tbuckley/cabot-search huggingface dataset:
Estimation and correction of non-specific binding in a large-scale spike-in experiment
Authors: Eugene F Schuster, Eric Blanc, Linda Partridge, Janet M Thornton
Journal: Genome biology (2007)

The availability of a recently published large-scale spike-in microarray dataset helps us to understand the influence of probe sequence in non-specific binding (NSB) signal and enables the benchmarking of several models for the estimation of NSB. In a typical microarray experiment using Affymetrix whole genome chips, 30% to 50% of the probes will apparently have absent target transcripts and show only NSB signal, and these probes can have significant repercussions for normalization and the statistical analysis of the data if NSB is not estimated correctly. We have found that the MAS5 perfect match-mismatch (PM-MM) model is a poor model for estimation of NSB, and that the Naef and Zhang sequence-based models can reasonably estimate NSB. In general, using the GC robust multi-array average, which uses Naef binding affinities, to calculate NSB (GC-NSB) outperforms other methods for detecting differential expression. However, there is an intensity dependence of the best performing methods for generating probeset expression values. At low intensity, methods using GC-NSB outperform other methods, but at medium intensity, MAS5 PM-MM methods perform best, and at high intensity, MAS5 PM-MM and Zhang's position-dependent nearest-neighbor (PDNN) methods perform best. A combined statistical analysis using the MAS5 PM-MM, GC-NSB and PDNN methods to generate probeset values results in an improved ability to detect differential expression and estimates of false discovery rates compared with the individual methods. Additional improvements in detecting differential expression can be achieved by a strict elimination of empty probesets before normalization. However, there are still large gaps in our understanding of the Affymetrix GeneChip technology, and additional large-scale datasets, in which the concentration of each transcript is known, need to be produced before better models of specific binding can be created.
Randomized, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD) plus ribavirin with or without amantadine in treatment-naïve patients with chronic hepatitis C genotype 1 infection
Authors: Peter Ferenci, Elisabeth Formann, Hermann Laferl, Michael Gschwantler, Franz Hackl, Harald Brunner, Rainer Hubmann, Christian Datz, Rudolf Stauber, Petra Steindl-Munda, Harald H. Kessler, Anton Klingler, Alfred Gangl
Journal: Journal of Hepatology (2005)
Plasma-Cell Granuloma Producing Calcitriol and Hypercalcemia
Authors: MARY ALICE HELIKSON
Journal: Annals of Internal Medicine (1986)

A teenage boy presented with hypercalcemia and a large intrathoracic mass. Results of an extensive evaluation, including normal findings on parathyroid hormone and urinary 3 , 5-cyclic adenosine monophosphate assays, failed to explain his hypercalcemia. During surgery, a large plasma-cell granuloma of the right middle and lower lobes was resected. Within 2 weeks, serum calcium levels returned to normal. Serum calcitriol (1,25-dihydroxyvitamin D3) levels were elevated before surgery and decreased to normal afterward, correlating with the serum calcium level. Homogenates of the plasma-cell granuloma synthesized a compound indistinguishable from calcitriol.
Association Between Nonalcoholic Fatty Liver Disease and Risk for Hepatocellular Cancer, Based on Systematic Review
Authors: Donna L. White, Fasiha Kanwal, Hashem B. El–Serag
Journal: Clinical Gastroenterology and Hepatology (2012)

Nonalcoholic fatty liver disease (NAFLD) has been implicated as a cause of hepatocellular carcinoma (HCC). We performed a systematic review of epidemiology studies to confirm the association between these disorders.We searched PubMed for original reports published from January 1992 to December 2011 that evaluated the association between NAFLD, nonalcoholic steatohepatitis (NASH), cryptogenic cirrhosis presumed to be NASH-related, and the risk of HCC. Studies were categorized as offering potential direct evidence (eg, cohort studies) or indirect evidence (eg, case-control, cross-sectional, or case-series studies) for an association. We analyzed data from a total of 17 cohort studies (3 population based, 9 clinic based [6 limited to patients with cirrhosis], and 5 natural history), 18 case-control and cross-sectional studies, and 26 case series.NAFLD or NASH cohorts with few or no cases of cirrhosis cases had a minimal risk for HCC (cumulative HCC mortality of 0%-3% for study periods up to 20 y). Cohorts with NASH and cirrhosis had a consistently higher risk (cumulative incidence ranging from 2.4% over 7 y to 12.8% over 3 y). However, the risk for HCC was substantially lower in these cohorts than for cohorts with hepatitis C-related cirrhosis. Factors that increased risk among cohorts with NASH and cirrhosis could not be determined, because most studies were not sufficiently powered for multivariate analysis.This systematic review shows that despite several limitations, there is epidemiologic evidence to support an association between NAFLD or NASH and an increased risk of HCC; risk seems to be limited to individuals with cirrhosis.
Transcriptional activation of a hybrid promoter composed of cytomegalovirus enhancer and β-actin/β-globin gene in glomerular epithelial cells in vivo
Authors: Yoshitaka Akagi, Yoshitaka Isaka, Akiko Akagi, Masahito Ikawa, Masaru Takenaka, Toshiki Moriyama, Atsushi Yamauchi, Masaru Horio, Naohiko Ueda, Masaru Okabe, Enyu Imai
Journal: Kidney International (1997)
Government makes U turn on private practice ban
Authors: S. Hargreaves
Journal: BMJ (2002)

