tbuckley/cabot-search huggingface dataset:
Circulating anti-skin basement membrane zone antibodies in a patient with Goodpasture's syndrome
Authors: A. DAVENPORT, J.L. VERBOV, H.J. GOLDSMITH
Journal: British Journal of Dermatology (1987)

Journal Article Circulating anti‐skin basement membrane zone antibodies in a patient with Goodpasture's syndrome Get access A. DAVENPORT, A. DAVENPORT Renal Unit Royal Liverpool Hospital, Liverpool, U.K. Dr A.Davenport, Renal Unit, St James's University Hospital, Beckett Street, Leeds, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.L. VERBOV, J.L. VERBOV Department of Dermatology, Royal Liverpool Hospital, Liverpool, U.K. Search for other works by this author on: Oxford Academic Google Scholar H.J. GOLDSMITH H.J. GOLDSMITH Renal Unit Royal Liverpool Hospital, Liverpool, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 1, 1 July 1987, Pages 125–127, https://doi.org/10.1111/j.1365-2133.1987.tb04102.x Published: 01 July 1987
Generation-Biased Gene Expression in a Bryophyte Model System
Authors: P. Szovenyi, S. A. Rensing, D. Lang, G. A. Wray, A. J. Shaw
Journal: Molecular Biology and Evolution (2010)

The evolution of land plants is tightly linked to the evolution of the alternation of generations. Because alternating ploidal generations share their genomes, investigating generation-biased gene expression can give insight into the evolution of life cycles in land plants. Toward this end, we describe gene expression differences associated with the alternation of isogenic sporophyte and gametophyte generations in bryophytes, extant representatives of early diverging land plants, using a moss model system (Funaria hygrometrica). We found that differentiation in gene expression between the sporophyte and gametophyte generations is weaker in the bryophyte model system than in Arabidopsis thaliana. This is in line with the basal phylogenetic position of bryophytes and with the origin of alternating generations from a purely haplontic life cycle. Comparative analysis of F. hygrometrica and A. thaliana gene expression data shows that there is limited conservation of generation-biased gene expression across land plants. However, genes showing shared sporophyte-biased expression in both F. hygrometrica and A. thaliana appear to be enriched for biological pathways representing critical molecular adaptations to terrestrial life. Comparative analyses of the expression of F. hygrometrica and A. thaliana regulatory genes suggest that conserved regulatory networks may be involved in growth and reproductive tissue development of the angiosperm and bryophyte sporophyte generations despite their morphological divergence. This study represents the first attempt to describe generation-biased gene expression in a plant with a well-developed sporophyte and gametophyte generations, and as such it lays the foundation for future targeted research on the developmental mechanisms underlying evolutionary diversification of plant sporophytes.
A prospective trial evaluating the role of mesothelin in undiagnosed pleural effusions
Authors: C. E. Hooper, A. J. Morley, P. Virgo, J. E. Harvey, B. Kahan, N. A. Maskell
Journal: European Respiratory Journal (2012)

Mesothelin has been proposed as a useful tool in the diagnosis of malignant pleural mesothelioma (MPM). We aimed to examine its diagnostic utility and the impact of renal impairment on results. We prospectively recruited 230 patients with new undiagnosed pleural effusions, testing serum (n=216) and pleural fluid (n=206) mesothelin (by ELISA) during the initial consultation. 28 (12%) out of 230 patients had MPM. Serum mesothelin gave sensitivity 59.3%, specificity 64.7%, negative predictive value (NPV) 91.2%, positive predictive value (PPV) 20.5%, and pleural fluid sensitivity 72.0%, specificity 87.5%, NPV 95.5%, PPV 46.2% for distinguishing effusions due to MPM. In a matched comparison, diagnostic characteristics of pleural fluid mesothelin were superior to serum (p=0.0001). Serum mesothelin levels in patients without MPM were higher in patients with renal impairment (p=0.007) while pleural fluid levels were unaffected. 19 (54%) out of 35 patients with a benign pleural effusion and an estimated glomerular filtration rate ≤ 59 mL · min(-1) had a false-positive serum mesothelin result. The diagnostic accuracy of pleural fluid mesothelin is superior to that of serum and is unaffected by renal function. In patients with a low pre-test probability of mesothelioma, a negative mesothelin test could be reassuring, because of its high NPV. Routine use of mesothelin testing in undiagnosed pleural effusions at presentation appears to be unhelpful.
Cost Effectiveness of Adjuvant Interferon in Node-Positive Melanoma
Authors: Janice N. Cormier, Yan Xing, Meichun Ding, Scott B. Cantor, Kristi J. Salter, Jeffrey E. Lee, Paul F. Mansfield, Jeffrey E. Gershenwald, Merrick I. Ross
Journal: Journal of Clinical Oncology (2007)

