bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal change in quality of life following hospitalisation for acute exacerbations of COPD
Authors: Steer John , Gibson G John , Bourke Stephen C 
Published: January 2015

BackgroundCurrent guidelines for management of patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (COPD) recommend that clinical decisions, including escalation to assisted ventilation, be informed by an estimate of the patients’ likely postdischarge quality of life. There is little evidence to inform predictions of outcome in terms of quality of life, psychological well-being and functional status. Undue nihilism might lead to denial of potentially life-saving therapy, while undue optimism might prolong suffering when alternative palliation would be more appropriate. This study aimed to detail longitudinal changes in quality of life following hospitalisation for acute exacerbations of COPD.MethodsWe prospectively recruited two cohorts (exacerbations requiring assisted ventilation during admission and exacerbations not ventilated). Admission clinical data, and mortality and readmission details were collected. Quality of life, psychological well-being and functional status were formally assessed over the subsequent 12 months. Time-adjusted mean change in quality of life was examined.Results183 patients (82 ventilated; 101 not ventilated) were recruited. On average, overall quality of life improved by a clinically important amount in those not ventilated and did not decline in ventilated patients. Both groups showed clinically important improvements in respiratory symptoms and an individual's sense of control over their condition, despite the tendency for functional status to decline.ConclusionsOn average, postdischarge quality of life improved in non-ventilated and did not decline in ventilated patients. Certain quality of life domains (ie, symptoms and mastery) improved significantly. Better understanding of longitudinal change in postdischarge quality of life should help to inform decision-making.
Short-term and long-term storage stability of heparin plasma ammonia
Authors: Dukic Lora , Simundic Ana-Maria 
Published: January 2015

AimsAmmonia is an extremely unstable analyte and requires special attention during sampling, transport and storage. The aim of this study was to evaluate the stability of ammonia in lithium-heparin plasma during short-term (at +4°C) and long-term (at −20°C) storage.MethodsTwenty plasma samples were used for short-term stability assessment. Each sample was divided into five aliquots and stored in stoppered tubes at +4°C, for 1, 2, 3, 4 and 24 h from initial testing. Fifteen plasma samples were used for long-term stability assessment. Each sample was divided into eight aliquots and stored in stoppered tubes at −20°C for 3, 24, 48 h and 1, 2, 4, 8 and 12 weeks from initial testing. Ammonia concentration was determined on a Beckman Coulter AU2700 chemistry analyser using Randox ammonia enzymatic UV method. Bias was calculated from initial value for each time point and compared with quality specifications defined by Royal College of Pathologists of Australasia.ResultsThe average bias exceeded the total allowable error after storage of samples for 1 h at +4°C and 3 h at −20°C.ConclusionAmmonia is not stable during storage at +4°C and −20°C in lithium-heparinised plasma and should therefore be analysed immediately.
Low IQ has become less important as a risk factor for early disability pension. A longitudinal population-based study across two decades among Swedish men
Authors: Karnehed Nina , Rasmussen Finn , Modig Karin 
Published: January 2015

BackgroundLow IQ has been shown to be an important risk factor for disability pension (DP) but whether the importance has changed over time remains unclear. It can be hypothesised that IQ has become more important for DP over time in parallel with a more demanding working life. The aim of this study was to investigate the relative risk of low IQ on the risk of DP before age 30 between 1971 and 2006.MethodsThis study covered the entire Swedish male population born between 1951 and 1976, eligible for military conscription. Information about the study subjects was obtained by linkage of national registers. Associations between IQ and DP over time were analysed by descriptive measures (mean values, proportions, etc) and by Cox proportional hazards regressions. Analyses were adjusted for educational level.ResultsThe cohort consisted of 1 229 346 men. The proportion that received DP before the age of 30 increased over time, from 0.68% in the cohort born between 1951 and 1955 to 0.95% in the cohort born between 1971 and 1976. The relative risk of low IQ (adjusted for education) in relation to high IQ decreased from 5.68 (95% CI 4.71 to 6.85) in the cohort born between 1951 and 1955 to 2.62 (95% CI 2.25 to 3.05) in the cohort born between 1971 and 1976.ConclusionsOur results gave no support to the idea that the importance of low IQ for the risk of DP has increased in parallel with increasing demands in working life. In fact, low IQ has become less important as a risk factor for DP compared with high IQ between the early 1970s and 1990s. An increased educational level over the same time period is likely to be part of the explanation.
Current challenges in palliative care provision for heart failure in the UK: a survey on the perspectives of palliative care professionals
Authors: Cheang Mun Hong , Rose Gabrielle , Cheung Chi-Chi , Thomas Martin 
Published: January 2015

