tbuckley/cabot-search huggingface dataset:
A tailored approach to reduce dose of anti-TNF drugs may be equally effective, but substantially less costly than standard dosing in patients with ankylosing spondylitis over 1 year: a propensity score-matched cohort study
Authors: Jakub Závada, Michal Uher, Katarína Sisol, Šárka Forejtová, Kateřina Jarošová, Heřman Mann, Jiří Vencovský, Karel Pavelka
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To compare the effectiveness, safety and costs of standard versus individually tailored reduced doses of anti-tumour necrosis factor (TNF) drugs in patients with ankylosing spondylitis (AS) after achieving low-disease activity. <h3>Methods</h3> This was a single-centre prospective observational study performed within the ATTRA registry. The anti-TNF dose tapering strategy was chosen by treating physicians, without prespecified protocol. We used propensity score (PS) methodology to identify two cohorts of patients matched for relevant baseline characteristics who were treated with either reduced (n=53) or standard (n=83) doses of TNF inhibitors. One-year outcomes and costs of anti-TNF drugs were compared between both PS-matched cohorts. <h3>Results</h3> In the reduced dosing group, the median dose of TNF inhibitor corresponded to 0.67 and 0.5 of the standard dose initially and at 12 months respectively, and 21% of patients required return to standard dosing regimen. The mean change per year in Bath Ankylosing Spondylitis Activity Index, C-reactive protein , Health Assessment Questionnaire Disability Index and Bath AS functional index, as well as quality-adjusted life-year area under the curve were no different between both groups. The HR (95% CI) of reduced versus standard dosing group for relapse and any adverse event was 1.46 (0.66 to 3.19) and 0.56 (0.22 to 1.44), respectively. Mean difference (95% CI) in cost of anti-TNF drugs was €−4214 (−4707 to −3701) per year of treatment in favour of reduced dosing strategy. <h3>Conclusions</h3> In patients with AS after reaching low-disease activity, a tailored approach to reduce doses of anti-TNF drugs produced similar clinical outcomes at 1 year, but was substantially less costly.
Evolution and Functional Diversification of Fructose Bisphosphate Aldolase Genes in Photosynthetic Marine Diatoms
Authors: Andrew E. Allen, Ahmed Moustafa, Anton Montsant, Angelika Eckert, Peter G. Kroth, Chris Bowler
Journal: Molecular Biology and Evolution (2011)

Diatoms and other chlorophyll-c containing, or chromalveolate, algae are among the most productive and diverse phytoplankton in the ocean. Evolutionarily, chlorophyll-c algae are linked through common, although not necessarily monophyletic, acquisition of plastid endosymbionts of red as well as most likely green algal origin. There is also strong evidence for a relatively high level of lineage-specific bacterial gene acquisition within chromalveolates. Therefore, analyses of gene content and derivation in chromalveolate taxa have indicated particularly diverse origins of their overall gene repertoire. As a single group of functionally related enzymes spanning two distinct gene families, fructose 1,6-bisphosphate aldolases (FBAs) illustrate the influence on core biochemical pathways of specific evolutionary associations among diatoms and other chromalveolates with various plastid-bearing and bacterial endosymbionts. Protein localization and activity, gene expression, and phylogenetic analyses indicate that the pennate diatom Phaeodactylum tricornutum contains five FBA genes with very little overall functional overlap. Three P. tricornutum FBAs, one class I and two class II, are plastid localized, and each appears to have a distinct evolutionary origin as well as function. Class I plastid FBA appears to have been acquired by chromalveolates from a red algal endosymbiont, whereas one copy of class II plastid FBA is likely to have originated from an ancient green algal endosymbiont. The other copy appears to be the result of a chromalveolate-specific gene duplication. Plastid FBA I and chromalveolate-specific class II plastid FBA are localized in the pyrenoid region of the chloroplast where they are associated with β-carbonic anhydrase, which is known to play a significant role in regulation of the diatom carbon concentrating mechanism. The two pyrenoid-associated FBAs are distinguished by contrasting gene expression profiles under nutrient limiting compared with optimal CO2 fixation conditions, suggestive of a distinct specialized function for each. Cytosolically localized FBAs in P. tricornutum likely play a role in glycolysis and cytoskeleton function and seem to have originated from the stramenopile host cell and from diatom-specific bacterial gene transfer, respectively.
An unsuitable and degraded diet? Part three: Victorian consumption patterns and their health benefits
Authors: Judith Rowbotham, Paul Clayton
Journal: Journal of the Royal Society of Medicine (2008)

