tbuckley/cabot-search huggingface dataset:
A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function
Authors: Jared M Bischof, Christopher J Ott, Shih-Hsing Leir, Nehal Gosalia, Lingyun Song, Darin London, Terrence S Furey, Calvin U Cotton, Gregory E Crawford, Ann Harris
Journal: Thorax (2011)

<h3>Background</h3> Distal cell-type-specific regulatory elements may be located at very large distances from the genes that they control and are often hidden within intergenic regions or in introns of other genes. The development of methods that enable mapping of regions of open chromatin genome wide has greatly advanced the identification and characterisation of these elements. <h3>Methods</h3> Here we use DNase I hypersensitivity mapping followed by deep sequencing (DNase-seq) to generate a map of open chromatin in primary human tracheal epithelial (HTE) cells and use bioinformatic approaches to characterise the distribution of these sites within the genome and with respect to gene promoters, intronic and intergenic regions. <h3>Results</h3> Genes with HTE-selective open chromatin at their promoters were associated with multiple pathways of epithelial function and differentiation. The data predict novel cell-type-specific regulatory elements for genes involved in HTE cell function, such as structural proteins and ion channels, and the transcription factors that may interact with them to control gene expression. Moreover, the map of open chromatin can identify the location of potentially critical regulatory elements in genome-wide association studies (GWAS) in which the strongest association is with single nucleotide polymorphisms in non-coding regions of the genome. We demonstrate its relevance to a recent GWAS that identifies modifiers of cystic fibrosis lung disease severity. <h3>Conclusion</h3> Since HTE cells have many functional similarities with bronchial epithelial cells and other differentiated cells in the respiratory epithelium, these data are of direct relevance to elucidating the molecular basis of normal lung function and lung disease.
A phase I trial of arsenic trioxide chemoradiotherapy for infiltrating astrocytomas of childhood
Authors: K. J. Cohen, I. C. Gibbs, P. G. Fisher, R. J. Hayashi, M. E. Macy, L. Gore
Journal: Neuro-Oncology (2013)

Arsenic trioxide (ATO) has demonstrated preclinical evidence of activity in the treatment of infiltrating astrocytomas. We conducted a phase I trial of ATO given concomitantly with radiation therapy in children with newly diagnosed anaplastic astrocytoma, glioblastoma, or diffuse intrinsic pontine glioma. Eligible patients received a fixed daily dose of 0.15 mg/kg of ATO once a week, with each subsequent cohort of patients receiving an additional dose per week up to a planned frequency of ATO administration 5 days per week as tolerated. Twenty-four children were enrolled and 21 children were evaluable. ATO was well tolerated throughout the entire dose escalation, resulting in confirmation of safety when administered 5 days per week during irradiation. The recommended dose of ATO during conventional irradiation is 0.15 mg/kg given on a daily basis with each fraction of radiation therapy administered.
Patient Involvement in Surgery Treatment Decisions for Breast Cancer
Authors: Steven J. Katz, Paula M. Lantz, Nancy K. Janz, Angela Fagerlin, Kendra Schwartz, Lihua Liu, Dennis Deapen, Barbara Salem, Indu Lakhani, Monica Morrow
Journal: Journal of Clinical Oncology (2005)

High rates of mastectomy and marked regional variations have motivated lingering concerns about overtreatment and failure to involve women in treatment decisions. We examined the relationship between patient involvement in decision making and type of surgical treatment for women with breast cancer.All women with ductal carcinoma-in-situ and a 20% random sample of women with invasive breast cancer aged 79 years and younger who were diagnosed in 2002 and reported to the Detroit and Los Angeles Surveillance, Epidemiology, and End Results registries were identified and surveyed shortly after receipt of surgical treatment (response rate, 77.4%; n = 1,844).Mean age was 60.1 years; 70.2% of the women were white, 18.0% were African American, and 11.8% were from other ethnic groups. Overall, 30.2% of women received mastectomy as initial treatment. Most women reported that they made the surgical decision (41.0%) or that the decision was shared (37.1%); 21.9% of patients reported that their surgeon made the decision with or without their input. Among white women, only 5.3% of patients whose surgeon made the decision received mastectomy compared with 16.8% of women who shared the decision and 27.0% of women who made the decision (P < .001, adjusted for clinical factors, predisposing factors, and number of surgeons visited). However, this association was not observed for African American women (Wald test 10.0, P = .041).Most women reported that they made or shared the decision about surgical treatment. More patient involvement in decision making was associated with greater use of mastectomy. Racial differences in the association of involvement with receipt of treatment suggest that the decision-making process varies by racial groups.
Apolipoprotein E Polymorphism and Renal Function in German Type 1 and Type 2 Diabetic Patients
Authors: Egon Werle, Walter Fiehn, Christoph Hasslacher
Journal: Diabetes Care (1998)

