bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mediastinectomy for management of chronic pyogranulomatous pleural disease in dogs
Authors: Trinterud T. , Nelissen P. , Caine A. R. , White R. A. S. 
Published: April 2014

The medical records of 12 dogs with chronic pyogranulomatous pleural disease unresponsive to medical management were reviewed retrospectively. Resection of the mediastinal pleura (mediastinectomy) was performed through a median sternotomy to remove all diseased and surgically accessible mediastinal pleural tissue. Dogs were re‐examined two weeks postoperatively, and long‐term outcome was evaluated by contacting owners by phone. Twelve dogs underwent mediastinectomy; additional surgeries included subtotal pericardiectomy (8), lung lobectomy (4) and partial diaphragmatic resection (2). Histology of resected tissue consistently revealed neutrophilic, pyogranulomatous cellulitis/serositis. Foreign material was evident in the mediastinal tissue of five dogs and microorganisms were recovered from three dogs. Two dogs developed pneumothorax immediately postoperatively; one dog developed haemothorax one month postoperatively and was euthanased. Median follow‐up time was eight months (range: 6–43 months); eleven dogs were alive and considered to be symptom‐free by their owners. Mediastinectomy resulted in complete resolution of symptoms in most dogs (92 per cent) and was associated with a low incidence of major complications. The results of this study indicated that mediastinectomy results in favourable outcome for dogs with chronic pleural pyogranulomatous pleural disease unresponsive to medical management.
Analytic Models of SSD Write Performance
Authors: Desnoyers Peter 
Published: April 2014

Solid-state drives (SSDs) update data by writing a new copy, rather than overwriting old data, causing prior copies of the same data to be
invalidated
. These writes are performed in units of
pages
, while space is reclaimed in units of multipage
erase blocks
, necessitating copying of any remaining valid pages in the block before reclamation. The efficiency of this cleaning process greatly affects performance under random workloads; in particular, in SSDs, the write bottleneck is typically internal media throughput, and
write amplification
due to additional internal copying directly reduces application throughput.

We present the first nearly-exact closed-form solution for write amplification under greedy cleaning for uniformly-distributed random traffic, validate its accuracy via simulation, and show that its inaccuracies are negligible for reasonable block sizes and overprovisioning ratios. In addition, we also present the first models which predict performance degradation for both LRW (least-recently-written) cleaning and greedy cleaning under simple nonuniform traffic conditions; simulation results show the first model to be exact and the second to be accurate within 2%. We extend the LRW model to arbitrary combinations of random traffic and demonstrate its use in predicting cleaning performance for real-world workloads.
Using these analytic models, we examine the strategy of separating “hot” and “cold” data, showing that for our traffic model, such separation eliminates any loss in performance due to nonuniform traffic. We then show how a system which segregates hot and cold data into different block pools may shift free space between these pools in order to achieve improved performance, and how numeric methods may be used with our model to find the optimum operating point, which approaches a write amplification of 1.0 for increasingly skewed traffic. We examine online methods for achieving this optimal operating point and show a control strategy based on our model which achieves high performance for a number of real-world block traces.
Endothelial Cell-Secreted EGF Induces Epithelial to Mesenchymal Transition and Endows Head and Neck Cancer Cells with Stem-like Phenotype
Authors: Zhang Zhaocheng , Dong Zhihong , Lauxen Isabel S. , Filho Manoel Sant'Ana , Nör Jacques E. 
Published: April 2014

AbstractEmerging evidence suggests that endothelial cell-secreted factors contribute to the pathobiology of squamous cell carcinoma (SCC) by enhancing invasive migration and resistance to anoikis. Here, we report that SCC cells within the perivascular niche have undergone epithelial to mesenchymal transition (EMT) in a primary human SCC of a patient that developed distant metastases. Endothelial cell–secreted EGF induced EMT of human SCC cells in vitro and also induced acquisition of a stem-like phenotype. In vivo, tumor xenografts vascularized with EGF-silenced endothelial cells exhibited a smaller fraction of cancer stem-like cells (ALDH+CD44+) and were less invasive than tumors vascularized with control endothelial cells. Collectively, these results demonstrated that endothelial cell-EGF induces EMT and acquisition of stem-like properties by head and neck tumor cells. On this basis, we suggest that vascular endothelial cells contribute to tumor dissemination by secreting factors that endow carcinoma cells with enhanced motility and stemness. Cancer Res; 74(10); 2869–81. ©2014 AACR.
LEO1 Is Regulated by PRL-3 and Mediates Its Oncogenic Properties in Acute Myelogenous Leukemia
Authors: Chong Phyllis S.Y. , Zhou Jianbiao , Cheong Lip-Lee , Liu Shaw-Cheng , Qian Jingru , Guo Tiannan , Sze Siu Kwan , Zeng Qi , Chng Wee Joo 
Published: April 2014