Principal findings
Where our previous two papers documented the volume and variety of the mid-Victorian diet, this final paper reveals that the mid-Victorian diet conferred extremely significant protection against the major degenerative diseases, even amongst those who, because of their extremely limited incomes, might be considered to be significantly under-nourished and so vulnerable to such afflictions.
Diabetes mellitus is an independent prognostic factor for major liver-related outcomes in patients with cirrhosis and chronic hepatitis C
Authors: Laure Elkrief, Pascale Chouinard, Noelle Bendersky, David Hajage, Béatrice Larroque, Gérard Babany, Blaise Kutala, Claire Francoz, Nathalie Boyer, Richard Moreau, François Durand, Patrick Marcellin, Pierre-Emmanuel Rautou, Dominique Valla
Journal: Hepatology (2014)

In patients with chronic hepatitis C (CHC), cirrhosis is associated with age, gender, diabetes, alcohol abuse, and coinfection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV). The effect of these factors on the outcome of cirrhosis is unknown. This study in CHC patients with cirrhosis aimed to assess the influence of these factors on decompensation, liver transplantation, and death. Consecutive patients with CHC and cirrhosis hospitalized between January 1, 2006 and December 31, 2008 were followed up until death, transplantation, or study closure in March 2013. Gender, age, Model for End-Stage Liver Disease (MELD) score, diabetes, alcohol abuse, HIV, or HBV coinfection were collected at inclusion. The complications of cirrhosis, death, and liver transplantation were recorded at inclusion and during follow-up. The association between baseline factors and liver-related outcomes at inclusion and during follow-up were tested using logistic regression and Cox's model, respectively. A total of 348 patients with CHC and cirrhosis (68% men; median age: 59 years; median MELD: 10) were included. At baseline, 40% of the patients had diabetes, 29% alcohol abuse, and 6% HIV or HBV coinfection. Baseline MELD ≥10 ( P &lt; 0.001), diabetes ( P = 0.027), and HBV coinfection ( P = 0.001) were independently associated with transplantation-free survival. Baseline diabetes was independently associated with ascites ( P = 0.05), bacterial infections ( P = 0.001), and encephalopathy ( P &lt; 0.001) at inclusion. Baseline diabetes was independently associated with development of ascites ( P = 0.057), renal dysfunction ( P = 0.004), bacterial infections ( P = 0.007), and hepatocellular carcinoma ( P = 0.016) during the follow-up. Conclusion : In patients with CHC and cirrhosis, diabetes is an independent prognostic factor. Improving diabetes control may improve the outcome of cirrhosis. (Hepatology 2014;60:823–831)
SUBOPTIMAL RISK FACTOR CONTROL IN PATIENTS UNDERGOING ELECTIVE CARDIOVASCULAR INTERVENTION
Authors: Lisa Tully, Eugenia Gianos, Anish Vani, Yu Guo, Revathi Balakrishnan, Omad Ullah, Michael Schloss, Arthur Schwartzbard, James Slater, Richard Stein, James Underberg, Howard Weintraub, Edward Fisher, Jeffrey Berger
Journal: Journal of the American College of Cardiology (2013)
Tumor-Targeting Properties of Novel Antibodies Specific to the Large Isoform of Tenascin-C
Authors: Simon S. Brack, Michela Silacci, Manfred Birchler, Dario Neri
Journal: Clinical Cancer Research (2006)

Abstract Background: The targeted delivery of bioactive molecules with antibodies specific to tumor-associated antigens represents a promising strategy for improving the efficacy of tumor therapy. The large isoform of tenascin-C, an abundant glycoprotein of the tumor extracellular matrix, is strongly overexpressed in adult tissue undergoing tissue remodeling, including wound healing and neoplasia, and has been implicated in a variety of different cancers while being virtually undetectable in most normal adult tissues. Experimental Design: We have used antibody phage technology to generate good-quality human recombinant antibodies (F16 and P12) specific to the alternatively spliced domains A1 and D of the large isoform of tenascin-C. The tumor-targeting properties of F16 and P12 were assessed by biodistribution studies in tumor xenografts using the antibodies in small immunoprotein (SIP) format. Results: SIP(F16) selectively accumulated at the tumor site with 4.5%ID/g at 24 hours in the U87 glioblastoma model but was rapidly cleared from other organs (tumor-to-organ ratios, ∼10:1). The accumulation of SIP(P12) in the tumor was lower compared with SIP(F16) and persistent levels of radioactivity were observed in the intestine. Conclusions: These data suggest that the F16 antibody, specific to domain A1 of tenascin-C, is a promising building block for the development of antibody-based pharmaceuticals in view of its excellent tumor-targeting performance and the strong expression of the antigen in a variety of primary and metastatic tumors.
Recruitment of Slp-76 to the Membrane and Glycolipid-Enriched Membrane Microdomains Replaces the Requirement for Linker for Activation of T Cells in T Cell Receptor Signaling
Authors: Nancy J. Boerth, Jeffrey J. Sadler, Daniel E. Bauer, James L. Clements, Shereen M. Gheith, Gary A. Koretzky
Journal: The Journal of Experimental Medicine (2000)

