tbuckley/cabot-search huggingface dataset:
Directional Evolution of Size Coupled with Ascertainment Bias for Variation in Drosophila Microsatellites
Authors: W. Amos
Journal: Molecular Biology and Evolution (2003)

Species-specific differences in microsatellite locus length and ascertainment bias have both been proposed to explain differences in microsatellite variability and length usually observed when loci isolated in one species are used to survey variation in a related species. Here we provide a simple algebraic approach to independently estimate the contributions of true species-specific length differences and ascertainment bias. We apply this approach to a reciprocal-isolation microsatellite study and show contributions of both ascertainment bias and a true longer average microsatellite length in Drosophila melanogaster compared with D. simulans.
IgM anti-Fc gamma R autoantibodies trigger neutrophil degranulation.
Authors: P Boros, J A Odin, T Muryoi, S K Masur, C Bona, J C Unkeless
Journal: The Journal of Experimental Medicine (1991)

Anti-Fc gamma R IgM monoclonal antibodies (mAbs) isolated from lipopolysaccharide-stimulated spleen cells from tightskin (TSK) mice were found to be polyspecific, reacting with a wide variety of molecules, including double-stranded DNA, topoisomerase, RNA polymerase, and different collagen types. Approximately 60% of the polyspecific IgM mAbs have anti-Fc gamma R specificity. These anti-Fc gamma R mAbs induce the release of hydrolases from both azurophil and specific granules of human neutrophils. 25-45% of the total cellular content (determined in Nonidet P-40 lysates) of neutrophil elastase, 10-25% of beta-glucuronidase, and 30-50% of alkaline phosphatase was released after incubation with the mAbs. The degranulation process was accompanied by dramatic morphological changes shown by scanning and transmission electron microscopy. The release of hydrolytic enzymes stimulated by the IgM anti-Fc gamma R mAbs was inhibited by preincubation of neutrophils with Fab fragments of either anti-human Fc gamma RII (IV.3) or anti-human Fc gamma RIII (3G8) mAbs. The binding of the anti-Fc gamma R TSK mAbs to human neutrophils was inhibited by Fab fragments of mAb 3G8. However, we found that the TSK anti-Fc gamma R mAbs do not bind to human Fc gamma RII expressed in either CHO cells or the P388D1 mouse macrophage cell line. Since the enzyme release could be inhibited by Fab fragments of mAb IV.3, we suggest that the signal transduction may require Fc gamma RII activation subsequent to crosslinking of the glycan phosphatidyl inositol-anchored Fc gamma RIII-1. These data demonstrate for the first time that polyspecific autoantibodies with Fc gamma R specificity can trigger neutrophil enzyme release via human Fc gamma RIII-1 in vitro and indicate a possible role for such autoantibodies in autoimmune inflammatory processes.
Plasma 9 ,11 -PGF2, a PGD2 metabolite, as a sensitive marker of mast cell activation by allergen in bronchial asthma
Authors: G Bochenek, E Nizankowska, A Gielicz, M Swierczynska, A Szczeklik
Journal: Thorax (2004)

Prostaglandin D(2) (PGD(2)) is a major cyclooxygenase product generated by activated mast cells during an allergic response. Assessment of PGD(2) and its metabolites in patients with asthma has mostly been performed in urine, bronchoalveolar lavage fluid and induced sputum, whereas human plasma determinations have been performed only sporadically.In 32 patients with allergic asthma and 50 healthy non-allergic controls, baseline plasma and urinary levels of 9alpha,11beta-PGF(2), a primary PGD(2) metabolite, were assessed by gas chromatography/mass spectrometry. Serum tryptase levels were measured by fluoroenzyme immunoassay and urinary leukotriene E(4) (LTE(4)) by ELISA. In a subgroup of 10 asthmatics (randomly selected from the 32 study patients) in whom bronchial allergen challenges with specific allergens (Dermatophagoides pteronyssinus, n = 4, mixed grass pollens, n = 6) were carried out, measurements were taken both before and after provocation.At baseline no significant differences between mean plasma and urinary levels of the PGD(2) metabolite and serum tryptase levels were found in asthmatics or controls. Asthmatic patients had significantly higher urinary LTE(4) levels. Allergen challenge resulted in a significant early increase in the mean plasma 9alpha,11beta-PGF(2) level and only a borderline but significant increase in the urinary 9alpha,11beta-PGF(2) level within 2 hours after provocation. The challenge did not produce statistically significant changes in serum tryptase levels. Urinary LTE(4) levels remained significantly increased 4 hours after provocation.PGD(2) is actively involved in the early asthmatic response to allergens. Measurement of 9alpha,11beta-PGF(2) release into plasma rather than urine following allergen challenge is a sensitive marker of enhanced PGD(2) synthesis, most probably due to mast cell activation.
The small intestinal bacterial overgrowth. Irritable bowel syndrome hypothesis: implications for treatment
Authors: S Vanner
Journal: Gut (2008)

