tbuckley/cabot-search huggingface dataset:
Cytogenetic and Molecular Tumor Profiling for Type 1 and Type 2 Papillary Renal Cell Carcinoma
Authors: Tobias Klatte, Allan J. Pantuck, Jonathan W. Said, David B. Seligson, Nagesh P. Rao, Jeffrey C. LaRochelle, Brian Shuch, Amnon Zisman, Fairooz F. Kabbinavar, Arie S. Belldegrun
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The goal of this study was to evaluate immunohistochemical and cytogenetic features and their prognostic value in papillary renal cell carcinoma (PRCC) subtypes. Experimental Design: One hundred fifty-eight cases of PRCC were identified and reclassified by subtype. Tumoral expression of 29 molecular markers was determined by immunohistochemistry. Cytogenetic analyses were done on a prospective series of 65 patients. Associations with clinicopathologic information and disease-specific survival were assessed. Results: Fifty-one patients (32%) had type 1 and 107 (68%) type 2 PRCC. Type 2 patients had worse Eastern Cooperative Oncology Group performance status, higher T stages, nodal and distant metastases, higher grades, and a higher frequency of necrosis, collecting system invasion and sarcomatoid features. Type 2 showed greater expression of vascular endothelial growth factor (VEGF)-R2 in the tumor epithelium, and of VEGF-R3 in both tumor epithelium and endothelium. Loss of chromosome 1p, loss of 3p, and gain of 5q were exclusively observed in type 2, whereas type 1 more frequently had trisomy 17. Type 2 PRCC was associated with worse survival than type 1, but type was not retained as an independent prognostic factor. Lower PTEN, lower EpCAM, lower gelsolin, higher CAIX, and higher VEGF-R2 and VEGF-R3 expression, loss of 1p, 3p, or 9p, and absence trisomy 17 were all associated with poorer prognosis. Conclusions: Type 2 PRCC is associated with more aggressive clinicopathologic features and worse outcome. Molecular and chromosomal alterations can distinguish between PRCC subtypes and influence their prognosis. The effect of 3p loss on survival in PRCC is opposite to the relationship seen in clear cell RCC.
Clinical Trial Registration
Authors: Catherine De Angelis, Jeffrey M. Drazen, Frank A. Frizelle, Charlotte Haug, John Hoey, Richard Horton, Sheldon Kotzin, Christine Laine, Ana Marusic, A. John P.M. Overbeke, Torben V. Schroeder, Hal C. Sox, Martin B. Van Der Weyden
Journal: Circulation (2005)
Systematic Review of Guidelines on Imaging of Asymptomatic Coronary Artery Disease
Authors: Bart S. Ferket, Tessa S.S. Genders, Ersen B. Colkesen, Jacob J. Visser, Sandra Spronk, Ewout W. Steyerberg, M.G. Myriam Hunink
Journal: Journal of the American College of Cardiology (2011)
Monocyte migration to arthritis in the rat utilizes both CD11/CD18 and very late activation antigen 4 integrin mechanisms.
Authors: A C Issekutz, T B Issekutz
Journal: The Journal of Experimental Medicine (1995)

In human and experimental models of arthritis, blood monocytes migrate into the inflamed synovium and joint space. The mechanisms required for monocyte migration across the vascular endothelium in joints is poorly defined. Radiolabeled rat blood monocytes were used to measure monocyte migration to the inflamed joints of rats with adjuvant arthritis, and the role of monocyte adhesion molecules was analyzed. Monocyte accumulation in the inflamed joints was maximal 14-21 d after immunization with adjuvant, when arthritis had fully developed. Blocking mAbs to lymphocyte function-associated antigen 1 (LFA-1), Mac-1, and very late activation antigen 4 (VLA-4) were used to evaluate the role of these integrins in the migration. Migration to the joints was not inhibited by treatment of the animals with mAb to LFA-1, Mac-1, or VLA-4 alone, and was partially (50%) inhibited in only the most arthritic joint, the talar joint, by the combination of mAb to LFA-1 plus Mac-1. In contrast, this combination inhibited migration to dermal inflammation induced by C5ades Arg, endotoxin, tumor necrosis factor alpha, and polyinosine-cytosine by 60-70%. When mAbs to LFA-1 and VLA-4 were combined, migration to all the inflamed joints was strongly inhibited (80-98%, depending on the joint). Treatment with the combination of the three mAbs to LFA-1, Mac-1, and VLA-4 completely eliminated monocyte migration to all joints and dermal inflammation. The results show that 51Cr blood monocytes can be used to quantify monocyte migration to arthritic joints in the rat. LFA-1 alone or VLA-4 alone is sufficient to mediate most of this migration, and either LFA-1 or VLA-4 is required for monocyte migration to joint inflammation. These results indicate that both the VLA-4 and LFA-1 integrins should be therapeutic targets for suppression of monocyte infiltration of joints in arthritis.
Competing Risks for Death and Cardiac Transplantation in Children With Dilated Cardiomyopathy
Authors: Jorge A. Alvarez, E. John Orav, James D. Wilkinson, Lora E. Fleming, David J. Lee, Lynn A. Sleeper, Paolo G. Rusconi, Steven D. Colan, Daphne T. Hsu, Charles E. Canter, Steven A. Webber, Gerald F. Cox, John L. Jefferies, Jeffrey A. Towbin, Steven E. Lipshultz
Journal: Circulation (2011)