The UK government has been forced to backtrack on its commitment to ban newly qualified NHS consultants from working privately for at least seven years after qualification.

As part of a new consultants' contract, launched last week at a BMA conference in London, the heavily criticised ban on private practice outlined in the government's July 2000 NHS Plan will be abandoned ( BMJ 2001; 321:317). Several changes in the pay structure and working practices of consultants will be implemented in its place.

“The government has had to …
Validity and responsiveness of the Osnabrück Hand Eczema Severity Index (OHSI): a methodological study
Authors: M. Dulon, C. Skudlik, M. Nübling, S.M. John, A. Nienhaus
Journal: British Journal of Dermatology (2008)

The Osnabrück Hand Eczema Severity Index (OHSI) is a scoring system for the assessment of the severity of hand eczema (HE).To assess the clinimetric value of the OHSI and to validate the longitudinal responsiveness of the OHSI using the Manuscore as a gold standard.OHSI and Manuscore scores were compared before and after 3 weeks' inpatient treatment of 62 patients with occupational HE. Correlation coefficients and 95% limits of agreement were calculated and the ability of OHSI to identify severe HE was analysed. The responsiveness of the OHSI in monitoring skin changes over time was evaluated by calculating effect sizes.High correlation was found between the OHSI and Manuscore at both scoring occasions (around r(s) = 0.77). Differences between both measurements were within the 95% limits of agreement for 94% of patients, with a tendency for the OHSI to underestimate the severity at very low and at very high values compared with the Manuscore. Responsiveness to change was good. Both instruments showed significant improvement between the scoring occasions. Using the OHSI values, the proportion of classification to the correct tertile of score change was 69%. Effect size from untreated to treated was 0.6 for the Manuscore and 1.1 for the OHSI, with higher effect sizes in individuals with severe HE.Even though the OHSI allows less differentiation than the Manuscore, it shows adequate validity and responsiveness to change. Thus the OHSI is suitable for both monitoring the severity of HE and the effects of treatment.
NICE work: Level playing field requires transparency
Authors: Rubin Minhas
Journal: BMJ (2006)

EDITOR—Ferner and McDowell highlight the direct marketing of product messages via the media.1 This is important, but it is obvious, unsophisticated, and has begun to attract condemnation.2

“Specialist societies” and “disease interest groups” have an important role. These are often dependent on pharmaceutical sponsorship, and their leadership is heavily targeted by the marketing arm of the drugs industry. The grey market of “satellite symposia” and ad hoc promotional meetings provides fertile ground where self interest, disease promotion, and marketing combine. Opinion leaders can be provided with soft research grants, included as investigators …
Book: The Baltimore Case: A Trial of Politics, Science, and Character
Authors: S. Lock
Journal: BMJ (1999)

Daniel J Kevles W W Norton, £21, pp 448 ISBN 0393041034 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> The story would make a marvellous soap opera. The research, into immunological genetics and published in Cell , is complex, made worse by the inadequate English of Teresa Imanishi-Kari, the Brazilian-Japanese research worker. Accused of fraud, she is defended by her charismatic but hubristic boss, the Nobel laureate David Baltimore, who takes on a congressional committee. The whistleblower, Margot O'Toole, a young Irish radical, loses her job, house, and career—but receives international honours and publicity for her courage. After 10 years and seven inquiries, reviews, and the final, successful, appeal, the US immunological establishment has disagreed about guilt or innocence, and even the secret service has examined the research … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
PEDIATRICS AS A SPECIALTY.CHAIRMAN'S ADDRESS. Read in the Section on Diseases of Children, at the Forty-fifth Annual Meeting of the American Medical Association, held at San Francisco, June 5-8, 1894.
Authors: W. S. CHRISTOPHER
Journal: JAMA (1894)

