bluuebunny/crossref_metadata_2025_split huggingface dataset:
[18F]FDG accumulation in an experimental model of multistage progression of cholangiocarcinoma
Authors: Laverman Peter , Blokx Willeke A.M. , Te Morsche René H.M. , Frielink Cathelijne , Boerman Otto C. , Oyen Wim J.G. , Drenth Joost P.H. 
Published: September 2010

Aim:  The diagnosis of cholangiocarcinoma (CCA) is difficult, and due to the insidious course of the disease, most cases present at a relatively late stage. Positron emission tomography (PET), using [18F]fluoro‐2‐deoxyglucose ([18F]FDG) as a tracer is one the most powerful molecular imaging techniques available. We hypothesized that [18F]FDG accumulates at sites of early CCA development and that FDG‐PET may be of value for the early diagnosis of CCA.Methods:  We added 300 mg/L thioacetamide to the drinking water of rats who went on to develop CCA within 20 weeks. From eight weeks onwards, groups of three rats were injected with [18F]FDG, subsequently the liver was perfused, dissected and subjected to quantitative autoradiography using a phosphor imaging system. The liver sections were stained for histology, and glutathione S‐transferase (GST) enzyme activity was determined. We correlated [18F]FDG uptake with pathological liver changes.Results:  The experiments demonstrate that thioacetamide causes atypical bile ducts and invasive CCA. Rat livers harvested early after the start of administration of thioacetamide contained only cirrhosis and/or atypical bile ducts, but CCA and FDG accumulation were absent. At 20 weeks, all rats had developed CCA and all, except two animals with a very small carcinoma, had strongly elevated focal FDG uptake. Quantitative autoradiography revealed tumor‐to‐normal‐liver ratios as high as 5:4. In all rats with a carcinoma, there was a backdrop of cirrhosis, and interestingly cirrhotic areas did not show elevated FDG accumulation.Conclusion:  [18F]FDG accumulates in CCA, is able to distinguish CCA from liver cirrhosis, but is probably unsuitable to detect very early CCA lesions.
Equine clinical genomics: A clinician's primer
Authors: BROSNAHAN M. M. , BROOKS S. A. , ANTCZAK D. F. 
Published: September 2010

SummaryThe objective of this review is to introduce equine clinicians to the rapidly evolving field of clinical genomics with a vision of improving the health and welfare of the domestic horse. For 15 years a consortium of veterinary geneticists and clinicians has worked together under the umbrella of The Horse Genome Project. This group, encompassing 22 laboratories in 12 countries, has made rapid progress, developing several iterations of linkage, physical and comparative gene maps of the horse with increasing levels of detail. In early 2006, the research was greatly facilitated when the US National Human Genome Research Institute of the National Institutes of Health added the horse to the list of mammalian species scheduled for whole genome sequencing. The genome of the domestic horse has now been sequenced and is available to researchers worldwide in publicly accessible databases. This achievement creates the potential for transformative change within the horse industry, particularly in the fields of internal medicine, sports medicine and reproduction. The genome sequence has enabled the development of new genome‐wide tools and resources for studying inherited diseases of the horse. To date, researchers have identified 11 mutations causing 10 clinical syndromes in the horse. Testing is commercially available for all but one of these diseases. Future research will probably identify the genetic bases for other equine diseases, produce new diagnostic tests and generate novel therapeutics for some of these conditions. This will enable equine clinicians to play a critical role in ensuring the thoughtful and appropriate application of this knowledge as they assist clients with breeding and clinical decision‐making.
Sports chiropratic in prevention of pain and injury
Authors: Lawrence DJ , Hoskins W 
Published: September 2010

Hoskins W, Pollard H. The effect of a sports chiropractic manual therapy intervention on the prevention of back pain, hamstring and lower limb injuries in semi‐elite Australian Rules footballers: a randomised controlled trial. BMC Musculoskel Disord 2010; 11: 64.
Weak benefit of aqua lymphatic therapy for mild lymphoedema after breast cancer
Authors: Kraft K , Tidhar D , Katz‐Leurer M 
Published: September 2010

Tidhar D, Katz‐Leurer M. Aqua lymphatic therapy in women who suffer from breast cancer treatment‐related lymphedema: a randomized controlled study. Support Care Cancer 2010; 18: 383–92.
Shark cartilage does not prolong the life of lung cancer patients
Authors: Ernst E 
Published: September 2010