Abstract
PRL-3, an oncogenic dual-specificity phosphatase, is overexpressed in 50% of acute myelogenous leukemia (AML) and associated with poor survival. We found that stable expression of PRL-3 confers cytokine independence and growth advantage of AML cells. However, how PRL-3 mediates these functions in AML is not known. To comprehensively screen for PRL3-regulated proteins in AML, we performed SILAC-based quantitative proteomics analysis and discovered 398 significantly perturbed proteins after PRL-3 overexpression. We show that Leo1, a component of RNA polymerase II–associated factor (PAF) complex, is a novel and important mediator of PRL-3 oncogenic activities in AML. We described a novel mechanism where elevated PRL-3 protein increases JMJD2C histone demethylase occupancy on Leo1 promoter, thereby reducing the H3K9me3 repressive signals and promoting Leo1 gene expression. Furthermore, PRL-3 and Leo1 levels were positively associated in AML patient samples (N = 24; P &lt; 0.01). On the other hand, inhibition of Leo1 reverses PRL-3 oncogenic phenotypes in AML. Loss of Leo1 leads to destabilization of the PAF complex and downregulation of SOX2 and SOX4, potent oncogenes in myeloid transformation. In conclusion, we identify an important and novel mechanism by which PRL-3 mediates its oncogenic function in AML. Cancer Res; 74(11); 3043–53. ©2014 AACR.
Zoledronic Acid Has Differential Antitumor Activity in the Pre- and Postmenopausal Bone MicroenvironmentIn Vivo
Authors: Ottewell Penelope D. , Wang Ning , Brown Hannah K. , Reeves Kimberly J. , Fowles C. Anne , Croucher Peter I. , Eaton Colby L. , Holen Ingunn 
Published: April 2014

AbstractPurpose: Clinical trials in early breast cancer have suggested that benefits of adjuvant bone-targeted treatments are restricted to women with established menopause. We developed models that mimic pre- and postmenopausal status to investigate effects of altered bone turnover on growth of disseminated breast tumor cells. Here, we report a differential antitumor effect of zoledronic acid (ZOL) in these two settings.Experimental design: Twleve-week-old female Balb/c-nude mice with disseminated MDA-MB-231 breast tumor cells in bone underwent sham operation or ovariectomy (OVX), mimicking the pre- and postmenopausal bone microenvironment, respectively. To determine the effects of bone-targeted therapy, sham/OVX animals received saline or 100 μg/kg ZOL weekly. Tumor growth was assessed by in vivo imaging and effects on bone by real-time PCR, micro-CT, histomorphometry, and measurements of bone markers. Disseminated tumor cells were detected by two-photon microscopy.Results: OVX increased bone resorption and induced growth of disseminated tumor cells in bone. Tumors were detected in 83% of animals following OVX (postmenopausal model) compared with 17% following sham operation (premenopausal model). OVX had no effect on tumors outside of bone. OVX-induced tumor growth was completely prevented by ZOL, despite the presence of disseminated tumor cells. ZOL did not affect tumor growth in bone in the sham-operated animals. ZOL increased bone volume in both groups.Conclusions: This is the first demonstration that tumor growth is driven by osteoclast-mediated mechanisms in models that mimic post- but not premenopausal bone, providing a biologic rationale for the differential antitumor effects of ZOL reported in these settings. Clin Cancer Res; 20(11); 2922–32. ©2014 AACR.
Treatment Response Evaluation Using 18F-FDOPA PET in Patients with Recurrent Malignant Glioma on Bevacizumab Therapy
Authors: Schwarzenberg Johannes , Czernin Johannes , Cloughesy Timothy F. , Ellingson Benjamin M. , Pope Whitney B. , Grogan Tristan , Elashoff David , Geist Cheri , Silverman Daniel H.S. , Phelps Michael E. , Chen Wei 
Published: April 2014