Is disease in children sufficiently distinct from disease in adults to merit separate and special consideration? It is not intended to submit this question to the members of this Section, for doubtless the answer would be unanimously in the affirmative. It is not so certain, however, that the answer would be the same if the question were submitted to the profession at large. Here I can only use it as a text upon which to set forth some of the reasons for our answer. A few years ago Dr. Goodhart, of London, in his address as Chairman of the Section on Diseases of Children, of the British Medical Association, took the ground that there was no such thing as a specialty of diseases of children. A similar stand is taken by Ewald with reference to "Diseases of the Stomach." With Ewald I can heartily agree; with Goodhart as heartily disagree,
Role of NAD(P)H oxidase in the regulation of cardiac L-type Ca channel function during acute hypoxia
Authors: L HOOL, C DIMARIA, H VIOLA, P ARTHUR
Journal: Cardiovascular Research (2005)

The role of NAD(P)H oxidase in regulating cellular production of reactive oxygen species (ROS) and the L-type Ca2+ channel during acute hypoxia was examined in adult ventricular myocytes from guinea pig.The fluorescent indicator dihydroethidium (DHE) was used to detect superoxide and the response of the L-type Ca2+ channel to beta-adrenergic receptor stimulation was used as a functional reporter since hypoxia increases the sensitivity of the L-type Ca2+ channel (I(Ca-L)) to isoproterenol (Iso).Hypoxia caused a 41.2+/-5.2% decrease in the rate of the DHE signal (n=21; p<0.01). Of the classical NAD(P)H oxidase inhibitors, DPI but not apocynin mimicked the effect of hypoxia on the sensitivity of I(Ca-L) to Iso. However, the potent NAD(P)H oxidase agonist angiotensin II had no effect on cellular superoxide or the sensitivity of I(Ca-L) to Iso. Although DPI inhibits NAD(P)H oxidase, it also decreased superoxide in isolated mitochondria in a concentration-dependent manner. Partial inhibition of mitochondrial function with nanomolar concentrations of FCCP or myxothiazol mimicked the effect of hypoxia on cellular superoxide and the sensitivity of I(Ca-L) to Iso. In addition, hypoxia caused a 69.3+/-0.8% decrease in superoxide in isolated mitochondria (n=4; p<0.01), providing direct evidence for a role for the mitochondria.Our data suggest that mitochondria appear to be involved in oxygen sensing, regulation of cellular ROS, and the function of I(Ca-L) during acute hypoxia in cardiac myocytes and NAD(P)H oxidase does not appear to contribute substantially.
ANTIMETABOLITES AND PSORIASIS
Authors: PeterC. H. Newbold
Journal: British Journal of Dermatology (1972)

Journal Article ANTIMETABOLITES AND PSORIASIS Get access PeterC. H. Newbold PeterC. H. Newbold Postgraduate Medical School, Hills Road, Cambridge CB2 lQT Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 86, Issue 1, 1 January 1972, Pages 87–90, https://doi.org/10.1111/j.1365-2133.1972.tb01899.x Published: 01 January 1972
The red cell.
Authors: J E Malcolm
Journal: BMJ (1972)

colleagues they should estimate the require- ments for the next 12 months, and based on this assessment and the antici- pated fractionation yields collect the neces- sary raw material within their region for the patients for whom they are directly responsible.This done, the ball is firmly in the court of the central fractionation units to make the necessary capacity available to pre- pare and deliver high quality products to the regional transfusion centres in the quantity requested.This principle should hold for all plasma fractionation products and would thus throw the burden of responsibility for patient care where it belongs-to the regional transfusion centres.-Weare, etc.,
CDK 4/6 Inhibitors Sensitize PIK3CA Mutant Breast Cancer to PI3K Inhibitors
Authors: Sadhna R. Vora, Dejan Juric, Nayoon Kim, Mari Mino-Kenudson, Tiffany Huynh, Carlotta Costa, Elizabeth L. Lockerman, Sarah F. Pollack, Manway Liu, Xiaoyan Li, Joseph Lehar, Marion Wiesmann, Markus Wartmann, Yan Chen, Z. Alexander Cao, Maria Pinzon-Ortiz, Sunkyu Kim, Robert Schlegel, Alan Huang, Jeffrey A. Engelman
Journal: Cancer Cell (2014)
Antibiotic resistance and transrectal prostate biopsies
Authors: R. J. Davies, B. M. Stephenson, M. Llewelyn, A. C. Carter, E. Kubiak
Journal: BMJ (2013)