Traditionally, small intestinal bacterial overgrowth (SIBO) has been characterised by symptoms of diarrhoea, bloating and sometimes signs of malabsorption. It has been defined as >105 colony-forming units (cfu)/ml of bacteria in aspirates obtained from the small intestine.1 This condition has typically been diagnosed in patients with readily identifiable alterations in small bowel function which predispose patients to SIBO (eg, resected ileocaecal valve, small intestinal hypomotility and possibly hypochlorhydria). Recently, however, this clinical paradigm has been challenged by new theories about the aetiology of irritable bowel syndrome (IBS) and has led to renewed scrutiny of the tests employed to diagnose this condition and controversy concerning the use of antibiotics to treat IBS for suspected SIBO.

The proposal that SIBO accounts for the symptoms of IBS2 3 is a novel and interesting hypothesis, given the rapidly growing evidence that luminal bacteria have previously unrecognised actions on multiple intestinal functions.4 While it has long been recognised that increased numbers of luminal bacteria in the small intestine disrupt digestion and absorption, it is now clear that they have other important actions, such as immune activation4 5 Immune-mediated cytokines could have multiple actions including altered epithelial secretion, exaggerated nociceptive signalling and abnormal motility.4 Together, these changes could lead to symptoms which meet the criteria for IBS. It has also been proposed that this mechanism could account for overlap syndromes, such as fibromyalgia.6

The publication of Pimentel and colleagues in 20007 played a pivotal role in establishing the concept that SIBO is a major pathogenic mechanism underlying IBS. Two major tenets emerged from this study: (1) based on the results of the lactulose hydrogen breath test (LHBT), the large majority of patients with IBS have SIBO, and (2) when SIBO is eradicated with antibiotics based on the findings …
Effects of Treatment with Anti-immunoglobulin E Antibody Omalizumab on Airway Inflammation in Allergic Asthma
Authors: Ratko Djukanović, Susan J. Wilson, Monica Kraft, Nizar N. Jarjour, Mark Steel, K. Fan Chung, Weibin Bao, Angel Fowler-Taylor, John Matthews, William W. Busse, Stephen T. Holgate, John V. Fahy
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

IgE plays an important role in allergic asthma. We hypothesized that reducing IgE in the airway mucosa would reduce airway inflammation. Forty-five patients with mild to moderate persistent asthma with sputum eosinophilia of 2% or more were treated with humanized monoclonal antibody against IgE (omalizumab) (n = 22) or placebo (n = 23) for 16 weeks. Outcomes included inflammatory cells in induced sputum and bronchial biopsies, and methacholine responsiveness. Treatment with omalizumab resulted in marked reduction of serum IgE and a reduction of IgE+ cells in the airway mucosa. The mean percentage sputum eosinophil count decreased significantly (p < 0.001) from 6.6 to 1.7% in the omalizumab group, a reduction significantly (p = 0.05) greater than with placebo (8.5 to 7.0%). This was associated with a significant reduction in tissue eosinophils; cells positive for the high-affinity Fc receptor for IgE; CD3+, CD4+, and CD8+ T lymphocytes; B lymphocytes; and cells staining for interleukin-4, but not with improvement in airway hyperresponsiveness to methacholine. This study shows antiinflammatory effects of omalizumab treatment and provides clues for mechanisms whereby omalizumab reduces asthma exacerbations and other asthma outcomes in more severe asthma. The lack of effect of omalizumab on methacholine responsiveness suggests that IgE or eosinophils may not be causally linked to airway hyperresponsiveness to methacholine in mild to moderate asthma.
Cellular Heterogeneity and Molecular Evolution in Cancer
Authors: Vanessa Almendro, Andriy Marusyk, Kornelia Polyak
Journal: Annual Review of Pathology Mechanisms of Disease (2012)

