bluuebunny/crossref_metadata_2025_split huggingface dataset:
Living with advanced cancer and an uncertain disease trajectory: an emerging patient population in palliative care?
Authors: Lobb Elizabeth A , Lacey Judith , Kearsley John , Liauw Winston , White Lesley , Hosie Annmarie 
Published: January 2013

ObjectiveThis study explored how patients diagnosed with advanced cancer cope with an uncertain disease trajectory.Subjects27 patients with advanced cancer and with a prognosis of 12 months or more were recruited from the medical/radiation oncology and palliative care service at three metropolitan hospitals.MethodsA semistructured face-to-face interview was conducted. Interviews were audio-taped and transcribed verbatim. Data analysis was based on Grounded Theory using the constant comparison method.ResultsResults indicate that patients cope by avoidance, remaining positive, maintaining as normal a life as possible, minimising the impact of the disease on their daily lives, comparing themselves favourably with others in a similar situation and focusing on the outcome of treatment to control disease progression. Most did not wish to discuss prognosis or have detailed information on disease progression.ConclusionsParticipants in this study represent an emerging cancer patient population who are receiving palliative therapies. While they have incurable cancer, they self-report as clinically well, they describe a good quality of life and the trajectory of their disease, while unpredictable, may extend over many months to years. Our study suggests that a flexible model of care is needed to support the needs of people who may still be receiving some form of chemotherapy and/or radiotherapy, and remain well. This model may need to take more of an intermittent approach, that is, as required for specific symptom management, rather than patients being linked continuously to a palliative care service for long periods of time.
Deficiency of Phospholipase A2 Group 7 Decreases Intestinal Polyposis and Colon Tumorigenesis in ApcMin/+ Mice
Authors: Xu Changxin , Reichert Ethan C. , Nakano Tomoyuki , Lohse Mariah , Gardner Alison A. , Revelo Mónica P. , Topham Matthew K. , Stafforini Diana M. 
Published: January 2013

Abstract
Platelet-activating factor (PAF) is a naturally occurring phospholipid that mediates diverse effects such as physiological and pathological inflammation, immunosuppression, and cancer. Several lines of evidence support both positive and negative roles for PAF in carcinogenesis. PAF stimulates cell growth, oncogenic transformation, and metastasis, but can also limit proliferation and induce apoptosis. The biological context and microenvironment seem to define whether PAF has pro- or anticarcinogenic effects. To investigate the role of exacerbated PAF signaling in colon cancer, we conducted cell-based and in vivo studies using genetically engineered mice lacking expression of phospholipase A2 group 7 (PLA2G7), an enzyme that specifically metabolizes PAF and structurally related glycerophospholipids. Absence of Pla2g7 robustly decreased intestinal polyposis and colon tumor formation in ApcMin/+ mice, suggesting an antitumorigenic role for PAF in settings characterized by aberrant function of the tumor suppressor Adenomatous polyposis coli (Apc). In colonic epithelial cells, exposure to a PAF analog led to dephosphorylation of Akt at serine-473 and induction of apoptosis. The mechanism of this response involved formation of a complex between β-arrestin 1 and the Akt phosphatase PHLPP2, and activation of the intrinsic pathway of apoptosis. Our results suggest that strategies based on inhibiting PLA2G7 activity or increasing PAF-mediated signaling hold promise for the treatment of intestinal malignancies that harbor mutations in APC. Cancer Res; 73(9); 2806–16. ©2013 AACR.
Efficacy, Safety, Pharmacokinetics, and Biomarkers of Cediranib Monotherapy in Advanced Hepatocellular Carcinoma: A Phase II Study
Authors: Zhu Andrew X. , Ancukiewicz Marek , Supko Jeffrey G. , Sahani Dushyant V. , Blaszkowsky Lawrence S. , Meyerhardt Jeffrey A. , Abrams Thomas A. , McCleary Nadine Jackson , Bhargava Pankaj , Muzikansky Alona , Sheehan Susan , Regan Eileen , Vasudev Eamala , Knowles Michelle , Fuchs Charles S. , Ryan David P. , Jain Rakesh K. , Duda Dan G. 
Published: January 2013

