tbuckley/cabot-search huggingface dataset:
Prevalence and Correlates of Myocardial Scar in a US Cohort
Authors: Evrim B. Turkbey, Marcelo S. Nacif, Mengye Guo, Robyn L. McClelland, Patricia B. R. P. Teixeira, Diane E. Bild, R. Graham Barr, Steven Shea, Wendy Post, Gregory Burke, Matthew J. Budoff, Aaron R. Folsom, Chia-Ying Liu, João A. Lima, David A. Bluemke
Journal: JAMA (2015)

<h3>Importance</h3> Myocardial scarring leads to cardiac dysfunction and poor prognosis. The prevalence of and factors associated with unrecognized myocardial infarction and scar have not been previously defined using contemporary methods in a multiethnic US population. <h3>Objective</h3> To determine prevalence of and factors associated with myocardial scar in middle- and older-aged individuals in the United States. <h3>Design, Setting, and Participants</h3> The Multi-Ethnic Study of Atherosclerosis (MESA) study is a population-based cohort in the United States. Participants were aged 45 through 84 years and free of clinical cardiovascular disease (CVD) at baseline in 2000-2002. In the 10th year examination (2010-2012), 1840 participants underwent cardiac magnetic resonance (CMR) imaging with gadolinium to detect myocardial scar. Cardiovascular disease risk factors and coronary artery calcium (CAC) scores were measured at baseline and year 10. Logistic regression models were used to estimate adjusted odds ratios (ORs) for myocardial scar. <h3>Exposures</h3> Cardiovascular risk factors, CAC scores, left ventricle size and function, and carotid intima-media thickness. <h3>Main Outcomes and Measures</h3> Myocardial scar detected by CMR imaging. <h3>Results</h3> Of 1840 participants (mean [SD] age, 68 [9] years, 52% men), 146 (7.9%) had myocardial scars, of which 114 (78%) were undetected by electrocardiogram or by clinical adjudication. In adjusted models, age, male sex, body mass index, hypertension, and current smoking at baseline were associated with myocardial scar at year 10. The OR per 8.9-year increment was 1.61 (95% CI, 1.36-1.91;<i>P</i> &lt; .001); for men vs women: OR, 5.76 (95% CI, 3.61-9.17;<i>P</i> &lt; .001); per 4.8-SD body mass index: OR, 1.32 (95% CI, 1.09-1.61,<i>P</i> = .005); for hypertension: OR, 1.61 (95% CI, 1.12-2.30;<i>P</i> = .009); and for current vs never smokers: 2.00 (95% CI, 1.22-3.28;<i>P</i> = .006). Age-, sex-, and ethnicity-adjusted CAC scores at baseline were also associated with myocardial scar at year 10. Compared with a CAC score of 0, the OR for scores from 1 through 99 was 2.4 (95% CI, 1.5-3.9); from 100 through 399, 3.0 (95% CI, 1.7-5.1), and 400 or higher, 3.3 (95% CI, 1.7-6.1) (<i>P</i> ≤ .001). The CAC score significantly added to the association of myocardial scar with age, sex, race/ethnicity, and traditional CVD risk factors (<i>C</i>statistic, 0.81 with CAC vs 0.79 without CAC,<i>P</i> = .01). <h3>Conclusions and Relevance</h3> The prevalence of myocardial scars in a US community-based multiethnic cohort was 7.9%, of which 78% were unrecognized by electrocardiography or clinical evaluation. Further studies are needed to understand the clinical consequences of these undetected scars.
The immunophenotypic and immunogenotypic B-cell differentiation arrest in bone marrow of RAG-deficient SCID patients corresponds to residual recombination activities of mutated RAG proteins
Authors: Jeroen G. Noordzij, Sandra de Bruin-Versteeg, Nicole S. Verkaik, Jaak M. J. J. Vossen, Ronald de Groot, Ewa Bernatowska, Anton W. Langerak, Dik C. van Gent, Jacques J. M. van Dongen
Journal: Blood (2002)
Comparison of serum, salivary, and rapid whole blood diagnostic tests for Helicobacter pylori and their validation against endoscopy based tests.
Authors: T G Reilly, V Poxon, D S Sanders, T S Elliott, R P Walt
Journal: Gut (1997)