Abstract
Purpose: This study compares the value of 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (18F-FDOPA) positron emission tomography (PET) and MRI in assessing outcome during antiangiogenic treatment in patients with recurrent high-grade gliomas.
Experimental Design: Thirty patients were prospectively studied with 18F-FDOPA PET scans immediately before, and two and six weeks after start of bevacizumab therapy. 18F-FDOPA metabolic tumor volumes (MTV) as well as max and mean standardized uptake values (SUV) within this MTV were obtained. MRI treatment response was assessed at six weeks. The predictive ability of 18F-FDOPA PET and MRI response assessment were evaluated with regard to progression-free survival (PFS) and overall survival (OS).
Results: A total of 30, 28, and 24 18F-FDOPA PET scans at baseline, two weeks, and six weeks, were available for analysis, respectively. 18F-FDOPA PET SUVs as well as their changes through therapy were not predictive of outcome. However, MTV parameters such as MTV changes were highly prognostic. Interestingly, absolute MTV at the first follow up scan provides the most significant prediction for increased OS (P &lt; 0.0001) as well as PFS (P = 0.001). This surprising result was scrutinized with cross-validation and simulation analysis. Responders based on 18F-FDOPA PET data survived 3.5 times longer (12.1 months vs. 3.5 months, median OS, P &lt; 0.001) than nonresponders (17 patients vs. 11 patients, respectively). In comparison, responders based on MRI data lived 1.5 times longer (11.4 months vs 7.7 months, P = 0.03) than nonresponders (22 patients vs. 7 patients, respectively).
Conclusions: 18F-FDOPA PET identifies treatment responders to antiangiogenic therapy as early as two weeks after treatment initiation. Clin Cancer Res; 20(13); 3550–9. ©2014 AACR.
KRAS Mutation Status Is Associated with Enhanced Dependency on Folate Metabolism Pathways in Non–Small Cell Lung Cancer Cells
Authors: Moran Diarmuid M. , Trusk Patricia B. , Pry Karen , Paz Keren , Sidransky David , Bacus Sarah S. 
Published: April 2014

Abstract
KRAS gene mutation is linked to poor prognosis and resistance to therapeutics in non–small cell lung cancer (NSCLC). In this study, we have explored the possibility of exploiting inherent differences in KRAS-mutant cell metabolism for treatment. This study identified a greater dependency on folate metabolism pathways in KRAS mutant compared with KRAS wild-type NSCLC cell lines. Microarray gene expression and biologic pathway analysis identified higher expression of folate metabolism– and purine synthesis–related pathways in KRAS-mutant NSCLC cells compared with wild-type counterparts. Moreover, pathway analysis and knockdown studies suggest a role for MYC transcriptional activity in the expression of these pathways in KRAS-mutant NSCLC cells. Furthermore, KRAS knockdown and overexpression studies demonstrated the ability of KRAS to regulate expression of genes that comprise folate metabolism pathways. Proliferation studies demonstrated higher responsiveness to methotrexate, pemetrexed, and other antifolates in KRAS-mutant NSCLC cells. Surprisingly, KRAS gene expression is downregulated in KRAS wild-type and KRAS-mutant cells by antifolates, which may also contribute to higher efficacy of antifolates in KRAS-mutant NSCLC cells. In vivo analysis of multiple tumorgraft models in nude mice identified a KRAS-mutant tumor among the pemetrexed-responsive tumors and also demonstrated an association between expression of the folate pathway gene, methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), and antifolate activity. Collectively, we identify altered regulation of folate metabolism in KRAS-mutant NSCLC cells that may account for higher antifolate activity in this subtype of NSCLC. Mol Cancer Ther; 13(6); 1611–24. ©2014 AACR.
Husserl and the Question of Animality
Authors: Di Martino Carmine 
Published: April 2014