Intratumor heterogeneity represents a major obstacle to effective cancer treatment and personalized medicine. However, investigators are now elucidating intratumor heterogeneity at the single-cell level due to improvements in technologies. Better understanding of the composition of tumors, and monitoring changes in cell populations during disease progression and treatment, will improve cancer diagnosis and therapeutic design. Measurements of intratumor heterogeneity may also be used as biomarkers to predict the risk of progression and therapeutic resistance. We summarize important considerations related to intratumor heterogeneity during tumor evolution. We also discuss experimental approaches that are commonly used to infer intratumor heterogeneity and describe how these methodologies can be translated into clinical practice.
Standardizing chemotherapy education for quality improvement.
Authors: Carole Kathleen Dalby, Marylou Nesbitt, Kathleen Kennerley, Lisa Lacoursiere, Carol Frechette, Stephen Flaherty, Paul J. Catalano, Frances Fuller, Jodi Thiele, Heather Gilchrist, Judith Kostka, Lori A. Buswell
Journal: Journal of Clinical Oncology (2013)

136 Background: Variation of chemotherapy teaching at three affiliated regional oncology centers was associated with a low patient satisfaction PS; Press Ganey Survey for Adult Oncology score of 83.7% in understanding what to expect during chemotherapy treatment and 72.9% in how to manage chemotherapy side effects. Nursing staff collaborated to standardize content to improve PS and quality of care. Methods: Chemotherapy teaching tools varied across practice locations. From September-January 2012, three plan-do-study-act cycles were implemented. 1) A standardized teaching checklist, 2) electronic patient calendars, 3) 3 weeks later a patient education assessment survey (EAS). The teaching checklist detailed: 1) relevant chemotherapy information; 2) calendars listing (clinic appointments, symptoms requiring MD/NP notification, how to contact providers); and 3) ES assessed patient’s level of comprehension. Results: We used logistic regression for each PS score, estimating the time-trend of scores for each period and compared the time trend slopes pre versus post using a two-sided test for interaction. For each item, the Table displays the slope estimate (log odds-ratio per month) for each relevant intervention period, the associated 95% confidence intervals and the interaction test p-value. Negative slope indicates decreasing score trend with time while positive slope indicates increasing trend. The interaction test for each PS measure showed statistically significantly different slopes when comparing pre versus post periods for each PS item. Post intervention, scores for what to expect during chemotherapy rose 83.7% to 92.1%. Explanation of how to manage chemotherapy side effects rose 72.9% to 91.9%. Staff reported high satisfaction, highlighting its benefit to patients. Conclusions: Standardizing chemotherapy teaching improves PS as evidenced by statistically significant improvement in scores. Future endeavors will involve sharing chemotherapy teaching tools throughout the institution to improve PS scores for chemotherapy education. [Table: see text]
Metric properties of advanced imaging methods in osteoarthritis of the hand: a systematic review
Authors: Michael S Saltzherr, Ruud W Selles, Sita M A Bierma-Zeinstra, Galied S R Muradin, J Henk Coert, Johan W van Neck, Jolanda J Luime
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To assess the value of advanced imaging techniques in the detection of hand osteoarthritis (OA) and hand OA progression. <h3>Methods</h3> PubMed/Medline and Embase were searched until April 2012 for studies on imaging of hand OA that presented quantitative data on validity, reliability or responsiveness. Articles presenting only data on conventional radiography (CR) were excluded. Methodological quality was assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist for validity, the Quality Appraisal of Reliability Studies (QAREL) for reliability and the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) for responsiveness. <h3>Results</h3> Of 627 citations, 25 studies on ultrasonography (US), MRI or scintigraphy were included. No studies on CT, positron emission tomography or single photon emission CT met our eligibility criteria. Validity was generally assessed against healthy controls, CR or clinical examination. Overall, US and MRI detected more disease than CR and found significant differences between patients and healthy controls. Scintigraphy detected fewer pathological joints than CR. Intra- and inter-reader reliability varied for US (κ=0.01–1.0) and MRI (κ=0.15–0.84 and intraclass correlation coefficient=0.21–0.99) and was good for scintigraphy (κ=0.61–0.84). There were no responsiveness studies for MRI. US responsiveness studies showed a reduction of soft-tissue changes after treatment which correlated with decrease in pain (r=0.7–0.8). For scintigraphy, scores decreased over time while CR showed progression of hand OA. <h3>Conclusions</h3> MRI and US seem to be the most promising candidates for early detection of hand OA and for future use in clinical trials. However, further research is needed to improve scoring methods, to compare US with MRI, to confirm reliability of MRI and to further determine the responsiveness of US and MRI.
Observations on the Normal Anatomy of the Bronchial Arteries
Authors: L. Cudkowicz, J. B. Armstrong
Journal: Thorax (1951)

