bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-Selective Inhibition of NF-κB Signaling Improves Therapeutic Index in a Melanoma Chemotherapy Model
Authors: Enzler Thomas , Sano Yasuyo , Choo Min-Kyung , Cottam Howard B. , Karin Michael , Tsao Hensin , Park Jin Mo 
Published: September 2011

Abstract
The transcription factor NF-κB promotes the survival of cancer cells exposed to doxorubicin and other chemotherapeutic agents. IκB kinase is essential for chemotherapy-induced NF-κB activation and considered a prime target for anticancer treatment. An IκB kinase inhibitor sensitized human melanoma xenografts in mice to killing by doxorubicin yet also exacerbated treatment toxicity in the host animals. By using mouse models that simulate cell-selective targeting, we found that impaired NF-κB activation in melanoma and host myeloid cells accounts for therapeutic and adverse effects, respectively. Ablation of tumor-intrinsic NF-κB activity resulted in apoptosis-driven tumor regression after treatment with doxorubicin. By contrast, chemotherapy in mice with myeloid-specific loss of NF-κB activation led to a massive intratumoral recruitment of interleukin-1β–producing neutrophils and necrotic tumor lesions, a condition associated with increased host mortality but not accompanied by tumor regression. Therefore, a molecular target-based therapy may be steered toward different clinical outcomes depending on the drug's cell-specific effects.
Significance: Our findings show that the IκB kinase–NF-κB signaling pathway is important for both promoting treatment resistance and preventing host toxicity in cancer chemotherapy; however, the two functions are exerted by distinct cell type–specific mechanisms and can therefore be selectively targeted to achieve an improved therapeutic outcome. Cancer Discovery; 1(6); 496–507. ©2011 AACR.
Read the Commentary on this article by Aggarwal and Sung, p. 469
This article is highlighted in the In This Issue feature, p. 457
Development of a nationwide consensus syllabus of palliative medicine for undergraduate medical education in Japan: A modified Delphi method
Authors: Kizawa Yoshiyuki , Tsuneto Satoru , Tamba Kaichiro , Takamiya Yusuke , Morita Tatsuya , Bito Seiji , Otaki Junji 
Published: September 2011

Background: There is currently no consensus syllabus of palliative medicine for undergraduate medical education in Japan, although the Cancer Control Act proposed in 2007 covers the dissemination of palliative care. Aim: To develop a nationwide consensus syllabus of palliative medicine for undergraduate medical education in Japan using a modified Delphi method. Design: We adopted the following three-step method: (1) a workshop to produce the draft syllabus; (2) a survey-based provisional syllabus; (3) Delphi rounds and a panel meeting (modified Delphi method) to produce the working syllabus. Educators in charge of palliative medicine from 63% of the medical schools in Japan collaborated to develop a survey-based provisional syllabus before the Delphi rounds. A panel of 32 people was then formed for the modified Delphi rounds comprising 28 educators and experts in palliative medicine, one cancer survivor, one bereaved family member, and two medical students. Results: The final consensus syllabus consists of 115 learning objectives across seven sections as follows: basic principles; disease process and comprehensive assessment; symptom management; psychosocial care; cultural, religious, and spiritual issues; ethical issues; and legal frameworks. Learning objectives were categorized as essential or desirable (essential: 66; desirable: 49). Conclusions: A consensus syllabus of palliative medicine for undergraduate medical education was developed using a clear and innovative methodology. The final consensus syllabus will be made available for further dissemination of palliative care education throughout the country.
The personal value of being a palliative care Community Volunteer Worker in Uganda: A qualitative study
Authors: Jack Barbara A , Kirton Jennifer A , Birakurataki Jerith , Merriman Anne 
Published: September 2011

