bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diplomatic Training and the Challenges Facing the EEAS
Authors: Duke Simon 
Published: January 2012

Summary
Following a difficult birth, the European External Action Service (EEAS) is now a much scrutinized reality. Much of the analysis has concentrated on its quasi-institutional nature, its relations with the principal external action actors in the European Union and beyond, as well as the question of its legal capacity. Relatively little attention, however, has been paid to the important training dimensions, which are critical to the smooth development of the Service, especially considering the disparate backgrounds of EEAS constituents. This article argues that there is no ‘one-size-fits-all’ solution to the training dilemma. Differentiation rather than standardization, within the constraints of a programme (rather than a full-blown European Diplomatic Academy), will be the salient features of the first years of training in the EEAS. It is also argued that training can be a key strategic tool for the Service’s development and, more generally, the external relations of the EU itself.
How do dentists understand evidence and adopt it in practice?
Authors: Sbaraini Alexandra , Carter Stacy M , Evans R Wendell 
Published: January 2012

Although there is now a large evidence-based dentistry literature, previous investigators have shown that dentists often consider research evidence irrelevant to their practice. To understand why this is the case, we conducted a qualitative study. Objective: Our aim was to identify how dentists define evidence and how they adopt it in practice. Methods: A qualitative study using grounded theory methodology was conducted. Ten dentists working in eight dental practices were interviewed about their experience and work processes while adopting evidence-based preventive care. Analysis involved transcript coding, detailed memo writing, and data interpretation. Results: Findings revealed that dentists’ direct observations – referred to as clinical evidence – provided the most tangible and trusted evidence in practice and during discussions with colleagues. Dentists described a detailed process used to gather, compare and implement clinical evidence. This process began when they were exposed to novelty in daily practice and proceeded through self-driven testing, producing clinical or tangible evidence that clinicians could use in practice. Conclusion: Based on these findings, we propose an alternative to the linear form of knowledge transfer commonly represented in the literature.
Coercion in psychiatric care: Can paternalism justify coercion?
Authors: Seo Mi Kyung , Kim Seung Hyun , Rhee MinKyu 
Published: January 2012

Background: It has long been debated whether coercion can be justified as paternalism in the field of mental health and it is still a continuing issue of controversy today. Aims: This study analyses whether coercive intervention in mental health can be justified by the basic assumptions of paternalists: the assumption of incompetence, the assumption of dangerousness and the assumption of impairment. Method: This study involved 248 patients: 158 (63.7%) were diagnosed with schizophrenia and 90 (36.3%) were diagnosed with mood disorder. In this study, experiences of coercion were divided into legal status, subjective (perceived coercion) and objective experiences (experienced coercion). Results: The assumption of incompetence was justified in all three categories of coercion whereas the assumption of dangerousness was not justified in any. The assumption of impairment was not justified in legal status and perceived coercion, but provided a partial explanation to serve as a basis for justifying experienced coercive measures. Conclusions: It can be noted that mental health experts who support paternalism without question must reconsider their previous methods. Above all, the reason why the assumption of dangerousness was not justified in any of the categories of coercion was because coercive intervention used to prevent harm to oneself and others must be very carefully carried out.
Margin Photocoagulation in Laser Surgery for Early Glottic Cancer
Authors: Lucioni Marco , Bertolin Andy , D’Ascanio Luca , Rizzotto Giuseppe 
Published: January 2012