The existence of systemic arteries to the lungs has been known for many centuries.Ruysch (1732) claimed to be the first to have described the bronchial arteries, but Galen had already done so in the second century A.D.During the nineteenth century the anatomy of the bronchial arteries was studied in detail and their possible function considered.Reisseisen and von Soemmering (1808) defined the bronchial arteries as " vasa nutritiva " of the lungs, and showed that they accompanied the bronchi.Le Fort (1858) showed that the bronchial arteries continue along the bronchial tree as far as the respiratory bronchioli.Von Luschka (1863) drew attention to the ramification of the bronchial arterioles in the bronchial mucosa and suggested that the capillaries of the bronchial arterioles com- municated near the alveolar ducts with those derived from the pulmonary arteries.Virchow (1856) showed that occlusion of a lobar pulmonary artery branch did not result in necrosis of the lobe.He concluded therefore that the viability of the lobe,did not depend on the pulmonary artery, but was maintained by the bronchial arteries.Rindfleisch (1878) considered the bronchial arteries to be end arteries.Kuttner (1878), by dye injections in rabbit lungs, showed that the terminal branches of the pulmonary arteries were nowhere in communication with vessels of a similar calibre, and concluded that communication between the pulmonary artery bed and the bronchial arteries, if it existed, must be capillary only.Zuckerkandl (1881 and 1883) demonstrated that the bronchial arteries supplied the visceral pleura in man, and thought that the capillaries of the pulmonary and bronchial arteries were in communication.Miller (1947), at the beginning of this century, described the course of the bronchial arteries.He showed that they ran from the aorta to the main bronchi and followed these distally to the hila.There they divided and continued in the walls of the bronchi as far as the alveolar ducts.From the fibrous tunic, in which an arterial plexus was formed, small branches penetrated the muscle layer to reach the tunica propria of the bronchus and then continued to run in the long axis of the bronchus.Miller did not think that the problem of anastomosis between the two circulations had been adequately studied by previous workers, and contended that the use of a
Prognostic Factors in Children With Extragonadal Malignant Germ Cell Tumors: A Pediatric Intergroup Study
Authors: Neyssa Marina, Wendy B. London, A. Lindsay Frazier, Stephen Lauer, Frederick Rescorla, Barbara Cushing, Marcio H. Malogolowkin, Robert P. Castleberry, Richard B. Womer, Thomas Olson
Journal: Journal of Clinical Oncology (2006)

To investigate prognostic factors for pediatric extragonadal malignant germ cell tumors (PEMGCT).Between 1990 and 1996, patients with stage I through IV PEMGCT were eligible for a trial of cisplatin dose intensity. We retrospectively investigated prognostic factors for PEMGCT, including age, stage, primary site, treatment, and elevated alfa fetoprotein by univariate and multivariate analysis.The 165 patients had a median age of 1.9 years (range, 3 days to 18.5 years); 109 were female; and 99 had alfa fetoprotein > or = 10,000. There were 30 stage I/II, 61 stage III, and 74 stage IV tumors; primary sites included 88 sacrococcygeal, 39 thoracic, and 38 others. The 5-year overall survival (OS) and event-free survival (EFS) rates with standard deviations were 83.4% +/- 3.7% and 79.0% +/- 4.1%, respectively. Univariate analysis identified age > or = 12 years as a highly significant prognostic factor for EFS (5-year EFS, 48.9% +/- 15.6% v 84.1% +/- 3.9%; P < .0001) and for OS (5-year OS, 53.7% +/- 14.9% v 88.5% +/- 3.4%; P < .0001), whereas treatment was of borderline significance (P = .0777). Multivariate Cox proportional hazards regression identified only age > or = 12 years as a significant prognostic factor for EFS (P = .0002). In multivariate Cox regression for OS, the combination of age and primary site was highly significant (P < .0001). Patients > or = 12 years of age with thoracic tumors had six times the risk of death compared with patients younger than 12 years with other primaries.Age is the most predictive factor of EFS in PEMGCT. There is a significant interaction between age and primary site, suggesting that patients > or = 12 years of age with thoracic tumors are a biologically distinct group.
Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations
Authors: Nicole Sonneveld, Sanja Stanojevic, Reshma Amin, Paul Aurora, Jane Davies, J. Stuart Elborn, Alex Horsley, Philipp Latzin, Katherine O'Neill, Paul Robinson, Emma Scrase, Hiran Selvadurai, Padmaja Subbarao, Liam Welsh, Sophie Yammine, Felix Ratjen
Journal: European Respiratory Journal (2015)

