tbuckley/cabot-search huggingface dataset:
Long-Term Maintenance of Treatment Outcomes: Diabetes Personal Trainer Intervention for Youth With Type 1 Diabetes
Authors: Tonja R. Nansel, Ronald J. Iannotti, Bruce G. Simons-Morton, Leslie P. Plotnick, Loretta M. Clark, Linda Zeitzoff
Journal: Diabetes Care (2009)

To describe a 2-year follow-up of A1C outcomes of a self-regulation intervention for youth with type 1 diabetes.A total of 81 youths with type 1 diabetes ages 11-16 years were randomized to usual care versus a diabetes personal trainer intervention consisting of six self-monitoring, goal-setting, and problem-solving sessions with trained nonprofessionals. A1C data were obtained from medical records 2 years postintervention, and ANCOVA adjusting for age and baseline A1C was conducted.An overall intervention effect on A1C (8.93% control vs. 8.43% intervention; F = 8.24, P = 0.05) and a significant intervention-by-age interaction (F = 9.88; P = 0.002) were observed, indicating a greater effect among older than younger youths. Subgroup analyses demonstrated no treatment group differences among pre-/early adolescents but a significant difference in A1C among middle adolescents (9.61% control vs. 8.46% intervention; F = 7.20, P = 0.011).Findings indicate maintenance of intervention effects on A1C observed at 1-year follow-up.
Association of Serum Immunoglobulin G Antibodies Against Human Papillomavirus Type 16 Capsids With Anal Epidermoid Carcinoma
Authors: Pirkko Heino, Carina Eklund, Vanoohi Fredriksson-Shanazarian, Sven Goldman, John T. Schiller, Joakim Dillner
Journal: JNCI Journal of the National Cancer Institute (1995)

Background : Anal epidermoid carcinoma is a relatively rare tumor, but its incidence has been increasing rapidly during the past few years. Genetic material from the major oncogenic types of human papillomavirus (HPV), types 16 and 18, has regularly been demonstrated in a substantial proportion of anal cancers, suggesting an etiologic role of HPV infection. Recently, serum antibodies against HPV type 16 capsids were shown to be a serologic measure of HPV16 infection. Purpose : We investigated whether serum antibodies against HPV16 capsids are associated with an increased risk of developing anal cancer. Methods : Serum samples from 64 patients (48 women and 16 men) with untreated anal epidermoid cancer and from 79 age- and sex-matched healthy blood donors were analyzed for the levels of serum immunoglobulin G (IgG) against capsids of HPV16 by the enzyme-linked immunosorbent assay. The levels of serum IgG against HPV type 6 and bovine papillomavirus (BPV) capsids, as well as against HPV16 peptide antigens, were also measured. Results : Whereas antibodies against HPV6 or BPV capsids were not significantly associated with anal cancer, the presence of IgG against HPV16 capsids exceeding the anti-BPV antibody levels was demonstrated among 55% (35 of 64) of the case patients but only among 4% (three of 79) of the control subjects (odds ratio (OR) = 30.4; 95% confidence interval (CI) = 8.4–161.5). Antibodies against HPV16 E2 and E7 peptides were also more common among case patients (OR = 12.8 and 95% CI = 5.4–31.5 for E2; OR = 3.0 and 95% CI = 1.4–6.7 for E7). Conclusion : The results suggest that HPV16 capsid antibodies are serologic markers for anal cancer. Implication : Exposure to HPV16 or related viruses appears to be a major risk factor in the majority of anal cancers. (J Natl Cancer Inst 87: 437–440, 1995.
1205 GS-6620, A NOVEL ANTI-HEPATITIS C VIRUS NUCLEOTIDE PRODRUG, HAS A HIGH BARRIER TO RESISTANCE IN VITRO
Authors: M. Fenaux, G. Cheng, E. Mabery, K. Ku, S. Eng, J. Vela, J. Feng, W. Delaney, H. Mo, A. Ray, W. Zhong
Journal: Journal of Hepatology (2011)
Obesity and Cancer: Local and Systemic Mechanisms
Authors: Neil M. Iyengar, Clifford A. Hudis, Andrew J. Dannenberg
Journal: Annual Review of Medicine (2015)