ObjectiveAssess the impact of surgical margin CO2 laser photocoagulation (LPC) on disease local control in patients submitted to endoscopic surgery for early glottic cancer in comparison with subjects treated with laser cordectomy without borders LPC.Study DesignHistorical cohort study.SettingRegional referral cancer center.Subjects and MethodsA total 281 patients with early glottic cancer (T1a, T1b, T2) were treated with endoscopic laser cordectomy according to the European Laryngological Society Classification between 1999 and 2006. Among the patients, 123 (treated between 2003 and 2006) were submitted to postresection LPC of surgical margins (group 1), whereas 158 (operated between 1999 and 2002) underwent laser cordectomy without margin LPC (group 2). Median follow‐up was 51 months (range, 36‐101 months).ResultsLocal recurrence was found in 43 of 281 (15.30%) subjects (18 with T1a, 13 with T1b, 12 with T2). A significant difference in recurrence rate was found among patients treated with margin LPC in comparison with group 2 (P =. 022). In particular, a lower recurrence rate in LPC patients was noticed in case of close (≤1 mm), nondefinable, and positive margins with infiltration of the superficial border. No significant difference was noticed in the case of negative edges (>1 mm) or involvement of either deep margin or both superficial and deep edges.ConclusionsSurgical margin LPC increases disease local control in the case of close and superficial margin positivity. In such cases, no further treatment (surgical revision or radiotherapy) seems to be required in LPC patients. In case of deep border involvement, surgical revision or radiotherapy should be performed.
Osteoarthritis in the cat
Authors: Bennett David , Zainal Ariffin Siti Mariam bt , Johnston Pamela 
Published: January 2012

Practical relevance Osteoarthritis (OA) is very common in the cat and in many cases is associated with significant long-term pain, which limits mobility and activity, and severely compromises the animal’s quality of life. Clinical challenges The treatment of chronic arthritic pain is a major challenge and many analgesic drugs used in other species are not licensed, not available or not tested for use in the cat. Many older cats with painful OA have some degree of chronic kidney disease (CKD) and many clinicians are reluctant to use non-steroidal anti-inflammatory drugs (NSAIDs) in these animals because of the potential for nephrotoxicity. Evidence base There are several publications that show that meloxicam is an effective NSAID for the cat and can be used long-term. It is easy to administer and there is published evidence that meloxicam can actually slow the progression of CKD in this species. Many other drugs are used to treat chronic pain in the cat but there is no documented evidence of their efficacy in OA. Unlike the dog, there is limited evidence for the effectiveness of omega-3 fatty acid-rich diets in managing feline OA and further work is required. There is no published data as yet for the usefulness or otherwise of nutraceuticals (glucosamine and chondroitin) in managing feline OA; studies in the authors’ clinic suggest some pain-relieving effect. Research into environmental enrichment as a way of improving quality of life in cats with painful OA is lacking, but it is an approach worth using where possible. Modifications to the environment (eg, provision of comfortable bedding and ramps) are also important.
A rapid diagnostic test for human regulatory T-cell function to enable regulatory T-cell therapy
Authors: Canavan James B. , Afzali Behdad , Scottà Cristiano , Fazekasova Henrieta , Edozie Francis C. , Macdonald Thomas T. , Hernandez-Fuentes Maria P. , Lombardi Giovanna , Lord Graham M. 
Published: January 2012

AbstractRegulatory T cells (CD4+CD25hiCD127loFOXP3+ T cells [Tregs]) are a population of lymphocytes involved in the maintenance of self-tolerance. Abnormalities in function or number of Tregs are a feature of autoimmune diseases in humans. The ability to expand functional Tregs ex vivo makes them ideal candidates for autologous cell therapy to treat human autoimmune diseases and to induce tolerance to transplants. Current tests of Treg function typically take up to 120 hours, a kinetic disadvantage as clinical trials of Tregs will be critically dependent on the availability of rapid diagnostic tests before infusion into humans. Here we evaluate a 7-hour flow cytometric assay for assessing Treg function, using suppression of the activation markers CD69 and CD154 on responder T cells (CD4+CD25− [Tresp]), compared with traditional assays involving inhibition of CFSE dilution and cytokine production. In both freshly isolated and ex vivo expanded Tregs, we describe excellent correlation with gold standard suppressor cell assays. We propose that the kinetic advantage of the new assay may place it as the preferred rapid diagnostic test for the evaluation of Treg function in forthcoming clinical trials of cell therapy, enabling the translation of the large body of preclinical data into potentially useful treatments for human diseases.
Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease
Authors: Lieber Daniel S , Vafai Scott B , Horton Laura C , Slate Nancy G , Liu Shangtao , Borowsky Mark L , Calvo Sarah E , Schmahmann Jeremy D , Mootha Vamsi K 
Published: January 2012

Abstract

Background
Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA) and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci.

Case Presentation
Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C) missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome.