Abstract
Is it possible to speak of a Husserlian phenomenology of the animal? In his phenomenological analyses, Husserl thematizes animals as a case of “abnormality” in order to investigate the subjectivity that constitutes the human world as a normal world. With respect to other perspectives—such as the Heideggerian one—which imply a drastic separation from animality, Husserl’s standpoint has the advantage of keeping a path of communication open between the phenomenological and the scientific investigation of the problem, in the multifarious forms taken on today by the latter. However, what is the original contribution of phenomenology on this issue, in comparison with that of the empirical sciences? Phenomenology addresses the experience of lifeworld as its own field of activity and as the implicit ground for every scientific observation and reconstruction. Phenomenology, thus, provides a new approach to animal life, avoiding naive ontological assumptions about it.
A Simple Model of the Northeast Pacific Stratocumulus to Cumulus Transition Based on the Climatological Surface Energy Budget
Authors: Karlsson Johannes , Teixeira João 
Published: April 2014

Abstract
Air advected equatorward by the trade winds off the coast of California is associated with decreasing cloud cover and is subjected to increasingly warmer sea surface temperatures. These gradients imply large gradients in the surface energy fluxes. Based on the surface energy balance and on the assumption of a small net surface energy flux, which is supported by reanalysis data, a cloud cover model of the climatological stratocumulus to cumulus transition in the northeastern subtropical Pacific Ocean is developed. Using climatological meteorological surface variables, the model, despite its simplicity, is able to describe the transition from stratocumulus to cumulus reasonably well in terms of cloud cover.
The ‘constant size neighbourhood trap’ in accessibility and health studies
Authors: Vallée Julie , Le Roux Guillaume , Chaix Basile , Kestens Yan , Chauvin Pierre 
Published: April 2014

In literature on neighbourhood effects and resources accessibility, the number of neighbourhood resources to which residents may have access are often estimated from spatial units whose constant size fails to account for unique ways residents experience their neighbourhoods. To investigate this ‘constant size neighbourhood trap’, we compared numbers of healthcare resources included in Constant Size Buffers (CSBs) and in Perceived Neighbourhood Polygons (PNPs) from cognitive neighbourhood data collected among 653 residents of the Paris metropolitan area. We observed that residents of deprived and peripheral areas had smaller PNPs than their counterparts. Studying residents assessments of the quantity of neighbourhood practitioners, we then assessed the validity of using PNPs rather than CSBs to estimate number of neighbourhood resources. Lastly, resource inequalities across the Paris metropolitan area were found to be far wider when considering PNPs rather than CSBs. Using constant neighbourhood delineation can lead to inaccurately measured individual accessibility to neighbourhood resources and to downplay the extent of inequalities in urban resources.
An integrative review of dignity in end-of-life care
Authors: Guo Qiaohong , Jacelon Cynthia S 
Published: April 2014

Background: Dying with dignity is regarded as a goal of quality end-of-life care. However, the meaning of dying with dignity is ambiguous, and no comprehensive synthesis of the existing literature has been published. Aim: To synthesize the meaning of dying with dignity and to identify common aspects of dignity in end-of-life care. Design: This is an integrative review article. Methodological strategies specific to the integrative review method proposed by Whittemore and Knafl were followed to conduct data analysis. The matrix method was used to summarize characteristics of included articles. Data sources: Five electronic databases were searched in October 2012, with no date restriction: PubMed, CINAHL, PsycINFO, Academic Search Premier, and Social Sciences Abstracts. Theoretical reports, and both qualitative and quantitative empirical reports, focused on dignity in end-of-life care were included. Results: Themes of dying with dignity are as follows: a human right, autonomy and independence, relieved symptom distress, respect, being human and being self, meaningful relationships, dignified treatment and care, existential satisfaction, privacy, and calm environment. Factors influencing dignity include demographic, illness-related, and treatment-/care-related factors, as well as communication. Models of dignity in end-of-life care and instruments to measure dignity were reported. Interventions to support dignity stressed physical, psychological, and spiritual supports not only to dying patients but also to family members. Conclusion: This review clarified the meaning of dying with dignity and synthesized common aspects of dignity in end-of-life care. Further research is needed to evaluate the meaning of dying with dignity across cultures and to explore individualized dignity-based care.
Stressful life-events in childhood and risk of multiple sclerosis: a Danish nationwide cohort study
Authors: Nielsen Nete Munk , Pedersen Bo V , Stenager Egon , Koch-Henriksen Nils , Frisch Morten 
Published: April 2014