Background: Volunteers in palliative care play a key role, particularly in the hospice setting. The expansion of palliative care into developing countries has been accompanied by the emergence of volunteer workers, who are providing a main source of support and care for patients, many of whom never see a health professional. Aim: The aim of this study was to evaluate the motivation for becoming a volunteer and the personal impact of being a palliative care Community Volunteer Worker in Uganda. Design: A qualitative methodology using semi-structured individual and group digitally recorded interviews was adopted for the study. Data were analysed for emerging themes using thematic analysis. Setting/Participants: Forty-three interviews were undertaken, 32 with Community Volunteer Workers and 11 with the Hospice clinical teams, using semi-structured digitally recorded individual, group and focus group interviews at the Hospice Africa sites in Uganda. Results: The results identified the cultural wish to help people as a key motivator in becoming a volunteer. Additionally, the volunteers reported having a sense of pride in their volunteering role, and this role had a positive impact on their perceived status in their local community. Conclusion: This model of volunteering is clearly having an impact on the volunteers, both personally and also in terms of how they are treated in their communities. Further research to explore the long-term personal benefits of being a palliative care volunteer is recommended.
Maintaining absolute clearances in ballasted railway tracks using in situ three-dimensional polyurethane GeoComposites
Authors: Woodward P K , Kennedy J , Medero G M , Banimahd M 
Published: September 2011

Maintaining track clearances in ballasted railway tracks are a critical issue for the safety and operational performance of the railway environment. In general, railway standards aredefined with respect to the minimum gauge clearance allowed between the dynamic swept envelope of the train vehicles and the fixed structure for a given vehicle speed. Absolute clearance of a line is categorized based on the clearance level, for example, in the UK, it is defined in terms of normal, reduced, or special reduced clearance. In special reduced clearance, the level of track fixity is defined as high fixity, medium fixity, and low fixity. In high track fixity, a concrete-slab track solution must be adopted; in medium track fixity, some form of ballast stabilization and/or reinforcement can be used. The principal requirement is that using a standard methodology, the clearances should always be greater than zero; the clearance representing the margin for unknown events. In this article, an in situ three-dimensional (3D) polyurethane ballast reinforcement technique is used to provide a very robust level of track fixity. The performance of the reinforcement technique is shown through experimental tests using a 200 ton capacity cyclic compression machine. The experimental tests are used to show the performance of the technique for applications like railway tunnels and station platforms where clearances issues are paramount. The base and shoulder GeoComposite experimental tests are performed with the initial ballast poorly compacted thus representing a worse case on-site scenario. Based on the experimental results, a new track fixity category is proposed termed virtual high fixity. A case study showing the impact and site application of the 3D polyurethane reinforcement research to Grovehill Tunnel UK is presented and reference is also made to another reinforced clearance issue site at Hoxton Station UK.
Compliance with guidelines in the treatment of asthma exacerbations in primary care
Authors: Flor-Escriche Xavier , Rodríguez-Mas Montserrat , Espiau Maria , Castán-Enseñat Xavier , Vigatà-Reig Josep M. , Poblet-Cortés Roser , Miravitlles Marc 
Published: September 2011

Objective: To describe the approach to asthma exacerbations in a primary care centre in comparison with current guidelines and to ascertain the resolution of the episodes. Methods: A cross-sectional, descriptive study was performed in asthmatic patients over 14 years old who were consulting for asthma exacerbations in a primary care centre during a 6-month period. The treatment given and the resolution obtained were evaluated. Results: One hundred and twenty-three asthma exacerbations were registered, corresponding to 96 patients. A total of 74% were mild exacerbations, 24.4% moderate and 1.6% severe. The severity of asthma correlated directly with the severity of exacerbations. The frequency of resolution was 98.4%, with an average duration of medical attention of 30 min (SD 16.5). According to guidelines, 60.2% of the mild exacerbations were well treated, as were 26.7% of the moderate exacerbations and none of the severe episodes. Peak expiratory flow was measured in 54.5% of patients. In 82 cases (66.6%) salbutamol was given with a large-volume spacer chamber. Treatment after discharge was correct in 27.3% of the mild and 23.3% of the moderate exacerbations. A total of 23 (23.9%) patients presented more than one exacerbation during the study period. Conclusions: Most exacerbations seen in primary care are mild. Administration of salbutamol was sufficient for the resolution of these exacerbations. However, treatment after discharge was not compliant with guidelines in most cases. The primary care team was able to resolve most of the asthma exacerbations.
Multiple HLA class I and II associations in classical Hodgkin lymphoma and EBV status defined subgroups
Authors: Huang Xin , Kushekhar Kushi , Nolte Ilja , Kooistra Wierd , Visser Lydia , Bouwman Ilby , Kouprie Niels , Veenstra Rianne , van Imhoff Gustaaf , Olver Bianca , Houlston Richard S. , Poppema Sibrand , Diepstra Arjan , Hepkema Bouke , van den Berg Anke 
Published: September 2011