We wish to add to the comprehensive review of prostate screening.1 Before considering the management of any potential cancer, a persistently raised prostate specific antigen test result usually demands a tissue sample, most often obtained transrectally. However, such sampling …
Failure of Chloroquine in Human Babesiosis (<i>Babesia microti</i>)
Authors: LOUIS H. MILLER
Journal: Annals of Internal Medicine (1978)

The failure of a 3-week course of chloroquine to eliminate an infection of Babesia microti acquired on Martha's Vineyard led to tests of selected drugs in hamsters infected with the strain from this patient. The results showed response to several antitrypanosomal drugs (pentamidine and 4,4'-diazoaminobenzamidine) but not to antimalarial drugs (chloroquine, sulfadiazine, and pyrimethamine).
Teenage Sex and the Librarian
Authors: Geraldine Mattern
Journal: JAMA (1978)

<h3>To the Editor.—</h3> E. James Lieberman, MD (240:275, 1978), has written a concise, informative article on methods of birth control that teenagers should know about. He mentions the numerous books written for young people and their parents on the problem of teenage sex. From a librarian's standpoint, the problem is teenage access to such books. <i>Medical Books and Serials in Print 1978</i><sup>1</sup>lists 29 books under the subject "Sex Instruction for Children and Youth." Books<i>in Print 1978-1979</i><sup>2</sup>lists another 20 titles. It seems that there certainly are enough well-written books on sex and young people, some of which are listed.<sup>3-7</sup>But can these youngsters obtain these books? In almost every case, the answer is no. I have been a librarian in schools that included students in kindergarten through eighth grade. These schools included two in northern New Jersey and one in southern New Hampshire. In addition, I
Abstract 5415: Preclinical evaluation of telomerase-specific oncolytic virotherapy for human bone and soft tissue sarcomas
Authors: Tsuyoshi Sasaki, Hiroshi Tazawa, Jo Hasei, Toshiyuki Kunisada, Aki Yoshida, Yuki Morimoto, Yasuo Urata, Kazuhiro Nouso, Toshifumi Ozaki, Toshiyoshi Fujiwara
Journal: Cancer Research (2011)

Abstract Purpose: Bone and soft tissue sarcomas frequently occur in young children and show aggressive progression, resistance to conventional chemotherapy and poor prognosis, indicating a requirement for novel antitumor therapy to improve the clinical outcome. Tumor-specific replication-selective oncolytic virotherapy is a promising antitumor therapy for induction of cell death in tumor, but not of normal, cells. We previously developed an oncolytic adenovirus, OBP-301, that kills human epithelial malignant cells in a telomerase-dependent manner. Recent evidence suggests that non-epithelial malignant cells, which have low telomerase activity, maintain telomere length through alternative lengthening of telomeres (ALT). However, it remains unclear if OBP-301 is cytopathic for non-epithelial malignant cells. Here, we evaluated the antitumor effect of OBP-301 on human bone and soft tissue sarcoma cells. Experimental Design: The cytopathic activity of OBP-301, coxsackie and adenovirus receptor (CAR) expression, and telomerase activity were examined in 10 bones (OST, U2OS, HOS, HuO9, MNNG/HOS, SaOS-2, NOS-2, NOS-10, NDCS-1 and OUMS-27) and in 4 soft tissue (CCS, NMS-2, SYO-1 and NMFH-1) sarcoma cell lines. OBP-301 antitumor effects were assessed using orthotopic tumor xenograft models. The fiber-modified-OBP-301, (OBP-405), was used to confirm an antitumor effect on OBP-301-resistant sarcomas. Results: OBP-301 was cytopathic for 12 sarcoma cell lines but not for the non-CAR-expressing OUMS-27 and NMFH-1 cells. Sensitivity to OBP-301 was dependent on CAR expression, not on telomerase activity. ALT-type sarcomas were also sensitive to OBP-301 because of upregulation of human telomerase reverse transcriptase (hTERT) mRNA following virus infection. Intratumoral injection of OBP-301 significantly suppressed the growth of OST and SYO-1 tumors. Furthermore, fiber-modified OBP-405 showed antitumor effects on OBP-301-resistant OUMS-27 and NMFH-1 cells. Conclusions: We showed that OBP-301 has antitumor effects on both non-ALT-type and ALT-type sarcoma cells through upregulation of human telomerase reverse transcriptase mRNA. Furthermore, coxsackie and adenovirus receptor-negative sarcoma cells were efficiently killed by fiber-modified OBP-301-derived-OBP-405 through virus-integrin binding. A telomerase-specific oncolytic adenovirus is a promising antitumor reagent for the treatment of bone and soft tissue sarcomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5415. doi:10.1158/1538-7445.AM2011-5415
SARS virus identified, but the disease is still spreading
Authors: J. Parry
Journal: BMJ (2003)

