tbuckley/cabot-search huggingface dataset:
Commercialization, patenting and genomics: researcher perspectives
Authors: CJ Murdoch, Timothy Caulfield
Journal: Genome Medicine (2009)

The impact of commercialization and patenting pressure on genomics research is still a topic of considerable debate in academic, policy and popular literature. We interviewed genomic researchers to see if their perspectives offered fresh insights. Regional Genome Canada centers provided us with relevant researcher contact information, and in-depth structured interviews were conducted. Researcher perspectives were sharply divided, with both support and concern for commercialization regimes surfacing in interviews. Data withholding and publication delays were commonly reported, but the aggressive enforcement of patents was not. There are parallels to the Stem Cell community in Canada in these respects. Genomic researchers, as individuals directly implicated in the field of controversy, have developed varied and often novel insights which should be incorporated into the ongoing debates surrounding commercialization and patenting. Many researchers continue to raise concerns, particularly in relation to data withholding, thus emphasizing the need for a continued exploration of the complex issues associated with commercialization and patenting.
Anthropometric Measures and Lung Function Test in Asthmatic Pacients, Asthmatic Obese, Obese without Asthma and Healthy Pacients
Authors: J.E. Guillen Escalon, J.J.L. Sienra, G. Toussaint, M.A. Rosas, B.E. Del Rio
Journal: Journal of Allergy and Clinical Immunology (2006)
Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine
Authors: W Kruis
Journal: Gut (2004)

<b>Background and aim:</b> Evidence exists for the pathogenic role of the enteric flora in inflammatory bowel disease. Probiotics contain living microorganisms which exert health effects on the host. We compared the efficacy in maintaining remission of the probiotic preparation <i>Escherichia coli</i> Nissle 1917 and established therapy with mesalazine in patients with ulcerative colitis. <b>Patients and methods:</b> In total, 327 patients were recruited and assigned to a double blind, double dummy trial to receive either the probiotic drug 200 mg once daily (n = 162) or mesalazine 500 mg three times daily (n = 165). The study lasted for 12 months and patients were assessed by clinical and endoscopic activity indices (Rachmilewitz) as well as by histology. The primary aim of the study was to confirm equivalent efficacy of the two drugs in the prevention of relapses. <b>Results:</b> The per protocol analysis revealed relapses in 40/110 (36.4%) patients in the <i>E coli</i> Nissle 1917 group and 38/112 (33.9%) in the mesalazine group (significant equivalence p = 0.003). Subgroup analyses showed no differences between the treatment groups in terms of duration and localisation of disease or pretrial treatment. Safety profile and tolerability were very good for both groups and were not different. <b>Conclusions:</b> The probiotic drug <i>E coli</i> Nissle 1917 shows efficacy and safety in maintaining remission equivalent to the gold standard mesalazine in patients with ulcerative colitis. The effectiveness of probiotic treatment further underlines the pathogenetic significance of the enteric flora.
Accumulation of Gene Polymorphisms Related to Plaque Disruption and Thrombosis Is Associated With Cerebral Infarction in Subjects With Type 2 Diabetes
Authors: Naoto Katakami, Mitsuyoshi Takahara, Hideaki Kaneto, Ikki Shimizu, Keizo Ohno, Fukashi Ishibashi, Takeshi Osonoi, Atsunori Kashiwagi, Ryuzo Kawamori, Iichiro Shimomura, Munehide Matsuhisa, Yoshimitsu Yamasaki
Journal: Diabetes Care (2009)

OBJECTIVE It is believed that disruption of vulnerable atherosclerotic plaque and subsequent thrombus formation play critical roles in the pathogenesis of cerebral infarction. We simultaneously determined four relatively common genetic variants related to plaque rupture or subsequent local thrombus formation and evaluated the combined effect on cerebral infarction. RESEARCH DESIGN AND METHODS We enrolled 3,094 Japanese type 2 diabetic subjects (62.7% male; aged 61.5 ± 8.4 years) and determined their genotypes regarding matrix metalloproteinase 9 C-1562T, coagulation factor XII (F12) C46T, von Willebrand factor (VWF) G-1051A, and plasminogen activator inhibitor (PAI-1) 675 4G/5G polymorphisms. The diagnosis of cerebral infarction was performed based on history, physical examination, and neuroimaging. RESULTS The single association analysis revealed that there were no statistically significant associations between each polymorphism and the prevalence of cerebral infarction. Interestingly, the prevalence of cerebral infarction was higher with the increase of the total number of four concomitant unfavorable proatherothrombotic alleles in each subject (P value for linear trend = 0.004). Furthermore, a multiple logistic regression analysis showed that the number of proatherothrombotic alleles was a risk factor for cerebral infarction independently of conventional risk factors (odds ratio for one-point increase in the number of proatherothrombotic allele 1.15 [95% CI 1.05–1.26], P = 0.004). CONCLUSIONS Accumulation of gene polymorphisms related to plaque rupture and thrombus formation is likely associated with the prevalence of cerebral infarction in type 2 diabetic patients, suggesting that the combined information about these variants is useful to assess the risk of cerebral infarction.
Epoxyeicosatrienoic acids: a double-edged sword in cardiovascular diseases and cancer
Authors: Dingzhi Wang, Raymond N. DuBois
Journal: Journal of Clinical Investigation (2011)