AbstractThe pathogenesis of classical Hodgkin lymphoma (cHL) involves environmental and genetic factors. To explore the role of the human leukocyte antigen (HLA) genes, we performed a case-control genotyping study in 338 Dutch cHL patients and more than 5000 controls using a PCR-based sequence-specific oligonucleotide probe hybridization approach. HLA-A68 and HLA-DR11 (5) were significantly increased in the cHL patient population compared with the controls. Three class II associations were observed in the EBV− cHL population with an increase of HLA-DR15 (2) and a decrease of HLA-DR4 and HLA-DR7. Allele frequencies of HLA-A1, HLA-B37, and HLA-DR10 were significantly increased in the EBV+ cHL population; these alleles are in strong linkage disequilibrium and form a common haplotype in whites. The allele frequency of HLA-A2 was significantly decreased in the EBV+ cHL population. Sequence-specific oligonucleotide probe analysis revealed significant differences between EBV+ and EBV− cHL patients for 19 probes that discriminate between HLA-A*01 and HLA-A*02. In conclusion, the HLA-A1 and HLA-A2 antigens and not specific single nucleotide variants shared by multiple alleles are responsible for the association with EBV+ cHL. Furthermore, several new protective and predisposing HLA class I and II associations for the EBV+, the EBV−, and the entire cHL population were identified.
EZH2 mutational status predicts poor survival in myelofibrosis
Authors: Guglielmelli Paola , Biamonte Flavia , Score Joannah , Hidalgo-Curtis Claire , Cervantes Francisco , Maffioli Margherita , Fanelli Tiziana , Ernst Thomas , Winkelman Nils , Jones Amy V. , Zoi Katerina , Reiter Andreas , Duncombe Andrew , Villani Laura , Bosi Alberto , Barosi Giovanni , Cross Nicholas C. P. , Vannucchi Alessandro M. 
Published: September 2011

Abstract
We genotyped 370 subjects with primary myelofibrosis (PMF) and 148 with postpolycythemia vera/postessential thrombocythemia (PPV/PET) MF for mutations of EZH2. Mutational status at diagnosis was correlated with hematologic parameters, clinical manifestations, and outcome. A total of 25 different EZH2 mutations were detected in 5.9% of PMF, 1.2% of PPV-MF, and 9.4% of PET-MF patients; most were exonic heterozygous missense changes. EZH2 mutation coexisted with JAK2V617F or ASXL1 mutation in 12 of 29 (41.4%) and 6 of 27 (22.2%) evaluated patients; TET2 and CBL mutations were found in 2 and 1 patients, respectively. EZH2-mutated PMF patients had significantly higher leukocyte counts, blast-cell counts, and larger spleens at diagnosis, and most of them (52.6%) were in the high-risk International Prognostic Score System (IPSS) category. After a median follow-up of 39 months, 128 patients (25.9%) died, 81 (63.3%) because of leukemia. Leukemia-free survival (LFS) and overall survival (OS) were significantly reduced in EZH2-mutated PMF patients (P = .028 and P < .001, respectively); no such impact was seen for PPV/PET-MF patients, possibly due to the low number of mutated cases. In multivariate analysis, survival of PMF patients was predicted by IPSS high-risk category, a < 25% JAK2V617F allele burden, and EZH2 mutation status. We conclude that EZH2 mutations are independently associated with shorter survival in patients with PMF.
Detection of Pulmonary tuberculosis: comparing MR imaging with HRCT
Authors: Busi Rizzi Elisa , Schinina' Vincenzo , Cristofaro Massimo , Goletti Delia , Palmieri Fabrizio , Bevilacqua Nazario , Lauria Francesco N , Girardi Enrico , Bibbolino Corrado 
Published: September 2011

Abstract

Background
Computer Tomography (CT) is considered the gold standard for assessing the morphological changes of lung parenchyma. Although novel CT techniques have substantially decreased the radiation dose, radiation exposure is still high. Magnetic Resonance Imaging (MRI) has been established as a radiation- free alternative to CT for several lung diseases, but its role in infectious diseases still needs to be explored further. Therefore, the purpose of our study was to compare MRI with high resolution CT (HRCT) for assessing pulmonary tuberculosis.