As the epidemic of SARS (severe acute respiratory syndrome) continues to defy attempts to bring it under control, Chinese officials have recorded far more cases in Beijing than previously admitted—a total of 455 cases, or more than 12 times the number previously revealed.

Until 20 April, officials said that there were only 37 cases in the capital, despite estimates by the World Health Organization that at least 200 people there had contracted SARS. The health minister, Zhang Wenkang, and the mayor of Beijing, Meng Xuenong, have been fired over the cover up.

The news came as scientists conclusively identified the cause of the syndrome as a coronavirus that is unlike …
Work Disability in Rheumatoid Arthritis: Effects of Disease, Social, and Work Factors
Authors: EDWARD YELIN
Journal: Annals of Internal Medicine (1980)

We explore here the relative contribution of selected disease, social, and work-related factors to disability status in a population of persons with rheumatoid arthritis. Our study differs from previous studies in that it is limited to one diagnostic entity, yet at the same time evaluates a broad range of social and work-related factors in disability. One hundred-eighty persons with rheumatoid arthritis sampled from 19 socially diverse practice settings were given a structured survey about their medical and work histories and social backgrounds. We found significant effects of stage and duration of illness on continued employment but no positive effect of selected therapies. Social and work factors combined had a far larger effect on work disability than all disease factors. Among work factors, control over the pace and activities of work and self-employment status had the greatest effect on continued employment, suggesting that time control issues are crucial to the maintenance of one's job after onset of this illness.
INCIDENCE, RANGE AND CLINICAL IMPACT OF HEMOGLOBIN DECREASE AFTER TRANSRADIAL CORONARY STENTING AND MAXIMAL ANTIPLATELET THERAPY.
Authors: Olivier F. Bertrand, Josep Rodés-Cabau, éric Larose, Stéphane Rinfret, Stéphane Rinfret, Jean-Pierre Déry, Onil Gleeton, Can M. Nguyen, Guy Proulx, Louis Roy, Olivier Costerousse, Paul Poirier, Robert De Larochellière
Journal: Journal of the American College of Cardiology (2010)
Involving consumers in designing, conducting, and interpreting randomised controlled trials: questionnaire survey
Authors: B. Hanley
Journal: BMJ (2001)

Objective: To assess the extent to which consumers are involved in the work of clinical trial coordinating centres in the United Kingdom and the nature of consumers' involvement in randomised trials coordinated by these centres. Design: National surveys using structured questionnaires with some open ended sections. Setting: 103 clinical trial coordinating centres in the United Kingdom identified through a database assembled in 1997 by the NHS clinical trials adviser. Participants: Named contacts at 62 coordinating centres and investigators in 60 trials that were identified as involving consumers. Main outcome measures: Number of coordinating centres and number of trials in which consumers were involved and the nature of consumers' involvement. Results: Of the 62 eligible centres, 23 reported that consumers had already been involved in their work, and most respondents were positive about this involvement. 17 centres planned to involve consumers. 15 centres had no plans to involve consumers, but only four of these considered such involvement irrelevant. Responses from investigators about the 48 individual trials were mostly positive, with respondents commenting that input from consumers had helped refine research questions, improve the quality of patient information, and make the trial more relevant to the needs of patients. Conclusions: Consumer involvement in the design and conduct of controlled trials seems to be growing and seems to be welcomed by most researchers. Such involvement seems likely to improve the relevance to consumers of the questions addressed and the results obtained in controlled trials
ID1 promotes expansion and survival of primary erythroid cells and is a target of JAK2V617F-STAT5 signaling
Authors: Andrew D. Wood, Edwin Chen, Ian J. Donaldson, Shilpa Hattangadi, Karly A. Burke, Mark A. Dawson, Diego Miranda-Saavedra, Harvey F. Lodish, Anthony R. Green, Berthold Göttgens
Journal: Blood (2009)