BACKGROUND: A rapid, reliable, and accurate test for the diagnosis of infection with Helicobacter pylori is needed for screening dyspeptic patients before referral for endoscopy. AIM: To compare a new rapid whole blood test (Helisal rapid blood, Cortecs), two serum enzyme linked immunosorbent assays (ELISAs; Helico-G, Shield and Helisal serum, Cortecs), and a salivary assay (Helisal saliva, Cortecs), with slide biopsy urease, 13C-urea breath test, and histology. METHODS: Three hundred and three consecutive dyspeptic patients attending for gastroscopy underwent two antral biopsies for histology, and one for rapid slide biopsy urease test for assessment of H pylori status. Blood and saliva were also collected. One hundred of the patients also underwent a 13C-urea breath test. Gold standard positives were defined as those with at least two positive tests among slide urease, breath test, or histology, and gold standard negatives as those with all these (or two when the breath test was not done) negative. RESULTS: Of 300 patients (median age 63, range 28-89) eligible for analysis, 137 (46%) were gold standard positives, of which Helisal rapid blood identified 116, Helico-G 129, Helisal serum 130, and Helisal saliva 120; 137 (46%) were gold standard negatives of which the number falsely identified as positive was 30 by Helisal rapid blood, 45 by Helico-G, 41 by Helisal serum, and 41 by Helisal saliva. Sensitivities and specificities were: for the whole blood test 85% and 78% respectively; for Helico-G 94% and 67%, for Helisal serum 95% and 70%, and for Helisal saliva 84% and 70%. CONCLUSIONS: If endoscopy had been undertaken only on patients with positive tests two of 16 duodenal ulcers would have been missed if the Helisal rapid blood test was used, and one if any of the ELISA tests were used. None of the blood tests would have missed any of six gastric ulcers, but the salivary test would have missed one.
Barriers to Efficient Development of Cancer Therapeutics
Authors: Philip S. Schein, Barbara Scheffler
Journal: Clinical Cancer Research (2006)

In 2001, in response to identified barriers to the efficient development of cancer therapeutics, one of us called for a comprehensive reappraisal of the national program, including the policies of the Food and Drug Administration (FDA; ref. [1][1]). Concern was expressed that the systems for cancer
Infusion of adrenomedullin improves acute myocarditis via attenuation of myocardial inflammation and edema
Authors: B YANAGAWA, M KATAOKA, S OHNISHI, M KODAMA, K TANAKA, Y MIYAHARA, H ISHIBASHIUEDA, Y AIZAWA, K KANGAWA, N NAGAYA
Journal: Cardiovascular Research (2007)

Objective Our aim was to assess whether adrenomedullin (AM), a potent vasodilator peptide with a variety of cardioprotective effects, has a therapeutic potential for the treatment of acute myocarditis in a rat model.
Experimental Approaches to Understanding the Role of Protein Phosphorylation in the Regulation of Neuronal Function
Authors: M B Kennedy
Journal: Annual Review of Neuroscience (1983)

Studies by Earl Sutherland and his colleagues on hormonal regulation of the breakdown of glycogen in liver resulted in the discovery that the first step in the action of many hormones is to increase the synthesis of cAMP by activating adenylate cyclase (Raft et al 1957, Sutherland & Rall 1958, Robison et al 1968). It was later established that cAMP exerts its effects by stimulating protein kinases that catalyze the phosphorylation of specific functional proteins and thereby regulate their activity (Walsh et al 1968, Kuo & Greengard 1969, Krebs & Beavo 1979). The discovery that the brain contains a high concentration of cAMP-dependent protein kinase led to the proposal that protein phosphorylation might play an important role in regulation of neuronal properties by neurotransmitters and neurohormones (Miyamoto et al 1969). In particular, it seemed that protein phosphorylation, which usually takes place on a time scale of hundreds of milliseconds or longer, might be a mechanism underlying relatively long-lasting changes in neuronal properties such as slow changes in post-synaptic potentials (McAfee & Greengard 1972), changes in the rate of transmitter synthesis (Morgenroth et al 1975), or changes in gene expression (Klein & Berg 1970). The biochemists and neurobiologists who took up the study of brain protein phosphorylation hoped to gain insight into some of the mechanisms underlying changes in neuronal excitability and synaptic efficacy and also, perhaps, into processes that govern the development of various neuronal types during the formation of the nervous system. This line of research was bolstered by the findings that the brain contains not only high concentrations of protein kinases, but also protein phosphatases, adenylate cyclase, and phosphodiesterase (Greengard 1976), and also by the discovery that several neurotransmitters stimulate the synthesis of second messengers such as cyclic AMP and cyclic GMP by binding to specific receptors on the surfaces of neurons (for reviews see Nathanson 1977, Greengard 1981).
Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD
Authors: Helgo Magnussen, Bernd Disse, Roberto Rodriguez-Roisin, Anne Kirsten, Henrik Watz, Kay Tetzlaff, Lesley Towse, Helen Finnigan, Ronald Dahl, Marc Decramer, Pascal Chanez, Emiel F.M. Wouters, Peter M.A. Calverley
Journal: New England Journal of Medicine (2014)

Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored.In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored.As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (P<0.001); a similar between-group difference (43 ml) was seen at week 52 (P=0.001). No change in dyspnea and minor changes in health status occurred in the glucocorticoid-withdrawal group.In patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.).
Molecular comparison of dominant microbiota associated with injured versus healthy mucosa in ulcerative colitis
Authors: H Sokol, P Lepage, P. Seksik, J Dore, P. Marteau
Journal: Gut (2006)

Deficiency for mannan-binding lectin is associated with antibodies to Saccharomyces cerevisiae in patients with Crohn's disease and their relatives Mannan-binding lectin (MBL) is a member of the collectin family and is an important component of the innate immune response.Three different MBL alleles in coding exon 1 (point mutations in codons 52, 54 and 57) result in low serum levels of MBL. 1 Earlier, we described cellular and humoral immune reactivity of a subgroup of patients with Crohn's disease to mannans, a cell wall antigen of yeasts. 2 The humoral immune response in these patients is commonly known as antibodies to Saccharomyces cerevisiae (ASCA).In a previous paper, we found considerably more patients with Crohn's disease with low MBL serum levels to be ASCA positive than in the subgroup with high MBL levels.The homozygotic or compound heterozygotic mutations in the exon were associated with the development of ASCA in patients with Crohn's disease. 3 This is in contrast with the data reported in this journal by another group that found an increased prevalence of ASCA in patients with MBL mutations in exon 1, which however, did not reach significance in their large independent cohort of patients with Crohn's disease. 4 In this paper, we confirmed in another cohort that patients with low serum MBL or MBL deficiency were considerably more often ASCA positive as compared with patients with normal levels of MBL.Low MBL levels (defined as ,500 ng/ml) were found in 30 of 52 (58%)
Is progressive osteoarthritis an atheromatous vascular disease?
Authors: P G Conaghan
Journal: Annals of the Rheumatic Diseases (2005)

Growing evidence from epidemiological studies suggests that osteoarthritis (OA) is linked to atheromatous vascular disease. This hypothesis article proposes that OA, or at least OA structural progression, may be an atheromatous vascular disease of subchondral bone. Further epidemiological studies, imaging investigations of relevant blood vessels, and trials of the effects of statins on the prevention and treatment of OA are needed to examine this hypothesis.
Borrelia burgdorferi and Treponema pallidum: a comparison of functional genomics, environmental adaptations, and pathogenic mechanisms
Authors: Stephen F. Porcella, Tom G. Schwan
Journal: Journal of Clinical Investigation (2001)

A striking difference between B. burgdorferi and T. pallidum is their total genomic structure.Although both pathogens have small genomes, compared with many well known bacteria such as Escherichia coli and Mycobacterium tuberculosis, the genomic structure of B. burgdorferi
Treating severe and complicated malaria
Authors: U. D'Alessandro
Journal: BMJ (2004)

Clinical attacks are usually uncomplicated and can be managed with an effective oral drug. Most occur in sub-Saharan Africa. Of the 200 million episodes of clinical malaria that occur each year among African children, 4-6 million are severe and life threatening, and most of the 1 million deaths from malaria worldwide are in Africa.1 Although some risk factors for severe malaria have been identified—for example, human leucocyte antigens (HLA Bw 53 is associated with protection from severe malaria), it is still unclear why only some children develop severe disease.

The clinical manifestations of severe malaria are complex and may vary between age groups and …
Bone mineral density in patients with rheumatoid arthritis: relation between disease severity and low bone mineral density
Authors: M C Lodder
Journal: Annals of the Rheumatic Diseases (2004)

To examine variables associated with bone mineral density (BMD) in patients with rheumatoid arthritis (RA).We investigated 373 patients with low to moderately active RA. Patients with low disease activity were recruited from a cohort of patients in clinical remission. Patients with moderately active disease were included in a trial comparing the effects of long term high intensity exercise programme and conventional physical therapy. Demographic and clinical data were collected. Bone mineral density (BMD) was measured by means of dual x ray absorptiometry (DXA). Associations between demographic and clinical measurements on the one hand and BMD on the other were investigated in regression analyses.The patient group consisted of middle aged, mainly female, patients. The median (interquartile range) disease duration was 7 (4 to 13) years, the mean disease activity score (standard deviation) was 3.2 (1.4). Of the group, 66% was rheumatoid factor positive, and 83% (n = 304) had never used corticosteroids. The median Larsen score of hands and feet was 27 (5 to 61). Greater age and low body mass index were related to low BMD at the hip and spine. High Larsen score for hands and feet was significantly associated with low BMD at the hip. The use of corticosteroids was not independently associated with BMD. The results of the multiple regression analyses also applied to the subgroup of corticosteroid naive patients.BMD data of patients with low to moderately active RA demonstrated an association between high radiological RA damage and low BMD at the hip, which suggests an association between the severity of RA and the risk of generalised bone loss, which also occurred in corticosteroid naive patients.
Melanoma Differentiation Associated Gene-7/Interleukin-24 Promotes Tumor Cell-Specific Apoptosis through Both Secretory and Nonsecretory Pathways
Authors: Moira Sauane, Irina V. Lebedeva, Zao-zhong Su, Heng-tong Choo, Aaron Randolph, Kristoffer Valerie, Paul Dent, Rahul V. Gopalkrishnan, Paul B. Fisher
Journal: Cancer Research (2004)