ObjectivePalliative care (PC) in heart failure (HF) is beneficial and recommended in international HF guidelines. However, there is a perception that PC is underutilised in HF in the UK. This exploratory study aims to investigate, from a PC perspective, this perceived underutilisation and identify problems with current practice that may impact on the provision of PC in HF throughout the UK.MethodsA prospective survey was electronically sent to PC doctors and nurses via the UK Association for Palliative Medicine and adult PC teams listed in the UK Hospice directory.ResultsWe received 499 responses (42%—PC consultants). Although PC provision for patients with HF was widespread, burden on PC services was low (47% received less than 10 referrals annually). While PC was acknowledged to have a role in end-stage HF, there were differing views about the optimal model of care. Levels of interdisciplinary collaboration (58%) and mutual education (36%) were low. There were frequent reports that end-of-life matters were not addressed by cardiology prior to PC referral. Moreover, 24% of respondents experienced difficulties with implantable cardioverter defibrillator deactivation.ConclusionsLow HF referrals despite widespread availability of PC services and insufficient efforts by cardiology to address PC issues may contribute to the perception that PC is underutilised in HF. The challenges facing PC and HF identified here need to be further investigated and addressed. These findings will hopefully promote awareness of PC issues in HF and encourage debate on how to improve PC support for this population.
Patients with diabetes requiring emergency department care for hypoglycaemia: characteristics and long-term outcomes determined from multiple data sources
Authors: Rajendran Rajesh , Hodgkinson David , Rayman Gerry 
Published: January 2015

ABSTRACT

Aim
To triangulate three data sources and report the characteristics and long-term outcomes of patients with diabetes requiring emergency department (ED) care for hypoglycaemia.

Method
Three data sources were used—ambulance electronic records, hospital episode statistics and patient administration system. Hypoglycaemia (capillary blood glucose &lt;4.0 mmol/L)-related attendances to a single hospital's ED between 1 April 2012 and 31 March 2013 were studied.

Results
Using the three sources, there were 165 hypoglycaemia-related attendances in 132 patients with diabetes [type 1–59 episodes in 43 patients, type 2–106 episodes in 89 patients (therapy—54 (51%) insulin, 35 (33%) sulfonylurea, 11 (10%) both, 6 (6%) others)]. At best only 65% of episodes would have been identified were a single data source used. Patients with type 2 vs type 1 diabetes were older (median age 79 vs 61 years, p&lt;0.0001), had more comorbidities (median Charlson comorbidity index (CCI) 4 vs 3, p=0.002) but no difference in HbA1c (median 7.8% vs 8.4%, p=0.065). Compared with insulin-treated type 2 patients with diabetes, sulfonylurea-treated patients (33%) were older (median age 82 vs 76 years, p=0.007), had worse renal function (median estimated glomerular filtration rate 38 vs 56 mL/min/1.73 m2, p=0.019) and lower HbA1c (median 6.7% vs 8.4%, p&lt;0.0001). At least 17 (10%) hypoglycaemic episodes resulted in additional serious harm. The 30-day, 90-day and 1-year all-cause mortality were 10.6% (14), 16.7% (22) and 28% (37), respectively. Age, CCI and hospitalisation were risk factors for long-term mortality.

Conclusions
Dependence on a single data source would have at best identified only 65% of episodes. One-third of episodes were sulfonylurea related in patients with type 2 diabetes, and one-fourth of all patients with diabetes who required ED care for hypoglycaemia died the following year.
ERBB3-Independent Activation of the PI3K Pathway in EGFR-Mutant Lung Adenocarcinomas
Authors: Song Xiaoling , Fan Pang-Dian , Bantikassegn Amlak , Guha Udayan , Threadgill David W. , Varmus Harold , Politi Katerina 
Published: January 2015