To assess the benefits of adjuvant high-dose interferon alfa (HDI) treatment for patients with high-risk melanoma.We designed a decision-analytic probabilistic Markov model to simulate the natural history of patients with stage IIIA, IIIB, and IIIC melanoma and evaluate the outcomes with and without HDI treatment. Outcomes were in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Probability estimates and costs were derived from primary patient level data, while the efficacy of HDI and associated utilities were determined from published reports. The base-case analysis was a cohort of 50-year-old patients.HDI increased the median life expectancy in patients with stage III melanoma from 3.75 years in the observation cohort to 4.42 years in the HDI cohort. The difference in QALYs ranged from 0.31 years for stage IIIA patients to 0.60 years for stage IIIC patients treated with HDI. HDI was cost effective in patients with stage IIIB and IIIC melanoma, with ICERs of $95,304 and $76,068 per QALY gained, respectively. Using a threshold of $100,000 per QALY gained, HDI was cost effective for all stage III patients younger than 52 years. HDI was not cost effective for patients with stage IIIA disease and for subsets of patients older than 63 years with stage IIIB disease.Our model demonstrates that the probability of HDI being cost effective varies substantially by melanoma substage. HDI showed the greatest benefit in terms of QALYs and was most cost effective in patients younger than 60 years with stage IIIC disease.
Fight or Flight and the Evolution of Pain
Authors: J. Caspermeyer
Journal: Molecular Biology and Evolution (2014)

Hard wired into the survival mechanisms of all animals is the perception of pain. Different stimuli, such as heat or cold, foul odors, chemicals, or a blunt blow can trigger pain receptors in the body that, in the blink of an eye, jolt the body into classic fight or flight responses. Researchers Saito et al. (2014) have performed the first evolutionary analysis of pain response in chickens by isolating the genes for pain receptors called TRPA1. They were able to examine the function of the receptor using different stimuli in comparison with other vertebrate species. They found that heat stimulation activated chicken TRPA1, sharing similar thermal properties with other cold blood animals such as frog and reptile TRPA1 rather than mammalian and human TRPA1. In addition, they identified for the first time in chickens that methyl anthranilate (MA), a repellent chemical for birds, also activates chicken TRPA1. MA-induced activity of TRPA1 varied among diverse vertebrate species, and three key amino acid residues involved in the TRPA1 activity by MA were identified. Thefindings add to the understanding of the functional evolution of TRPA1 and its sensitivity to heat as well as its diversification among vertebrate species.
Effects of antenatal multiple micronutrient supplementation on children's weight and size at 2 years of age in Nepal: follow-up of a double-blind randomised controlled trial
Authors: Anjana Vaidya, Naomi Saville, Bhim Prasad Shrestha, Anthony M de L Costello, Dharma S Manandhar, David Osrin
Journal: The Lancet (2008)
Additional Double Reading of Screening Mammograms by Radiologic Technologists: Impact on Screening Performance Parameters
Authors: Lucien E. M. Duijm, Johanna H. Groenewoud, Jacques Fracheboud, Harry J. de Koning
Journal: JNCI Journal of the National Cancer Institute (2007)