Abstract Melanoma differentiation associated gene-7/interleukin-24 (Mda-7/IL-24), a novel member of the IL-10 family of cytokines, uniquely displays cancer-specific apoptosis-inducing activity. Positive results in ongoing phase I/II clinical trials have strengthened the possibility of its utilization as a cancer gene therapeutic. Previous studies document that signaling events leading to Ad.mda-7-induced transformed cell apoptosis are tyrosine kinase-independent. These results suggest that mda-7/IL-24 cancer cell-specific activity could occur through mechanisms independent of binding to its currently recognized cognate receptors and might even occur independent of receptor function. An adenovirus vector expressing a nonsecreted version of MDA-7/IL-24 protein was generated via deletion of its signal peptide. This nonsecreted protein was as effective as wild-type secreted MDA-7/IL-24 in inducing apoptosis in prostate carcinoma cell lines and displayed transformed cell specificity and localization of MDA-7/IL-24 in the Golgi/endoplasmic reticulum compartments. Our results indicate that mda-7/IL-24-mediated apoptosis can be triggered through a combination of intracellular as well as secretory mechanisms and can occur efficiently in the absence of protein secretion.
Immigration and viral hepatitis
Authors: Suraj Sharma, Manuel Carballo, Jordan J. Feld, Harry L.A. Janssen
Journal: Journal of Hepatology (2015)

WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants.
Association of the <i>TNFAIP3</i> rs5029939 variant with systemic sclerosis in the European Caucasian population
Authors: P Dieudé, M Guedj, J Wipff, B Ruiz, G Riemekasten, M Matucci-Cerinic, I Melchers, E Hachulla, P Airo, E Diot, N Hunzelmann, J Cabane, L Mouthon, J L Cracowski, V Riccieri, J Distler, O Meyer, A Kahan, C Boileau, Y Allanore
Journal: Annals of the Rheumatic Diseases (2010)

Background TNFAIP3 encodes the ubiquitin-modifying enzyme, a key regulator of inflammatory signalling pathways. Convincing associations between TNFAIP3 variants and autoimmune diseases have been reported. Objective To investigate the association of TNFAIP3 polymorphisms with systemic sclerosis (SSc). Methods Three single nucleotide polymorphisms (SNPs) in a set of 1018 patients with SSc and 1012 controls of French Caucasian origin were genotyped. Two intergenic SNPs, rs10499194 and rs6920220, and one located in TNFAIP3 intron 2, rs5029939, were selected. The TNFAIP3 rs5029939 found to be associated with SSc in this first set was then genotyped in a second set of 465 patients with SSc and 182 controls from Germany and 184 patients with SSc and 124 controls from Italy. Pooled odd ratios were calculated by Mantel–Haenszel meta-analysis. Results The rs5029939 G allele was found to be significantly associated with SSc susceptibility (pooled OR=2.08 (95% CI 1.59 to 2.72); p=1.16×10 −7 ), whereas the rs10499194 and rs6920220 variants displayed no association. Only one of the predicted haplotypes investigated in the French sample was significantly associated with SSc (p=8.91×10 −8 ), and this haplotype was discriminating only in the presence of the rs5029939 risk allele, suggesting that this SNP tags the association signal. The strongest associations of rs5029939 with subphenotypes, having large magnitudes for complex genetic disorders, were observed for diffuse cutaneous SSc (pooled OR=2.71 (1.94 to 3.79), p=5.2×10 −9 ), fibrosing alveolitis (pooled OR=2.26 (1.61 to 3.17), p=2.5×10 −6 ) and pulmonary arterial hypertension (pooled OR=3.11 (1.86 to 5.17), p=1.3×10 −5 ). Conclusion These results suggest that TNFAIP3 is a genetic susceptibility factor for SSc.