Two hematopoietic-specific adapters, src homology 2 domain–containing leukocyte phosphoprotein of 76 kD (SLP-76) and linker for activation of T cells (LAT), are critical for T cell development and T cell receptor (TCR) signaling. Several studies have suggested that SLP-76 and LAT function coordinately to promote downstream signaling. In support of this hypothesis, we find that a fraction of SLP-76 localizes to glycolipid-enriched membrane microdomains (GEMs) after TCR stimulation. This recruitment of SLP-76 requires amino acids 224–244. The functional consequences of targeting SLP-76 to GEMs for TCR signaling are demonstrated using a LAT/SLP-76 chimeric protein. Expression of this construct reconstitutes TCR-inducted phospholipase Cγ1 phosphorylation, extracellular signal–regulated kinase activation, and nuclear factor of activated T cells (NFAT) promoter activity in LAT-deficient Jurkat T cells (J.CaM2). Mutation of the chimeric construct precluding its recruitment to GEMs diminishes but does not eliminate its ability to support TCR signaling. Expression of a chimera that lacks SLP-76 amino acids 224–244 restores NFAT promoter activity, suggesting that if localized, SLP-76 does not require an association with Gads to promote T cell activation. In contrast, mutation of the protein tyrosine kinase phosphorylation sites of SLP-76 in the context of the LAT/SLP-76 chimera abolishes reconstitution of TCR function. Collectively, these experiments show that optimal TCR signaling relies on the compartmentalization of SLP-76 and that one critical function of LAT is to bring SLP-76 and its associated proteins to the membrane.
Prioritization of Patient-Centered Comparative Effectiveness Research for Osteoarthritis
Authors: Jennifer M. Gierisch, Evan R. Myers, Kristine M. Schmit, Douglas C. McCrory, Remy R. Coeytaux, Matthew J. Crowley, Ranee Chatterjee, Amy S. Kendrick, Gillian D. Sanders
Journal: Annals of Internal Medicine (2014)

Osteoarthritis is a leading cause of disability in the United States. This article describes a prioritized research agenda about osteoarthritis management developed for the Patient-Centered Outcomes Research Institute. Evidence gaps were identified by reviewing existing literature and engaging diverse stakeholders to expand and refine gaps. Stakeholders ranked evidence gaps by importance from their perspectives.Prioritized evidence gaps included the need to determine or evaluate key patient-centered outcomes; optimal duration, intensity, and frequency of nonsurgical interventions; whether the comparative effectiveness of nonsurgical interventions varies by socioeconomic factors; when and how to transition from nonsurgical to surgical interventions; effective ways to engage patients in self-management and promote long-term behavior change; standardized screening tools that improve early diagnosis; biomechanical strategies that improve symptoms; mechanisms for promoting and delivering coordinated, longitudinal care; and comparative effectiveness of nonsurgical therapies. Searches of PubMed and ClinicalTrials.gov showed many recent and ongoing studies addressing comparative effectiveness of nonsurgical interventions; relatively few of these evaluated treatments across categories (for example, drug therapy vs. weight management) or combined categories of treatment. Few studies addressed other high-priority evidence gaps.
The echocardiographic determination of mitral valve opening and closure. Correlation with hemodynamic studies in man.
Authors: J J Rubenstein, G M Pohost, R E Dinsmore, J W Harthorne
Journal: Circulation (1975)