Abstract
Purpose: We conducted a single-arm phase II study of cediranib, a pan-VEGFR tyrosine kinase inhibitor, in patients with advanced hepatocellular carcinoma (HCC).
Experimental Design: Patients with histologically confirmed measurable advanced HCC and adequate hematologic, hepatic, and renal functions received cediranib 30-mg orally once daily (4 weeks/cycle). The primary endpoint was progression-free survival (PFS) rate at 3 months. Other endpoints included response rates, overall survival (OS), pharmacokinetics (PK), and biomarkers for cediranib.
Results: Cediranib treatment resulted in an estimated 3-month PFS rate of 77% (60%, 99%). Median PFS was 5.3 (3.5,9.7) months, stable disease was seen in 5/17 patients (29%), and median OS was 11.7 (7.5–13.6) months. Grade 3 toxicities included hypertension (29%), hyponatremia (29%), and hyperbilirubinemia (18%). Cediranib PK were comparable to those seen in cancer patients with normal hepatic function. Plasma levels of VEGF and PlGF increased and sVEGFR1, sVEGFR2, and Ang-2 decreased after cediranib treatment. PFS was inversely correlated with baseline levels of VEGF, sVEGFR2, and bFGF and with on-treatment levels of bFGF and IGF-1, and directly associated with on-treatment levels of IFN-γ. OS was inversely correlated with baseline levels of sVEGFR1, Ang-2, TNF-α, CAIX, and CD34+CD133+CD45dim circulating progenitor cells and on-treatment levels of sVEGFR2.
Conclusions: Despite the limitations of primary endpoint selection, cediranib at 30-mg daily showed a high incidence of toxicity and preliminary evidence of antitumor activity in advanced HCC. Hepatic dysfunction did not seem to affect the steady-state PK of cediranib. Exploratory studies suggested proangiogenic and inflammatory factors as potential biomarkers of anti-VEGF therapy in HCC. Clin Cancer Res; 19(6); 1557–66. ©2013 AACR.
CPEB1 Regulates the Expression of MTDH/AEG-1 and Glioblastoma Cell Migration
Authors: Kochanek Dawn M. , Wells David G. 
Published: January 2013

Abstract
Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) is an mRNA-binding protein present in both neurons and glia. CPEB1 is capable of both repressing mRNA translation and activating it depending upon its phosphorylation state. CPEB1-bound mRNAs are held in translational dormancy until CPEB1 is phosphorylated, leading to the cytoplasmic polyadenylation of the bound mRNA that triggers translation. Here, we show that CPEB1 can bind to and regulate translation of the mRNA-encoding metadherin (MTDH, also known as AEG-1 and Lyric) in the rat glioblastoma cell line CNS1. MTDH/AEG-1 is being revealed as a critical signaling molecule in tumor progression, playing roles in invasion, metastasis, and chemoresistance. By using a mutant of CPEB1 that cannot be phosphorylated (thereby holding target mRNAs in translational arrest), we show that inhibiting CPEB1-mediated translation blocks MTDH/AEG-1 expression in vitro and inhibits glioblastomas tumor growth in vivo. CPEB1-mediated translation is likely to impact several signaling pathways that may promote tumor progression, but we present evidence suggesting a role in directed cell migration in glioblastoma cells. In addition, reporter mRNA containing CPEB1-binding sites is transported to the leading edge of migrating cells and translated, whereas the same mRNA with point mutations in the binding sites is synthesized perinuclearly. Our findings show that CPEB1 is hyperactive in rat glioblastoma cells and is regulating an important cohort of mRNAs whose increased translation is fueling the progression of tumor proliferation and dispersal in the brain. Thus, targeting CPEB1-mediated mRNA translation might be a sound therapeutic approach. Mol Cancer Res; 11(2); 149–60. ©2012 AACR.
Genome-Wide Association Study Identifies Novel Loci Associated With Concentrations of Four Plasma Phospholipid Fatty Acids in the De Novo Lipogenesis Pathway
Authors: Wu Jason H.Y. , Lemaitre Rozenn N. , Manichaikul Ani , Guan Weihua , Tanaka Toshiko , Foy Millennia , Kabagambe Edmond K. , Djousse Luc , Siscovick David , Fretts Amanda M. , Johnson Catherine , King Irena B. , Psaty Bruce M. , McKnight Barbara , Rich Stephen S. , Chen Yii-Der I. , Nettleton Jennifer A. , Tang Weihong , Bandinelli Stefania , Jacobs David R. , Browning Brian L. , Laurie Cathy C. , Gu Xiangjun , Tsai Michael Y. , Steffen Lyn M. , Ferrucci Luigi , Fornage Myriam , Mozaffarian Dariush 
Published: January 2013

Background—
Palmitic acid (16:0), stearic acid (18:0), palmitoleic acid (16:1n-7), and oleic acid (18:1n-9) are major saturated and monounsaturated fatty acids that affect cellular signaling and metabolic pathways. They are synthesized via de novo lipogenesis and are the main saturated and monounsaturated fatty acids in the diet. Levels of these fatty acids have been linked to diseases including type 2 diabetes mellitus and coronary heart disease.