Epoxyeicosatrienoic acids (EETs) generated from arachidonic acid by cytochrome P450 (CYP) epoxygenases have beneficial effects in certain cardiovascular and kidney diseases. Hence, great efforts have been made to develop drugs targeting the EET pathway. Some of these agents are currently under evaluation in clinical trials for treatment of hypertension and diabetes. In this issue of the JCI, Panigrahy et al. evaluate in a systematic way the role of CYP epoxygenases and the metabolites they generate in cancer progression. Their findings, along with previous studies, raise concerns about using these drugs in humans.
Characterization of MOAT-C and MOAT-D, New Members of the MRP/cMOAT Subfamily of Transporter Proteins
Authors: M. G. Belinsky, L. J. Bain, B. B. Balsara, J. R. Testa, G. D. Kruh
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Multidrug resistanceassociated protein (MRP) and canalicular multispecific organic anion transporter (cMOAT) are transporter proteins that pump organic anions across cellular membranes and have been linked to resistance to cytotoxic drugs. We previously identified MOAT-B, an MRP/cMOAT-related transporter, by use of a polymerase chain reaction approach. However, analysis of expressed sequence tag (EST) databases indicated that there might be additional MRP/cMOATrelated transporters. To further define the MRP/cMOAT subfamily of transporters, we used EST probes to isolate complementary DNAs for two related transporter proteins, MOAT-C and MOAT-D. Methods: MOAT-C and MOAT-D expression patterns in human tissues were determined by RNA blot analysis, and chromosomal localization of the genes was determined by fluorescence in situ hybridization. Results: MOAT-C is predicted to encode a 1437-amino-acid protein that, among eukaryotic transporters, is most closely related to MRP, cMOAT, and MOAT-B (about 36% identity). However, MOAT-C is less related to MRP and cMOAT than MRP and cMOAT are to each other (about 48% identity). Like MOAT-B, MOAT-C lacks an Nterminal membrane-spanning domain, indicating that the topology of this protein is similarly distinct from that of MRP and cMOAT. MOAT-D is predicted to encode a 1527-amino-acid protein that is the closest known relative of MRP (about 58% identity). MOAT-D is also highly related to cMOAT (about 47% identity). The presence of an N-terminal membranespanning domain indicates that the topology of MOAT-D is quite similar to that of MRP and cMOAT. MOAT-C transcripts are widely expressed in human tissues; however, MOAT-D transcript expression is more restricted. The MOAT-C and MOAT-D genes are located at chromosomes 3q27 and 17q21.3, respectively. Conclusions: On the basis of amino acid identity and protein topology, the MRP/cMOAT transporter subfamily falls into two groups; the first group consists of MRP, cMOAT, and MOAT-D, and the second group consists of MOAT-B and MOAT-C.
Comparison of Clinical Features, Virulence, and Relapse among <i>Mycobacterium avium</i> Complex Species
Authors: Daniel P. Boyle, Teresa R. Zembower, Susheel Reddy, Chao Qi
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Traditionally, Mycobacterium avium complex (MAC) has been composed of M. avium and M. intracellulare; however, advances in genetic sequencing have allowed discovery of several novel species. With these discoveries, investigation of differences in risk factors, virulence, and clinical outcomes have emerged.We conducted a retrospective cohort study evaluating all MAC isolates obtained from pulmonary specimens at our institution from 2000 to 2012 and investigated the clinical courses associated with distinct MAC species.To classify isolates into distinct species, a multilocus sequence analysis using rpoB and internal transcribed spacer (ITS) as targets was performed. We reviewed patient medical records to analyze clinical characteristics and outcomes for the cohort.Of the isolates from the 448 included patients, 54% were M. avium, 18% were M. intracellulare, and 28% were M. chimaera. Using American Thoracic Society/Infectious Diseases Society of America criteria, patients whose isolates were identified as M. avium (adjusted odds ratio [AOR], 2.14; 95% confidence interval [CI], 1.33-3.44) or M. intracellulare (AOR, 3.12; 95% CI, 1.62-5.99) were more likely to meet criteria for infection than patients with M. chimaera. Patients infected with M. chimaera were more likely to be prescribed an immunosuppressant compared with all other patients (AOR, 2.75; 95% CI, 1.17-6.40). Patients treated for infections with M. avium (AOR, 5.64; 95% CI, 1.51-21.10) and M. chimaera (AOR, 4.47; 95% CI, 1.08-18.53) were more likely to have a clinical relapse/reinfection than those with M. intracellulare.Our findings suggest that specific MAC species have varying degrees of virulence and classifying MAC isolates into distinct species aids in identifying which patients are at higher risk of clinical relapse/reinfection.
Community acquired pneumonia.
Authors: J A Innes
Journal: BMJ (1987)