The ability of the echocardiogram to define mitral valve opening and closure was assessed by simultaneously recording the echocardiogram of the anterior leaflet (ECHO) with intracardiac pressures, aortic second sound, and ECG on 38 occasions in 14 patients undergoing cardiac catheterization. Hemodynamic opening and closure were defined by intersection of the pulmonary wedge and left ventricular pressures and the onset of left ventricular systole. The onset of the most rapid anterior motion (D') in early diastole and termination of the last rapid posterior movement in end diastole (Co) were used as echocardiographic markers of mitral valve opening and closure. Intervals measured included: the isovolumic relaxation period (IRP) from A2 to either hemodynamic (IRPH) or echocardiographic (IRPE) opening; the Q to closure interval (QCI) from the Q wave to either hemodynamic (QCIH) or echocardiographic (QCIE) closure; and diastolic filling period (DFP), either hemodynamic (DFPH) or echocardiographic (DFPE). The following significant (P less than .01) regression equations resulted: IRPE equals (.97) IRPH plus 30 (sem plus or minus 8 msec) r equals .89; QCIE equals (.68) QCIH plus 37 (sem plus or minus 7 msec) r equals .71; DEPE equals (.98) DFPH plus 10 (sem plus or minus 18 msec) r equals .98. Thus hemodynamic markers of opening and closure systematically precede echocardiographic markers of opening (D') and closure (Co) and the diastolic filling periods are equal within 10 msec. It is concluded that the echocardiogram of the anterior leaflet is a reliable indicator of hemodynamic markers of opening and closure of the mitral valve in man and is useful in the noninvasive determination of certain systolic and diastolic time intervals.
Differential switching to IgG and IgA in active smoking COPD patients and healthy controls
Authors: Corry-Anke Brandsma, Huib A.M. Kerstjens, Wouter H. van Geffen, Marie Geerlings, Dirkje S. Postma, Machteld N. Hylkema, Wim Timens
Journal: European Respiratory Journal (2012)

Several studies have demonstrated the presence of B-cell follicles and autoantibodies in chronic obstructive pulmonary disease (COPD). It is unclear against which antigens this B-cell response is directed and whether it contributes to development or worsening of disease. We assessed different B-cell subsets in blood and lung tissue from COPD patients and controls, and compared differences in B-cell responsiveness to stimulation with lung-specific antigens. Active smoking induced an adaptive immune response with relatively high levels of (class-switched) memory B-cells in blood and immunoglobulin (Ig)G memory B-cells in the lung. COPD smokers showed more switching to IgG, whereas healthy smokers switched more to IgA. COPD patients had higher levels of memory B-cells in the lung and stimulation with lung-specific antigens induced higher numbers of anti-decorin antibody-producing cells in COPD patients compared with healthy controls. Differential switching to IgG and IgA indicates that the adaptive immune response to smoke differs between COPD patients and healthy controls. A higher level of memory B-cells in the lungs of COPD patients may reflect an antigen-specific immune response, which could be directed against decorin, as suggested by the induction of anti-decorin antibody-producing cells in response to antigen-specific stimulation in COPD patients.
Bacterial endocarditis, mitral regurgitation, and intra-atrial thrombosis following mitral valve replacement
Authors: H. M. Windsor, P. Fagan, M. X. Shanahan
Journal: Thorax (1968)

Bacterial endocarditis with positive blood culture occurred on six occasions in a series of 140 mitral valve replacements. In three of these, extensive detachment of the prosthesis with severe mitral incompetence resulted. Re-operation was undertaken in two of these cases. Intra-atrial thrombosis occurred twice. In three other cases, in which intra-atrial thrombosis occurred, infection was strongly suspected to have been the responsible factor. Mitral regurgitation presented no difficulty in diagnosis, as all patients had severe congestive cardiac failure and typical physical signs. Confirmation was established by cinéangiography. Intra-atrial thrombosis presented difficulty in diagnosis. A persistently positive blood culture, continued pyrexia, and a history of sepsis were the most consistent and significant findings in the cases reported. The antibiotic regime described by Amoury and his colleagues has been used for the past year. There has not been a single case of bacterial endocarditis, intra-atrial thrombosis, or wound infection in 120 consecutive valve replacements on this regime. Because of the high mortality associated with intra-atrial thrombosis, and the close association between endocarditis and thrombosis, the presence of endocarditis with or without regurgitation might well be a compelling reason for re-operation. The mortality from these complications could, we believe, be reduced by the use of a more extensive antibiotic cover and a more vigorous attitude to surgical intervention. We have not had to consider re-operation since adopting the policy outlined, as these complications have not occurred.
Association Between Oral Isotretinoin Therapy and Unmasked Latent Immuno-Mediated Diabetes
Authors: Ilaria Dicembrini, Gianluca Bardini, Carlo M. Rotella
Journal: Diabetes Care (2009)

