tbuckley/cabot-search huggingface dataset:
The optimal assessment of the rheumatoid arthritis hindfoot: a comparative study of clinical examination, ultrasound and high field MRI
Authors: R J Wakefield, J E Freeston, P O'Connor, N Reay, A Budgen, E M A Hensor, P S Helliwell, P Emery, J Woodburn
Journal: Annals of the Rheumatic Diseases (2008)

<h3>AIMS</h3> Slit lamp fundus biomicroscopy allows for high magnification, stereoscopic diagnosis, and treatment of macular diseases. Variable contrast, narrow field of view, and specular reflections arising from the cornea, sclera, and examining lens reduce image quality; these images are of limited clinical utility for diagnosis, treatment planning, and photodocumentation when compared with fundus camera images. Algorithms are being developed to segment fundus imagery from slit lamp biomicroscopic video image sequences in order to improve clinical utility. <h3>METHODS</h3> Video fundus image sequences of human volunteers were acquired with a video equipped, Nikon NS-1V slit lamp biomicroscope. Custom developed software identified specular reflections based on brightness and colour content, and extracted the illuminated fundus image based on colour image analysis and size constraints. <h3>RESULTS</h3> In five subjects with variable image quality, the approach allowed for automatic, robust, accurate extraction of that portion of the video image corresponding to the illuminated portion of the fundus. Non-real time analysis allowed for fundus image segmentation for each frame of the image sequence. In real time, segmentation occurs at 2 Hz, and improvements are being implemented for video rate performance. <h3>CONCLUSIONS</h3> Computer vision algorithms allow for real time extraction of fundus imagery from marginal quality, slit lamp fundus biomicroscope image sequences.
Survey of sports injury prevention programmes in the European Community
Authors: A W S Watson
Journal: British Journal of Sports Medicine (2000)

Editor,—I would like to provide a brief report of a survey of sports injury prevention programmes and related research projects in the European Community between September and December 1998.

With the cooperation of partners in the Netherlands (the Netherlands Olympic Committee and the Netherlands Sports Federation), Austria (the Austrian Institute for Home and Leisure Safety), and Belgium (Flanders Red Cross) a questionnaire on sports injury prevention and related research was devised, piloted, and distributed to a sample of 368 sports, health, or safety organisations in Europe. The objective of the study was to determine the number of institutions involved in injury prevention work, and also to seek information on the nature and quality of the work being undertaken.

A total of 86 questionnaires were …
Clonal dominance of chronic myelogenous leukemia is associated with diminished sensitivity to the antiproliferative effects of neutrophil elastase
Authors: Frank El Ouriaghli, Elaine Sloand, Lori Mainwaring, Hiroshi Fujiwara, Keyvan Keyvanfar, J. Joseph Melenhorst, Katayoun Rezvani, Giuseppe Sconocchia, Scott Solomon, Nancy Hensel, A. John Barrett
Journal: Blood (2003)
Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface
Authors: Kristy Red-Horse, Yan Zhou, Olga Genbacev, Akraporn Prakobphol, Russell Foulk, Michael McMaster, Susan J. Fisher
Journal: Journal of Clinical Investigation (2004)

Trophoblasts, the specialized cells of the placenta, play a major role in implantation and formation of the maternal-fetal interface. Through an unusual differentiation process examined in this review, these fetal cells acquire properties of leukocytes and endothelial cells that enable many of their specialized functions. In recent years a great deal has been learned about the regulatory mechanisms, from transcriptional networks to oxygen tension, which control trophoblast differentiation. The challenge is to turn this information into clinically useful tests for monitoring placental function and, hence, pregnancy outcome.
Zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine
Authors: Katharine J Webb, William HJ Norton, Dietrich Trümbach, Annemarie H Meijer, Jovica Ninkovic, Stefanie Topp, Daniel Heck, Carsten Marr, Wolfgang Wurst, Fabian J Theis, Herman P Spaink, Laure Bally-Cuif
Journal: Genome biology (2009)

Abstract Background Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction ( nad dne 3256 ), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. Results Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes. Conclusions Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction.
Type I Gaucher disease with severe skeletal destruction, extraosseous extension, and monoclonal gammopathy
Authors: A. Kaloterakis, E. Cholongitas, E. Pantelis, C. Papadimitriou, Sp. Durakis, A. Filiotou
Journal: American Journal of Hematology (2004)