Lu C, Lee JJ, Komaki R, Herbst RS, Feng L, Evans WK, Choy H, Desjardins P, Esparaz BT, Truong MT, Saxman S, Kelaghan J, Bleyer A, Fisch MJ. Chemoradiotherapy with or without AE‐941 in stage III non‐small cell lung cancer: a randomized phase III trial. J Natl Cancer Inst 2010; 102: 859–65.
Schisandra extract elevates concentration of tacrolimus in blood of liver transplant patients
Authors: Awang DVC , Kong L , Jiang W 
Published: September 2010

Jiang W, Wang X, Xu X, Kong L. Effect of Schisandra sphenanthera extract on the concentration of tacrolimus in the blood of liver transplant patients. Int J Clin Pharmacol Ther 2010; 48: 224–9.
Eleven themes of patient-centred professionalism in community pharmacy: innovative approaches to consulting
Authors: Rapport Frances , Doel Marcus A , Hutchings Hayley A , Wright Sarah , Wainwright Paul , John Dai N , Jerzembek Gabrielle S 
Published: September 2010

Abstract

Objectives
The study aimed to clarify patient-centred professionalism within and across community pharmacy settings; position that knowledge in a modern-day environment, accessing the opinions and experiences of patients and professionals; inform the literature on the value of consultation workshops within this context; and develop a template of positive and challenging exemplars of patient-centred professionalism within these contexts.

Methods
Thirty-nine study participants contributed to extended consultation workshops. Sessions were supported by bio-photographic data of healthcare practices across a range of different settings, and a final forum event.

Key findings
Thematic analysis of qualitative data, supported by the Nominal Group Work technique, led to a template containing 11 themes of positive and challenging aspects of patient-centred professionalism: safety, professional characteristics, relationships with patients, confidentiality and privacy, accessibility, training, professional pressures, services, environment, changing professional roles and patient characteristics. Themes, while descriptive and rich, highlight difficulties in defining this notion, which is both nuanced and ambiguous. While study participants were interested in the everyday examples of practice and interaction, they were strongly influenced by their different agendas and experiences. Patients, for example, wanted a quick and efficient dispensing service, where their needs and expectations came first. Pharmacists, on the other hand, found that pressing patient demands and overarching company policies led to professional anxiety that distracted them from what they perceived to be the defining aspect of their professionalism, dispensary work.

Conclusions
The study outcomes indicate, in line with international literature, that while proud of supporting patients, many pharmacists feel demoralised, torn between pressing public and professional demands and the expectations of advice-giving in unfamiliar, formal situations within nondescript, corporate workspaces.
Discussing side effects of over-the-counter medicines: impact of adding percentage data
Authors: Seyed-Hosseini Mahsa , Taylor Jeff , Quest Dale 
Published: September 2010

Abstract

Objectives
Discussing side effects with patients continues to be a difficult area of practice. Questions arise as to how many should be mentioned and which ones. The way such information is presented can affect drug-taking decisions. This study examined how over-the-counter (OTC) medicine users are influenced by numerical risk estimates of side effects.

Methods
As part of a larger study on patient decision-making, 30 participants aged over 50 years were asked to consider three OTC headache medicines. They responded to one of two headache scenarios, one with symptoms described as mild but common and the other severe but rare. Participants made their selection based on drug efficacy and side effects, at first not linked to occurrence rates and then with this information provided.

Key findings
Average age was 66.6 years and the majority were female. Most were currently using some form of drug therapy. Drug choices differed in relation to mild versus severe headache scenarios. A stronger preference for drug X (50% effective and two side effects) was evident when the headaches were mild, shifting to a more effective agent (but with more side effects) when more severe. Addition of occurrence rates to the side effects had the greatest effect within the severe headache scenario, where more participants opted for the most effective agent (drug Z at 100% effective but six side effects) upon seeing the numbers. Overall, however, most kept the same drug in spite of the numerical information.