Obesity is a leading modifiable risk factor for the development of several epithelial malignancies. In addition to increasing risk, obesity also confers worse prognosis for many cancers. Obesity represents an overall state of energy imbalance frequently associated with systemic effects including insulin resistance, altered hormone signaling, and high circulating levels of proinflammatory mediators. In addition to its systemic effects, obesity causes subclinical white adipose inflammation including increased tissue levels of proinflammatory mediators. Both local and systemic effects are likely to contribute to the development and progression of cancer. An understanding of the interplay between local and systemic alterations involved in the obesity–cancer link provides the basis for developing interventions aimed at mitigating the protumorigenic effects.
A Controlled Trial of Phenylbutazone, Oxyphenbutazone, and a Placebo in the Treatment of Rheumatoid Arthritis
Authors: R. I. Meanock, E. Lewis-Faning
Journal: Annals of the Rheumatic Diseases (1961)

<h3>Abstract</h3> mRNA levels are determined by the balance between mRNA synthesis and decay. Factors that mediate both processes, including the 5’ to 3’ exonuclease Xrn1, are responsible for the cross talk between the two processes in a manner that buffers steady-state mRNA levels. However, these proteins’ roles in transcription remain elusive and controversial. Applying NET-seq to yeast cells, we show that Xrn1 functions mainly as a transcriptional activator and that its disruption manifests via the reduction of RNA polymerase II (Pol II) occupancy downstream of transcription start sites. We combine our data and novel mathematical modeling of transcription to suggest that transcription initiation and elongation of targeted genes is modulated by Xrn1. Furthermore, Pol II occupancy markedly increases near cleavage and polyadenylation sites in <i>xrn</i>1Δ cells while its activity decreases, a characteristic feature of backtracked Pol II. We also provide indirect evidence that Xrn1 is involved in transcription termination downstream of polyadenylation sites. Two additional decay factors, Dhh1 and Lsm1, seem to function similarly to Xrn1 in transcription, perhaps as a complex, while the decay factors Ccr4 and Rpb4 also perturb transcription in other ways. Interestingly, DFs are capable of differentiating between SAGA- and TFIID-dominated promoters. These two classes of genes respond differently to <i>XRN</i>1 deletion in mRNA synthesis and differentially utilize mRNA decay pathways, raising the possibility that one distinction between the two types of genes lies in the mechanism(s) that balance these processes.
Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C
Authors: M. E. Miquilena-Colina, E. Lima-Cabello, S. Sanchez-Campos, M. V. Garcia-Mediavilla, M. Fernandez-Bermejo, T. Lozano-Rodriguez, J. Vargas-Castrillon, X. Buque, B. Ochoa, P. Aspichueta, J. Gonzalez-Gallego, C. Garcia-Monzon
Journal: Gut (2011)