Pediatric dilated cardiomyopathy (DCM) is the leading indication for heart transplantation after 1 year of age. Risk factors by etiology at clinical presentation have not been determined separately for death and transplantation in population-based studies. Competing risks analysis may inform patient prioritization for transplantation listing.The Pediatric Cardiomyopathy Registry enrolled 1731 children diagnosed with DCM from 1990 to 2007. Etiologic, demographic, and echocardiographic data collected at diagnosis were analyzed with competing risks methods stratified by DCM etiology to identify predictors of death and transplantation. For idiopathic DCM (n=1192), diagnosis after 6 years of age, congestive heart failure, and lower left ventricular (LV) fractional shortening z score were independently associated with both death and transplantation equally. In contrast, increased LV end-diastolic dimension z score was associated only with transplantation, whereas lower height-for-age z score was associated only with death. For neuromuscular disease (n=139), lower LV fractional shortening was associated equally with both end points, but increased LV end-diastolic dimension was associated only with transplantation. The risks of death and transplantation were increased equally for older age at diagnosis, congestive heart failure, and increased LV end-diastolic dimension among those with myocarditis (n=272) and for congestive heart failure and decreased LV fractional shortening among those with familial DCM (n=79).Risk factors for death and transplantation in children varied by DCM etiology. For idiopathic DCM, increased LV end-diastolic dimension was associated with increased transplantation risk but not mortality. Conversely, short stature was significantly related to death but not transplantation. These findings may present an opportunity to improve the transplantation selection algorithm.
Effects of twice-daily aclidinium bromide in COPD patients: A long-term extension of ACCORD-COPD I
Authors: Anthony D'Urzo, Edward Kerwin, James Donohue, Stephen Rennard, Arthur Gelb, Hassan Lakkis, Esther Garcia Gil, Cynthia Caracta
Journal: European Respiratory Journal (2012)

INTRODUCTION:  The long-term effects of twice-daily (BID) aclidinium 200 µg and 400 µg were assessed in patients with moderate-to-severe COPD.  METHODS:  In this 52-week, double-blind, extension study, COPD patients on aclidinium 200 µg or 400 µg BID during the 12-week lead-in continued the same treatment while patients in the placebo group were re-randomized (1:1) to aclidinium 200 µg or 400 µg BID. Baseline was prespecified as Visit 2 of the lead-in study. Spirometry, SGRQ, and adverse events (AEs) were assessed.  RESULTS:  A total of 467 patients completed the lead-in study and 291 patients volunteered for the extension study. At study end, placebo patients re-randomized to aclidinium 400 µg and those on either dose of continuous aclidinium treatment showed improvements from baseline in trough FEV 1 . All groups showed improvements from baseline in SGRQ Total score (range, 4.85-7.92 point improvement). The percentages of patients with an AE were similar for both doses. Incidence of anticholinergic AEs was low and similar for both groups; dry mouth occurred in 1 patient (400 µg). The incidence of cardiac AEs was low across treatments (  CONCLUSIONS:  Patients continuing long-term treatment with aclidinium 200 µg or 400 µg BID maintained improvements in lung function and health status compared to baseline. Aclidinium was well tolerated throughout this 1-year extension study.
Evolutionary Model Selection with a Genetic Algorithm: A Case Study Using Stem RNA
Authors: S. L. Kosakovsky Pond, F. V. Mannino, M. B. Gravenor, S. V. Muse, S. D. W. Frost
Journal: Molecular Biology and Evolution (2006)