Isotretinoin is an effective drug for the treatment of acne, but elevated liver enzymes, dyslipidemia, insulin resistance, and type 2 diabetes during isotretinoin therapy have been reported. We recently managed a 28-year-old male outpatient (BMI 24 kg/m2) affected by severe facial acne. There was no familial history of diabetes. All laboratory determinations, including hepatic function and fasting plasma glucose (FPG) levels (95 mg/dl), were in the reference range. C-peptide and A1C were not evaluated.

In July 2008, a dermatologist prescribed isotretinoin (30 mg/day) for the patient. After 1 month, the patient had an FPG of 118 mg/dl and a substantially normal lipid profile (total cholesterol [TC] 191 mg/dl, HDL cholesterol 34 mg/dl, LDL cholesterol …
Children’s Reaction to Depictions of Healthy Foods in Fast-Food Television Advertisements
Authors: Amy M. Bernhardt, Cara Wilking, Mark Gottlieb, Jennifer Emond, James D. Sargent
Journal: JAMA Pediatrics (2014)

Since 2009, quick-service restaurant chains, or fast-food companies, have agreed to depict healthy foods in their advertising targeted at children.To determine how children interpreted depictions of milk and apples in television advertisements for children's meals by McDonald's and Burger King (BK) restaurants.Descriptive qualitative study in a rural pediatric practice setting in Northern New England. A convenience sample of 99 children (age range, 3-7 years) was shown depictions of healthy foods in fast-food advertisements that aired from July 1, 2010, through June 30, 2011. The images from McDonald's and BK showed milk and apples. Children were asked what they saw and not prompted to respond specifically to any aspect of the images.Two still images drawn from advertisements for healthy meals at McDonald's and BK.Children's responses were independently content coded to food category by 2 researchers.Among the 99 children participating, only 51 (52%) and 69 (70%) correctly identified milk from the McDonald's and BK images, respectively, with a significantly greater percentage correct (P = .02 for both) among older children. The children's recall of apples was significantly different by restaurant, with 79 (80%) mentioning apples when describing the McDonald's image and only 10 (10%) for the BK image (P < .001). The percentage correct was not associated with age in either case. Conversely, although french fries were not featured in either image, 80 children (81%) recalled french fries after viewing the BK advertisement.Of the 4 healthy food images, only depiction of apples by McDonald's was communicated adequately to the target audience. Representations of milk were inadequately communicated to preliterate children. Televised depictions of apple slices by BK misled the children in this study, although no action was taken by government or self-regulatory bodies.
Efficacy and safety of IV ferumoxytol for adults with iron deficiency anemia previously unresponsive to or unable to tolerate oral iron
Authors: Saroj Vadhan‐Raj, William Strauss, David Ford, Kristine Bernard, Ralph Boccia, Joe Li, Lee F. Allen
Journal: American Journal of Hematology (2013)

Although oral iron is the initial treatment approach for iron deficiency anemia (IDA), some patients fail to respond to or cannot tolerate oral iron. This double-blind safety and efficacy study of the intravenous (IV) iron, ferumoxytol, randomized patients with a history of unsatisfactory oral iron therapy, or in whom oral iron could not be used, to ferumoxytol (n = 609) or placebo (n = 203). The proportion of patients achieving the primary endpoint (hemoglobin increase ≥2.0 g/dL at Week 5) was 81.1% with ferumoxytol versus 5.5% with placebo (P < 0.0001). The mean increase in hemoglobin from Baseline to Week 5, a secondary endpoint (also the alternative preplanned primary efficacy endpoint for other health authorities), was 2.7 versus 0.1 g/dL (P < 0.0001). Achievement of a hemoglobin ≥12 g/dL, time to a hemoglobin increase ≥2.0 g/dL, and improvement in the Functional Assessment of Chronic Illness Therapy Fatigue score also significantly favored ferumoxytol over placebo at Week 5 (P < 0.0001). Ferumoxytol treatment-emergent adverse events were mainly mild to moderate. Ferumoxytol was effective and well tolerated in patients with IDA of any underlying cause in whom oral iron was ineffective or could not be used. This trial was registered at www.clinicaltrials.gov as #NCT01114139.