Fatty acid translocase CD36 (FAT/CD36) mediates uptake and intracellular transport of long-chain fatty acids in diverse cell types. While the pathogenic role of FAT/CD36 in hepatic steatosis in rodents is well-defined, little is known about its significance in human liver diseases.To examine the expression of FAT/CD36 and its cellular and subcellular distribution within the liver of patients with non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection.34 patients with non-alcoholic steatosis (NAS), 30 with non-alcoholic steatohepatitis (NASH), 66 with HCV genotype 1 (HCV G1) and 32 with non-diseased liver (NL).Real-time PCR and western blot analysis were used to assess hepatic FAT/CD36 expression. Computational image analysis of immunostained liver biopsy sections was performed to determine subcellular distribution and FAT/CD36 expression index.Compared with NL, hepatic mRNA and protein levels of FAT/CD36 were significantly higher in patients with NAS (median fold increase 0.84 (range 0.15-1.61) and 0.66 (range 0.33-1.06), respectively); NASH (0.91 (0.22-1.81) and 0.81 (0.38-0.92), respectively); HCV G1 without steatosis (0.30 (0.17-1.59) and 0.33 (0.29-0.52), respectively); and HCV G1 with steatosis (0.85 (0.15-1.98) and 0.87 (0.52-1.26), respectively). In contrast to NL, FAT/CD36 was predominantly located at the plasma membrane of hepatocytes in patients with NAFLD and HCV G1 with steatosis. A significant correlation was observed between hepatic FAT/CD36 expression index and plasma insulin levels, insulin resistance (HOMA-IR) and histological grade of steatosis in patients with NASH (r=0.663, r=0.735 and r=0.711, respectively) and those with HCV G1 with steatosis (r=0.723, r=0.769 and r=0.648, respectively).Hepatic FAT/CD36 upregulation is significantly associated with insulin resistance, hyperinsulinaemia and increased steatosis in patients with NASH and HCV G1 with fatty liver. Translocation of this fatty acid transporter to the plasma membrane of hepatocytes may contribute to liver fat accumulation in patients with NAFLD and HCV.
Percutaneous Transcatheter Closure of Patent Foramen Ovale in Patients With Paradoxical Embolism
Authors: Francisco Martín, Pedro L. Sánchez, Elizabeth Doherty, Pedro J. Colon-Hernandez, Gabriel Delgado, Ignacio Inglessis, Nandita Scott, Judy Hung, Mary Etta E. King, Ferdinando Buonanno, Zareh Demirjian, Michael de Moor, Igor F. Palacios
Journal: Circulation (2002)

Background— Percutaneous transcatheter closure of patent foramen ovale (PFO) is used as an alternative to surgery or long-term anticoagulation for the treatment of patients with paradoxical embolism and PFO. Methods and Results— We report the immediate and long-term clinical and echocardiographic outcome of 110 consecutive patients (58 males, mean age 47±14 years) who underwent transcatheter closure of PFO because of paradoxical embolism between 1995 and 2001. Procedural success, defined as successful deployment of the device and effective occlusion (no, or trivial, shunt after device placement), was achieved in all (100%) patients. There was no in-hospital mortality, 1 device migration requiring surgical intervention (0.9%), and 1 episode of cardiac tamponade (0.9%) requiring pericardiocentesis. A progressive increment in full occlusion was observed (44%, 51%, 66%, and 71% at 1 day, 6 months, and 1 and 2 years, respectively, after device placement). At a mean follow-up of 2.3 years, 2 patients experienced recurrent neurological events (1 fatal stroke and 1 transient ischemic attack), representing an annual risk of recurrence of 0.9%. In addition, 4 (3.6%) of the patients required reintervention for device malalignment or significant shunt. Kaplan-Meier analysis showed a freedom from recurrent embolic events and reintervention of 96% and 90% at 1 and 5 years, respectively. Conclusions— Transcatheter closure of PFO is a safe and effective therapy for patients with paradoxical embolism and PFO. It is associated with a high success rate, low incidence of hospital complications, and low frequency of recurrent systemic embolic events.
Coronary Pressure Measurement to Assess the Hemodynamic Significance of Serial Stenoses Within One Coronary Artery
Authors: Nico H.J. Pijls, Bernard De Bruyne, G. Jan Willem Bech, Francesco Liistro, Guy R. Heyndrickx, Hans J.R.M. Bonnier, Jacques J. Koolen
Journal: Circulation (2000)