Abstract
ERBB3, a member of the EGFR family of receptor tyrosine kinases, has been implicated in activation of the PI3K pathway in human lung adenocarcinomas driven by EGFR mutations. We investigated the contribution of ERBB3 to the initiation, progression, and therapeutic response of EGFR-induced lung adenocarcinomas using tetracycline- and tamoxifen-inducible transgenic mouse models. Deletion of Erbb3 at the time of induction of mutant EGFR had no effect on tumorigenesis, demonstrating that ERBB3 is not required to initiate tumorigenesis. Tumors that developed in the absence of ERBB3 remained sensitive to EGFR tyrosine kinase inhibitors and retained activation of the PI3K–AKT pathway. Interestingly, acute loss of Erbb3 suppressed further growth of established EGFRL858R-mediated lung tumors. Four weeks after deletion of Erbb3, the tumors exhibited phosphorylation of EGFR, of the adaptor proteins GAB1 and GAB2, and of the downstream signaling molecules AKT and ERK, suggesting that alternative signaling pathways could compensate for loss of Erbb3. Similar to our observations with mouse tumors, we found that GAB adaptor proteins play a role in ERBB3-independent activation of the PI3K pathway by mutant EGFR in EGFR-mutant human cell lines. Finally, in such cell lines, increased levels of phosphorylation of ERBB2 or MET were associated with reduced sensitivity to acute loss of ERBB3, suggesting remarkable plasticity in the signaling pathways regulated by mutant EGFR with important therapeutic implications. Cancer Res; 75(6); 1035–45. ©2015 AACR.
Tumorigenic Activity of Merkel Cell Polyomavirus T Antigens Expressed in the Stratified Epithelium of Mice
Authors: Spurgeon Megan E. , Cheng Jingwei , Bronson Roderick T. , Lambert Paul F. , DeCaprio James A. 
Published: January 2015

Abstract
Merkel cell polyomavirus (MCPyV) is frequently associated with Merkel cell carcinoma (MCC), a highly aggressive neuroendocrine skin cancer. Most MCC tumors contain integrated copies of the viral genome with persistent expression of the MCPyV large T (LT) and small T (ST) antigen. MCPyV isolated from MCC typically contains wild-type ST but truncated forms of LT that retain the N-terminus but delete the C-terminus and render LT incapable of supporting virus replication. To determine the oncogenic activity of MCC tumor-derived T antigens in vivo, a conditional, tissue-specific mouse model was developed. Keratin 14-mediated Cre recombinase expression induced expression of MCPyV T antigens in stratified squamous epithelial cells and Merkel cells of the skin epidermis. Mice expressing MCPyV T antigens developed hyperplasia, hyperkeratosis, and acanthosis of the skin with additional abnormalities in whisker pads, footpads, and eyes. Nearly half of the mice also developed cutaneous papillomas. Evidence for neoplastic progression within stratified epithelia included increased cellular proliferation, unscheduled DNA synthesis, increased E2F-responsive genes levels, disrupted differentiation, and presence of a DNA damage response. These results indicate that MCPyV T antigens are tumorigenic in vivo, consistent with their suspected etiologic role in human cancer. Cancer Res; 75(6); 1068–79. ©2015 AACR.
Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205
Authors: Hirata Hiroshi , Hinoda Yuji , Shahryari Varahram , Deng Guoren , Nakajima Koichi , Tabatabai Z. Laura , Ishii Nobuhisa , Dahiya Rajvir 
Published: January 2015

Abstract
Recently, long noncoding RNAs (lncRNA) have emerged as new gene regulators and prognostic markers in several cancers, including renal cell carcinoma (RCC). In this study, we investigated the contributions of the lncRNA MALAT1 in RCC with a specific focus on its transcriptional regulation and its interactions with Ezh2 and miR-205. We found that MALAT1 expression was higher in human RCC tissues, where it was associated with reduced patient survival. MALAT1 silencing decreased RCC cell proliferation and invasion and increased apoptosis. Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos and that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was increased, whereas β-catenin expression was decreased through Ezh2. Reciprocal interaction between MALAT1 and miR-205 was also observed. Lastly, MALAT1 bound Ezh2 and oncogenesis facilitated by MALAT1 was inhibited by Ezh2 depletion, thereby blocking epithelial–mesenchymal transition via E-cadherin recovery and β-catenin downregulation. Overall, our findings illuminate how overexpression of MALAT1 confers an oncogenic function in RCC that may offer a novel theranostic marker in this disease. Cancer Res; 75(7); 1322–31. ©2015 AACR.
FDA Approval: Siltuximab for the Treatment of Patients with Multicentric Castleman Disease
Authors: Deisseroth Albert , Ko Chia-Wen , Nie Lei , Zirkelbach Jeanne F. , Zhao Liang , Bullock Julie , Mehrotra Nitin , Del Valle Pedro , Saber Haleh , Sheth Christopher , Gehrke Brenda , Justice Robert , Farrell Ann , Pazdur Richard 
Published: January 2015