Methods and Results—

Genome-wide association studies were conducted in 5 population-based cohorts comprising 8961 participants of European ancestry to investigate the association of common genetic variation with plasma levels of these 4 fatty acids. We identified polymorphisms in 7 novel loci associated with circulating levels of ≥1 of these fatty acids.
ALG14
(asparagine-linked glycosylation 14 homolog) polymorphisms were associated with higher 16:0 (
P
=2.7×10
−11
) and lower 18:0 (
P
=2.2×10
−18
).
FADS1
and
FADS2
(desaturases) polymorphisms were associated with higher 16:1n-7 (
P
=6.6×10
−13
) and 18:1n-9 (
P
=2.2×10
−32
) and lower 18:0 (
P
=1.3×10
−20
).
LPGAT1
(lysophosphatidylglycerol acyltransferase) polymorphisms were associated with lower 18:0 (
P
=2.8×10
−9
).
GCKR
(glucokinase regulator;
P
=9.8×10
−10
) and
HIF1AN
(factor inhibiting hypoxia-inducible factor-1;
P
=5.7×10
−9
) polymorphisms were associated with higher 16:1n-7, whereas
PKD2L1
(polycystic kidney disease 2-like 1;
P
=5.7×10
−15
) and a locus on chromosome 2 (not near known genes) were associated with lower 16:1n-7 (
P
=4.1×10
−8
).

Conclusions—
Our findings provide novel evidence that common variations in genes with diverse functions, including protein-glycosylation, polyunsaturated fatty acid metabolism, phospholipid modeling, and glucose- and oxygen-sensing pathways, are associated with circulating levels of 4 fatty acids in the de novo lipogenesis pathway. These results expand our knowledge of genetic factors relevant to de novo lipogenesis and fatty acid biology.
Procedural Safety and Predictors of Acute Outcome of Intracoronary Administration of Progenitor Cells in 775 Consecutive Procedures Performed for Acute Myocardial Infarction or Chronic Heart Failure
Authors: De Rosa Salvatore , Seeger Florian H. , Honold Jörg , Fischer-Rasokat Ulrich , Lehmann Ralf , Fichtlscherer Stephan , Schächinger Volker , Dimmeler Stefanie , Zeiher Andreas M. , Assmus Birgit 
Published: January 2013

Background—
Cell-based therapies are a promising option in patients with acute myocardial infarction or chronic heart failure (CHF). However, administration of cells requires intracoronary or intracardiac instrumentation, which is potentially associated with periprocedural risks. Therefore, we analyzed periprocedural complications and 30-day outcome in 775 consecutive procedures of intracoronary administration of progenitor cells using the stop-flow technique.

Methods and Results—

Indications for cell administration were acute myocardial infarction (n=126) and CHF of ischemic (n=562) or nonischemic (n=87) etiology. Vessel injury was observed in a total of 9 procedures (1.2%) and could be promptly managed by additional progenitor cell injection (PCI) in all but 1 case. No procedural deaths were observed. A periprocedural increase in troponin T was observed in 3.2% of the CHF procedures, in which no concomitant PCI was performed and troponin levels were not elevated before the procedure. Independent significant predictors of troponin T increase were higher New York Heart Association (NYHA) class (NYHA I versus NYHA IV;
P
=0.01; NYHA I versus III;
P
=0.19; NYHA I versus II;
P
=0.55), concomitant revascularization (
P
<0.01), presence of elevated troponin T before the procedure (
P
<0.01), and peripheral occlusive disease (
P
=0.04). At 30 days, there were 4 deaths (0.5%), 1 stroke (0.13%), 8 acute myocardial infarctions (1%), and 5 hospitalizations for exacerbation of heart failure (0.64%).

Conclusions—
Intracoronary infusion of progenitor cells can be performed with adequate safety in patients with acute myocardial infarction or CHF, because the safety profile was similar to what is usually expected from a coronary angiogram in the present cohort.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00962364, NCT00284713, and NCT00289822.
Intra-arterial Cell Transplantation Provides Timing-Dependent Cell Distribution and Functional Recovery After Stroke
Authors: Ishizaka Shunsuke , Horie Nobutaka , Satoh Katsuya , Fukuda Yuhtaka , Nishida Noriyuki , Nagata Izumi 
Published: January 2013

Background and Purpose—
Intra-arterial cell transplantation offers a novel therapeutic strategy for stroke; however, it remains unclear how the timing of cell administration affects cell distribution, brain repair processes, and functional recovery. Here, we investigate the hypothesis that the timing of cell transplantation changes the behavior of the cell graft and the host environment in a way that affects functional recovery.

