bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgen Receptor Splice Variants Dimerize to Transactivate Target Genes
Authors: Xu Duo , Zhan Yang , Qi Yanfeng , Cao Bo , Bai Shanshan , Xu Wei , Gambhir Sanjiv S. , Lee Peng , Sartor Oliver , Flemington Erik K. , Zhang Haitao , Hu Chang-Deng , Dong Yan 
Published: June 2015

Abstract
Constitutively active androgen receptor splice variants (AR-V) lacking the ligand-binding domain have been implicated in the pathogenesis of castration-resistant prostate cancer and in mediating resistance to newer drugs that target the androgen axis. AR-V regulates expression of both canonical AR targets and a unique set of cancer-specific targets that are enriched for cell-cycle functions. However, little is known about how AR-V controls gene expression. Here, we report that two major AR-Vs, termed AR-V7 and ARv567es, not only homodimerize and heterodimerize with each other but also heterodimerize with full-length androgen receptor (AR-FL) in an androgen-independent manner. We found that heterodimerization of AR-V and AR-FL was mediated by N- and C-terminal interactions and by the DNA-binding domain of each molecule, whereas AR-V homodimerization was mediated only by DNA-binding domain interactions. Notably, AR-V dimerization was required to transactivate target genes and to confer castration-resistant cell growth. Our results clarify the mechanism by which AR-Vs mediate gene regulation and provide a pivotal pathway for rational drug design to disrupt AR-V signaling as a rational strategy for the effective treatment of advanced prostate cancer. Cancer Res; 75(17); 3663–71. ©2015 AACR.
Refining the Mantle Cell Lymphoma Paradigm: Impact of Novel Therapies on Current Practice
Authors: Avivi Irit , Goy Andre 
Published: June 2015

AbstractAlthough mantle cell lymphoma (MCL) is a rare subtype of non–Hodgkin lymphoma, proactive research efforts fueled by challenges in the management of MCL have led to an increase in median overall survival (OS) of 2.5 years in the mid 1990s to beyond 5 years nowadays. This improvement is due mostly to the use of dose-intensive strategies, particularly cytarabine-containing regimens [with or without high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) consolidation], which are associated with deeper remission (and higher molecular complete response rate), as well as better salvage therapies. Along this line, MCL became the first lymphoma for which four novel agents have been approved in the relapsed/refractory setting: temsirolimus, lenalidomide, ibrutinib, and bortezomib (the last agent approved both in relapsed/refractory disease and in first-line combination therapy). In addition, the use of rituximab maintenance has helped reduce relapse rates and improve outcome. However, in routine practice (i.e., outside clinical trials), the outcome of MCL remains overall unchanged with standard immunochemotherapy, and even after HDT-ASCT, most patients still relapse and frequently develop chemoresistance. The persistent lack of consensus for the treatment of MCL explains the rather impressive variability in management of these patients. The integration of newer therapies, either in combination with immunochemotherapy or as consolidation/maintenance postinduction, offers new opportunities for patients with MCL. This review highlights how such developments can help refine the current MCL paradigm. Clin Cancer Res; 21(17); 3853–61. ©2015 AACR.
Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis
Authors: Moe Sharon M. , Chertow Glenn M. , Parfrey Patrick S. , Kubo Yumi , Block Geoffrey A. , Correa-Rotter Ricardo , Drüeke Tilman B. , Herzog Charles A. , London Gerard M. , Mahaffey Kenneth W. , Wheeler David C. , Stolina Maria , Dehmel Bastian , Goodman William G. , Floege Jürgen 
Published: June 2015

Background—
Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events.

Methods and Results—
This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69–0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50–0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37–0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48–0.99).