Studies have shown that having mammography technologists review screening mammograms in addition to radiologist review may increase the number of breast cancers that are detected at screening mammography. We prospectively examined the effects on screening performance of adding independent double reading of screening mammograms by technologists to standard double reading by radiologists.Twenty-one screening mammography technologists and eight certified screening radiologists participated in this study. From January 1, 2003, to January 1, 2005, all 61,251 screening mammograms obtained at two mammography screening units in The Netherlands were independently read (although the second reader was not blinded to the first reader's interpretation) by two technologists and, in turn, by two radiologists. Radiologists were blinded to the referral opinion of the technologists. During a 2-year follow-up period, we collected clinical data, breast imaging reports, biopsy results, and breast surgery reports of all women with a positive screening result (i.e., those that required additional imaging) from any reader. The distributions of categorical variables between subgroups were compared using chi-square or Fisher's exact tests. Differences in referral and detection by radiologists and technologists were assessed using McNemar's test. All statistical tests were two-sided.The radiologists referred 905 women (referral rate = 1.48%, 95% confidence interval [CI] = 1.38% to 1.57%), of whom 323 had breast cancer, corresponding to a positive predictive value of referral (PPV) of 35.7% (95% CI = 32.6% to 38.8%). Review of 446 additional technologist-positive readings led to another 80 referrals, resulting in the detection of 22 additional cancers. These extra referrals increased the initial referral rate from 1.48% to 1.61% (difference = 0.13%; 95% CI = 0.10% to 0.16%) and the cancer detection rate (CDR) from 5.27 to 5.63 cancers per 1000 women screened (difference = 0.36 cancers per 1000 women screened; 95% CI = 0.24 to 0.55). With technologist double reading only, 829 women would have been referred (referral rate = 1.35%, 95% CI = 1.26% to 1.45%); among these women, 286 cancers were diagnosed (PPV = 34.5%, 95% CI = 31.3% to 37.7%; CDR = 4.67 cancers per 1000 women screened, 95% CI = 4.13 to 5.21). Referral of all 1351 radiologist- and/or technologist-positive readings would have led to 362 cancers found at screening. The cancer detection rate for radiologist double reading would have increased from 5.27 to 5.91 cancers per 1000 women screened (relative increase = 12.1%, 95% CI = 8.8% to 16.5%; difference = 0.64 cancers per 1000 women screened, 95% CI = 0.47 to 0.87).A referral strategy that includes all technologist-positive readings, which would have increased the cancer detection rate while maintaining a low referral rate, should be considered.
Skin rash with the histological absence of metachromatic granules as the presenting feature of Hunter syndrome in a 6-year-old boy
Authors: S. Sakata, D. Orchard, G. Mason
Journal: British Journal of Dermatology (2008)

Journal Article Skin rash with the histological absence of metachromatic granules as the presenting feature of Hunter syndrome in a 6‐year‐old boy Get access S. Sakata, S. Sakata Department of Dermatology, The Royal Children’s Hospital, Parkville, Vic. 3052, Australia Search for other works by this author on: Oxford Academic Google Scholar D. Orchard, D. Orchard Department of Dermatology, The Royal Children’s Hospital, Parkville, Vic. 3052, Australia Search for other works by this author on: Oxford Academic Google Scholar G. Mason G. Mason Melbourne Patology, Melbourne, Vic., Australia E‐mail: shin.sakata@gmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 159, Issue 1, 1 July 2008, Pages 249–250, https://doi.org/10.1111/j.1365-2133.2008.08595.x Published: 01 July 2008
Discovering naturally processed antigenic determinants that confer protective T cell immunity
Authors: Pavlo Gilchuk, Charles T. Spencer, Stephanie B. Conant, Timothy Hill, Jennifer J. Gray, Xinnan Niu, Mu Zheng, John J. Erickson, Kelli L. Boyd, K. Jill McAfee, Carla Oseroff, Sine R. Hadrup, Jack R. Bennink, William Hildebrand, Kathryn M. Edwards, James E. Crowe, John V. Williams, Søren Buus, Alessandro Sette, Ton N.M. Schumacher, Andrew J. Link, Sebastian Joyce
Journal: Journal of Clinical Investigation (2013)