Abstract Extraosseous extensions of Gaucher‐cell deposits simulate malignant diseases. We describe a 65‐year‐old male with type‐I Gaucher disease, confirmed by low leukocyte glucocerebrosidase activity, high plasma chitotriosidase, and N370/L444P gene‐mutations, who had severe skeletal involvement, IgG‐κ monoclonal gammopathy, and a soft‐tissue mass within the left iliac muscle. Bone marrow biopsy showed heavy infiltration by Gaucher cells, and histopathology of the excised extraosseous mass revealed infiltration by Gaucher cells. Thus, malignant diseases were excluded and the diagnosis of an extraosseous Gaucher‐cell extension was well documented. Our case is reported because it is very interesting and unique in the literature. Am. J. Hematol. 77:377–380, 2004. © 2004 Wiley‐Liss, Inc.
Phase II Clinical Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Patients With Taxane-Resistant Metastatic Breast Cancer
Authors: Eva Thomas, Josep Tabernero, Monica Fornier, Pierfranco Conté, Pierre Fumoleau, Ana Lluch, Linda T. Vahdat, Craig A. Bunnell, Howard A. Burris, Patrice Viens, José Baselga, Edgardo Rivera, Valentina Guarneri, Valerie Poulart, Judith Klimovsky, David Lebwohl, Miguel Martin
Journal: Journal of Clinical Oncology (2007)

Purpose Ixabepilone (BMS-247550) is an epothilone analog that optimizes the properties of naturally occurring epothilone B. Natural epothilones and their analogs promote tumor cell death by binding to tubulin and stabilizing microtubules, causing apoptosis. This international phase II trial assessed the activity of ixabepilone in patients with metastatic breast cancer (MBC) that was resistant to taxane therapy. Patients and Methods MBC patients, who had experienced disease progression while receiving or within 4 months of taxane therapy (6 months if adjuvant taxane only), and who had a taxane as their last regimen, received ixabepilone (1- or 3-hour infusion of 50 mg/m 2 or 3-hour infusion of 40 mg/m 2 every 3 weeks). Results Of 49 patients treated with 40 mg/m 2 ixabepilone during 3 hours, 35 (73%) had experienced disease progression within 1 month of their last taxane dose. The response rate was 12% (95% CI, 4.7% to 26.5%). All responses (n = 6) were partial; five of six patients had not responded to prior taxane therapy. In responders, the median response duration was 10.4 months. In 20 patients (41%), stable disease was the best outcome. Median time to progression was 2.2 months (95% CI, 1.4 to 3.2 months); median survival was 7.9 months. For treated patients across all cohorts (intent-to-treat population), the response rate was also 12% (eight of 66). Treatment-related adverse events in the study were manageable and primarily grade 1/2. Treatment-related neuropathy was mostly sensory and mild to moderate. Conclusion Ixabepilone (40 mg/m 2 as a 3-hour infusion every 3 weeks) demonstrates promising antitumor activity and an acceptable safety profile in patients with taxane-resistant MBC.
509 SERUM IP10 LEVELS AT BASELINE AND DURING THERAPY DO NOT PREDICT SVR IN CHRONIC HEPATITIS C PATIENTS TREATED WITH HIGH INDUCTION DOSE INTERFERON
Authors: S.B. Willemse, H.C. Gelderblom, R. Molenkamp, H.W. Reesink, J. Schinkel
Journal: Journal of Hepatology (2013)
OC-139 Time trends in rates of first surgical resection and thiopurine use in crohn's disease: retrospective cohort study
Authors: S Chatu, S Saxena, V Subramanian, V Curcin, G Yadegarfar, A Majeed, R C Pollok
Journal: Gut (2012)