Conclusion
This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients.
Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia
Authors: Mansur Marcela Braga , Hassan Rocio , Barbosa Thayana C , Splendore Alessandra , Jotta Patricia Y , Yunes José Andrés , Wiemels Joseph L , Pombo-de-Oliveira Maria S 
Published: January 2012

Abstract

Background
Molecular alterations occur frequently in T-ALL and the potential impact of those abnormalities on outcome is still controversial. The current study aimed to test whether NOTCH1 mutations and additional molecular abnormalities would impact T-ALL outcome in a series of 138 T-ALL paediatric cases.

Methods
T-ALL subtypes, status of SIL-TAL1 fusion, ectopic expression of TLX3, and mutations in FBXW7, KRAS, PTEN and NOTCH1 were assessed as overall survival (OS) and event-free survival (EFS) prognostic factors. OS and EFS were determined using the Kaplan-Meier method and compared using the log-rank test.

Results
The frequencies of mutations were 43.5% for NOTCH1, while FBXW7, KRAS and PTEN exhibited frequencies of 19.1%, 9.5% and 9.4%, respectively. In 78.3% of cases, the coexistence of NOTCH1 mutations and other molecular alterations was observed. In multivariate analysis no statistical association was revealed between NOTCH1 mutations and any other variable analyzed. The mean length of the follow-up was 68.4 months and the OS was 50.7%. SIL-TAL1 was identified as an adverse prognostic factor. NOTCH1 mutation status was not associated with outcome, while the presence of NOTCH1 complex mutations (indels) were associated with a longer overall survival (p = 0.031) than point mutations.

Conclusion

NOTCH1 mutations alone or in combination with FBXW7 did not impact T-ALL prognosis. Nevertheless, complex NOTCH1 mutations appear to have a positive impact on OS and the SIL-TAL1 fusion was validated as a negative prognostic marker in our series of T-ALL.
Photoluminescence characteristics of Cd1-xMn
x
Te single crystals grown by the vertical Bridgman method
Authors: Hwang Younghun , Um Youngho , Park Hyoyeol 
Published: January 2012

Abstract
In this paper, we report a systematic investigation of band-edge photoluminescence for Cd1-x
Mn
x
Te crystals grown by the vertical Bridgman method. The near-band-edge emissions of neutral acceptor-bound excitons (labeled as L1) were systematically investigated as a function of temperature and of alloy composition. The parameters that describe the temperature variation of the energy were evaluated by the semiempirical Varshni relation. From the temperature dependence of the full width at half maximum of the L1 emission line, the broadening factors Γ(T) were determined from the fit to the data. The activation energies of thermal quenching were obtained for the L1 peak from the temperature dependence of the bound exciton peaks and were found to decrease with increasing Mn concentration.
Fabrication and characterization of carbon-based counter electrodes prepared by electrophoretic deposition for dye-sensitized solar cells
Authors: Kim Hyunkook , Choi Hyonkwang , Hwang Sookhyun , Kim Youngjoo , Jeon Minhyon 
Published: January 2012

Abstract
Three different carbon-based counter electrodes are investigated in light of catalytic activities such as electrochemical frequencies and interface impedances. We fabricated carbon-based counter electrodes of dye-sensitized solar cells [DSSCs] using graphene, single-walled carbon nanotubes [SWNTs], and graphene-SWNT composites by electrophoretic deposition method. We observed the optical and electrochemical properties of the carbon-based counter electrodes. The DSSC with the graphene-deposited counter electrode demonstrated the best conversion efficiency of 5.87% under AM 1.5 and 1 sun condition. It could be utilized for a low-cost and high-throughput process for DSSCs.
Adeno-associated virus-mediated brain delivery of 5-lipoxygenase modulates the AD-like phenotype of APP mice
Authors: Chu Jin , Giannopoulos Phillip F , Ceballos-Diaz Carolina , Golde Todd E , Pratico Domenico 
Published: January 2012