<h3>Abstract</h3> Calcium-dependent exocytosis of the microneme organelles that facilitate host cell invasion is critical for obligate intracellular apicomplexan parasites such as <i>Toxoplasma gondii</i>. Ferlins represent a protein family with roles in exocytosis containing multiple Ca<sup>2+</sup>-sensing C2 domains. Here we defined the role of <i>T. gondii</i>’s ferlin 1 (FER1) in microneme biology. FER1 localized dynamically to several compartments of the parasite’s secretory pathway as well as to an apical spot near the site of microneme secretion. FER1 function was dissected by overexpression of a variety of N-terminally tagged alleles causing dominant negative phenotypes. This demonstrated FER1 traffics microneme organelles at several discrete steps of their natural trajectories: 1. from ELC to the subpellicular microtubules; 2. along the subpellicular microtubules to the apical end; 3. into the conoid; 4. and inferred from observed retrograde transport from the subpellicular microtubules, recycling of micronemes from mother to daughter parasites. Furthermore, full-length FER1 overexpression results in a squirt of microneme release sufficient for host cell egress. This indicates FER1 facilitates fusion of the most apical, radially organized micronemes with the plasma membrane. Moreover, FER1 acts differentially on the Rab5A/C-dependent and - independent microneme sub-populations. Finally, apical FER1 overlaps with the presence of VP1, a pyrophosphatase proton pump. Integrating all new insights, we propose a model of microneme exocytosis wherein the radial micronemes constitute a readily releasable vesicle pool primed by acidification.
Basic assumptions concerning eye-movement control during reading
Authors: George W. McConkie, Shun-Nan Yang
Journal: Behavioral and Brain Sciences (2003)

Reichle et al. specify two assumptions as being basic to E-Z Reader: Words are sequentially attended during fixations, and saccades are triggered by a cognitive event. We point out that there is little evidence for the first assumption and counterevidence for the second. Also, the labile/nonlabile stage distinction in saccade preparation seems to be contrary to current evidence. An alternative explanation of saccade onset times in reading assumes that saccades are strategically generated, independent of language processing, but are delayed on a probabilistic basis by processing difficulties.
Screening for breast cancer.
Authors: B A Thomas
Journal: BMJ (1976)

imagining himself to be volumes and so years ahead of the rest of us is that you have erroneously imputed such notions to him; though as between the possibility of the editor of World Medicine having delusions of grandeur and that of the editor of the British Medical Journal ignoring convention I should prefer not to speculate.Perhaps next time, however, you will put your editorial heads together and so avoid supplying an occasion for their being banged together later.
Meta-Analysis: Secondary Prevention Programs for Patients with Coronary Artery Disease
Authors: Alexander M. Clark, Lisa Hartling, Ben Vandermeer, Finlay A. McAlister
Journal: Annals of Internal Medicine (2005)