Conclusions—
Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00345839.
Anticoagulation strategies and difficulties in neonatal and paediatric extracorporeal membrane oxygenation (ECMO)
Authors: Stocker Christian F , Horton Stephen B 
Published: June 2015

Objective: The aim of this review is to highlight an emerging problem with anticoagulation-related complications in neonatal and paediatric ECMO, to explore for flaws in the currently recommended anticoagulation management responsible for these problems and to discuss possible strategies mitigating further escalation of the issue. Data Sources: Pertinent neonatal and paediatric literature on the topic of interest and international Extracorporeal Life Support Organisation (ELSO) registry data request. Conclusions: The international ELSO registry data reveals increasing rates of anticoagulation-related complications during neonatal and paediatric ECMO worldwide. The causes are multifactorial and the proposed solution to the problem is to match anticoagulation management to the pathophysiological complexity of haemostasis on ECMO.
Expressing care in narratives about occupations
Authors: Taylor Jackie 
Published: June 2015

Introduction Engagement in occupations impacts on wellbeing, but this relationship needs to be better understood by occupational therapists. A focus on the meanings of occupations, rather then their purpose, might help further this understanding. Being meaningful, an occupation enables the individual to participate in society in a way that reflects personal and societal values. This paper explores how people can express personal values and caring in the narratives that they tell about leisure occupations. Method Seventeen serious leisure enthusiasts were interviewed and encouraged to talk about their chosen occupation. Narratives were extracted from the transcripts and analysed, giving attention to content, structure and interaction. Those narratives that appeared to have a meaning associated with caring were examined further in order to establish the types of caring that they revealed. Findings Thirty-one narratives were found to have a meaning associated with values or caring, relating either to a moral struggle, caring close to home or caring further afield. Conclusion For some individuals, the meaningfulness of their leisure occupations lies, in part, in using them as a vehicle to express care towards themself, towards others or towards the environment. This has implications for the uses of occupations in therapy.
Survival in cats with primary and secondary cardiomyopathies
Authors: Spalla Ilaria , Locatelli Chiara , Riscazzi Giulia , Santagostino Sara , Cremaschi Elena , Brambilla Paola 
Published: June 2015

Objectives Feline cardiomyopathies (CMs) represent a heterogeneous group of myocardial diseases. The most common CM is hypertrophic cardiomyopathy (HCM), followed by restrictive cardiomyopathy (RCM). Studies comparing survival and outcome for different types of CM are scant. Furthermore, little is known about the cardiovascular consequences of systemic diseases on survival. The aim of this retrospective study was to compare survival and prognostic factors in cats affected by HCM, RCM or secondary CM referred to our institution over a 10 year period. Methods The study included 94 cats with complete case records and echocardiographic examination. Fifty cats presented HCM, 14 RCM and 30 secondary CM. Results A statistically significant difference in survival time was identified for cats with HCM (median survival time of 865 days), RCM (273 days) and secondary CM (<50% cardiac death rate). In the overall population and in the primary CM group (HCM + RCM), risk factors in the multivariate analysis, regardless of the CM considered, were the presence of clinical signs, an increased left atrial to aortic root (LA/Ao) ratio and a hypercoagulable state. Conclusions and relevance Primary CMs in cats share some common features (ie, LA dimension and hypercoagulable state) linked to feline cardiovascular physiology, which influence survival greatly in end-stage CM. The presence of clinical signs has to be regarded as a marker of disease severity, regardless of the underlying CM. Secondary CMs are more benign conditions, but if the primary disease is not properly managed, the prognosis might also be poor in this group of patients.
Overexpression of microRNA-155 increases IL-21 mediated STAT3 signaling and IL-21 production in systemic lupus erythematosus
Authors: Rasmussen Tue Kruse , Andersen Thomas , Bak Rasmus Otkjær , Yiu Gloria , Sørensen Christian Møller , Stengaard-Pedersen Kristian , Mikkelsen Jacob Giehm , Utz Paul Joseph , Holm Christian Kanstrup , Deleuran Bent 
Published: June 2015

Abstract
Introduction
Interleukin (IL)-21 is a key cytokine in autoimmune diseases such as systemic lupus erythematosus (SLE) by its regulation of autoantibody production and inflammatory responses. The objective of this study is to investigate the signaling capacity of IL-21 in T and B cells and assess its possible regulation by microRNA (miR)-155 and its target gene suppressor of cytokine signaling 1 (SOCS1) in SLE.