Background —When several stenoses are present within 1 coronary artery, the hemodynamic significance of each stenosis is influenced by the presence of the other(s), and the calculation of coronary and fractional flow reserve (CFR and FFR) for each individual stenosis is confounded. Recently, we developed and experimentally validated a method to determine the true FFR of each stenosis as it would be after the removal of the other stenosis; the true FFR can be reliably predicted by coronary pressures measured before treatment at specific locations within the coronary artery using equations accounting for stenosis interaction. The aim of the present study was to test the validity of these equations in humans. Methods and Results —In this study of 32 patients with 2 serial stenoses in 1 coronary artery, relevant pressures were measured before the intervention, after the treatment of 1 stenosis, and after the treatment of both stenoses. The true FFR of each stenosis (FFR true ) was directly measured after the elimination of the other stenosis and compared with the value predicted (FFR pred ) from the initial pressure measurements before treatment. Although the hyperemic gradient across 1 stenosis increased significantly (from 10±7 to 19±11 mm Hg after treatment of the other stenosis), FFR pred was close to FFR true in all patients (0.78±0.12 versus 0.78±0.11 mm Hg; r =0.92; Δ%=4±0%). Without accounting for stenosis interaction, the value of FFR for each stenosis would have been significantly overestimated (0.85±0.08; P &lt;0.01). Conclusions —Coronary pressure measurements made by a pressure wire at maximum hyperemia provide a simple, practical method for assessing the individual hemodynamic significance of multiple stenoses within the same artery.
Randomized Phase II Study of the Anti–Epidermal Growth Factor Receptor Monoclonal Antibody Cetuximab With Cisplatin Versus Cisplatin Alone in Patients With Metastatic Triple-Negative Breast Cancer
Authors: José Baselga, Patricia Gómez, Richard Greil, Sofia Braga, Miguel A. Climent, Andrew M. Wardley, Bella Kaufman, Salomon M. Stemmer, António Pêgo, Arlene Chan, Jean-Charles Goeminne, Marie-Pascale Graas, M. John Kennedy, Eva Maria Ciruelos Gil, Andreas Schneeweiss, Angela Zubel, Jutta Groos, Helena Melezínková, Ahmad Awada
Journal: Journal of Clinical Oncology (2013)

Epidermal growth factor receptor is overexpressed in metastatic triple-negative breast cancers (mTNBCs), an aggressive subtype of breast cancer. Our randomized phase II study investigated cisplatin with or without cetuximab in this setting.Patients who had received no more than one previous chemotherapy regimen were randomly assigned on a 2:1 schedule to receive no more than six cycles of cisplatin plus cetuximab or cisplatin alone. Patients receiving cisplatin alone could switch to cisplatin plus cetuximab or cetuximab alone on disease progression. The primary end point was overall response rate (ORR). Secondary end points studied included progression-free survival (PFS), overall survival (OS), and safety profiles. Analyses included a significance level of α = .10 with no adjustments for multiplicity.The full analysis set comprised 115 patients receiving cisplatin plus cetuximab and 58 receiving cisplatin alone; 31 patients whose disease progressed on cisplatin alone switched to cetuximab-containing therapy. The ORR was 20% (95% CI, 13 to 29) with cisplatin plus cetuximab and 10% (95% CI, 4 to 21) with cisplatin alone (odds ratio, 2.13; 95% CI, 0.81 to 5.59; P = .11). Cisplatin plus cetuximab resulted in longer PFS compared with cisplatin alone (median, 3.7 v 1.5 months; hazard ratio [HR], 0.67; 95% CI, 0.47 to 0.97; P = .032). Corresponding median OS was 12.9 versus 9.4 months (HR, 0.82; 95% CI, 0.56 to 1.20; P = .31). Common grade 3/4 adverse events included acne-like rash, neutropenia, and fatigue.While the primary study end point was not met, adding cetuximab to cisplatin doubled the ORR and appeared to prolong PFS and OS, warranting further investigation in mTNBC.
Selective Activation of Adenosine A <sub>2A</sub> Receptors on Immune Cells by a CD73-Dependent Prodrug Suppresses Joint Inflammation in Experimental Rheumatoid Arthritis
Authors: Ulrich Flögel, Sandra Burghoff, Peter L. E. M. van Lent, Sebastian Temme, Lisa Galbarz, Zhaoping Ding, Ali El-Tayeb, Sandra Huels, Florian Bönner, Nadine Borg, Christoph Jacoby, Christa E. Müller, Wim B. van den Berg, Jürgen Schrader
Journal: Science Translational Medicine (2012)