To examine the association of renal function in diabetic patients with apolipoprotein (apo) E polymorphism.Apo E genotypes, lipid and lipoprotein serum levels, creatinine clearance (CCr), and excretion of marker proteins were determined in German type 1 (IDDM; n = 162) and type 2 (NIDDM; n = 124) diabetic patients. Albumin and immunoglobulin (Ig) G are considered to reflect charge-size permselectivity of the glomerular capillary basement membrane, and increased alpha 1-microglobulin (MG) excretion indicates compromised reabsorptive capacity of the renal tubules.Patients with NIDDM had higher lipid levels and lower CCrs than patients with IDDM. In patients with IDDM, age- and sex-adjusted analysis of variance showed an association between apo E genotypes and CCr, and the Jonckheere-Terpstra test demonstrated a decreasing glomerular filtration rate in the following order of genotypes: epsilon 4 epsilon 4/epsilon 4 epsilon 3 > epsilon 3 epsilon 3 > epsilon 2 epsilon 2/epsilon 2 epsilon 3. Multiple linear regression analyses revealed that in patients with IDDM, the epsilon 2 allele was a negative predictor of CCr and a positive predictor of urinary excretion of albumin, IgG and alpha 1-MG independent from HDL and LDL cholesterol, TG concentration, age, and sex.Apo E polymorphism influences serum lipoprotein levels in patients with IDDM and NIDDM. Apo E polymorphism may be a renal risk factor of clinical relevance in normolipidemic patients with IDDM.
Endotoxins Inhibit Endocytotic Catabolism of Low–Density Lipoproteins in Hep G2 Cells
Authors: Wei Liao, Claes-Henrik Florén
Journal: Hepatology (1992)

The effects of endotoxins on the uptake and degradation of low-density lipoproteins in Hep G2, a well-differentiated human hepatoma cell line, were studied. The results showed that incubation of Hep G2 cells with 125I-labeled low-density lipoprotein in the presence of endotoxins caused decreased uptake and degradation of 125I-labeled low-density lipoprotein. The inhibitory effects of endotoxins on the uptake and degradation of 125I-labeled low-density lipoprotein were dose and time dependent. With a monoclonal low-density lipoprotein receptor antibody, it was found that endotoxins interfered with both low-density lipoprotein receptor-mediated and non-low-density lipoprotein receptor-mediated uptake. If, however, the cells were pretreated with endotoxins for 1 or 24 hr and then incubated with new medium without endotoxins, no inhibitory effect on the subsequent uptake and degradation of 125I-labeled low-density lipoprotein occurred. Endotoxins had no toxic effects on Hep G2 cells as judged by [3H]thymidine incorporation and by determination of cell growth. Also, endotoxins did not under our experimental conditions induce oxidative modification of low-density lipoprotein. Furthermore, reisolated low-density lipoprotein that had previously been incubated with endotoxin was catabolized to a lower extent by Hep G2 cells than was control low-density lipoprotein. We speculate that the inhibitory effect of endotoxins on cellular low-density lipoprotein catabolism is due to the formation of endotoxin-low-density lipoprotein complexes, which interfere with the binding of low-density lipoprotein to the cell surface.
Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2
Authors: Kush M. Parmar, H. Benjamin Larman, Guohao Dai, Yuzhi Zhang, Eric T. Wang, Sripriya N. Moorthy, Johannes R. Kratz, Zhiyong Lin, Mukesh K. Jain, Michael A. Gimbrone, Guillermo García-Cardeña
Journal: Journal of Clinical Investigation (2005)