AbstractBackgroundThe 5-lipoxygenase (5LO) enzymatic pathway is widely distributed within the central nervous system. Previous works showed that this protein is up-regulated in Alzheimer's disease (AD), and that its genetic absence results in a reduction of Amyloid beta (Aβ) levels in the Tg2576 mice.Here by employing an adeno-associated viral (AAV) vector system to over-express 5LO in the same mouse model, we examined its contribution to their cognitive impairments and brain AD-like amyloid pathology.ResultsOur results showed that compared with controls, 5LO-targeted gene brain over-expression in Tg2576 mice results in significant memory deficits. On the other hand, brain tissues had a significant elevation in the levels of Aβ peptides and deposition, no change in the steady state levels of amyloid-β precursor protein (APP), BACE-1 or ADAM-10, but a significant increase in PS1, nicastrin, and Pen-2, three major components of the γ-secretase complex. Additional data indicate that the transcription factor CREB was elevated and so were the mRNA levels for PS1, nicastrin and Pen-2.ConclusionsThese data demonstrate that neuronal 5LO plays a functional role in the pathogenesis of AD-like amyloidotic phenotype by modulating the γ-secretase pathway. They support the hypothesis that this enzyme is a novel therapeutic target for the treatment and prevention of AD.
Effect of ulinastatin on growth inhibition, apoptosis of breast carcinoma cells is related to a decrease in signal conduction of JNk-2 and NF-κB
Authors: Wang Hong , Sun Xin , Gao Feng , Zhong Biao , Zhang Yong-hua , Sun Zhijun 
Published: January 2012

AbstractObjectiveThis study aims to investigate thein vitroeffects of Ulinastatin (UTI) and Taxotere (TXT) on cell proliferation; cell apoptosis; xenografted tumor growth; and expression of insulin-like growth factor receptor 1 (IGF-1R), platelet-derived growth factor A (PDGFA), nerve growth factor (NGF), c-Jun N-terminal kinase 2 (JNk-2), and NF-κB in a human primary breast cancer cells and breast cancer cell line MDA-MB-231.MethodsThe cell lines cultured were divided into four groups: 1) control group, 2) UTI group, 3) TXT group, and 4) UTI+TXT group. The method of MTT essay, flow cytometry, and RT-PCR were used to detect cell proliferation, cell apoptosis, and expression of IGF-1R, PDGFA, NGF, NF-κB, JNk-2, respectively. The growth of xenografted tumor in nude mice was used to calculate the anti-tumor rate. Immunohistochemistry staining (SP) was used to detect the expression of IGF-1R, PDGFA, NGF, ki-67, caspase-3, JNk-2, and NF-κB.ResultsProliferation of human breast cancer cells and MDA-MB-231 cell lines, and growth rate of xenografted tumor decreased in order of UTI+TXT > TXT > UTI > control, apoptosis increased in the order control < UTI < TXT < UTI+TXT. The gene expression and protein expression of IGF-1R, PDGFA, NGF, NF-κB and JNk-2 in breast cancer cells was inhibited by UTI and TXT.ConclusionsUTI 1) inhibits the proliferation of human breast cancer cells and the growth of xenografted tumors, 2) induces cancer cell apoptosis, and 3) enhances the anti-tumor effect of TXT. This mechanism might be related to decreasing signal transduction of JNk-2 and NF-κB, and then expression of IGF-1R, PDGFA, NGF.
Mechanisms of allergen‐specific immunotherapy
Authors: Fujita Hiroyuki , Soyka Michael B , Akdis Mübeccel , Akdis Cezmi A 
Published: January 2012

AbstractAllergen‐specific immunotherapy (allergen‐SIT) is a potentially curative treatment approach in allergic diseases. It has been used for almost 100 years as a desensitizing therapy. The induction of peripheral T cell tolerance and promotion of the formation of regulatory T‐cells are key mechanisms in allergen‐SIT. Both FOXP3+CD4+CD25+ regulatory T (Treg) cells and inducible IL‐10‐ and TGF‐β‐producing type 1 Treg (Tr1) cells may prevent the development of allergic diseases and play a role in successful allergen‐SIT and healthy immune response via several mechanisms. The mechanisms of suppression of different pro‐inflammatory cells, such as eosinophils, mast cells and basophils and the development of allergen tolerance also directly or indirectly involves Treg cells. Furthermore, the formation of non‐inflammatory antibodies particularly IgG4 is induced by IL‐10. Knowledge of these molecular basis is crucial in the understanding the regulation of immune responses and their possible therapeutic targets in allergic diseases.
Adiponectin associates with markers of cartilage degradation in osteoarthritis and induces production of proinflammatory and catabolic factors through mitogen-activated protein kinase pathways
Authors: Koskinen Anna , Juslin Sami , Nieminen Riina , Moilanen Teemu , Vuolteenaho Katriina , Moilanen Eeva 
Published: January 2012