Methods
The signaling capacity of IL-21 was quantified by stimulating peripheral blood mononuclear cells (PBMCs) with IL-21 and measuring phosphorylation of STAT3 (pSTAT3) in CD4+ T cells, B cells, and natural killer cells. Induction of miR-155 by IL-21 was investigated by stimulating purified CD4+ T cells with IL-21 and measuring miR-155 expression levels. The functional role of miR-155 was assessed by overexpressing miR-155 in PBMCs from SLE patients and healthy controls (HCs) and measuring its effects on STAT3 and IL-21 production in CD4+ and CD8+ T cells.

Results
Induction of pSTAT3 in CD4+ T cells in response to IL-21 was significantly decreased in SLE patients compared to HCs (p < 0.0001). Further, expression levels of miR-155 were significantly decreased and SOCS1 correspondingly increased in CD4+ T cells from SLE patients. Finally, overexpression of miR-155 in CD4+ T cells increased STAT3 phosphorylation in response to IL-21 treatment (p < 0.01) and differentially increased IL-21 production in SLE patients compared to HCs (p < 0.01).

Conclusion
We demonstrate that SLE patients have reduced IL-21 signaling capacity, decreased miR-155 levels, and increased SOCS1 levels compared to HCs. The reduced IL-21 signaling in SLE could be rescued by overexpression of miR-155, suggesting an important role for miR-155 in the reduced IL-21 signaling observed in SLE.
The impact of diabetes on cognitive decline: potential vascular, metabolic, and psychosocial risk factors
Authors: Feinkohl Insa , Price Jackie F. , Strachan Mark W.J. , Frier Brian M. 
Published: June 2015

AbstractOlder people with type 2 diabetes are at increased risk of developing cognitive impairment, for which several potential risk factors have been proposed. The present article reviews evidence in people with type 2 diabetes for associations of cognitive impairment with a range of vascular, metabolic, and psychosocial risk factors, many of which have a higher prevalence in people with type 2 diabetes than in non-diabetic adults of a similar age. Definitive research studies in this field are few in number. The risk factors may be involved in causal pathways or may act as useful markers of cerebrovascular damage (or both), and for which relatively consistent evidence is available, include poor glycemic control, hypoglycemia, microvascular disease, inflammation, and depression. For macrovascular disease, the strength of the association with cognitive impairment appears to depend on which vascular system has been examined. A role for pre-morbid ability in young adulthood as influencing the risk of both diabetes and cognitive impairment has also been suggested. The importance of considering inter-relationships between risk factors when investigating their potential contribution to cognitive impairment in future investigations is discussed.
Testing of the voice communication in smart home care
Authors: Vanus Jan , Smolon Marek , Martinek Radek , Koziorek Jiri , Zidek Jan , Bilik Petr 
Published: June 2015

AbstractThis article is aimed to describe the method of testing the implementation of voice control over operating and technical functions of Smart Home Come. Custom control over operating and technical functions was implemented into a model of Smart Home that was equipped with KNX technology. A sociological survey focused on the needs of seniors has been carried out to justify the implementation of voice control into Smart Home Care. In the real environment of Smart Home Care, there are usually unwanted signals and additive noise that negatively affect the voice communication with the control system. This article describes the addition of a sophisticated system for filtering the additive background noise out of the voice communication with the control system. The additive noise significantly lowers the success of recognizing voice commands to control operating and technical functions of an intelligent building. Within the scope of the proposed application, a complex system based on fuzzy-neuron networks, specifically the ANFIS (Adaptive Neuro-Fuzzy Interference System) for adaptive suppression of unwanted background noises was created. The functionality of the designed system was evaluated both by subjective and by objective criteria (SSNR, DTW). Experimental results suggest that the studied system has the potential to refine the voice control of technical and operating functions of Smart Home Care even in a very noisy environment.
FDG-PET findings of Ameloblastoma: a case report
Authors: Seno Satoshi , Kitajima Kazuhiro , Inokuchi Go , Nibu Ken-ichi , Itoh Tomoo , Ejima Yasuo , Sasaki Ryohei , Sugimoto Koji , Sugimura Kazuro 
Published: June 2015