Adenosine A(2A) receptor (A(2A)R) agonists are both highly effective anti-inflammatory agents and potent vasodilators. To separate these two activities, we have synthesized phosphorylated A(2A)R agonists (prodrugs) that require the presence of ecto-5'-nucleotidase (CD73) to become activated. In the model of collagen-induced arthritis, 2-(cyclohexylethylthio)adenosine 5'-monophosphate (chet-AMP), but not 2-(cyclohexylethylthio)adenosine (chet-adenosine), potently reduced inflammation as assessed by fluorine-19 ((19)F) magnetic resonance imaging and by histology. The prodrug effect was blunted by inhibition of CD73 and A(2A)R. The selectivity of drug action is due to profound up-regulation of CD73 and adenosine A(2A)R expression in neutrophils and inflammatory monocytes as found in recovered cells from the synovial fluid of arthritic mice. Plasma chet-adenosine was in the subnanomolar range when chet-AMP was applied, whereas concentrations required for vasodilation were about 100 times higher. Thus, chet-AMP is a potent immunosuppressant with negligible vasodilatory activity. These data suggest that phosphorylated A(2A)R agonists may serve as a promising new group of drugs for targeted immunotherapy of inflammation.
GATA-1 as a Regulator of Mast Cell Differentiation Revealed by the Phenotype of the GATA-1low Mouse Mutant
Authors: Anna Rita Migliaccio, Rosa Alba Rana, Massimo Sanchez, Rodolfo Lorenzini, Lucia Centurione, Lucia Bianchi, Alessandro Maria Vannucchi, Giovanni Migliaccio, Stuart H. Orkin
Journal: The Journal of Experimental Medicine (2003)

Here it is shown that the phenotype of adult mice lacking the first enhancer (DNA hypersensitive site I) and the distal promoter of the GATA-1 gene (neoΔHS or GATA-1low mutants) reveals defects in mast cell development. These include the presence of morphologically abnormal alcian blue+ mast cells and apoptotic metachromatic− mast cell precursors in connective tissues and peritoneal lavage and numerous (60–70% of all the progenitors) “unique” trilineage cells committed to erythroid, megakaryocytic, and mast pathways in the bone marrow and spleen. These abnormalities, which were mirrored by impaired mast differentiation in vitro, were reversed by retroviral-mediated expression of GATA-1 cDNA. These data indicate an essential role for GATA-1 in mast cell differentiation.
Tartrate resistant acid phosphatase (TRAP) positive cells in rheumatoid synovium may induce the destruction of articular cartilage
Authors: H Tsuboi
Journal: Annals of the Rheumatic Diseases (2003)