CD8+ T cells (TCD8) confer protective immunity against many infectious diseases, suggesting that microbial TCD8 determinants are promising vaccine targets. Nevertheless, current T cell antigen identification approaches do not discern which epitopes drive protective immunity during active infection - information that is critical for the rational design of TCD8-targeted vaccines. We employed a proteomics-based approach for large-scale discovery of naturally processed determinants derived from a complex pathogen, vaccinia virus (VACV), that are presented by the most frequent representatives of four major HLA class I supertypes. Immunologic characterization revealed that many previously unidentified VACV determinants were recognized by smallpox-vaccinated human peripheral blood cells in a variegated manner. Many such determinants were recognized by HLA class I-transgenic mouse immune TCD8 too and elicited protective TCD8 immunity against lethal intranasal VACV infection. Notably, efficient processing and stable presentation of immune determinants as well as the availability of naive TCD8 precursors were sufficient to drive a multifunctional, protective TCD8 response. Our approach uses fundamental insights into T cell epitope processing and presentation to define targets of protective TCD8 immunity within human pathogens that have complex proteomes, suggesting that this approach has general applicability in vaccine sciences.
Transcriptional slippage in bacteria: distribution in sequenced genomes and utilization in IS element gene expression.
Authors: Pavel V Baranov, Andrew W Hammer, Jiadong Zhou, Raymond F Gesteland, John F Atkins
Journal: Genome biology (2005)

Abstract Background Transcription slippage occurs on certain patterns of repeat mononucleotides, resulting in synthesis of a heterogeneous population of mRNAs. Individual mRNA molecules within this population differ in the number of nucleotides they contain that are not specified by the template. When transcriptional slippage occurs in a coding sequence, translation of the resulting mRNAs yields more than one protein product. Except where the products of the resulting mRNAs have distinct functions, transcription slippage occurring in a coding region is expected to be disadvantageous. This probably leads to selection against most slippage-prone sequences in coding regions. Results To find a length at which such selection is evident, we analyzed the distribution of repetitive runs of A and T of different lengths in 108 bacterial genomes. This length varies significantly among different bacteria, but in a large proportion of available genomes corresponds to nine nucleotides. Comparative sequence analysis of these genomes was used to identify occurrences of 9A and 9T transcriptional slippage-prone sequences used for gene expression. Conclusions IS element genes are the largest group found to exploit this phenomenon. A number of genes with disrupted open reading frames (ORFs) have slippage-prone sequences at which transcriptional slippage would result in uninterrupted ORF restoration at the mRNA level. The ability of such genes to encode functional full-length protein products brings into question their annotation as pseudogenes and in these cases is pertinent to the significance of the term 'authentic frameshift' frequently assigned to such genes.
Real-life use of inhaled corticosteroids in COPD patients versus the GOLD proposals: a paradigm shift in GOLD 2011?
Authors: Pierre-Régis Burgel, Gaetan Deslée, Gilles Jebrak, Graziella Brinchault, Denis Caillaud, Pascal Chanez, Isabelle Court-Fortune, Roger Escamilla, Pascale Nesme-Meyer, Jean-Louis Paillasseur, Thierry Perez, Nicolas Roche
Journal: European Respiratory Journal (2013)

To the Editor: 

Clinical trials in chronic obstructive pulmonary disease (COPD) patients have shown that the long-term use of inhaled corticosteroids (ICS) in COPD patients reduced the number of exacerbations per patient per year and improved health status [1]. Early studies have suggested increased ICS efficacy in patients with low lung function and frequent exacerbations [2]. The efficacy was reinforced when ICS was used in conjunction with long-acting β2-agonists (LABA) [3]. In most countries, health authorities approved ICS/LABA combinations in COPD patients with severe airflow impairment and frequent exacerbations, as also recommended in the Global Initiative for Obstructive Lung Disease (GOLD) 2007 document [4]. However, several surveys found poor adherence to this proposal among primary care physicians and pulmonologists in “real life”, ICS being often prescribed at a milder stage of the disease.