Background: Current knowledge concerning the association between exposure to stressful life-events (SFLEs) in childhood and later risk of multiple sclerosis (MS) is sparse. Objectives: We studied the associations between SFLEs in childhood and subsequent risk of MS in a nationwide cohort of 2.9 million Danes born from 1968 to 2011. Methods: A SFLE in childhood was defined as exposure before age 18 years to parental divorce, parental death, or death of a sibling, using information from the Danish Civil Registration System. MS cases in the cohort were identified in the Danish Multiple Sclerosis Registry. Associations of SFLE with MS risk were evaluated by incidence rate ratios (RR) of MS obtained in log-linear Poisson regression models. Results: Persons exposed to any SFLE in childhood were at 11% elevated risk of MS (RR = 1.11; 95% confidence interval: 1.03–1.20), compared to non-exposed persons. Stratification by subtype of SFLE showed that parental death and death of a sibling were not associated with MS risk. However, persons exposed to parental divorce were at 13% increased risk of developing MS compared to non-exposed (RR = 1.13; 1.04–1.23). Conclusions: Associations of SFLEs in childhood with risk of MS are weak. However, parental divorce is somehow associated with modestly increased risk of MS.
Open Fracture Dislocation of the Talus With Total Extrusion
Authors: Dumbre Patil Sampat Shivajirao , Abane Sachin Ramdas , Dumbre Patil Vaishali Sampat , Nande Prasanna Narendra 
Published: April 2014

Open fractures with complete extrusion of talus are high-energy injuries. While treating these injuries, union of the fracture, vascularity of the body, and possibility of infection are main issues predicting less favorable outcomes. At present, there are no recommended treatment protocols for the management of such injuries. Early debridement, wound care, anatomic reduction, and adequate fixation are key factors in the management of compound injuries of the talus. There are few reports in the literature on successful reimplantation of talus when it is completely extruded. Encouraging functional outcomes of reimplantation of extruded talus suggest that excision of the talus with or without tibiocalcaneal fusion should be kept as a salvage procedure. We report a case of a farmer who sustained fracture of the talar neck. Both head and body fragments were completely extruded from the wound on the anterolateral aspect of the ankle. The patient was treated 18 hours postinjury. Thorough debridement of wound and bony fragments was done. Talus was reimplanted and fixation was performed with Kirschner wires. At 3-year follow-up, satisfactory functional outcome was noted with AOFAS (American Orthopaedic Foot and Ankle Society) score of 83 and MOXFQ (Manchester–Oxford Foot Questionnaire) scale score of 23. The purpose of presenting this case is to demonstrate the successful outcome of reimplantation of talus. Level of Evidence: Therapeutic, Level IV: Case study
Glycemic effects of vildagliptin in patients with type 2 diabetes before, during and after the period of fasting in Ramadan
Authors: Malha Line P. , Taan Ghazi , Zantout Mira S. , Azar Sami T. 
Published: April 2014

Objective To study the incidence of hypoglycemia, glycemic control and body weight changes in patients with type 2 diabetes treated with vildagliptin and metformin versus another group treated with sulphonylureas and metformin during and after the period of fasting in Ramadan. Patients and methods This is a randomized open-label clinical trial that recruited 69 patients previously treated with a combination therapy of metformin and sulphonylurea. Patients in the control group were maintained on their usual metformin and sulphonylurea regimen with dose adjustment for the fasting period. Patients in the study group were given vildagliptin 50 mg twice daily (at Suhur and at Iftar). One group remained on the previous background therapy unchanged and the other group was switched from sulphonylurea to vildagliptin in combination with metformin. Four visits were scheduled, one before the beginning of Ramadan (baseline), a second visit at mid Ramadan, a third at the end of Ramadan and a final visit 1 month after the end of Ramadan. At every visit, patients were assessed for hypoglycemic events and patient education was given on lifestyle needs and hypoglycemia monitoring and management. Results The calculated change in hemoglobin A1c from baseline to last visit was similar for both groups. The incidence of hypoglycemia during Ramadan was higher in the control group (26 episodes versus 19 episodes in the study group); this result was not statistically significant ( p = 0.334). However, the number of patients who dropped out from the study because of discomfort due to treatment and fear of hypoglycemia was higher in the control group. Conclusion For patients who insist on observing the fast, physicians can allow it only with close follow up and monitoring for hypoglycemic events, and vildagliptin may be a better agent than sulphonylurea.