perform the molecular and nutritional fingerprint analyses in batches after finishing the clinical phase of the study.Ethics and disseminationThe approval of the study was granted by the NHS Research Ethics Committee (Ref number NRES 12/EM/0002), the Medicines and Healthcare products Regulatory Agency (MHRA), and the Nottingham University Hospitals Trust Research and Development department. All participants shall provide written informed consent before being randomised into allocated treatment groups.Trial registration numberProtocol V.2.0; EudraCT number: 2011-002425-21;http://www.clinicaltrials.gov;NCT01572025; CTA reference: 03057/0053/001-0002
Discontinuing Inappropriate Medication in Nursing Home Residents (DIM-NHR Study): protocol of a cluster randomised controlled trial
Authors: Wouters Hans , Quik Elise H , Boersma Froukje , Nygård Peder , Bosman Judith , Böttger Wendelien M , Mulder Hans , Maring Jan-Gerard , Wijma-Vos Linda , Beerden Tim , van Doormaal Jasperien , Postma Maarten J , Zuidema Sytse U , Taxis Katja 
Published: October 2014

IntroductionNursing home residents often have a high number of comorbidities resulting in polypharmacy. Inappropriate prescribing is therefore likely to occur, which in turn is expected to worsen cognitive impairment, to increase the fall risk and to decrease residents’ quality of life. The objective of the ‘Discontinuing Inappropriate Medication in Nursing Home Residents’ (DIM-NHR) study is to examine the efficacy and cost-effectiveness of the Multidisciplinary Multistep Medication Review (3MR) that is aimed at optimising prescribing and discontinuing inappropriate medication.MethodsA cluster randomised controlled trial will be conducted. Elderly care physicians and their wards (clusters) will be randomised. Data will be collected at baseline and 4 months after the 3MR has taken place. Six hundred nursing home residents will be recruited of whom more than half are expected to suffer from dementia. The 3MR will be based on consensus criteria and the relevant literature and will be performed by the patient’s elderly care physician in collaboration with a pharmacist.AnalysisPrimary outcomes—the difference in proportion of residents who successfully discontinuedinappropriatemedication between the intervention and control group at follow-up.Secondary outcomes—undertreatment, exposure to anticholinergic and sedative medicines, neuropsychiatric symptoms, cognitive function, falls, hospital admission, quality of life and cost-effectiveness.Ethics and disseminationParticipant burden will be kept at a minimum. The elderly care physician will remain free to adjust medication when symptoms relapse or adverse events occur, rendering serious adverse events highly unlikely. Study findings will be published in peer-reviewed journals and a 3MR toolkit will be developed.Trial registration numberThis study has been registered athttp://www.ClinicalTrials.gov(trial registration number:NCT01876095)
Sonic hedgehog signalling proteins are frequently expressed in retinoblastoma and are associated with aggressive clinicopathological features
Authors: Choe Ji-Young , Yun Ji Yun , Jeon Yoon Kyung , Kim Se Hoon , Choung Ho-Kyung , Oh Sohee , Park Mira , Kim Ji Eun 
Published: October 2014

AimsThis study aimed to examine the expression of Sonic hedgehog (SHH) signalling proteins in retinoblastoma and to evaluate its clinical significance.MethodsSeventy-nine enucleated retinoblastoma tumours were investigated immunohistochemically using antibodies against SHH pathway proteins, such as SHH, glioma-associated oncogene homologue (GLI) 1, GLI2, GLI3 and ABC binding cassette G2 (ABCG2). Western blotting of SHH signalling proteins was performed in two retinoblastoma cell lines.ResultsSHH was expressed in most retinoblastoma cases (78 of 79, 98.7%), with 21 cases (26.6%) showing strong expression. GLI1 and GLI2 were also frequently expressed: 67 of 78 cases (85.9%) and 71 of 77 cases (92.2%), respectively. GLI3, a transcriptional repressor, was expressed at low levels in 23 of the 78 cases (29.5%). High ABCG2 expression was found in 23 of the 78 cases (29.5%). High expression levels of these proteins in retinoblastoma cell lines were confirmed by western blotting. The expression of SHH was associated with advanced stages, local invasion and metastasis (all p<0.05).ConclusionsSHH signalling molecules were frequently expressed in retinoblastoma tumour cells, and high SHH expression was closely related to an advanced disease status. Our results suggest that the SHH signalling pathway may play a role in the progression of retinoblastoma.
CD47 in the Tumor Microenvironment Limits Cooperation between Antitumor T-cell Immunity and Radiotherapy
Authors: Soto-Pantoja David R. , Terabe Masaki , Ghosh Arunima , Ridnour Lisa A. , DeGraff William G. , Wink David A. , Berzofsky Jay A. , Roberts David D. 
Published: October 2014

