bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experts’ opinions on terminology for complementary and integrative medicine – a qualitative study with leading experts
Authors: Holmberg Christine , Brinkhaus Benno , Witt Claudia 
Published: November 2012

Abstract

Background
Integrative medicine (IM) is currently the most commonly used term to describe the integration of complementary and alternative medicine (CAM) into conventional medicine. In the definitions of IM the most important feature is the focus on evidence as crucial factor for therapeutic decision-making. However, there are discussions on the term “integrative medicine” with the most notable critique from within CAM that it describes the integration of complementary methods into conventional institutions and into a “conventional framework of thinking”. The aim of this qualitative study was to understand the thoughts of leading experts on IM and on the scientific debate in the field as well as their personal opinions about terminology in general.

Methods
We have conducted semi-standardized interviews with ten leading experts in the field of CAM and integrative medicine in the USA, England, and Germany, who have had leading positions at medical schools or the NIH in 2010 and 2011. Interviews were recorded, transcribed and analyzed using content analysis with the qualitative analysis software maxqda.

Results
Overall the current terminology was seen as a problem, although most experts agreed that the term “integrative medicine” (IM) described well what they do or they think is useful for medical care. The terminology debate was discussed from four perspectives: 1) from the perspective of medical practice, 2) from the perspective of research, 3) from the perspective of public relations, and 4) from the perspective of health care delivery. These perspectives may be used to evaluate the appropriateness of different terms in use in the field. When interviewees discussed the terminology question, they also discussed the type of health care system they envisioned. Such reflections led the interviewees to caution about too narrow a focus on the terminology question. The question of naming was one about influencing and changing medicine.

Conclusion
The discussion of the experts demonstrated that the discussion about terminology is an important debate about the shaping of medicine. The experts discussed terminology in the light of "how health care systems" should look like in the future.
The pressure/volume relationship during dobutamine stress echocardiography in transplanted heart: comparison with quality of life and coronary anatomy
Authors: Minardi Giovanni , Zampi Giordano , Pergolini Amedeo , Pulignano Giovanni , Scappaticci Massimiliano , Orsini Francesca Moschella , Pero Gaetano , Monica Paola Lilla Della , Cioffi Giovanni , Musumeci Francesco 
Published: November 2012

Abstract

Background
Cardiac allograft vasculopathy (CAV) is a major late complication in cardiac transplant recipients and has a relevant impact on outcome of these patients. Aims of this study: to compare, in cardiac transplant recipients patients, the diagnostic value of pressure/volume relationship (ESPVR) during dobutamine stress echocardiography (DSE) for coronary artery disease, assessed by Multislice Computed Tomography (MSCT), and by coronary angiography (CA). We also analyzed any possible relationship between ESPVR and the Health Related Quality of Life of the patients (HRQoL), evaluated by SF–36 questionnaire.

Methods
25 consecutive patients underwent DSE within 24 hours after MSCT coronary angiogram and then they underwent CA. The HRQoL questionnaire was administered to the patients in the settings of DSE. They were followed-up for 6 months.

Results
DSE has a sensitivity in detecting CAV of 67%, specificity of 95%, positive predictive value of 67% and negative predictive value of 95%; DSE with ESPVR has a sensitivity of 100%, specificity of 95%, positive predictive value of 75%, negative predictive value of 100%; MSCT has a sensitivity of 100%; specificity of 82%; positive predictive value of 43%; negative predictive value of 100%. Htx recipients with a flat-biphasic ESPVR, although asymptomatic, perceived a worst HRQoL compared with the up-sloping ESPVR population, and this is statistically significant for the general health (p 0.0004), the vitality (p 0.0013) and the mental health (p 0.021) SF-36 subscale.