Conclusions
Inclusion of numerical data for side effects did not negatively influence potential OTC medicine users. For most, effectiveness and side effects were the concern before receiving the percentages, while effectiveness became more important when the frequency data seemed to instil a sense of reassurance.
Neutralizing Epitopes of Influenza Virus Hemagglutinin: Target for the Development of a Universal Vaccine against H5N1 Lineages
Authors: Prabakaran Mookkan , He Fang , Meng Tao , Madhan Selvaraj , Yunrui Tan , Jia Qiang , Kwang Jimmy 
Published: September 2010

ABSTRACTThe nature of influenza virus to randomly mutate and evolve into new types with diverse antigenic determinants is an important challenge in the control of influenza infection. Particularly, variations within the amino acid sequences of major neutralizing epitopes of influenza virus hemagglutinin (HA) hindered the development of universal vaccines against H5N1 lineages. Based on distribution analyses of the identified major neutralizing epitopes of hemagglutinin, we selected three vaccine strains that cover the entire variants in the neutralizing epitopes among the H5N1 lineages. HA proteins of selected vaccine strains were expressed on the baculovirus surface (BacHA), and the preclinical efficacy of the vaccine formulations was evaluated in a mouse model. The combination of three selected vaccine strains could effectively neutralize viruses from clades 1, 2.1, 2.2, 4, 7, and 8 of influenza H5N1 viruses. In contrast, a vaccine formulation containing only adjuvanted monovalent BacHA (mono-BacHA) or a single strain of inactivated whole viral vaccine was able to neutralize only clade 1 (homologous), clade 2.1, and clade 8.0 viruses. Also, the trivalent BacHA vaccine was able to protect 100% of the mice against challenge with three different clades (clade 1.0, clade 2.1, and clade 7.0) of H5N1 strains compared to mono-BacHA or inactivated whole viral vaccine. The present findings provide a rationale for the development of a universal vaccine against H5N1 lineages. Furthermore, baculoviruses displaying HA will serve as an ideal choice for a vaccine in prepandemic or pandemic situations and expedite vaccine technology without the requirement of high-level-biocontainment facilities or tedious protein purification processes.
Key success factors in an ASR scheme
Authors: Eastwood John C. , Stanfield Paul J. 
Published: September 2010

Wessex Water in conjunction with CH2 MHill and the British Geological Survey (BGS) has recently completed a major 3 year investigation into the resource potential of Aquifer Storage and Recovery (ASR) in a confined Chalk aquifer. The main part of the investigation followed the approach that has been successfully adopted in developing many ASR schemes in America in which the aim is to create a reservoir of potable water within a non-potable aquifer. In the Wessex Water case study it was found that elevated levels of fluoride prevented a potable reservoir being created, even after a 2 year programme of injection and recovery cycles. In terms of strict water quality criteria ASR was deemed unsuccessful. However when modelling the hydraulic response of the aquifer it confirmed that an ASR abstraction regime created little or no environmental impact and offered significant environmental advantages when compared with conventional groundwater development. It has always been assumed that ASR schemes have this inherent environmental advantage, but it is believed that this is the first time these benefits have been clearly demonstrated at a specific ASR site.
The lesson that can be drawn from these results is that environmental acceptability is fundamental to the success of an ASR scheme whereas securing water quality improvements is more likely to be important in determining scheme cost effectiveness. At a time when finding environmentally acceptable resource schemes is becoming increasingly difficult, ASR has a potentially significant advantage over alternative forms of resource development. However, the authors are concerned that because most case studies in England are focusing on water quality issues, these will be viewed as the key success factors for ASR and that its inherent environmental advantages will be overlooked. With most case studies reporting difficulties in meeting water quality objectives this could lead to the general perception that ASR is unlikely to be successful in this country and result in potentially beneficial applications being rejected or not even considered.
MET and KRAS Gene Amplification Mediates Acquired Resistance to MET Tyrosine Kinase Inhibitors
Authors: Cepero Virna , Sierra J. Rafael , Corso Simona , Ghiso Elena , Casorzo Laura , Perera Tim , Comoglio Paolo Maria , Giordano Silvia 
Published: September 2010