<h3>Introduction</h3> The efficacy of thiopurines in treating Crohn9s disease is well established but their role in altering the long term natural history of Crohn9s disease remains controversial. Using a national population based cohort we aimed to determine temporal trends in surgery and use of thiopurines. <h3>Methods</h3> We undertook a retrospective study of electronic medical records from primary care. We identified newly diagnosed patients with Crohn9s disease between 1989 and 2005 in the General Practise Research database (GPRD) which contains prescription and clinical data for over 13 million people in the UK and has been validated for research. Incident cases were eligible if registered for more than 12 months before their diagnosis. Patients were allocated to three cohorts according to year of diagnosis: group A (1989–1993), group B (1994–1999) and group C (2000–2005). We calculated rates of first surgical resection and thiopurine prescribing (azathiopurine and 6-mercaptopurine) within 5 years of diagnosis to examine temporal trends. <h3>Results</h3> 5654 patients met our inclusion criteria. The mean age was 37 years and 57% were female. During the study period from 1989 to 2010 rates of intestinal surgery decreased while prescription of thiopurines increased. Rates of first surgery were 17, 11, and 6/1000/year (χ<sup>2</sup> p&lt;0.05) and thiopurine prescriptions were 27, 33 and 45/1000/year (χ<sup>2</sup> p&lt;0.05) in groups A, B and C respectively. Furthermore rates of thiopurine prescription within the first year of diagnosis were 11, 15, and 26/1000/year (χ<sup>2</sup> p&lt;0.05) in groups A, B and C respectively. <h3>Conclusion</h3> Rates of first surgical resection have markedly decreased with concomitant earlier and increased use of thiopurines over the same time frame. Further work is proposed to explain these trends. <h3>Competing interests</h3> None declared.
Challenges in Systematic Reviews That Evaluate Drug Efficacy or Effectiveness
Authors: P. Lina Santaguida
Journal: Annals of Internal Medicine (2005)

Increasingly, consumers, clinicians, regulatory bodies, and insurers are using systematic reviews of drug interventions to select treatments and set policies. Although a systematic review cannot provide all the information a clinician needs to make an informed choice for therapy, it can help decision makers distinguish what claims about effectiveness are based on evidence, identify critical information gaps, desc ribe features of the evidence that limit applicability in practice, and address whether drug effectiveness differs for particular subgroups of patients. To improve the relevance and validity of reviews of drug therapies, reviewers need to delineate clinically important subgroups, specific aims of therapy, and most important outcomes. They may need to find unpublished trials, studies other than direct comparator (head-to-head) trials, and additional details of published trials from pharmaceutical manufacturers and regulatory agencies. In this paper, we address ways to formulate questions relevant to specific clinical therapeutic aims; discuss types of studies to include in drug efficacy and effectiveness reviews and how to find them; and describe ways to assess applicability of studies to actual practice.
Association between variants in the interferon lambda 4 locus and substitutions in the hepatitis C virus non-structural protein 5A
Authors: Sakura Akamatsu, C. Nelson Hayes, Hidenori Ochi, Takuro Uchida, Hiromi Kan, Eisuke Murakami, Hiromi Abe, Masataka Tsuge, Daiki Miki, Rie Akiyama, Nobuhiko Hiraga, Michio Imamura, Hiroshi Aikata, Tomokazu Kawaoka, Yoshiiku Kawakami, Kazuaki Chayama
Journal: Journal of Hepatology (2015)
Circulating Tumor Cells in Perioperative Esophageal Cancer Patients: Quantitative Assay System and Potential Clinical Utility
Authors: Zhian Liu, Ming Jiang, Jianhua Zhao, Huangxian Ju
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To establish a quantitative system for evaluating the role of circulating tumor cells (CTC) in peripheral blood samples in patients who undergo surgery for treatment of esophageal cancer. Experimental Design: One hundred fifty-five peripheral blood samples from 53 esophageal cancer patients were collected before surgery (B-1), immediately after surgery (B0), and on the 3rd day postoperatively (B+3). Eighty-nine samples from 22 benign patients who underwent thoracotomy and 30 healthy volunteers were obtained as controls. A real-time reverse transcription-PCR quantitative analysis system based on carcinoembryonic antigen (CEA) mRNA gene expression was designed for detection of CTC. Results: This developed system can detect CEA mRNA-positive cells down to 3 cells per milliliter of peripheral blood. The cells in negative control groups were lower than the detection limit. The medians of 188 [95% confidence interval (95% CI), 155-498], 1513 (95% CI, 660-7,974) and 707 (95% CI, 737-3,005) CEA mRNA-positive cells per mL with the CEA-positive rates of 28.3%, 60.4%, and 42.9% in B-1, B0, and B+3 peripheral blood samples were obtained, respectively. There was statistically significant difference between B-1 and B0 (P = 0.0001) and between B-1 and B+3 (P = 0.0209). Fifty percent of patients with R &amp;gt; 0.4 showed metastasis in 1 year after surgery, whereas the probability was only 14.3% for patients with R &amp;lt; 0.4 (where R is CTC ratio of B+3 to B0, P = 0.043). Conclusions: Esophageal cancer operation results in tumor cells dissemination and significant increase of CTC in peripheral blood, which is related to the developed metastasis. CTC are helpful for evaluating micrometastasis and have the potential for predicting recurrence in esophageal cancer.
Pancreatic Digestive Enzyme Blockade in the Intestine Increases Survival After Experimental Shock
Authors: Frank A. DeLano, David B. Hoyt, Geert W. Schmid-Schönbein
Journal: Science Translational Medicine (2013)