In the face of systemic risk factors, certain regions of the arterial vasculature remain relatively resistant to the development of atherosclerotic lesions. The biomechanically distinct environments in these arterial geometries exert a protective influence via certain key functions of the endothelial lining; however, the mechanisms underlying the coordinated regulation of specific mechano-activated transcriptional programs leading to distinct endothelial functional phenotypes have remained elusive. Here, we show that the transcription factor Kruppel-like factor 2 (KLF2) is selectively induced in endothelial cells exposed to a biomechanical stimulus characteristic of atheroprotected regions of the human carotid and that this flow-mediated increase in expression occurs via a MEK5/ERK5/MEF2 signaling pathway. Overexpression and silencing of KLF2 in the context of flow, combined with findings from genome-wide analyses of gene expression, demonstrate that the induction of KLF2 results in the orchestrated regulation of endothelial transcriptional programs controlling inflammation, thrombosis/hemostasis, vascular tone, and blood vessel development. Our data also indicate that KLF2 expression globally modulates IL-1beta-mediated endothelial activation. KLF2 therefore serves as a mechano-activated transcription factor important in the integration of multiple endothelial functions associated with regions of the arterial vasculature that are relatively resistant to atherogenesis.
PREVALENCE OF ANTIBODIES TO HEPATITIS C VIRUS IN SPANISH PATIENTS WITH HEPATOCELLULAR CARCINOMA AND HEPATIC CIRRHOSIS
Authors: Jordi Bruix, Xavier Calvet, Josep Costa, Miquel Ventura, Miquel Bruguera, Ricard Castillo, Josep María Barrera, Guadalupe Ercilla, José María Sanchez-Tapias, Marti Vall, Concepciò Bru, Joan Rodes
Journal: The Lancet (1989)
The new World Health Organization classification of lung tumours
Authors: E. Brambilla, W.D. Travis, T.V. Colby, B. Corrin, Y. Shimosato
Journal: European Respiratory Journal (2001)

Tumour classification systems provide the foundation for tumour diagnosis and patient therapy and a critical basis for epidemiological and clinical studies. This updated classification was developed with the aim to adhere to the principles of reproducibility, clinical significance, and simplicity in order to minimize the number of unclassifiable lesions. Major changes in the revised classification as compared to the previous one (WHO 1981 1) include the addition of two pre-invasive lesions to squamous dysplasia and carcinoma in situ ; atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Another change is the subclassification of adenocarcinoma: the definition of bronchioalveolar carcinoma has been restricted to noninvasive tumours. There has been substantial evolution of concepts in neuroendocrine lung tumour classification. Large cell neuroendocrine carcinoma (LCNEC) is now recognized as a histologically high grade non small cell carcinoma showing histopathological features of neuroendocrine differentiation as well as immunohistochemical neuroendocrine markers. The large cell carcinoma class has been enriched with several variants, including the LCNEC and the basaloid carcinoma, both with a dismal prognosis. Finally, a new class was defined called carcinoma with pleomorphic, sarcomatoid, or sarcomatous elements, which brings together a number of proliferations characterized by a spectrum of epithelial to mesenchymal differentiation. Immunohistochemistry and electron microscopy are invaluable techniques for diagnosis and subclassification, but our intention was to render the classification simple and practical to every surgical laboratory, so that most lung tumours could be classified by light microscopic criteria.
The MUC1 Ectodomain: A Novel and Efficient Target for Gold Nanoparticle Clustering and Vapor Nanobubble Generation
Authors: Brian P. Danysh, Pamela E. Constantinou, Ekaterina Y. Lukianova-Hleb, Dmitri O. Lapotko, Daniel D. Carson
Journal: Theranostics (2012)