Abstract

Introduction
Ameloblastoma is a benign odontogenic neoplasm of the jaw, rarely presenting as a malignant tumor. Although it is very important to discriminate ameloblastoma from ameloblastic carcinoma in order to decide the appropriate operative procedure, this is difficult using conventional CT and MRI.

Case descriptions
We report a case of maxillar ameloblastoma in a 78-year-old man where FDG-PET/CT was useful for making this discrimination. CT demonstrated a 31 × 43 × 46-mm mass in the left posterior maxillary sinus with destruction of its posterior and lateral wall and alveolar bone. MRI demonstrated a hypo- to isointense heterogeneous pattern on T1WI, heterogeneous hyperintensity with a prominent high-signal spot on T2WI, high signal intensity on DWI reflecting restricted diffusion, and strong heterogeneous enhancement. Because FDG-PET/CT showed mild FDG uptake (SUVmax 2.40) by the mass, ameloblastoma, rather than ameloblastic carcinoma, was considered to be the correct diagnosis.

Discussion and evaluation
It appears that ameloblastic carcinoma shows intense FDG uptake, whereas ameloblastoma shows mild or moderate FDG uptake, and only rarely intense FDG uptake. Our experience suggests that FDG-PET/CT may be effective for discriminating ameloblastoma from ameloblastic carcinoma. Especially, in cases showing mild FDG uptake, benign ameloblastoma would seem the most likely diagnosis.

Conclusions
FDG-PET/CT may be useful as an adjunctive modality for diagnosis, treatment planning and surveillance of ameloblastoma and ameloblastic carcinoma.
Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens
Authors: Niesvizky Ruben , Flinn Ian W. , Rifkin Robert , Gabrail Nashat , Charu Veena , Clowney Billy , Essell James , Gaffar Yousuf , Warr Thomas , Neuwirth Rachel , Zhu Yanyan , Elliott Jennifer , Esseltine Dixie-Lee , Niculescu Liviu , Reeves James 
Published: June 2015

Purpose The US community-based, phase IIIB UPFRONT trial was designed to compare three frontline bortezomib-based regimens in transplantation-ineligible patients with myeloma. Patients and Methods Patients (N = 502) were randomly assigned 1:1:1 to 24 weeks (eight 21-day cycles) of induction with bortezomib-dexamethasone (VD; n = 168; intravenous bortezomib 1.3 mg/m2, days 1, 4, 8, and 11 plus oral dexamethasone 20 mg, days 1, 2, 4, 5, 8, 9, 11, and 12 [cycles 1 to 4], or 1, 2, 4, and 5 [cycles 5 to 8]), bortezomib-thalidomide-dexamethasone (VTD; n = 167; bortezomib and dexamethasone as before plus oral thalidomide 100 mg, days 1 to 21), or bortezomib-melphalan-prednisone (VMP; n = 167; bortezomib as before plus oral melphalan 9 mg/m2 and oral prednisone 60 mg/m2, days 1 to 4, every other cycle), followed by 25 weeks (five 35-day cycles) of bortezomib maintenance (1.6 mg/m2, days 1, 8, 15, and 22). The primary end point was progression-free survival. Results After 42.7 months' median follow-up, median progression-free survival with VD, VTD, and VMP was 14.7, 15.4, and 17.3 months, respectively; median overall survival was 49.8, 51.5, and 53.1 months, with no significant differences among treatments for either end point (global P = .46 and P = .79, respectively, Wald test). Overall response rates were 73% (VD), 80% (VTD), and 70% (VMP). Adverse events were more common with VTD than VD or VMP. Bortezomib maintenance was feasible without producing cumulative toxicity. Conclusion Although all bortezomib-containing regimens produced good outcomes, VTD and VMP did not appear to offer an advantage over VD in transplantation-ineligible patients with myeloma treated in US community practice.
Prospective Cohort Study of Hospital Palliative Care Teams for Inpatients With Advanced Cancer: Earlier Consultation Is Associated With Larger Cost-Saving Effect
Authors: May Peter , Garrido Melissa M. , Cassel J. Brian , Kelley Amy S. , Meier Diane E. , Normand Charles , Smith Thomas J. , Stefanis Lee , Morrison R. Sean 
Published: June 2015