Conclusions
Evaluation with DSE and ESPVR is accurate in the clinical control of heart transplant recipients reserving invasive evaluation only for patients with abnormal contractility indexes.
Identification of SLC26A4 c.919-2A>G compound heterozygosity in hearing-impaired patients to improve genetic counseling
Authors: Li Qi , Zhu Qing-wen , Yuan Yong-yi , Huang Sha-sha , Han Dong-yi , Huang De-liang , Dai Pu 
Published: November 2012

Abstract

Background
Mutations in the SLC26A4 gene, which encodes the anion transporter, pendrin, are a major cause of autosomal recessive non-syndromic hearing loss (NSHL) in some Asian populations. SLC26A4 c.919-2A>G (IVS7-2A>G) is the most common mutation in East Asian deaf populations. To provide a basis for improving the clinical diagnosis of deaf patients, we evaluated 80 patients with the SLC26A4 c.919-2A>G monoallelic mutation from 1065 hearing-impaired subjects and reported the occurrence of a second mutant allele in these patients.

Methods
The occurrence of a second mutant allele in these 80 patients with a single c.919-2A>G mutation was investigated. Mutation screening was performed by bidirectional sequencing in SLC26A4 exons 2 to 6 and 9 to 21.

Results
We found that 47/80 patients carried another SLC26A4 c.919-2A>G compound mutation. The five most common mutations were: p.H723R, p.T410M, 15+5G>A (c.1705+5G>A), p.L676Q and p.N392Y. We found a Chinese-specific SLC26A4 mutation spectrum and an associated SLC26A4 contribution to deafness.

Conclusion
Our study illustrates that mutation analysis of other SLC26A4 exons should be undertaken in deaf patients with a single heterozygous SLC26A4 mutation. Moreover, a model of compound heterozygosity may partially explain the disease phenotype.
Immunoediting: evidence of the multifaceted role of the immune system in self-metastatic tumor growth
Authors: Enderling Heiko , Hlatky Lynn , Hahnfeldt Philip 
Published: November 2012

Abstract

Background
The role of the immune system in tumor progression has been a subject for discussion for many decades. Numerous studies suggest that a low immune response might be beneficial, if not necessary, for tumor growth, and only a strong immune response can counter tumor growth and thus inhibit progression.

Methods
We implement a cellular automaton model previously described that captures the dynamical interactions between the cancer stem and non-stem cell populations of a tumor through a process of self-metastasis. By overlaying on this model the diffusion of immune reactants into the tumor from a peripheral source to target cells, we simulate the process of immune-system-induced cell kill on tumor progression.

Results
A low cytotoxic immune reaction continuously kills cancer cells and, although at a low rate, thereby causes the liberation of space-constrained cancer stem cells to drive self-metastatic progression and continued tumor growth. With increasing immune system strength, however, tumor growth peaks, and then eventually falls below the intrinsic tumor sizes observed without an immune response. With this increasing immune response the number and proportion of cancer stem cells monotonically increases, implicating an additional unexpected consequence, that of cancer stem cell selection, to the immune response.

Conclusions
Cancer stem cells and immune cytotoxicity alone are sufficient to explain the three-step “immunoediting” concept – the modulation of tumor growth through inhibition, selection and promotion.
Effect of early anti-retroviral therapy on the pathogenic changes in mucosal tissues of SIV infected rhesus macaques
Authors: Malzahn Jessica , Shen Chengli , Caruso Lori , Ghosh Priyanka , Sankapal Soni Ramachandra , Barratt-Boyes Simon , Gupta Phalguni , Chen Yue 
Published: November 2012