Methods
50 patients with culture-proven pulmonary tuberculosis underwent chest HRCT as the standard of reference and were evaluated by MRI within 24 h after HRCT. Altogether we performed 60 CT and MRI examinations, because 10 patients were also examined by CT and MRI at follow- up. Pulmonary abnormalities, their characteristics, location and distribution were analyzed by two readers who were blinded to the HRCT results.

Results
Artifacts did not interfere with the diagnostic value of MRI. Both HRCT and MRI correctly diagnosed pulmonary tuberculosis and identified pulmonary abnormalities in all patients. There were no significant differences between the two techniques in terms of identifying the location and distribution of the lung lesions, though the higher resolution of MRI did allow for better identification of parenchymal dishomogeneity, caseosis, and pleural or nodal involvement.

Conclusion
Technical developments and the refinement of pulse sequences have improved the quality and speed of MRI. Our data indicate that in terms of identifying lung lesions in non-AIDS patients with non- miliary pulmonary tuberculosis, MRI achieves diagnostic performances comparable to those obtained by HRCT but with better and more rapid identification of pulmonary tissue abnormalities due to the excellent contrast resolution.
Reliable likelihood ratios for statistical model-based voice activity detector with low false-alarm rate
Authors: Kim Younggwan , Suh Youngjoo , Kim Hoirin 
Published: September 2011

Abstract
The role of the statistical model-based voice activity detector (SMVAD) is to detect speech regions from input signals using the statistical models of noise and noisy speech. The decision rule of SMVAD is based on the likelihood ratio test (LRT). The LRT-based decision rule may cause detection errors because of statistical properties of noise and speech signals. In this article, we first analyze the reasons why the detection errors occur and then propose two modified decision rules using reliable likelihood ratios (LRs). We also propose an effective weighting scheme considering spectral characteristics of noise and speech signals. In the experiments proposed in this study, with almost no additional computations, the proposed methods show significant performance improvement in various noise conditions. Experimental results also show that the proposed weighting scheme provides additional performance improvement over the two proposed SMVADs.
Computational modelling elucidates the mechanism of ciliary regulation in health and disease
Authors: Kotov Nikolay V , Bates Declan G , Gizatullina Antonina N , Gilaziev Bulat , Khairullin Rustem N , Chen Michael ZQ , Drozdov Ignat , Umezawa Yoshinori , Hundhausen Christian , Aleksandrov Alexey , Yan Xing-gang , Spurgeon Sarah K , Smales C Mark , Valeyev Najl V 
Published: September 2011

Abstract

Background
Ciliary dysfunction leads to a number of human pathologies, including primary ciliary dyskinesia, nephronophthisis, situs inversus pathology or infertility. The mechanism of cilia beating regulation is complex and despite extensive experimental characterization remains poorly understood. We develop a detailed systems model for calcium, membrane potential and cyclic nucleotide-dependent ciliary motility regulation.

Results
The model describes the intimate relationship between calcium and potassium ionic concentrations inside and outside of cilia with membrane voltage and, for the first time, describes a novel type of ciliary excitability which plays the major role in ciliary movement regulation. Our model describes a mechanism that allows ciliary excitation to be robust over a wide physiological range of extracellular ionic concentrations. The model predicts the existence of several dynamic modes of ciliary regulation, such as the generation of intraciliary Ca2+ spike with amplitude proportional to the degree of membrane depolarization, the ability to maintain stable oscillations, monostable multivibrator regimes, all of which are initiated by variability in ionic concentrations that translate into altered membrane voltage.