The choice of a probabilistic model to describe sequence evolution can and should be justified. Underfitting the data through the use of overly simplistic models may miss out on interesting phenomena and lead to incorrect inferences. Overfitting the data with models that are too complex may ascribe biological meaning to statistical artifacts and result in falsely significant findings. We describe a likelihood-based approach for evolutionary model selection. The procedure employs a genetic algorithm (GA) to quickly explore a combinatorially large set of all possible time-reversible Markov models with a fixed number of substitution rates. When applied to stem RNA data subject to well-understood evolutionary forces, the models found by the GA 1) capture the expected overall rate patterns a priori; 2) fit the data better than the best available models based on a priori assumptions, suggesting subtle substitution patterns not previously recognized; 3) cannot be rejected in favor of the general reversible model, implying that the evolution of stem RNA sequences can be explained well with only a few substitution rate parameters; and 4) perform well on simulated data, both in terms of goodness of fit and the ability to estimate evolutionary rates. We also investigate the utility of several distance measures for comparing and contrasting inferred evolutionary models. Using widely available small computer clusters, our approach allows, for the first time, to evaluate the performance of existing RNA evolutionary models by comparing them with a large pool of candidate models and to validate common modeling assumptions. In addition, the new method provides the foundation for rigorous selection and comparison of substitution models for other types of sequence data.
A Randomized Clinical Trial to Evaluate the Safety and Efficacy of a Percutaneous Left Ventricular Assist Device Versus Intra-Aortic Balloon Pumping for Treatment of Cardiogenic Shock Caused by Myocardial Infarction
Authors: Melchior Seyfarth, Dirk Sibbing, Iris Bauer, Georg Fröhlich, Lorenz Bott-Flügel, Robert Byrne, Josef Dirschinger, Adnan Kastrati, Albert Schömig
Journal: Journal of the American College of Cardiology (2008)
Estimation of Nucleotide Substitution Rates in Eurotiomycete Fungi
Authors: Takao Kasuga, Thomas J. White, John W. Taylor
Journal: Molecular Biology and Evolution (2002)

In the entire fungal kingdom, only DNA substitution rates in the SSU rRNA gene (Berbee and Taylor 1993, 2001) and amino acid substitution rates (Heckman et al. 2001) have been estimated and used to date fungal divergences. However, these molecules are not sufficiently variable to date events at or below the genus level. DNA sequences of protein-coding genes and the internal transcribed spacer (ITS) region are sufficiently variable, but their substitution rates are not known. In this article, we investigated the DNA substitution rates in the protein-coding genes and the ITS region by comparison with the SSU rDNA divergence in a representative fungal lineage, Eurotiomycetes (5plectomycetes) (Eriksson and Winka 1998). The Eurotiomycete lineage is a monophyletic class of Ascomycota (Berbee and Taylor 1992) and includes many economically important fungi, such as Penicillium chrysogenum (antibiotic production) and Aspergillus oryzae (soy sauce production), as well as many human pathogens such as Coccidioides immitis (lung disease), Histoplasma capsulatum (lung disease), and Trichophyton rubrum (athlete’s foot). Estimating DNA substitution rates in quickly evolving molecules such as the ITS and protein-coding genes will not only provide a means to estimate the divergence times between lineages at and below the genus level, but in conjunction with coalescent theory, it may provide information for estimating epidemiological parameters such as effective population size (Watterson 1975) and recombination rates (Hey and Wakeley 1997). With the aid of published Eurotiomycete phylogenies based on SSU rDNA (Ogawa, Yoshimura, and Sugiyama 1997; Sugiyama, Ohara, and Mikawa 1999), we searched for pairs of closely related species which had not only SSU rDNA sequences but also sequences of homologous protein-coding genes. Next, we compared the extent of differentiation at synonymous sites of protein-coding genes between sister taxa. It was found that saturation at synonymous sites of protein-coding loci is attained before divergence of the SSU rDNA sequences reaches 1%–2%. A 1%–2% divergence usually corresponds to divergences seen within a genus or among closely related genera. Therefore, the protein genes should be well suited to dating divergences at and below the genus level.
Colonization of residents and staff of a long-term-care facility and adjacent acute-care hospital geriatric unit by multiresistant bacteria
Authors: A. March, R. Aschbacher, H. Dhanji, D.M. Livermore, A. Böttcher, F. Sleghel, S. Maggi, M. Noale, C. Larcher, N. Woodford
Journal: Clinical Microbiology and Infection (2009)
Isoform-Specific Effects of Apolipoprotein E on Atherogenesis
Authors: Hiroaki Yoshida, Alyssa H. Hasty, Amy S. Major, Hiroyuki Ishiguro, Yan Ru Su, Linda A. Gleaves, Vladimir R. Babaev, MacRae F. Linton, Sergio Fazio
Journal: Circulation (2001)