To examine the role of tartrate resistant acid phosphatase (TRAP) positive mononuclear and multinucleated cells in the destruction of articular cartilage in patients with rheumatoid arthritis (RA).The presence of TRAP positive cells in the synovial tissue of patients with RA was examined by enzyme histochemistry and immunohistochemistry. Expression of mRNAs for matrix metalloproteinases (MMPs) was assessed by the reverse transcriptase-polymerase chain reaction (RT-PCR) and northern blot analysis. Production of MMPs by mononuclear and multinucleated TRAP positive cells was examined by immunocytochemistry, enzyme linked immunosorbent assay (ELISA) of conditioned medium, and immunohistochemistry of human RA synovial tissue. In addition, a cartilage degradation assay was performed by incubation of (35)S prelabelled cartilage discs with TRAP positive cells.TRAP positive mononuclear cells and multinucleated cells were found in proliferating synovial tissue adjacent to the bone-cartilage interface in patients with RA. Expression of MMP-2 (gelatinase A), MMP-9 (gelatinase B), MMP-12 (macrophage metalloelastase), and MMP-14 (MT1-MMP) mRNA was detected in TRAP positive mononuclear and multinucleated cells by both RT-PCR and northern blot analysis. Immunocytochemistry for these MMPs showed that MMP-2 and MMP-9 were produced by both TRAP positive mononuclear and multinucleated cells, whereas MMP-12 and MMP-14 were produced by TRAP positive multinucleated cells. MMP-2 and MMP-9 were detected in the conditioned medium of TRAP positive mononuclear cells. TRAP positive mononuclear cells also induced the release of (35)S from prelabelled cartilage discs.This study suggests that TRAP positive mononuclear and multinucleated cells located in the synovium at the cartilage-synovial interface produce MMP-2 and MMP-9, and may have an important role in articular cartilage destruction in patients with RA.
HALYs and QALYs and DALYs, Oh My: Similarities and Differences in Summary Measures of Population Health
Authors: Marthe R. Gold, David Stevenson, Dennis G. Fryback
Journal: Annual Review of Public Health (2002)

▪ Abstract Health-adjusted life years (HALYs) are population health measures permitting morbidity and mortality to be simultaneously described within a single number. They are useful for overall estimates of burden of disease, comparisons of the relative impact of specific illnesses and conditions on communities, and in economic analyses. Quality-adjusted life years (QALYs) and disability-adjusted life years (DALYs) are types of HALYs whose original purposes were at variance. Their growing importance and the varied uptake of the methodology by different U.S. and international entities makes it useful to understand their differences as well as their similarities. A brief history of both measures is presented and methods for calculating them are reviewed. Methodological and ethical issues that have been raised in association with HALYs more generally are presented. Finally, we raise concerns about the practice of using different types of HALYs within different decision-making contexts and urge action that builds and clarifies this useful measurement field.
Systematic Review: Impact of Health Information Technology on Quality, Efficiency, and Costs of Medical Care
Authors: Basit Chaudhry, Jerome Wang, Shinyi Wu, Margaret Maglione, Walter Mojica, Elizabeth Roth, Sally C. Morton, Paul G. Shekelle
Journal: Annals of Internal Medicine (2006)

Background: Experts consider health information technology key to improving efficiency and quality of health care. Purpose: To systematically review evidence on the effect of health information technology on quality, efficiency, and costs of health care. Data Sources: The authors systematically searched the English-language literature indexed in MEDLINE (1995 to January 2004), the Cochrane Central Register of Controlled Trials, the Cochrane Database of Abstracts of Reviews of Effects, and the Periodical Abstracts Database. We also added studies identified by experts up to April 2005. Study Selection: Descriptive and comparative studies and systematic reviews of health information technology. Data Extraction: Two reviewers independently extracted information on system capabilities, design, effects on quality, system acquisition, implementation context, and costs. Data Synthesis: 257 studies met the inclusion criteria. Most studies addressed decision support systems or electronic health records. Approximately 25% of the studies were from 4 academic institutions that implemented internally developed systems; only 9 studies evaluated multifunctional, commercially developed systems. Three major benefits on quality were demonstrated: increased adherence to guideline-based care, enhanced surveillance and monitoring, and decreased medication errors. The primary domain of improvement was preventive health. The major efficiency benefit shown was decreased utilization of care. Data on another efficiency measure, time utilization, were mixed. Empirical cost data were limited. Limitations: Available quantitative research was limited and was done by a small number of institutions. Systems were heterogeneous and sometimes incompletely described. Available financial and contextual data were limited. Conclusions: Four benchmark institutions have demonstrated the efficacy of health information technologies in improving quality and efficiency. Whether and how other institutions can achieve similar benefits, and at what costs, are unclear.