Abstract

Introduction

Adiponectin is an adipokine that regulates energy metabolism and insulin sensitivity, but recent studies have pointed also to a role in inflammation and arthritis. The purpose of the present study was to investigate the association and effects of adiponectin on inflammation and cartilage destruction in osteoarthritis (OA).

Methods

Cartilage and blood samples were collected from 35 male OA patients undergoing total knee replacement surgery. Preoperative radiographs were evaluated using Ahlbäck classification criteria for knee OA. Circulating concentrations of adiponectin and biomarkers of OA, that is, cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase 3 (MMP-3), were measured. Cartilage samples obtained at the time of surgery were cultured ex vivo, and the levels of adiponectin, nitric oxide (NO), IL-6, MMP-1 and MMP-3 were determined in the culture media. In addition, the effects of adiponectin on the production of NO, IL-6, MMP-1 and MMP-3 were studied in cartilage and in primary chondrocyte cultures.

Results

Plasma adiponectin levels and adiponectin released from OA cartilage were higher in patients with the radiologically most severe OA (Ahlbäck grades 4 and 5) than in patients with less severe disease (Ahlbäck grades 1 to 3). Plasma adiponectin concentrations correlated positively with biomarkers of OA, that is, COMP (r = 0.55, P = 0.001) and MMP-3 (r = 0.34, P = 0.046). Adiponectin was released by OA cartilage ex vivo, and it correlated positively with production of NO (r = 0.43, P = 0.012), IL-6 (r = 0.42, P = 0.018) and MMP-3 (r = 0.34, P = 0.051). Furthermore, adiponectin enhanced production of NO, IL-6, MMP-1 and MMP-3 in OA cartilage and in primary chondrocytes in vitro in a mitogen-activated protein kinase (MAPK)-dependent manner.

Conclusions

The findings of this study show that adiponectin is associated with, and possibly mediates, cartilage destruction in OA.
A 10‐Year Evaluation of Implants Placed in Fresh Extraction Sockets: A Prospective Cohort Study
Authors: Covani Ugo , Chiappe Giacomo , Bosco Mario , Orlando Bruno , Quaranta Alessandro , Barone Antonio 
Published: January 2012

Background: The placement of an implant into a fresh extraction socket has been identified as a reliable technique, allowing a reduction in the time needed for prosthetic rehabilitation. This treatment modality is widely reported in the scientific literature; however, the long‐term outcomes and the need for guided bone regeneration (GBR) are still topics of debate. The aim of this prospective study is to evaluate the clinical and radiologic findings from the 10‐year follow‐up of immediately placed implants, with and without the GBR procedure.Methods: A total of 159 implants in 91 patients are included in this study; 101 implants required a GBR procedure simultaneously with placement. All implants were used to support a single crown restoration. The clinical/radiographic measurements were repeated each year up to the 10‐year follow‐up. At the 10‐year follow‐up visit, the papilla index and the apico‐coronal location of mid‐buccal soft tissue positions were recorded.Results: The 10‐year cumulative success rate was 91.8% (87.9% in the non‐GBR group and 94.1% in the GBR group). The clinical attachment level (CAL) measurements were stable throughout the study, and 82% of the implants showed marginal bone loss (MBL) of 0.6 to 1.5 mm at the 10‐year visit; moreover, these two parameters did not show significant differences between the GBR and non‐GBR groups. Seventy percent of the implant sites showed acceptable outcomes in terms of interproximal papilla. The facial gingival level was more apical in the non‐GBR group than in the GBR group (P <0.05).Conclusions: The present prospective clinical study shows that implants placed in fresh extraction sockets had a high cumulative success rate, namely 91.8% after 10 years. No differences were detected in survival and success rate of implants whether GBR procedures were performed or not. The CAL, MBL, and marginal level of soft tissue measurements were stable throughout the 10‐year evaluation.