Methods—
Rats received human mesenchymal stem cells via the internal carotid artery at 1, 4, or 7 days (D1, D4, or D7) after middle cerebral artery occlusion and reperfusion. Animals were euthanized at various time points to assess cell distribution, infiltration of activated microglia, expression of brain-derived neurotrophic factor, reactive astrocytes, angiogenesis, and functional recovery.

Results—
Human mesenchymal stem cells were widely distributed both in the peri-infarct and core in D1, and dominantly in the peri-infarct in D4. Very few cells were observed on D7. At day 7 poststroke, microglia activation was significantly suppressed in both the peri-infarct and core in D1, and predominantly in the peri-infarct in D4. At day 21 poststroke, brain-derived neurotrophic factor was widely distributed throughout the peri-infarct in D1 and D4, along with many reactive astrocytes and considerable angiogenesis. Motor function improved earlier in D1 and later in D4, but no recovery was obtained in D7.

Conclusions—
Our results indicate that intra-arterial cell transplantation provides timing-dependent cell distribution and poststroke functional recovery via a combination of neuroprotection, reactive astrocyte enhancement, and angiogenesis.
Short-Term Dose–Response Characteristics of 2-Iminobiotin Immediately Postinsult in the Neonatal Piglet After Hypoxia-Ischemia
Authors: Bjorkman S. Tracey , Ireland Zoe , Fan Xiyong , van der Wal Willem M. , Roes Kit C.B. , Colditz Paul B. , Peeters-Scholte Cacha M.P.C.D. 
Published: January 2013

Background and Purpose—
To determine the optimal dose of 2-iminobiotin (2-IB) for the treatment of moderate to severe asphyxia in a neonatal piglet model of hypoxia-ischemia.

Methods—
Newborn piglets were subjected to a 30-minute hypoxia-ischemia insult and randomly treated with vehicle or 2-IB (0.1 mg/kg, 0.2 mg/kg, or 1.0 mg/kg). aEEG background and seizure activity were scored after hypoxia-ischemia every 4 h until 24 h and at 48 h and neurobehavioral scores were obtained. Brain tissue was collected and processed for analysis of caspase-3 activity, histology, and tyrosine nitration.

Results—
A dose range of 0.1 to 1.0 mg/kg/dose of 2-IB improved short-term outcome as demonstrated by an increased survival with a normal aEEG and decreased nitrotyrosine staining in the 2-IB–treated animals, indicating decreased cellular damage. Neurobehavior, caspase-3 activity in thalamus, and histology scores were not significantly different.

Conclusions—
Based on survival with a normal aEEG, 0.2 mg/kg 2-IB is likely to be the most appropriate dose for use in future clinical trials in neonates with perinatal hypoxia-ischemia.
Effects of Institutional Caseload of Subarachnoid Hemorrhage on Mortality
Authors: McNeill Lisa , English Shane W. , Borg Nicholas , Matta Basil F. , Menon David K. 
Published: January 2013

Background and Purpose—
Procedures requiring specific skill sets often have been shown to depend on institutional volume, that is, centers receiving a higher volume observe better outcomes in those patients. This relationship recently has been shown to exist for subarachnoid hemorrhage(SAH) patients in a large study in the United States. We aim to examine this relationship for SAH patients in England, restricting analysis to specialist neurosurgical units.

Methods—
Aggregate counts of patients with SAH in 25 specialist neuroscience centers in England, from 2005 to 2011, were obtained from the Hospital Episode Statistics database maintained by the National Health Service Information Center. These data were linked with national mortality statistics to obtain counts of deaths. Poisson regression was used to investigate the relationship between institutional caseload of SAH and 6-month mortality from any cause. Six-month mortality rates and mortality ratios were computed.

Results—

Annual institutional caseload of admissions with SAH was inversely related to 6-month mortality (
P
=0.009;
r
2
=0.26). Each 100-patient increase in annual patient volume was associated with a 24% reduction in mortality (adjusted mortality ratio, 0.76; confidence interval, 0.67–0.87). This relationship was consistent across the entire range of annual institutional caseloads examined (29–367 cases for the lowest and highest volumes seen in a single center in 1 year).