We recently used a bone marrow-based gene therapy approach to show that small amounts of retrovirus-derived human apolipoprotein E3 (apoE3) produced by macrophages are protective against early atherosclerosis in apoE-deficient mice.In the present study, we evaluated whether the effect produced by macrophage-derived apoE3 is related to its ability to bind cellular membranes. To this end, we used apoE2 and apoEcys142, dysfunctional human variants with reduced binding to the LDL receptor or to heparan sulfate proteoglycans, respectively. ApoE-deficient mice, 5 weeks of age, received transplants of apoE(-/-) bone marrow cells transduced with either parental retrovirus or apoE3, apoE2, or apoEcys142 retroviral vectors. Human apoE was detected by ELISA in the serum of apoE3, apoE2, and apoEcys142 mice as early as 4 weeks after bone marrow transplantation, and at 8 weeks, plasma apoE levels were 55.5+/-20.3, 50.5+/-8.7, and 15.3+/-7.3 microgram/dL, respectively. In all groups, cholesterol levels increased with age but were not affected by apoE expression. As previously demonstrated, the lesion area in male apoE3 mice (3808+/-2224 micrometer(2)/section) was 40% smaller than that in control mice (6503+/-3475 micrometer(2)/section). In apoE2 mice, however, the lesion area was similar to that of controls (5991+/-2771 micrometer(2)/section), and apoEcys142 mice showed an unexpected and significant increase in lesion size (10 320+/-6128 micrometer(2)/section). Thus, transplantation with marrow transfected with receptor binding-defective apoE variants did not replicate the antiatherogenic effect of apoE3.These data provide in vivo evidence suggesting that macrophage-derived apoE delays development of atherosclerosis through a receptor-dependent pathway.
Dipeptidyl Peptidase-4 Inhibition and the Treatment of Type 2 Diabetes
Authors: Daniel J. Drucker
Journal: Diabetes Care (2007)

Dipeptidyl peptidase (DPP)-4 is a complex enzyme that exists as a membrane-anchored cell surface peptidase that transmits intracellular signals via a short intracellular tail and as a second smaller soluble form present in the circulation. DPP-4 cleaves a large number of chemokines and peptide hormones in vitro, but comparatively fewer peptides have been identified as endogenous physiological substrates for DPP-4 in vivo. Both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are endogenous physiological substrates for DPP-4, and chemical inhibition of DPP-4 activity, or genetic inactivation of DPP-4 in rodents, results in increased levels of intact bioactive GIP and GLP-1. Furthermore, mice and rats with genetic inactivation or inhibition of DPP-4 exhibit improved glucose tolerance, elevated levels of GLP-1 and GIP, and resistance to diet-induced obesity and hyperglycemia. Sustained DPP-4 inhibition lowers blood glucose via stimulation of insulin and inhibition of glucagon secretion and is associated with preservation of β-cell mass in preclinical studies. Although DPP-4 cleaves dozens of regulatory peptides and chemokines in vitro, studies of mice with genetic inactivation of incretin receptors demonstrate that GIP and GLP-1 receptor–dependent pathways represent the dominant mechanisms transducing the glucoregulatory actions of DPP-4 inhibitors in vivo. The available preclinical data suggests that highly selective DPP-4 inhibition represents an effective and safe strategy for the therapy of type 2 diabetes.