AbstractBackgroundThe gastrointestinal tissue plays an important role in the pathogenesis of HIV/SIV infection and serves as a viral reservoir in infected individuals under antiretroviral therapy (ART). However, the effect of ART administration in the very early stage of infection on HIV/SIV replication and pathogenesis in gastrointestinal tissue has not been fully studied. In this current study, rhesus monkeys infected with SIV were treated with ART starting at day 7 post-infection. The effect of early ART on SIV replication and infection-related pathogenic changes in mucosal tissues of the infected monkeys was examined.MethodsNuclear acids were extracted from snap frozen ileum and colon tissues and mesentery lymph nodes from SIV infected monkeys with or without ART. SIV RNA and DNA loads as well as levels of CD3, CD4 and cytokine mRNA were measured by PCR and RT PCR from the isolated nuclear acids. Tissue sections were stained by immuno-fluorescence labeled antibodies for CD3 and CD4.ResultsWithout ART treatment, these monkeys underwent a mild SIV infection with low viral loads and slightly decreased CD4+T cell counts in peripheral blood. In ART treated monkeys, SIV RNA loads were undetectable in blood with normal CD4+T cell counts, however, SIV RNA and DNA were detected in the intestinal tissues and mesentery lymph nodes although the levels were lower than those in untreated monkeys. The levels of CD3 and CD4 positive cells in the tissues were similar between the infected untreated monkeys and infected ART treated monkeys based on RT-PCR and immune-fluorescence staining of the tissue sections. Furthermore, compatible levels of IL-6, TNF-a, IL-1b and MyD88 mRNAs were detected in most of intestinal tissues and mesentery lymph nodes of infected ART treated and infected untreated monkeys.ConclusionsThese results suggest that early ART administration could not effectively inhibit SIV replication in intestinal tissues and mesentery lymph nodes and could not reduce the immune activation induced by SIV infection in the intestinal tissues.
Reliability and validity of the Wolfram Unified Rating Scale (WURS)
Authors: Nguyen Chau , Foster Erin R , Paciorkowski Alexander R , Viehoever Amy , Considine Colleen , Bondurant Aidena , Marshall Bess A , Hershey Tamara ,   Washington University Wolfram Study Group
Published: November 2012

Abstract

Background
Wolfram syndrome (WFS) is a rare, neurodegenerative disease that typically presents with childhood onset insulin dependent diabetes mellitus, followed by optic atrophy, diabetes insipidus, deafness, and neurological and psychiatric dysfunction. There is no cure for the disease, but recent advances in research have improved understanding of the disease course. Measuring disease severity and progression with reliable and validated tools is a prerequisite for clinical trials of any new intervention for neurodegenerative conditions. To this end, we developed the Wolfram Unified Rating Scale (WURS) to measure the severity and individual variability of WFS symptoms. The aim of this study is to develop and test the reliability and validity of the Wolfram Unified Rating Scale (WURS).

Methods
A rating scale of disease severity in WFS was developed by modifying a standardized assessment for another neurodegenerative condition (Batten disease). WFS experts scored the representativeness of WURS items for the disease. The WURS was administered to 13 individuals with WFS (6-25 years of age). Motor, balance, mood and quality of life were also evaluated with standard instruments. Inter-rater reliability, internal consistency reliability, concurrent, predictive and content validity of the WURS were calculated.

Results
The WURS had high inter-rater reliability (ICCs>.93), moderate to high internal consistency reliability (Cronbach’s α = 0.78-0.91) and demonstrated good concurrent and predictive validity. There were significant correlations between the WURS Physical Assessment and motor and balance tests (rs>.67, p<.03), between the WURS Behavioral Scale and reports of mood and behavior (rs>.76, p<.04) and between WURS Total scores and quality of life (rs=-.86, p=.001). The WURS demonstrated acceptable content validity (Scale-Content Validity Index=0.83).

Conclusions
These preliminary findings demonstrate that the WURS has acceptable reliability and validity and captures individual differences in disease severity in children and young adults with WFS.
The SNP at −592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development
Authors: Torres-Poveda Kirvis , Burguete-García Ana I , Cruz Miguel , Martínez-Nava Gabriela A , Bahena-Román Margarita , Ortíz-Flores Esmeralda , Ramírez-González Abrahan , López-Estrada Guillermina , Delgado-Romero Karina , Madrid-Marina Vicente 
Published: November 2012

AbstractBackgroundWomen with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL).MethodsPeripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL.ResultsNo significant differences were found between genotype frequencies at loci −819, -1082, and −1352. Individuals carrying at least one copy of risk allele A of polymorphism −592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A.ConclusionsThe −592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease.
Serum progranulin levels are elevated in patients with systemic lupus erythematosus, reflecting disease activity
Authors: Tanaka Atsushi , Tsukamoto Hiroshi , Mitoma Hiroki , Kiyohara Chikako , Ueda Naoyasu , Ayano Masahiro , Ohta Shun-ichiro , Inoue Yasushi , Arinobu Yojirou , Niiro Hiroaki , Horiuchi Takahiko , Akashi Koichi 
Published: November 2012