Abstract
On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. The approval was primarily based on the results of a randomized, double-blind trial in which 79 symptomatic patients with MCD were allocated (2:1) to siltuximab plus best supportive care (BSC) or to placebo plus BSC. The primary efficacy endpoint was the proportion of patients in each arm achieving a durable tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure. Tumor response was based on independent review of CT scans using the revised Response Criteria for Malignant Lymphoma, and symptomatic response was defined as complete resolution or stabilization of 34 MCD-related signs and symptoms as reported by the investigator. Thirty-four percent of patients in the siltuximab arm and no patients in the placebo arm met the primary endpoint (P = 0.0012). The most common adverse reactions (&gt;10% compared with placebo) during treatment with siltuximab were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection. Clin Cancer Res; 21(5); 950–4. ©2015 AACR.
Rac1/Pak1/p38/MMP-2 Axis Regulates Angiogenesis in Ovarian Cancer
Authors: Gonzalez-Villasana Vianey , Fuentes-Mattei Enrique , Ivan Cristina , Dalton Heather J. , Rodriguez-Aguayo Cristian , Fernandez-de Thomas Ricardo J. , Aslan Burcu , del C. Monroig Paloma , Velazquez-Torres Guermarie , Previs Rebecca A. , Pradeep Sunila , Kahraman Nermin , Wang Huamin , Kanlikilicer Pinar , Ozpolat Bulent , Calin George , Sood Anil K. , Lopez-Berestein Gabriel 
Published: January 2015

Abstract
Purpose: Zoledronic acid is being increasingly recognized for its antitumor properties, but the underlying functions are not well understood. In this study, we hypothesized that zoledronic acid inhibits ovarian cancer angiogenesis preventing Rac1 activation.
Experimental Design: The biologic effects of zoledronic acid were examined using a series of in vitro [cell invasion, cytokine production, Rac1 activation, reverse-phase protein array, and in vivo (orthotopic mouse models)] experiments.
Results: There was significant inhibition of ovarian cancer (HeyA8-MDR and OVCAR-5) cell invasion as well as reduced production of proangiogenic cytokines in response to zoledronic acid treatment. Furthermore, zoledronic acid inactivated Rac1 and decreased the levels of Pak1/p38/matrix metalloproteinase-2 in ovarian cancer cells. In vivo, zoledronic acid reduced tumor growth, angiogenesis, and cell proliferation and inactivated Rac1 in both HeyA8-MDR and OVCAR-5 models. These in vivo antitumor effects were enhanced in both models when zoledronic acid was combined with nab-paclitaxel.
Conclusions: Zoledronic acid has robust antitumor and antiangiogenic activity and merits further clinical development as ovarian cancer treatment. Clin Cancer Res; 21(9); 2127–37. ©2015 AACR.
Relative Flow Reserve Derived From Quantitative Perfusion Imaging May Not Outperform Stress Myocardial Blood Flow for Identification of Hemodynamically Significant Coronary Artery Disease
Authors: Stuijfzand Wijnand J. , Uusitalo Valtteri , Kero Tanja , Danad Ibrahim , Rijnierse Mischa T. , Saraste Antti , Raijmakers Pieter G. , Lammertsma Adriaan A. , Harms Hans J. , Heymans Martijn W. , Huisman Marc C. , Marques Koen M. , Kajander Sami A. , Pietilä Mikko , Sörensen Jens , Royen Niels van , Knuuti Juhani , Knaapen Paul 
Published: January 2015

Background—
Quantitative myocardial perfusion imaging is increasingly used for the diagnosis of coronary artery disease. Quantitative perfusion imaging allows to noninvasively calculate fractional flow reserve (FFR). This so-called relative flow reserve (RFR) is defined as the ratio of hyperemic myocardial blood flow (MBF) in a stenotic area to hyperemic MBF in a normal perfused area. The aim of this study was to assess the value of RFR in the detection of significant coronary artery disease.

Methods and Results—

From a clinical population of patients with suspected coronary artery disease who underwent oxygen-15–labeled water cardiac positron emission tomography and invasive coronary angiography, 92 patients with single- or 2-vessel disease were included. Intermediate lesions (diameter stenosis, 30%–90%; n=75) were interrogated by FFR. Thirty-eight (41%) vessels were deemed hemodynamically significant (>90% stenosis or FFR ≤0.80). Hyperemic MBF, coronary flow reserve, and RFR were lower for vessels with a hemodynamically significant lesion (2.01±0.78 versus 2.90±1.16 mL·min
−1
·g
−1
;
P
<0.001, 2.27±1.03 versus 3.10±1.29;
P
<0.001, and 0.67±0.23 versus 0.93±0.15;
P
<0.001, respectively). The correlation between RFR and FFR was moderate (
r
=0.54;
P
<0.01). Receiver operator characteristic curve analysis showed an area under the curve of 0.82 for RFR, which was not significantly higher compared with that for hyperemic MBF and coronary flow reserve (0.76;
P
=0.32 and 0.72;
P
=0.08, respectively).