Conclusions—
Our results provide support for management of SAH at high-volume centers and suggest that health care policy in this setting should pursue regionalization while ensuring an adequate geographic spread of access to care.
Spatial Remapping in the Audio-tactile Ventriloquism Effect: A TMS Investigation on the Role of the Ventral Intraparietal Area
Authors: Renzi Chiara , Bruns Patrick , Heise Kirstin-Friederike , Zimerman Maximo , Feldheim Jan-Frederik , Hummel Friedhelm C. , Röder Brigitte 
Published: January 2013

AbstractPrevious studies have suggested that the putative human homologue of the ventral intraparietal area (hVIP) is crucially involved in the remapping of tactile information into external spatial coordinates and in the realignment of tactile and visual maps. It is unclear, however, whether hVIP is critical for the remapping process during audio-tactile cross-modal spatial interactions. The audio-tactile ventriloquism effect, where the perceived location of a sound is shifted toward the location of a synchronous but spatially disparate tactile stimulus, was used to probe spatial interactions in audio-tactile processing. Eighteen healthy volunteers were asked to report the perceived location of brief auditory stimuli presented from three different locations (left, center, and right). Auditory stimuli were presented either alone (unimodal stimuli) or concurrently to a spatially discrepant tactile stimulus applied to the left or right index finger (bimodal stimuli), with the hands adopting either an uncrossed or a crossed posture. Single pulses of TMS were delivered over the hVIP or a control site (primary somatosensory cortex, SI) 80 msec after trial onset. TMS to the hVIP, compared with the control SI-TMS, interfered with the remapping of touch into external space, suggesting that hVIP is crucially involved in transforming spatial reference frames across audition and touch.
Panda Diplomacy: The Cutest Part of China’s Public Diplomacy
Authors: Hartig Falk 
Published: January 2013

Summary
In late 2011 and early 2012, the People’s Republic of China drew on its most unique diplomatic tool: the giant panda. Although this phenomenon is widely covered by the global media, the practice of panda diplomacy is only barely discussed in diplomatic or international relations studies. This article uses the most recent revival of this diplomatic practice for a closer analysis and locates it as a special version of animal diplomacy within the frame of public diplomacy. It first argues that panda diplomacy is — besides all the efforts to promote and support animal conservation and biological research — a political undertaking, which is symbolically used by the Chinese government to win hearts and minds in selected foreign countries. Second, it highlights an important aspect of some Chinese public diplomacy initiatives, namely China’s ability to integrate international partners in its attempts to shape its global image.
Neural Network and Multiple Linear Regression for Estimating Surface Albedo from ASTER Visible and Near-Infrared Spectral Bands
Authors: Mokhtari Mohammad H. , Busu Ibrahim , Mokhtari Hossein , Zahedi Gholamreza , Sheikhattar Leila , Movahed Mohammad A. 
Published: January 2013

Abstract
The current Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER)-based broadband albedo model requires shortwave infrared bands 5 (2.145–2.185 nm), 6 (2.185–2.225 nm), 8 (2.295–2.365 nm), and 9 (2.360–2.430 nm) and visible/near-infrared bands 1 (0.52–0.60 nm) and 3 (0.78–0.86 nm). However, because of sensor irregularities at high temperatures, shortwave infrared wavelengths are not recorded in the ASTER data acquired after April 2008. Therefore, this study seeks to evaluate the performance of artificial neural networks (ANN) in estimating surface albedo using visible/near-infrared bands available in the data obtained after April 2008. It also compares the outcomes with the results of multiple linear regression (MLR) modeling. First, the most influential spectral bands used in the current model as well as band 2 (0.63–0.69 nm) (which is also available after April 2008 in the visible/near-infrared part) were determined by a primary analysis of the data acquired before April 2008. Then, multiple linear regression and ANN models were developed by using bands with a relatively high level of contribution. The results showed that bands 1 and 3 were the most important spectral ones for estimating albedo where land cover consisted of soil and vegetation. These two bands were used as the study input, and the albedo (estimated through a model that utilized bands 1, 3, 5, 6, 8, and 9) served as a target to remodel albedo. Because of its high collinearity with band 1, band 2 was identified less effectively by MLR as well as ANN. The study confirmed that a combination of bands 1 and 3, which are available in the current ASTER data, could be modeled through ANN and MLR to estimate surface albedo. However, because of its higher accuracy, ANN method was superior to MLR in developing objective functions.