AbstractAlthough significant advances in radiotherapy have increased its effectiveness in many cancer settings, general strategies to widen the therapeutic window between normal tissue toxicity and malignant tumor destruction would still offer great value. CD47 blockade has been found to confer radioprotection to normal tissues while enhancing tumor radiosensitivity. Here, we report that CD47 blockade directly enhances tumor immunosurveillance by CD8+ T cells. Combining CD47 blockade with irradiation did not affect fibrosarcoma growth in T cell–deficient mice, whereas adoptive transfer of tumor-specific CD8+ T cells restored combinatorial efficacy. Furthermore, ablation of CD8+ T cells abolished radiotherapeutic response in immunocompetent syngeneic hosts. CD47 blockade in either target cells or effector cells was sufficient to enhance antigen-dependent CD8+ CTL-mediated tumor cell killing in vitro. In CD47-deficient syngeneic hosts, engrafted B16 melanomas were 50% more sensitive to irradiation, establishing that CD47 expression in the microenvironment was sufficient to limit tumor radiosensitivity. Mechanistic investigations revealed increased tumor infiltration by cytotoxic CD8+ T cells in a CD47-deficient microenvironment, with an associated increase in T cell–dependent intratumoral expression of granzyme B. Correspondingly, an inverse correlation between CD8+ T-cell infiltration and CD47 expression was observed in human melanomas. Our findings establish that blocking CD47 in the context of radiotherapy enhances antitumor immunity by directly stimulating CD8+ cytotoxic T cells, with the potential to increase curative responses. Cancer Res; 74(23); 6771–83. ©2014 AACR.
Therapeutic Targeting of Cellular Metabolism in Cells with Hyperactive mTORC1: A Paradigm Shift
Authors: Medvetz Doug , Priolo Carmen , Henske Elizabeth P. 
Published: October 2014

Abstract
mTORC1 is an established master regulator of cellular metabolic homeostasis, via multiple mechanisms that include altered glucose and glutamine metabolism, and decreased autophagy. mTORC1 is hyperactive in the human disease tuberous sclerosis complex (TSC), an autosomal dominant disorder caused by germline mutations in the TSC1 or TSC2 gene. In TSC-deficient cells, metabolic wiring is extensively disrupted and rerouted as a consequence of mTORC1 hyperactivation, leading to multiple vulnerabilities, including “addiction” to glutamine, glucose, and autophagy. There is synergy between two rapidly evolving trajectories: elucidating the metabolic vulnerabilities of TSC-associated tumor cells, and the development of therapeutic agents that selectively target cancer-associated metabolic defects. The current review focuses on recent work supporting the targeting of cellular metabolic dysregulation for the treatment of tumors in TSC, with relevance to the many other human neoplasms with mTORC1 hyperactivation. These data expose a fundamental paradox in the therapeutic targeting of tumor cells with hyperactive mTORC1: inhibition of mTORC1 may not represent the optimal therapeutic strategy. Inhibiting mTORC1 “fixes” the metabolic vulnerabilities, results in a cytostatic response, and closes the door to metabolic targeting. In contrast, leaving mTORC1 active allows the metabolic vulnerabilities to be targeted with the potential for a cytocidal cellular response. The insights provided here suggest that therapeutic strategies for TSC and other tumors with activation of mTORC1 are at the verge of a major paradigm shift, in which optimal clinical responses will be accomplished by targeting mTORC1-associated metabolic vulnerabilities without inhibiting mTORC1 itself. Mol Cancer Res; 13(1); 3–8. ©2014 AACR.
Calcium Channel Blockers and Outcomes in Older Patients With Heart Failure and Preserved Ejection Fraction
Authors: Patel Kanan , Fonarow Gregg C. , Ahmed Momanna , Morgan Charity , Kilgore Meredith , Love Thomas E. , Deedwania Prakash , Aronow Wilbert S. , Anker Stefan D. , Ahmed Ali 
Published: October 2014

Background—
Little is known about associations of calcium channel blockers (CCBs) with outcomes in patients with heart failure and preserved ejection fraction (EF).