Abstract
The establishment of the role of MET in human cancer has led to the development of small-molecule inhibitors, many of which are currently in clinical trials. Thus far, nothing is known about their therapeutic efficacy and the possible emergence of resistance to treatment, a problem that has been often observed with other receptor tyrosine kinase (RTK) inhibitors. To predict mechanisms of acquired resistance, we generated resistant cells by treating MET-addicted cells with increasing concentrations of the MET small-molecule inhibitors PHA-665752 or JNJ38877605. Resistant cells displayed MET gene amplification, leading to increased expression and constitutive phosphorylation of MET, followed by subsequent amplification and overexpression of wild-type (wt) KRAS. Cells harboring KRAS amplification progressively lost their MET dependence and acquired KRAS dependence. Our results suggest that MET and KRAS amplification is a general mechanism of resistance to specific MET inhibitors given that similar results were observed with two small inhibitors and in different cell lines of different histotypes. To our knowledge, this is the first report showing that overexpression of wt KRAS can overcome the inhibitory effect of a RTK inhibitor. In view of the fact that cellular models of resistance to inhibitors targeting other tyrosine kinases have predicted and corroborated clinical findings, our results provide insights into strategies for preventing and/or overcoming drug resistance. Cancer Res; 70(19); 7580–90. ©2010 AACR.
Unique DNA Methylation Patterns Distinguish Noninvasive and Invasive Urothelial Cancers and Establish an Epigenetic Field Defect in Premalignant Tissue
Authors: Wolff Erika M. , Chihara Yoshitomo , Pan Fei , Weisenberger Daniel J. , Siegmund Kimberly D. , Sugano Kokichi , Kawashima Kiyotaka , Laird Peter W. , Jones Peter A. , Liang Gangning 
Published: September 2010

AbstractUrothelial cancer (UC) develops along two different genetic pathways, resulting in noninvasive or invasive tumors. However, it is unknown whether there are also different epigenetic pathways in UC. UC is also characterized by a high rate of recurrence, and the presence of a field defect has been postulated. In this study, we compared the DNA methylation patterns between noninvasive and invasive UC and the DNA methylation patterns between normal-appearing urothelium from bladders with cancer and urothelium from cancer-free bladders. We used the Illumina GoldenGate methylation assay at 1,370 loci in 49 noninvasive urothelial tumors, 38 invasive tumors with matched normal-appearing urothelium, and urothelium from 12 age-matched UC-free patients. We found distinct patterns of hypomethylation in the noninvasive tumors and widespread hypermethylation in the invasive tumors, confirming that the two pathways differ epigenetically in addition to genetically. We also found that 12% of the loci were hypermethylated in apparently normal urothelium from bladders with cancer, indicating an epigenetic field defect. X-chromosome inactivation analysis indicated that this field defect did not result in clonal expansion but occurred independently across the urothelium of bladders with cancer. The hypomethylation present in noninvasive tumors may counterintuitively provide a biological explanation for the failure of these tumors to become invasive. In addition, an epithelium-wide epigenetic defect in bladders with cancer might contribute to a loss of epithelial integrity and create a permissible environment for tumors to arise. Cancer Res; 70(20); 8169–78. ©2010 AACR.
Heat Shock Protein 90 Inhibition Depletes LATS1 and LATS2, Two Regulators of the Mammalian Hippo Tumor Suppressor Pathway
Authors: Huntoon Catherine J. , Nye Monica D. , Geng Liyi , Peterson Kevin L. , Flatten Karen S. , Haluska Paul , Kaufmann Scott H. , Karnitz Larry M. 
Published: September 2010