Abstract
Introduction
Progranulin (PGRN) is the precursor of granulin (GRN), a soluble cofactor for toll-like receptor 9 (TLR9) signaling evoked by oligonucleotide (CpG)-DNA. Because TLR9 signaling plays an important role in systemic lupus erythematosus (SLE), we investigated whether PGRN is involved in the pathogenesis of SLE.

Methods
We measured concentrations of serum PGRN and interleukin-6 (IL-6) with enzyme-linked immunosorbent assay (ELISA) in patients with SLE (n = 68) and in healthy controls (n = 60). We assessed the correlation between the serum PGRN levels and established disease-activity indexes. The sera from the patients with high PGRN titers (>80 ng/ml) at the initial evaluation were reevaluated after the disease was ameliorated by treatment. We also measured the IL-6 concentration secreted by peripheral blood mononuclear cells (PBMCs) incubated with (a) oligonucleotide (CpG-B) in the presence or absence of recombinant human PGRN (rhPGRN); and (b) lupus sera in the presence or absence of a neutralizing anti-PGRN antibody.

Results
Serum PGRN levels were significantly higher in SLE patients than healthy controls. Their levels were significantly associated with activity of clinical symptoms. They also significantly correlated with values of clinical parameters, including the SLE Disease Activity Index and anti-double-stranded DNA antibody titers, and inversely with CH50, C3, and C4 levels. Moreover, serum PGRN levels significantly decreased after successful treatment of SLE. The rhPGRN significantly upregulated the production of IL-6 by PBMCs stimulated with CpG-B. Patients' sera stimulated production of IL-6 from PBMCs, which was significantly impaired by neutralization of PGRN. The serum PGRN levels significantly correlated with the serum IL-6 levels.

Conclusions
Serum PGRN could be a useful biomarker for disease activity of SLE. PGRN may be involved in the pathogenesis of SLE partly by enhancing the TLR9 signaling.
A novel tylophorine analog W-8 up-regulates forkhead boxP3 expression and ameliorates murine colitis
Authors: Meng Xianyi , Zhang Yun , Jia Zhenghu , Huo Xiaojing , He Xiangjun , Tian Gaofei , Wu Meng , Wang Ziwen , Zhou Xinglong , Xiong Sidong , Gao Xiaoming , Wu Zhenzhou , Han Jihong , Zhao Liqing , Wang Puyue , Hong Zhangyong , Wang Qingmin , Yin Zhinan 
Published: November 2012

Abstract
A novel tylophorine analog W-8 enhanced Foxp3 expression through both transcriptional and epigenetic programs, and its ameliorated TNBS induced colitis.
Tylophorine and analogs are phenanthroindolizidine alkaloids, several of which have been reported to have anticancer, antiviral, and anti-inflammatory properties. However, their function in the immune system remains widely unknown. Transcription factor Foxp3 is critical for the development and function of Treg, which down-regulates the immune system and maintains tolerance to self-antigens. In the present study, we defined a novel tylophorine analog, W-8, enhanced TGF-β-induced Foxp3 expression at the mRNA and the protein levels. Interestingly, W-8 synergistically increased the level of TGF-β-induced p-Smad3 through inhibition of the AKT/mTOR pathway and enhanced the demethylation of the promoter region of the Foxp3 through inhibition of the ERK pathway and DNMT1 expression. Moreover, administration of W-8 suppressed TNBS-induced murine colitis and increased Tregs in lymphoid tissues. Finally, W-8 enhanced conversion of naïve T cells to Tregs in vivo. In summary, our results defined a novel compound that enhanced Foxp3 expression through transcriptional and epigenetic programs, and it might serve as a therapeutic agent for inflammatory diseases.
Risk of Venous Thromboembolism in Patients With Cancer Treated With Cisplatin: A Systematic Review and Meta-Analysis
Authors: Seng Sonia , Liu Ziyue , Chiu Sophia K. , Proverbs-Singh Tracy , Sonpavde Guru , Choueiri Toni K. , Tsao Che-Kai , Yu Menggang , Hahn Noah M. , Oh William K. , Galsky Matthew D. 
Published: November 2012