DPP-4 is a widely expressed cell surface peptidase that exhibits a complex biology encompassing cell membrane–associated activation of intracellular signal transduction pathways, cell-cell interaction, and enzymatic activity exhibited by both the membrane-anchored and soluble forms of the enzyme (1). DPP-4, also originally known as the lymphocyte cell surface marker CD26, or as the adenosine deaminase (ADA)-binding protein, is a 766–amino acid serine protease that preferentially cleaves peptide hormones containing a position two alanine or proline. The human gene encoding DPP has been localized …
Application of the DAREA/DAPSA score for assessment of disease activity in psoriatic arthritis
Authors: M. Schoels, D. Aletaha, J. Funovits, A. Kavanaugh, D. Baker, J. S. Smolen
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background and objectives</h3> Instruments for measuring disease activity in psoriatic arthritis (PsA) are not yet firmly established, and most of the currently employed ones have been derived for rheumatoid arthritis. Some of these instruments are based on 28 joint counts, which do not capture joints frequently affected in PsA. Therefore, the reliability and validity of DAREA (for 'Disease Activity index for REactive Arthritis'), which was originally developed for reactive arthritis and employs a 66/68 joint count, was tested in patients with PsA. <h3>Methods</h3> Trial data from the Infliximab Multinational Psoriatic Arthritis Controlled Trial were analysed. Results were then independently validated using an observational data set. DAREA was compared to other composite indices regarding correlations with core set variables, sensitivity to change and criterion validity. <h3>Results</h3> Good correlation of the DAREA with single items of disease activity, other composite scores (r=0.6−0.9) and physical function (Health Assessment Questionnaire; r=0.5) was found. Likewise, DAREA was at least as sensitive to change as the other indices and more so in patients with distal interphalangeal joint involvement. Additionally, DAREA correlated well with radiographic changes. <h3>Conclusion</h3> The analyses of this study provide evidence of the utility and validity of the DAREA for PsA disease activity assessment. A second name should therefore be assigned to this score: DAPSA (for 'Disease Activity index for PSoriatic Arthritis').
Repeated Hypoglycemia Caused by the Overproduction of Anti-insulin Antibodies and Isolated ACTH Deficiency in a Type 2 Diabetic Patient Receiving Insulin Therapy
Authors: Masanori Yoshida, Miho Murakami, Koichiro Ogawa, Masato Asai, Misaki Miyata, Harumi Maeda, Yutaka Oiso
Journal: Diabetes Care (2013)

A 46-year-old man with untreated type 2 diabetes visited our hospital. His plasma glucose and HbA1c levels were 429 mg/dL and 11.5%, respectively. He had no renal dysfunction. Insulin therapy (18 units aspart and 22 units biphasic insulin aspart 30/70) was initiated, and the HbA1c level improved (5.7–6.4%). One year later, he started experiencing frequent hypoglycemic attacks, which persisted despite significantly reducing his insulin dosage (total 9 units). Fasting plasma glucose, serum immunoreactive insulin (IRI), C-peptide, and HbA1c levels were 75 mg/dL, 420 μU/mL (reference, 1.7–10.4), 1.2 ng/mL (reference, 0.6–1.8), and 5.4%, respectively. His anti-insulin immunoglobulin G antibody (IA) titer (125I-insulin binding rate) was 95.5% (reference, 0–7.0); free and total IRI levels were 11.0 and >240 μU/mL, respectively. After insulin cessation, …
Transducin β-like 1 X-linked receptor 1 suppresses cisplatin sensitivity in Nasopharyngeal Carcinoma via activation of NF-κB pathway
Authors: Shu-Peng Chen, Qi Yang, Chan-Juan Wang, Long-Juan Zhang, Yi Fang, Fang-Yong Lei, Shu Wu, Li-Bing Song, Xiang Guo, Ling Guo
Journal: Molecular Cancer (2014)

Transducin β-like 1 X-linked receptor 1 (TBL1XR1) is an important transcriptional cofactor involved in the regulation of many signaling pathways, and is associated with carcinogenesis and tumor progression. However, the precise role of TBL1XR1 in these processes is not well understood. We detected the expression of TBL1XR1 protein and mRNA in nasopharyngeal carcinoma (NPC) cell lines and biopsies by western blotting, real-time PCR and immunohistochemical staining (IHC). Overexpression of TBL1XR1 in NPC enhanced chemoresistance to cisplatin using two NPC cell lines in vitro and in vivo. TBL1XR1 was upregulated in NPC cell lines and clinical samples. The expression of TBL1XR1 was correlated with several clinicopathological factors including clinical stage, T classification, N classification and patient survival. Univariate and multivariate analysis revealed that TBL1XR1 was an independent prognostic factor for patient survival. In vitro and in vivo studies demonstrated that TBL1XR1 high expression induced resistance to cisplatin-induced apoptosis in NPC cells. Furthermore, we found that TBL1XR1 activated the NF-κB pathway and promoted transcription of genes downstream of NF-κB, especially anti-apoptotic genes. Upregulation of TBL1XR1 induces NPC cells resistance to cisplatin by activating the NF-κB pathway, and correlates with poor overall survival of NPC patients. TBL1XR1 has a pivotal role in NPC and could be a valuable prognostic factor as well as a novel biomarker for tailoring appropriate therapeutic regimes.