Methods and Results—
Of the 10 570 hospitalized patients with heart failure and preserved EF, ≥65 years, EF ≥40%, in the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF; 2003–2004), linked to Medicare data (through December 31, 2008), 7514 had no prior history of CCB use. Of these, 815 (11%) patients received new discharge prescriptions for CCBs. Propensity scores for CCB initiation, calculated for each of the 7514 patients, were used to assemble a matched cohort of 1620 (810 pairs) patients (mean age, 80 years; mean EF, 56%; 65% women; 10% black) receiving and not receiving CCBs, balanced on 114 baseline characteristics. The primary composite end point of all-cause mortality or heart failure hospitalization occurred in 82% and 81% of patients receiving and not receiving CCBs (hazard ratio for CCBs, 1.03; 95% confidence interval, 0.92–1.14). Hazard ratios (95% confidence intervals) for all-cause mortality, heart failure hospitalization, and all-cause hospitalization were 1.05 (0.94–1.18), 1.05 (0.91–1.21), and 1.03 (0.93–1.14), respectively. Similar associations were observed when we categorized patients into those receiving amlodipine and nonamlodipine CCBs. Among 7514 prematch patients, multivariable-adjusted and propensity-adjusted hazard ratios (95% confidence interval) for primary composite end point were 1.03 (0.95–1.12) and 1.02 (0.94–1.11), respectively.

Conclusions—
In hospitalized older patients with heart failure, new discharge prescriptions for CCBs had no associations with composite or individual end points of mortality or heart failure hospitalization, regardless of the class of CCBs.
Baroclinic and Barotropic Annular Variability in the Northern Hemisphere
Authors: Thompson David W. J. , Li Ying 
Published: October 2014

Abstract
Large-scale variability in the Northern Hemisphere (NH) circulation can be viewed in the context of three primary types of structures: 1) teleconnection patterns, 2) a barotropic annular mode, and 3) a baroclinic annular mode. The barotropic annular mode corresponds to the northern annular mode (NAM) and has been examined extensively in previous research. Here the authors examine the spatial structure and time-dependent behavior of the NH baroclinic annular mode (NBAM).
The NAM and NBAM have very different signatures in large-scale NH climate variability. The NAM emerges as the leading principal component (PC) time series of the zonal-mean kinetic energy. It dominates the variance in the wave fluxes of momentum, projects weakly onto the eddy kinetic energy and wave fluxes of heat, and can be modeled as Gaussian red noise with a time scale of ~10 days. In contrast, the NBAM emerges as the leading PC time series of the eddy kinetic energy. It is most clearly identified when the planetary-scale waves are filtered from the data, dominates the variance in the synoptic-scale eddy kinetic energy and wave fluxes of heat, and has a relatively weak signature in the zonal-mean kinetic energy and the wave fluxes of momentum. The NBAM is marked by weak but significant enhanced spectral power on time scales of ~20–25 days.
The NBAM is remarkably similar to its Southern Hemisphere counterpart despite the pronounced interhemispheric differences in orography and land–sea contrasts.
Assessing the Impact of the Tropopause on Mountain Waves and Orographic Precipitation Using Linear Theory and Numerical Simulations
Authors: Siler Nicholas , Durran Dale 
Published: October 2014

Abstract
The partial reflection of mountain waves at the tropopause has been studied extensively for its contribution to downslope windstorms, but its impact on orographic precipitation has not been addressed. Here linear theory and numerical simulations are used to investigate how the tropopause affects the vertical structure of mountain waves and, in turn, orographic precipitation. Relative to the no-tropopause case, wave-induced ascent above the windward slope of a two-dimensional ridge is found to be enhanced or diminished depending on the ratio of the tropopause height to the vertical wavelength of the mountain waves—defined here as the “nondimensional tropopause height” . In idealized simulations of flow over both two-dimensional and three-dimensional ridges, variations in are found to modulate the precipitation rate by roughly a factor of 2 under typical atmospheric conditions. The sensitivity of precipitation to is related primarily to the depth of windward ascent but also to the location and strength of leeside descent, with significant impacts on the distribution of precipitation across the range (i.e., the rain-shadow effect). Using a modified version of Smith and Barstad’s orographic precipitation model, variations in are found to produce significant rain-shadow variability in the Washington Cascades, perhaps explaining some of the variability in rain-shadow strength observed among Cascade storms.
Diagnostics for Near-Surface Wind Response to the Gulf Stream in a Regional Atmospheric Model*
Authors: Takatama Kohei , Minobe Shoshiro , Inatsu Masaru , Small R. Justin 
Published: October 2014

Abstract
The mechanisms acting on near-surface winds over the Gulf Stream are diagnosed using 5-yr outputs of a regional atmospheric model. The diagnostics for the surface-layer momentum vector, its curl, and its convergence are developed with a clear separation of pressure adjustment from downward momentum inputs from aloft in the surface-layer system. The results suggest that the downward momentum mixing mechanism plays a dominant role in contributing to the annual-mean climatological momentum curl, whereas the pressure adjustment mechanism plays a minor role. In contrast, the wind convergence is mainly due to the pressure adjustment mechanism. This can be explained by the orientation of background wind to the sea surface temperature front. The diagnostics also explain the relatively strong seasonal variation in surface-layer momentum convergence and the small seasonal variation in curl. Finally, the surface-layer response to other western boundary currents is examined using a reanalysis dataset.
Retrieval of Hourly Records of Surface Hydrometeorological Variables Using Satellite Remote Sensing Data
Authors: Moghim Sanaz , Bowen Andrew Jay , Sarachi Sepideh , Wang Jingfeng 
Published: October 2014