Background: Although supervised exercise programs reduce mortality in survivors of myocardial infarction, the effects of other types of cardiac secondary prevention programs are unknown. Purpose: To determine the effectiveness of secondary cardiac prevention programs with and without exercise components. Data Sources: The authors searched MEDLINE (1966–2004), the Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, SIGLE, and the Cochrane Effective Practice and Organization of Care Study Registry. They also contacted primary study authors and hand-searched bibliographies provided by the Centers for Medicare & Medicaid Services. Study Selection: Randomized clinical trials. Data Extraction: Two reviewers chose studies and extracted data independently; random-effects summary risk ratios were calculated. Data Synthesis: The authors identified 63 randomized trials (21 295 patients with coronary disease). The summary risk ratio was 0.85 (95% CI, 0.77 to 0.94) for all-cause mortality, but this result differed over time with a risk ratio of 0.97 (CI, 0.82 to 1.14) at 12 months and 0.53 (CI, 0.35 to 0.81) at 24 months. The summary risk ratio was 0.83 (CI, 0.74 to 0.94) for recurrent myocardial infarction over a median follow-up of 12 months. Effects were similar for programs that included risk factor education or counseling with a structured exercise component (risk ratio, 0.88 [CI, 0.74 to 1.04] for mortality and 0.62 [CI, 0.44 to 0.87] for myocardial infarction), for programs that included risk factor education or counseling without an exercise component (risk ratio, 0.87 [CI, 0.76 to 0.99] for mortality and 0.86 [CI, 0.72 to 1.03] for myocardial infarction), and for programs that were solely exercise-based (risk ratio, 0.72 [CI, 0.54 to 0.95] for mortality and 0.76 [CI, 0.57 to 1.01] for myocardial infarction). Most of these programs improved quality of life or functional status, but effect sizes were small. Limitations: Although these programs may reduce total health care costs, published data on the costs of the programs are inadequate to conclusively comment on their cost-effectiveness. Conclusions: A wide variety of secondary prevention programs improve health outcomes in patients with coronary disease.
Collagen gene expression by cultured human skin fibroblasts. Abundant steady-state levels of type VI procollagen messenger RNAs.
Authors: D R Olsen, J Peltonen, S Jaakkola, M L Chu, J Uitto
Journal: Journal of Clinical Investigation (1989)

Previous studies have suggested that procollagen types I and III are the major collagenous gene products of cultured human skin fibroblasts. In this study the expression of 10 different genes, encoding the subunit polypeptides for collagen types I-VI, by human skin fibroblasts in culture was analyzed by molecular hybridizations. Northern transfer analysis demonstrated the presence of specific mRNA transcripts for collagen types I, III, IV, V, and VI, but not for type II collagen. Quantitation of the abundance of these mRNAs by slot blot hybridizations revealed that type I, III, and VI procollagens were the major collagenous gene products of skin fibroblasts in culture. The mRNAs for type IV and V collagens represented only a small percentage of the total collagenous mRNA transcripts. Further analysis by in situ hybridization demonstrated that the majority of the cultured cells coexpressed the genes for type I, III, and VI procollagen pro-alpha chains. Further in situ hybridization analyses revealed the expression of type VI collagen genes in normal human skin. These data demonstrate that human skin fibroblast cultures can be used to study the transcriptional regulation of at least nine genetically distinct procollagen genes. The data further suggest that type VI collagen, in addition to types I and III, may be a major collagenous component of human skin.
Sigmoidoscopy Screening: Understanding the Trade-off Between Detection of Advanced Neoplasia and Diagnostic Efficiency
Authors: Thomas F. Imperiale
Journal: JNCI Journal of the National Cancer Institute (2013)