Shock, sepsis, and multiorgan failure are associated with inflammation, morbidity, and high mortality. The underlying pathophysiological mechanism is unknown, but evidence suggests that pancreatic enzymes in the intestinal lumen autodigest the intestine and generate systemic inflammation. Blocking these enzymes in the intestine reduces inflammation and multiorgan dysfunction. We investigated whether enzymatic blockade also reduces mortality after shock. Three rat shock models were used here: hemorrhagic shock, peritonitis shock induced by placement of cecal material into the peritoneum, and endotoxin shock. One hour after initiation of hemorrhagic, peritonitis, or endotoxin shock, animals were administered one of three different pancreatic enzyme inhibitors--6-amidino-2-naphtyl p-guanidinobenzoate dimethanesulfate, tranexamic acid, or aprotinin--into the lumen of the small intestine. In all forms of shock, blockade of digestive proteases with protease inhibitor attenuated entry of digestive enzymes into the wall of the intestine and subsequent autodigestion and morphological damage to the intestine, lung, and heart. Animals treated with protease inhibitors also survived in larger numbers than untreated controls over a period of 12 weeks. Surviving animals recovered completely and returned to normal weight within 14 days after shock. The results suggest that the active and concentrated digestive enzymes in the lumen of the intestine play a central role in shock and multiorgan failure, which can be treated with protease inhibitors that are currently available for use in the clinic.
Impact of a Single Nucleotide Polymorphism in the <i>MDM2</i> Gene on Neuroblastoma Development and Aggressiveness: Results of a Pilot Study on 239 Patients
Authors: Sara Cattelani, Raffaella Defferrari, Sonia Marsilio, Rita Bussolari, Olivia Candini, Francesca Corradini, Giovanna Ferrari-Amorotti, Clara Guerzoni, Luisa Pecorari, Chiara Menin, Roberta Bertorelle, Pierluigi Altavista, Heather P. McDowell, Renata Boldrini, Carlo Dominici, Gian Paolo Tonini, Giuseppe Raschellà, Bruno Calabretta
Journal: Clinical Cancer Research (2008)