Abstract
Heat shock protein 90 (HSP90), which regulates the functions of multiple oncogenic signaling pathways, has emerged as a novel anticancer therapeutic target, and multiple small-molecule HSP90 inhibitors are now in clinical trials. Although the effects of HSP90 inhibitors on oncogenic signaling pathways have been extensively studied, the effects of these agents on tumor suppressor signaling pathways are currently unknown. Here, we have examined how HSP90 inhibitors affect LATS1 and the related protein LATS2, two kinases that relay antiproliferative signals in the Hippo tumor suppressor pathway. Both LATS1 and LATS2 were depleted from cells treated with the HSP90 inhibitors 17-allylamino-17-demethoxygeldanamycin (17-AAG), radicicol, and PU-H71. Moreover, these kinases interacted with HSP90, and LATS1 isolated from 17-AAG–treated cells had reduced catalytic activity, thus showing that the kinase is a bona fide HSP90 client. Importantly, LATS1 signaling was disrupted by 17-AAG in tumor cell lines in vitro and clinical ovarian cancers in vivo as shown by reduced levels of LATS1 and decreased phosphorylation of the LATS substrate YAP, an oncoprotein transcriptional coactivator that regulates genes involved in cell and tissue growth, including the CTGF gene. Consistent with the reduced YAP phosphorylation, there were increased levels of CTGF, a secreted protein that is implicated in tumor proliferation, metastasis, and angiogenesis. Taken together, these results identify LATS1 and LATS2 as novel HSP90 clients and show that HSP90 inhibitors can disrupt the LATS tumor suppressor pathway in human cancer cells. Cancer Res; 70(21); 8642–50. ©2010 AACR.
Cancer-Related Epigenome Changes Associated with Reprogramming to Induced Pluripotent Stem Cells
Authors: Ohm Joyce E. , Mali Prashant , Van Neste Leander , Berman David M. , Liang Liang , Pandiyan Kurinji , Briggs Kimberly J. , Zhang Wei , Argani Pedram , Simons Brian , Yu Wayne , Matsui William , Van Criekinge Wim , Rassool Feyruz V. , Zambidis Elias , Schuebel Kornel E. , Cope Leslie , Yen Jonathan , Mohammad Helai P. , Cheng Linzhao , Baylin Stephen B. 
Published: September 2010

Abstract
The ability to induce pluripotent stem cells from committed, somatic human cells provides tremendous potential for regenerative medicine. However, there is a defined neoplastic potential inherent to such reprogramming that must be understood and may provide a model for understanding key events in tumorigenesis. Using genome-wide assays, we identify cancer-related epigenetic abnormalities that arise early during reprogramming and persist in induced pluripotent stem cell (iPS) clones. These include hundreds of abnormal gene silencing events, patterns of aberrant responses to epigenetic-modifying drugs resembling those for cancer cells, and presence in iPS and partially reprogrammed cells of cancer-specific gene promoter DNA methylation alterations. Our findings suggest that by studying the process of induced reprogramming, we may gain significant insight into the origins of epigenetic gene silencing associated with human tumorigenesis, and add to means of assessing iPS for safety. Cancer Res; 70(19); 7662–73. ©2010 AACR.
MicroRNA Mediates DNA Demethylation Events Triggered by Retinoic Acid during Neuroblastoma Cell Differentiation
Authors: Das Sudipto , Foley Niamh , Bryan Kenneth , Watters Karen M. , Bray Isabella , Murphy Derek M. , Buckley Patrick G. , Stallings Raymond L. 
Published: September 2010

AbstractNeuroblastoma is an often fatal pediatric cancer arising from precursor cells of the sympathetic nervous system. 13-Cis retinoic acid is included in the treatment regimen for patients with high-risk disease, and a similar derivative, all-trans-retinoic acid (ATRA), causes neuroblastoma cell lines to undergo differentiation. The molecular signaling pathways involved with ATRA-induced differentiation are complex, and the role that DNA methylation changes might play are unknown. The purpose of this study was to evaluate the genome-wide effects of ATRA on DNA methylation using methylated DNA immunoprecipitation applied to microarrays representing all known promoter and CpG islands. Four hundred and two gene promoters became demethylated, whereas 88 were hypermethylated post-ATRA. mRNA expression microarrays revealed that 82 of the demethylated genes were overexpressed by &gt;2-fold, whereas 13 of the hypermethylated genes were underexpressed. Gene ontology analysis indicated that demethylated and re-expressed genes were enriched for signal transduction pathways, including NOS1, which is required for neural cell differentiation. As a potential mechanism for the DNA methylation changes, we show the downregulation of methyltransferases, DNMT1 and DNMT3B, along with the upregulation of endogenous microRNAs targeting them. Ectopic overexpression of miR-152, targeting DNMT1, also negatively affected cell invasiveness and anchorage-independent growth, contributing in part to the differentiated phenotype. We conclude that functionally important, miRNA-mediated DNA demethylation changes contribute to the process of ATRA-induced differentiation resulting in the activation of NOS1, a critical determinant of neural cell differentiation. Our findings illustrate the plasticity and dynamic nature of the epigenome during cancer cell differentiation. Cancer Res; 70(20); 7874–81. ©2010 AACR.