Purpose Several reports suggest that cisplatin is associated with an increased risk of thromboembolism. However, because the excess risk of venous thromboembolic events (VTEs) with cisplatin-based chemotherapy has not been well described, we conducted a systemic review and meta-analysis of randomized controlled trials evaluating the incidence and risk of VTEs associated with cisplatin-based chemotherapy. Methods PubMed was searched for articles published from January 1, 1990, to December 31, 2010. Eligible studies included prospective randomized phase II and III trials evaluating cisplatin-based versus non–cisplatin-based chemotherapy in patients with solid tumors. Data on all-grade VTEs were extracted. Study quality was calculated using Jadad scores. Incidence rates, relative risks (RRs), and 95% CIs were calculated using a random effects model. Results A total of 8,216 patients with various advanced solid tumors from 38 randomized controlled trials were included. The incidence of VTEs was 1.92% (95% CI, 1.07 to 2.76) in patients treated with cisplatin-based chemotherapy and 0.79% (95% CI, 0.45 to 1.13) in patients treated with non–cisplatin-based regimens. Patients receiving cisplatin-based chemotherapy had a significantly increased risk of VTEs (RR, 1.67; 95% CI, 1.25 to 2.23; P = .01). Exploratory subgroup analysis revealed the highest RR of VTEs in patients receiving a weekly equivalent cisplatin dose > 30 mg/m2 (2.71; 95% CI, 1.17 to 6.30; P = .02) and in trials reported during 2000 to 2010 (1.72; 95% CI, 1.27 to 2.34; P = .01). Conclusion Cisplatin is associated with a significant increase in the risk of VTEs in patients with advanced solid tumors when compared with non–cisplatin-based chemotherapy.
Services and the Business Models of Product Firms: An Empirical Analysis of the Software Industry
Authors: Suarez Fernando F. , Cusumano Michael A. , Kahl Steven J. 
Published: November 2012

Some product firms increasingly rely on service revenues as part of their business models. One possible explanation is that they turn to services to generate additional profits when their product industries mature and product revenues and profits decline. We explore this assumption by examining the role of services in the financial performance of firms in the prepackaged software products industry (Standard Industrial Classification code 7372) from 1990 to 2006. We find a convex, nonlinear relationship between a product firm's fraction of total sales coming from services and its overall operating margins. As expected, firms with a very high level of product sales are most profitable, and rising services are associated with declining profitability. We find, however, that additional services start to have a positive marginal effect on the firm's overall profits when services reach a majority of a product firm's sales. We show that traditional industry maturity arguments cannot fully explain our data. It is likely that changes in both strategy and the business environment lead product firms to place more emphasis on services.This paper was accepted by Christoph Loch, R&D and product development.
Robust Solutions of Optimization Problems Affected by Uncertain Probabilities
Authors: Ben-Tal Aharon , den Hertog Dick , De Waegenaere Anja , Melenberg Bertrand , Rennen Gijs 
Published: November 2012

In this paper we focus on robust linear optimization problems with uncertainty regions defined by ϕ-divergences (for example, chi-squared, Hellinger, Kullback–Leibler). We show how uncertainty regions based on ϕ-divergences arise in a natural way as confidence sets if the uncertain parameters contain elements of a probability vector. Such problems frequently occur in, for example, optimization problems in inventory control or finance that involve terms containing moments of random variables, expected utility, etc. We show that the robust counterpart of a linear optimization problem with ϕ-divergence uncertainty is tractable for most of the choices of ϕ typically considered in the literature. We extend the results to problems that are nonlinear in the optimization variables. Several applications, including an asset pricing example and a numerical multi-item newsvendor example, illustrate the relevance of the proposed approach.This paper was accepted by Gérard P. Cachon, optimization.