Abstract Purpose: MDM2 is a key negative regulator of p53 activity, and a single nucleotide polymorphism (SNP309, T&amp;gt;G change; rs 2279744) in its promoter increases the affinity for the transcription factor SP1, enhancing MDM2 expression. We carried out a pilot study to investigate the effect of this polymorphism on development and behavior of neuroblastoma, an extracranial pediatric tumor with unfrequent genetic inactivation of p53. Experimental Design: We genotyped the MDM2-SNP309 alleles of tumor DNA from 239 neuroblastoma patients and peripheral blood DNA from 237 controls. In 40 of 239 neuroblastomas, the MDM2-SNP309 alleles were also genotyped in peripheral blood DNA. Data were analyzed by two-sided Fisher's exact test, log-rank test, and Kaplan-Meier statistics. Where appropriate, data are reported with 95% confidence intervals (CI). Results: The frequency of both the T/G and G/G genotypes or the G/G or T/G genotype only was higher in neuroblastoma DNA samples than in controls: 60.3% (95% CI, 54.1-66.5) versus 47.3% (95% CI, 40.9-53.6), 30.4% (95% CI, 22.4-37.8) versus 15.0% (95% CI, 9.2-20.7), and 52.0% (95% CI, 45.0-59.9) versus 41.9% (95% CI, 35.3-48.5), respectively; Two-Sided Fisher's Exact Test P values were 0.006, 0.003, and 0.048, respectively; Odds ratios were 1.69 (95% CI, 1.18-2.43), 2.45 (95% CI, 1.37-4.39) and 1.51 (95% CI, 1.02-2.22), respectively. A significant association (P = 0.016) between heterozygous (T/G)/homozygous (G/G) genotypes at SNP309 and advanced clinical stages was also shown. Homozygous/heterozygous SNP309 variant carriers had a shorter 5-year overall survival than patients with the wild-type allele (P = 0.046; log-rank test). A shorter overall survival in patients with heterozygous/homozygous SNP309 was also observed in the subgroups with age at diagnosis &amp;gt;1 year and adrenal primary tumor (P = 0.024 and P = 0.014, respectively). Conclusions: Data from this pilot study suggest that the MDM2 G/G and T/G-SNP309 alleles are markers of increased predisposition to tumor development and disease aggressiveness in neuroblastoma. However, additional studies with larger patient cohorts are required for a definitive assessment of the clinical relevance of these data.
A tool for measuring workers' sitting time by domain: the Workforce Sitting Questionnaire
Authors: Josephine Y Chau, Hidde P van der Ploeg, Scott Dunn, John Kurko, Adrian E Bauman
Journal: British Journal of Sports Medicine (2011)

Background Sitting time is an emerging health risk, and many working adults spend large amounts of time sitting each day. It is important to have reliable and accurate measurement tools to assess sitting time in different contexts. Objective To validate the Workforce Sitting Questionnaire (WSQ), an adapted measure of total and domain-specific sitting time based on work and non-workdays for use in working adults. Methods A convenience sample (N=95, 63.2% women) was recruited from two workplaces and by word-of-mouth in Sydney, Australia. Participants completed the WSQ, which asked about sitting time (1) while travelling to and from places; (2) while at work; (3) while watching TV; (4) while using a computer at home; and (5) while doing other leisure activities on work and non-workdays on two occasions, 7 days apart. Participants also wore an accelerometer for the 7 days between test and retest. They recorded the times they wore the accelerometer, the days they worked and their work times in a logbook. Analyses determined test–retest reliability with intraclass correlation coefficients (ICCs) and assessed criterion validity against accelerometers using Spearman's r and Bland–Altman plots. Results Measuring total sitting time based on a workday, non-workday and on average had fair to excellent test–retest reliability (ICC=0.46–0.90) and had sufficient criterion validity against accelerometry in women (r=0.22–0.46) and men (r=0.18–0.29). Measuring domain-specific sitting at work on a workday was also reliable (ICC=0.63) and valid (r=0.45). Conclusions The WSQ has acceptable measurement properties for measuring sitting time at work on a workday and for assessing total sitting time based on work and non-workdays. This questionnaire would be suitable for use in research investigating the relationships between sitting time and health in working populations.
New Strategies in Refractory and Recurrent Neuroblastoma: Translational Opportunities to Impact Patient Outcome
Authors: Kristina A. Cole, John M. Maris
Journal: Clinical Cancer Research (2012)

Neuroblastoma remains responsible for a disproportionate amount of childhood cancer morbidity and mortality despite recent significant advances in understanding the genetic basis of tumor initiation and progression. About half of newly diagnosed patients can be reliably identified as having tumors of low malignant potential, and these children have cure rates of greater than 95% with little or no cytotoxic therapy. On the other hand, the other half of neuroblastomas typically present in an explosive fashion with widely metastatic disease, and reliable tumor-specific biomarkers have been defined for this phenotype as well. Empiric approaches to high-risk neuroblastoma therapy have relied on dramatic escalation of chemotherapy dose intensity and, recently, the incorporation of targeted immunotherapy, but nearly 50% of children with high-risk disease will be refractory to therapy or suffer a relapse, both of which are invariably fatal. Future improvements in high-risk neuroblastoma outcomes will require the identification of disease and patient-specific oncogenic vulnerabilities that can be leveraged therapeutically. Rational development of novel approaches to neuroblastoma therapy requires forward-thinking strategies to unequivocally prove activity in the relapse setting and, ultimately, efficacy in curing patients when integrated into frontline treatment plans.