Abstract
A new algorithm is formulated for retrieving hourly time series of surface hydrometeorological variables including net radiation, sensible heat flux, and near-surface air temperature aided by hourly visible images from the Geostationary Operational Environmental Satellite (GOES) and in situ observations of mean daily air temperature. The algorithm is based on two unconventional, recently developed methods: the maximum entropy production model of surface heat fluxes and the half-order derivative–integral model that has been tested previously. The close agreement between the retrieved hourly variables using remotely sensed input and the corresponding field observations indicates that this algorithm is an effective tool in remote sensing of the earth system.
Evidence-based medicine and myocardial protection — where is the evidence?
Authors: Ferguson ZG , Yarborough DE , Jarvis BL , Sistino JJ 
Published: October 2014

Objective: Myocardial protection with cardioplegia is an integral component of most cardiac surgical procedures, providing protection of the heart by limiting metabolic activity and increasing the myocardium’s capacity to withstand ischemia for prolonged periods of time. Cardioplegia has greatly affected the landscape of cardiothoracic surgery since its introduction in the 1960s, but, to this day, there continues to be a debate over what the ideal cardioplegic solution should be. The goal of this analysis is to describe current practices in cardioplegia and to point out the lack of quality human research and subsequent publications that prevent best practices from being utilized. Methods: This study is a systematic review of journal publications pertaining to the composition of commonly used cardioplegic solutions. Four main types of cardioplegia were assessed to give a narrower field of examination; specifically, microplegia, del Nido, Custodiol HTK, and 4:1 blood cardioplegia. Other combinations of cardioplegia, including St. Thomas’s Solution and the University of Wisconsin (UW) Solution, were considered when applicable according to the context of the publication being reviewed. Factors being assessed consisted of scientific validity, nature of the test subject (isolated organ vs. animal vs. human studies), experimental setup (retrospective trials vs. randomized clinical trials) and patient outcomes. Results: There are very few randomized clinical trials with human subjects comparing commonly used cardioplegic solutions. Numerous retrospective studies exist, but often show similar intraoperative and postoperative outcomes between the solutions. Some solutions, del Nido cardioplegia in particular, were found to have few or no significant human trials to back the rigor required in such a highly specialized field as cardiovascular surgery. A wide variation in the types of surgeries and primary outcomes were included in the publications, so it is difficult to perform an accurate systematic review of the topic. Conclusion: Uniform variables among different studies would be preferable for analysis of this topic; thus, it is the researchers’ recommendation that the collection of multicenter data be undertaken in order to more fully answer this research question. Comparative effectiveness studies to associate commonly used solutions are needed. Without this research, surgeon preference remains the primary determining factor for deciding which cardioplegic solution to use. Cardioplegia selection should rely more on higher scientific research, using evidenced-based medicine and ranking of clinical studies.
Soluble factors from colonic epithelial cells contribute to gut homeostasis by modulating macrophage phenotype
Authors: Kristek Maja , Collins Laura E , DeCourcey Joseph , McEvoy Fiona A , Loscher Christine E 
Published: October 2014

Intestinal macrophages originate from inflammatory blood monocytes which migrate to the intestine, where they differentiate into anti-inflammatory macrophages through a number of transitional stages. These macrophages typically remain hypo-responsive to commensal bacteria and food Ags in the intestine, yet also retain the ability to react to invading pathogens. In this study we examined the role of epithelial cells in inducing this intestinal macrophage phenotype. Using an in vitro system we showed that, in two-dimensional culture, epithelial cell-derived factors from a murine cell line, CMT-93, are sufficient to induce phenotypic changes in macrophages. Exposure of monocyte-derived macrophages, J774A.1, to soluble factors derived from epithelial cells, induced an altered phenotype similar to that of intestinal macrophages with decreased production of IL-12p40, IL-6 and IL-23 and expression of MHC ІІ and CD80 following TLR ligation. Furthermore, these conditioned macrophages showed enhanced phagocytic activity in parallel with low respiratory burst and NO production, similar to the response seen in intestinal macrophages. Our findings suggest a role for colonic epithelial cells in modulation of macrophage phenotype for maintenance of gut homeostasis. Further understanding of the cell interactions that maintain homeostasis in the gut could reveal novel therapeutic strategies to restore the balance in disease.