Conclusions
Computational investigation of the model offers several new insights into the underlying molecular mechanisms of ciliary pathologies. According to our analysis, the reported dynamic regulatory modes can be a physiological reaction to alterations in the extracellular environment. However, modification of the dynamic modes, as a result of genetic mutations or environmental conditions, can cause a life threatening pathology.
Chemistry of Tetrasulfur Including Mysterious Rectangular S4 Metal Complexes
Authors: Isobe Kiyoshi 
Published: September 2011

Abstract
Of eleven possible isomers for neutral S4, rectangular S4 has been proposed theoretically as one of the most stable forms. There has, however, been no consensus as to the S4 ground-state geometric structure despite much effort over recent years, because of the lack of direct structural information from experimental work due to lack of preparation in a pure state. The principal question is whether the ground-state geometry is rectangular D2h or open planar C2v. Our group found first rectangular S4 in coordination compounds of Rh and Ir tetranuclear complexes as a ligand and disclosed mysterious rectangular S4 by X-ray analysis and theoretical studies. Here, the newly developed chemistry of rectangular S4 complexes together with the related tetrasulfur species is introduced both from experimental and theoretical view points. In addition, more accurate argument of the principal question mentioned above is also described using results obtained from recent high-level theoretical calculations.
Purified Anthocyanin Supplementation Improves Endothelial Function via NO-cGMP Activation in Hypercholesterolemic Individuals
Authors: Zhu Yanna , Xia Min , Yang Yan , Liu Fengqiong , Li Zhongxia , Hao Yuantao , Mi Mantian , Jin Tianru , Ling Wenhua 
Published: September 2011

BACKGROUND
Anthocyanins have been shown to improve endothelial function in animal models. However, whether these compounds have similar beneficial effects in humans is largely unknown.

METHODS
In a short-term crossover study, 12 hypercholesterolemic individuals were given oral anthocyanins (320 mg) isolated from berries or placebo. Brachial artery flow-mediated dilation (FMD) was assessed before and after the intervention. In a long-term intervention trial (12 weeks), 150 hypercholesterolemic individuals were given anthocyanins (320 mg/day, n = 75) or placebo (n = 75), after which we measured FMD, plasma cGMP, and other serum biomarkers. Another short-term intervention was conducted in the presence of NO-cGMP inhibitors in 6 people and in a rat aortic ring model (n = 8).

RESULTS
Significant increases of FMD from 8.3% (0.6%) at baseline to 11.0% (0.8%) at 1 h and 10.1% (0.9%) at 2 h were observed after short-term anthocyanin consumption, concomitantly with increases of plasma anthocyanin concentrations (P &lt; 0.05). In the study participants who received long-term anthocyanin intervention, compared with the control group, we observed significant increases in the FMD (28.4% vs 2.2%), cGMP (12.6% vs −1.2%), and HDL-cholesterol concentrations, but decreases in the serum soluble vascular adhesion molecule-1 and LDL cholesterol concentrations (P &lt; 0.05). The changes in the cGMP and HDL cholesterol concentrations positively correlated with FMD in the anthocyanin group (P &lt; 0.05). In the presence of NO-cGMP inhibitors, the effects of anthocyanin on endothelial function were abolished in human participants and in a rat aortic ring model.

CONCLUSIONS
Anthocyanin supplementation improves endothelium-dependent vasodilation in hypercholesterolemic individuals. This effect involves activation of the NO-cGMP signaling pathway, improvements in the serum lipid profile, and decreased inflammation.
State of art in heart transplantation
Authors: Spinarova L. 
Published: September 2011

Abstract
Heart transplantation (HTX) has become an accepted treatment for selected patients with end-stage heart failure. There are two transplant centres in the Czech Republic, Prague since 1984 and Brno since 1992, in which more than 1000 heart transplantations were performed. Pharmacotherapy after heart transplantation includes the problems of immunosuppression and interactions of immunosuppressant drugs and their adverse effects. The main task for future is to find better immunosuppression with less side effects, to replace invasive bioptic examination of rejection and to find alternatives to clasical transplantation: xenotransplantation, stem cell transplantation or development of new ventricle assisst devices.