Conclusions—
Noninvasive estimation of FFR by quantitative perfusion positron emission tomography by calculating RFR is feasible, yet only a trend toward a slight improvement of diagnostic accuracy compared with hyperemic MBF assessment was determined.
Diagnostic Accuracy of Stress Myocardial Perfusion Imaging Compared to Invasive Coronary Angiography With Fractional Flow Reserve Meta-Analysis
Authors: Takx Richard A.P. , Blomberg Björn A. , Aidi Hamza El , Habets Jesse , de Jong Pim A. , Nagel Eike , Hoffmann Udo , Leiner Tim 
Published: January 2015

Background—
Hemodynamically significant coronary artery disease is an important indication for revascularization. Stress myocardial perfusion imaging is a noninvasive alternative to invasive fractional flow reserve for evaluating hemodynamically significant coronary artery disease. The aim was to determine the diagnostic accuracy of myocardial perfusion imaging by single-photon emission computed tomography, echocardiography, MRI, positron emission tomography, and computed tomography compared with invasive coronary angiography with fractional flow reserve for the diagnosis of hemodynamically significant coronary artery disease.

Methods and Results—
The meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. PubMed, EMBASE, and Web of Science were searched until May 2014. Thirty-seven studies, reporting on 4721 vessels and 2048 patients, were included. Meta-analysis yielded pooled sensitivity, pooled specificity, pooled likelihood ratios (LR), pooled diagnostic odds ratio, and summary area under the receiver operating characteristic curve. The negative LR (NLR) was chosen as the primary outcome. At the vessel level, MRI (pooled NLR, 0.16; 95% confidence interval [CI], 0.13–0.21) was performed similar to computed tomography (pooled NLR, 0.22; 95% CI, 0.12–0.39) and positron emission tomography (pooled NLR, 0.15; 95% CI, 0.05–0.44), and better than single-photon emission computed tomography (pooled NLR, 0.47; 95% CI, 0.37–0.59). At the patient level, MRI (pooled NLR, 0.14; 95% CI, 0.10–0.18) performed similar to computed tomography (pooled NLR, 0.12; 95% CI, 0.04–0.33) and positron emission tomography (pooled NLR, 0.14; 95% CI, 0.02–0.87), and better than single-photon emission computed tomography (pooled NLR, 0.39; 95% CI, 0.27–0.55) and echocardiography (pooled NLR, 0.42; 95% CI, 0.30–0.59).

Conclusions—
Stress myocardial perfusion imaging with MRI, computed tomography, or positron emission tomography can accurately rule out hemodynamically significant coronary artery disease and can act as a gatekeeper for invasive revascularization. Single-photon emission computed tomography and echocardiography are less suited for this purpose.
Deficiency of Endothelium-Specific Transcription Factor
Sox17
Induces Intracranial Aneurysm
Authors: Lee Seungjoo , Kim Il-Kug , Ahn Jae Sung , Woo Dong-Cheol , Kim Sang-Tae , Song Sukhyun , Koh Gou Young , Kim Hyung-Seok , Jeon Byeong Hwa , Kim Injune 
Published: January 2015

Background—
Intracranial aneurysm (IA) is a common vascular disorder that frequently leads to fatal vascular rupture. Although various acquired risk factors associated with IA have been identified, the hereditary basis of IA remains poorly understood. As a result, genetically modified animals accurately modeling IA and related pathogenesis have been lacking, and subsequent drug development has been delayed.

Methods and Results—

The transcription factor Sox17 is robustly expressed in endothelial cells of normal intracerebral arteries. The combination of
Sox17
deficiency and angiotensin II infusion in mice induces vascular abnormalities closely resembling the cardinal features of IA such as luminal dilation, wall thinning, tortuosity, and subarachnoid hemorrhages. This combination impairs junctional assembly, cell-matrix adhesion, regeneration capacity, and paracrine secretion in endothelial cells of intracerebral arteries, highlighting key endothelial dysfunctions that lead to IA pathogenesis. Moreover, human IA samples showed reduced Sox17 expression and impaired endothelial integrity, further strengthening the applicability of this animal model to clinical settings.

Conclusions—

Our findings demonstrate that
Sox17
deficiency in mouse can induce IA under hypertensive conditions, suggesting
Sox17
deficiency as a potential genetic factor for IA formation. The
Sox17
-deficient mouse model provides a novel platform to develop therapeutics for incurable IA.