MUC1 is a large, heavily glycosylated transmembrane glycoprotein that is proposed to create a protective microenvironment in many adenocarcinomas. Here we compare MUC1 and the well studied cell surface receptor target, EGFR, as gold nanoparticle (AuNP) targets and their subsequent vapor nanobubble generation efficacy in the human epithelial cell line, HES. Although EGFR and MUC1 were both highly expressed in these cells, TEM and confocal images revealed MUC1 as a superior target for nanoparticle intracellular accumulation and clustering. The MUC1-targeted AuNP intracellular clusters also generated significantly larger vapor nanobubbles. Our results demonstrate the promising opportunities MUC1 offers to improve the efficacy of targeted nanoparticle based approaches.
Impact of NHS walk-in centres on the workload of other local healthcare providers: time series analysis
Authors: M. Chalder
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives:</b> To assess the impact of NHS walk-in centres on the workload of local accident and emergency departments, general practices, and out of hours services. <b>Design:</b> Time series analysis in walk-in centre sites with no-treatment control series in matched sites. <b>Setting:</b> Walk-in centres and matched control towns without walk-in centres in England. <b>Participants:</b> 20 accident and emergency departments, 40 general practices, and 14 out of hours services within 3 km of a walk-in centre or the centre of a control town. <b>Main outcome measures:</b> Mean number (accident and emergency departments) or rate (general practices and out of hours services) of consultations per month in the 12 month periods before and after an index date. <b>Results:</b> A reduction in consultations at emergency departments (−175 (95% confidence interval-387 to 36) consultations per department per month) and general practices (−19.8 (−53.3 to 13.8) consultations per 1000 patients per month) close to walk-in centres became apparent, although these reductions were not statistically significant. Walk-in centres did not have any impact on consultations on out of hours services. <b>Conclusion:</b> It will be necessary to assess the impact of walk-in centres in a larger number of sites and over a prolonged period, to determine whether they reduce the demand on other local NHS providers. <h3>What is already known on this topic</h3> One of the objectives for NHS walk-in centres was to reduce demand on other NHS services, particularly general practitioners9 services and accident and emergency departments Studies of walk-in centres in North America have indicated that such centres do not reduce demand on other healthcare services Studies of minor injuries units in the United Kingdom (which have some similarities with walk-in centres) indicate that these units substitute mainly for consultations in accident and emergency departments <h3>What this study adds</h3> The data imply that walk-in centres may moderate the increasing demand on general practice and reduce the number of consultations in accident and emergency departments The high level of background variability in consultation rates means that any impact of a walk-in centre is not statistically significant To draw robust conclusions about the impact of walk-in centres on other health providers will require study of a large number of sites over an extended period of time
Sixty-five gene-based risk score classifier predicts overall survival in hepatocellular carcinoma
Authors: Soo Mi Kim, Sun-Hee Leem, In-Sun Chu, Yun-Yong Park, Sang Cheol Kim, Sang-Bae Kim, Eun Sung Park, Jae Yun Lim, Jeonghoon Heo, Yoon Jun Kim, Dae-Ghon Kim, Ahmed Kaseb, Young Nyun Park, Xin Wei Wang, Snorri S. Thorgeirsson, Ju-Seog Lee
Journal: Hepatology (2011)

Clinical application of the prognostic gene expression signature has been delayed due to the large number of genes and complexity of prediction algorithms. In the current study we aimed to develop an easy-to-use risk score with a limited number of genes that can robustly predict prognosis of patients with hepatocellular carcinoma (HCC). The risk score was developed using Cox coefficient values of 65 genes in the training set (n = 139) and its robustness was validated in test sets (n = 292). The risk score was a highly significant predictor of overall survival (OS) in the first test cohort (P = 5.6 × 10(-5), n = 100) and the second test cohort (P = 5.0 × 10(-5) , n = 192). In multivariate analysis, the risk score was a significant risk factor among clinical variables examined together (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.13-1.64; P = 0.001 for OS).The risk score classifier we have developed can identify two clinically distinct HCC subtypes at early and late stages of the disease in a simple and highly reproducible manner across multiple datasets.
Dietary folates and cancer risk in a network of case–control studies
Authors: A. Tavani, S. Malerba, C. Pelucchi, L. Dal Maso, A. Zucchetto, D. Serraino, F. Levi, M. Montella, S. Franceschi, A. Zambon, C. La Vecchia
Journal: Annals of Oncology (2012)
MINER'S NYSTAGMUS: SUGGESTIONS FOR ITS PREVENTION
Authors: D. L. Anderson
Journal: BMJ (1920)