Purpose Previous studies report that early palliative care is associated with clinical benefits, but there is limited evidence on economic impact. This article addresses the research question: Does timing of palliative care have an impact on its effect on cost? Patients and Methods Using a prospective, observational design, clinical and cost data were collected for adult patients with an advanced cancer diagnosis admitted to five US hospitals from 2007 to 2011. The sample for economic evaluation was 969 patients; 256 were seen by a palliative care consultation team, and 713 received usual care only. Subsamples were created according to time to consult after admission. Propensity score weights were calculated, matching the treatment and comparison arms specific to each subsample on observed confounders. Generalized linear models with a γ distribution and a log link were applied to estimate the mean treatment effect on cost within subsamples. Results Earlier consultation is associated with a larger effect on total direct cost. Intervention within 6 days is estimated to reduce costs by −$1,312 (95% CI, −$2,568 to −$56; P = .04) compared with no intervention and intervention within 2 days by −$2,280 (95% CI, −$3,438 to −$1,122; P < .001); these reductions are equivalent to a 14% and a 24% reduction, respectively, in cost of hospital stay. Conclusion Earlier palliative care consultation during hospital admission is associated with lower cost of hospital stay for patients admitted with an advanced cancer diagnosis. These findings are consistent with a growing body of research on quality and survival suggesting that early palliative care should be more widely implemented.
Vibrissal sensitivity in a harbor seal (Phoca vitulina)
Authors: Murphy Christin T. , Reichmuth Colleen , Mann David 
Published: June 2015

Prior efforts to characterize the capabilities of the vibrissal system in seals have yielded conflicting results. Here we measured the sensitivity of the vibrissal system of a harbor seal (Phoca vitulina) to directly coupled sinusoidal stimuli delivered by a vibrating plate. A trained seal was tested in a psychophysical paradigm to determine the smallest velocity that was detectable at nine frequencies ranging from 10 Hz to 1000 Hz. The stimulus plate was driven by a vibration shaker and the velocity of the plate at each frequency-amplitude combination was calibrated with a laser vibrometer. To prevent cueing from other sensory stimuli, the seal was fitted with a blindfold and headphones playing broadband masking noise. The seal was sensitive to vibrations across the range of frequencies tested, with best sensitivity of 0.09 mm/s at 80 Hz. Velocity thresholds as a function of frequency showed a characteristic U-shaped curve with decreasing sensitivity below 20 Hz and above 250 Hz. To ground-truth the experimental setup, four human subjects were tested in the same paradigm using their thumb to contact the vibrating plate. Threshold measurements for the humans were similar to those of the seal, demonstrating comparable tactile sensitivity for their structurally different mechanoreceptive systems. The thresholds measured for the harbor seal in this study were about 100 times more sensitive than previous in-air measures of vibrissal sensitivity for this species. The results were similar to those reported by others for the detection of waterborne vibrations, but show an extended range of frequency sensitivity.