colonoscopy vs biennial fecal immunochemical testing (FIT) (10) to compare the three sets of criteria for colonoscopy referral. The criteria sets were compared in asymptomatic persons aged 50–69 years who were either randomly assigned to the colonoscopy arm of the trial or who were randomly assigned to and eligible for the FIT arm but requested a screening colonoscopy instead. The end points for comparison were 1) detection rate for any advanced neoplasia; 2) test characteristics for APN; and 3) number needed to screen to detect one person with APN. All estimates were based on simulation of sigmoidoscopy from colonoscopic findings. Two definitions of distal were considered—one with and one without the descending colon. Test characteristics were measured in age- and sex-specific subgroups. Distal findings were explored as predictors of APN (9). Colonoscopy referral would have occurred for 6.2% of the study population using the UK criteria, 12.0% using the SCORE criteria, and 17.9% using the NORCCAP criteria. NORCCAP criteria were most sensitive for APN whereas UK criteria were most specific and efficient. Colonoscopy detected any advanced neoplasia in 520 of 5059 (10.3%) individuals, whereas detection with the three sets of criteria ranged from 6.3% for the UK criteria to 7.0% for NORCCAP, which is 61% to 68% of all advanced neoplasia. Colonoscopy identified APN in 255 (5.0%) persons. Sensitivity of the referral criteria for APN ranged from 22% for the UK criteria to 37% for NORCCAP. Among persons referred, the number needed to screen with colonoscopy to detect one person with APN was six for the U.K. criteria, eight for SCORE, and 10 for NORCCAP. Including the descending colon with the distal colon improved APN sensitivity by absolute amounts of 2% to 4% overall, by 5% to 8% for men aged 50–59 years, and by 8% to 9% for women aged 60–69 years. A large (≥10 mm) distal adenoma was the strongest independent predictor of APN.
Practical Implementation of the Guidelines for Unstable Angina/Non–ST-Segment Elevation Myocardial Infarction in the Emergency Department
Authors: W. Brian Gibler, Christopher P. Cannon, Andra L. Blomkalns, Douglas M. Char, Barbara J. Drew, Judd E. Hollander, Allan S. Jaffe, Robert L. Jesse, L. Kristin Newby, E. Magnus Ohman, Eric D. Peterson, Charles V. Pollack
Journal: Circulation (2005)

In the United States each year, &gt;5.3 million patients present to emergency departments with chest discomfort and related symptoms. Ultimately, &gt;1.4 million individuals are hospitalized for unstable angina and non–ST-segment elevation myocardial infarction. For emergency physicians and cardiologists alike, these patients represent an enormous challenge to accurately diagnose and appropriately treat. This update of the 2002 American College of Cardiology/American Heart Association Guidelines for the Management of Patients with Unstable Angina and Non–ST-Segment Elevation Myocardial Infarction (UA/NSTEMI) provides an evidence-based approach to the diagnosis and treatment of these patients in the emergency department, in-hospital, and after hospital discharge. Despite publication of the guidelines several years ago, many patients with UA/NSTEMI still do not receive guidelines-indicated therapy.
Ancient Vertebrate Conserved Noncoding Elements Have Been Evolving Rapidly in Teleost Fishes
Authors: A. P. Lee, S. Y. Kerk, Y. Y. Tan, S. Brenner, B. Venkatesh
Journal: Molecular Biology and Evolution (2010)

Vertebrate genomes contain thousands of conserved noncoding elements (CNEs) that often function as tissue-specific enhancers. In this study, we have identified CNEs in human, dog, chicken, Xenopus, and four teleost fishes (zebrafish, stickleback, medaka, and fugu) using elephant shark, a cartilaginous vertebrate, as the base genome and investigated the evolution of these ancient vertebrate CNEs (aCNEs) in bony vertebrate lineages. Our analysis shows that aCNEs have been evolving at different rates in different bony vertebrate lineages. Although 78-83% of CNEs have diverged beyond recognition ("lost") in different teleost fishes, only 24% and 40% have been lost in the chicken and mammalian lineages, respectively. Relative rate tests of substitution rates in CNEs revealed that the teleost fish CNEs have been evolving at a significantly higher rate than those in other bony vertebrates. In the ray-finned fish lineage, 68% of aCNEs were lost before the divergence of the four teleosts. This implicates the "fish-specific" whole-genome duplication in the accelerated evolution and the loss of a large number of both copies of duplicated CNEs in teleost fishes. The aCNEs are rich in tissue-specific enhancers and thus many of them are likely to be evolutionarily constrained cis-regulatory elements. The rapid evolution of aCNEs might have affected the expression patterns driven by them. Transgenic zebrafish assay of some human CNE enhancers that have been lost in teleosts has indicated instances of conservation or changes in trans-acting factors between mammals and fishes.
Tests on hypotheses about osteoarthritis and hip joints.
Authors: N Y Afoke, P D Byers, W C Hutton
Journal: Annals of the Rheumatic Diseases (1992)

Hypotheses suggesting that hip joints which develop osteoarthritis are congruent, have a single area of peak pressure, and have peak pressure which exceeds normal values were tested. Of 100 hip joints examined on necropsy; two showed an early stage of osteoarthritis and the geometry and pressure distribution under load were assessed in these joints. One joint was congruent, in agreement with the hypotheses, but the other was incongruent. In both joints there were several areas of high pressure, the number and location of which depended on the orientation of the joint. The measured values of pressure in the congruent joint exceeded values found previously in normal hip joints. In the incongruent hip joint the peak pressures were within normal limits.