The GOLD 2011 document proposed a new multidimensional system for the assessment and management of patients with COPD [5]. This system classifies COPD patients into four categories (A, B, C and D) based on the level of symptoms (dyspnoea or global clinical impact) and the risk of future exacerbations, as assessed using the severity of airflow limitation and the past history …
STUDIES ON THE VELOCITY OF BLOOD FLOW
Authors: Herrmann L. Blumgart, Otto C. Yens
Journal: Journal of Clinical Investigation (1927)

An adequate flow of blood to the tissues implies two things.In the first place an adequate amount of blood must be expelled from the heart per unit of time.In the second place this blood must be trans- ported to the site of utilization at an adequate speed.The former aspect of the circulation, the minute volume output, has received considerable study.The second aspect, the velocity of blood flow, has not.Nevertheless, discussions of the probable velocity and its sig- nificance in maintaining the physiological integrity of the body have frequently been reported. HISTORICAL RfSUMt OF METHODS EMPLOYED IN STUDYING THE VELOCITY OF BLOOD FLOWWith the discovery by Harvey in 1628 (1) of the movement of blood in a circuit, the problem of the velocity at which the blood flows first presented itself.Not until 1733, however, when Stephen Hales (2) published his penetrating inquiries was the question of the velocity of blood flow discussed in quantitative terms.His grasp of the es- sentials of the problem was extraordinary.From his estimation of the capacity of the left ventricle, the diameter of the base of the aorta, and the pulse rate he computed the velocity of blood flow in the aorta of the horse.The problem of the velocity of blood flow received its next impetus in 1827, when Eduard Hering (3) measured the velocity of blood flow by injecting a solution of potassium ferrocyanide at one point and 1 This study was aided by a grant from the Proctor Fund of the Harvard Medical School for the Study of Chronic Disease.
Aspirin for the Chemoprevention of Colorectal Adenomas: Meta-analysis of the Randomized Trials
Authors: Bernard F. Cole, Richard F. Logan, Susan Halabi, Robert Benamouzig, Robert S. Sandler, Matthew J. Grainge, Stanislas Chaussade, John A. Baron
Journal: JNCI Journal of the National Cancer Institute (2009)

Multiple lines of evidence indicate that aspirin has an antineoplastic effect in the large bowel. Randomized clinical trials have been conducted to evaluate the effectiveness of aspirin for reducing the risk of colorectal adenomas. A meta-analysis of these trials will provide more precise estimates of the aspirin effect, both overall and in subgroups.We combined data from all randomized double-blind placebo-controlled trials that evaluated aspirin for the prevention of colorectal adenomas. We used random-effects meta-analysis to estimate risk ratios and 95% confidence intervals (CIs) for the effect of aspirin on the occurrence of adenomas and of advanced lesions (ie, tubulovillous adenomas, villous adenomas, adenomas >or=1 cm in diameter, adenomas with high-grade dysplasia, or invasive cancer). All statistical tests were two-sided.We identified four clinical trials with 2967 randomly assigned participants. Each trial evaluated aspirin for the secondary prevention of colorectal adenomas. Doses of aspirin tested ranged from 81 to 325 mg/d. The average age of participants at baseline was 58 years, and 60% were male. Median follow-up was 33 months. A total of 2698 participants underwent colonoscopic follow-up and were included in the analysis of adenoma occurrence and advanced-lesion occurrence after randomization. Among these participants, adenomas were found in 424 (37%) of the 1156 participants allocated to placebo and in 507 (33%) of the 1542 participants allocated to any dose of aspirin. Advanced lesions were found in 12% of participants in the placebo group and in 9% of participants allocated to any dose of aspirin. The pooled risk ratio of any adenoma for any dose of aspirin vs placebo was 0.83 (95% CI = 0.72 to 0.96). This corresponded to an absolute risk reduction of 6.7% (95% CI = 3.2% to 10.2%). For any advanced lesion, the pooled risk ratio was 0.72 (95% CI = 0.57 to 0.90). We found no statistically significant effect modification for any of the baseline factors studied.Aspirin is effective for the prevention of colorectal adenomas in individuals with a history of these lesions.
Incidence of thyroid cancer in Italy, 1991–2005: time trends and age–period–cohort effects
Authors: L. Dal Maso, M. Lise, P. Zambon, F. Falcini, E. Crocetti, D. Serraino, C. Cirilli, R. Zanetti, M. Vercelli, S. Ferretti, F. Stracci, V. De Lisi, S. Busco, G. Tagliabue, M. Budroni, R. Tumino, A. Giacomin, S. Franceschi
Journal: Annals of Oncology (2010)