Pulmonary exacerbations are important clinical events for cystic fibrosis (CF) patients. Studies assessing the ability of the lung clearance index (LCI) to detect treatment response for pulmonary exacerbations have yielded heterogeneous results. Here, we conduct a retrospective analysis of pooled LCI data to assess treatment with intravenous antibiotics for pulmonary exacerbations and to understand factors explaining the heterogeneous response.A systematic literature search was performed to identify prospective observational studies. Factors predicting the relative change in LCI and spirometry were evaluated while adjusting for within-study clustering.Six previously reported studies and one unpublished study, which included 176 pulmonary exacerbations in both paediatric and adult patients, were included. Overall, LCI significantly decreased by 0.40 units (95% CI -0.60- -0.19, p=0.004) or 2.5% following treatment. The relative change in LCI was significantly correlated with the relative change in forced expiratory volume in 1 s (FEV1), but results were discordant in 42.5% of subjects (80 out of 188). Higher (worse) baseline LCI was associated with a greater improvement in LCI (slope: -0.9%, 95% CI -1.0- -0.4%).LCI response to therapy for pulmonary exacerbations is heterogeneous in CF patients; the overall effect size is small and results are often discordant with FEV1.
Diagnosis and treatment of very large polyps found within the bowel cancer screening programme: experience of practice in a large single screening centre
Authors: J. Neale, P. Patel, J. Snowball, S. Halloran
Journal: Gut (2011)

<h3>Introduction</h3> A high number of polyps are found in the English Bowel Cancer Screening Programme (BCSP). This includes a significant number of large (&gt;1 cm) and very large (&gt;2 cm) polyps. These are challenging to treat. Historically very large polyps have required surgical intervention. However, developing advanced polypectomy/EMR skills allow for the majority to be removed endoscopically by appropriately trained endoscopists. There is currently a lack of data on the outcome of very large polyps found during colonoscopy. <h3>Methods</h3> Data for all colonoscopies performed within the Hampshire Bowel Cancer Screening Centre was retrieved from the Bowel Cancer Screening Database at the Southern screening hub covering the period May 2008 to March 2010. This was subanalysed into those with high-risk polyps, all of which had benign histology. The data pertaining to these polyps and their management was reviewed. <h3>Results</h3> 125 patients were identified as having high-risk polyps. This covers 579 separate polyps. 38% (220) polyps were large, 15% (86) were very large (VL). The initial management of these polyps is set out in the table 1 below. 100% of very large polyps deferred for later endoscopic therapy/EMR have a sessile/flat morphology (compared to 12% removed at index endoscopy, p&lt;0.00001). 94% of these polyps are located outside the rectum or sigmoid colon (compared to 16% removed at index endoscopy, p&lt;0.00001). They are larger than those removed at index endoscopy, but this does not reach significance (mean size = 27 vs 25 mm, p=0.14). 45% of polyps referred for surgery have a sessile/flat morphology (12% at index, p=0.98). They share a similar distribution with 36% being found outside the rectum and sigmoid colon (16% at index, p=0.91). They are larger than those treated at index endoscopy (mean size 29 vs 25 mm, p=0.06). <h3>Conclusion</h3> Referral patterns for EMR/Surgery vary. These decisions differ between endoscopists with different experience, even within a single screening centre. The later endoscopy/EMR group have clear differences to those removed at index endoscopy. The polyps in the surgery group were more likely to be sessile and outside the recto-sigmoid, but this study was unable to detect this to a significant level. Multi-centre research is requested to explore this further. There are likely to be other criteria which cause referral to surgery such as surface morphology not picked up by the BCSP database.