UNi 8 suffering from "enteric" (?) was recently tested.In 15 there vwas no agglutination; 20 gave evidence of a pure typlhoid infection, but 5 gave evidence of a pure para- typhoid B infection.Further, in two othier cases of acute pleural effusion in civilians, paratyphoid B bacillus was igolated from the exudate.'2. Bacillary Dysentery.-Tihiswas formerly thought to be confined to asylums, yet Flexner Y bacillus was isolated from a boy with acute diarrlroea, and from two out of 504 healthy recruits in a training camD; Sliiga's bacillus was isolated from the spleen of a woman who had always lived in Liverpool, and wlho died of puerperal sepsis, but was found o08t mnortemn to lhave clhronic ulcerative colitis.2 3. Amzoebic Dysentery.-Fifty-ninepatients in an English asylum suffering from acute dysentery were examined for protozoa, "in 3 cases vegetative Entamoeba histolytica were fotind in the stools."5
335 LIVER GENIC EXPRESSION PROFILE DURING THE PROGRESSION OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IN MORBID OBESITY PATIENTS
Authors: A. Carazo, J. León, J. Casado, A. Gila, A. Martín, L. Sanjuan, S. Delgado, T. Caballero, J.L. Mundi, J. Salmerón
Journal: Journal of Hepatology (2010)
Association study of <i>TRAF1-C5</i> polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese
Authors: K Nishimoto, Y Kochi, K Ikari, K Yamamoto, A Suzuki, K Shimane, Y Nakamura, K Yano, N Iikuni, S Tsukahara, N Kamatani, H Okamoto, H Kaneko, Y Kawaguchi, M Hara, Y Toyama, T Horiuchi, K Tao, K Yasutomo, D Hamada, N Yasui, H Inoue, M Itakura, H Yamanaka, S Momohara
Journal: Annals of the Rheumatic Diseases (2009)

Objective: The primary aim of this study was to investigate the association of polymorphisms of TRAF1-C5 , a newly identified rheumatoid arthritis (RA) risk locus in Caucasians, with susceptibility to RA and systemic lupus erythematosus (SLE) in Japanese populations. Gene expression levels of TRAF1 and C5 to assess the functional significance of genotypes were also analysed. Methods: A multicentre association study consisting of 4 RA case-control series (4397 cases and 2857 controls) and 3 SLE case-control series (591 cases and 2199 shared controls) was conducted. Genotyping was performed using TaqMan genotyping assay for two single nucleotide polymorphisms (SNPs) that showed the best evidence of association in the previous Caucasian studies. Quantifications of TRAF1 and C5 expression were performed with TaqMan expression assay. Results: Significant differences in allele frequency for both SNPs were observed between RA and control subjects (combined odds ratio = 1.09), while no significant difference was detected between patients with SLE and controls. Interestingly, alleles rs3761847 A and rs10818488 G had increased the risk for RA in the present study, while they decreased the risk in the original studies. A significant difference was found between risk allele carriers and non-carriers of rs10818488 for the expression level of TRAF1 in phorbol myristate acetate-stimulated lymphoblastoid cell lines (p = 0.04). Conclusion: Association of TRAF1-C5 locus with RA susceptibility was detected in the Japanese populations with modest magnitude, while no significant association was observed for SLE. Significant positive effect of genotype on the expression of TRAF1 might support the genetic association between TRAF1 and RA.
Sports and exercise-related tendinopathies: a review of selected topical issues by participants of the second International Scientific Tendinopathy Symposium (ISTS) Vancouver 2012
Authors: Alex Scott, Sean Docking, Bill Vicenzino, Håkan Alfredson, Johannes Zwerver, Kirsten Lundgreen, Oliver Finlay, Noel Pollock, Jill L Cook, Angela Fearon, Craig R Purdam, Alison Hoens, Jonathan D Rees, Thomas J Goetz, Patrik Danielson
Journal: British Journal of Sports Medicine (2013)

In September 2010, the first International Scientific Tendinopathy Symposium (ISTS) was held in Umeå, Sweden, to establish a forum for original scientific and clinical insights in this growing field of clinical research and practice. The second ISTS was organised by the same group and held in Vancouver, Canada, in September 2012. This symposium was preceded by a round-table meeting in which the participants engaged in focused discussions, resulting in the following overview of tendinopathy clinical and research issues. This paper is a narrative review and summary developed during and after the second ISTS. The document is designed to highlight some key issues raised at ISTS 2012, and to integrate them into a shared conceptual framework. It should be considered an update and a signposting document rather than a comprehensive review. The document is developed for use by physiotherapists, physicians, athletic trainers, massage therapists and other health professionals as well as team coaches and strength/conditioning managers involved in care of sportspeople or workers with tendinopathy.
Microencapsulation of Dye‐ and Drug‐Loaded Particles for Imaging and Controlled Release of Multiple Drugs
Authors: Yit‐Lung Khung, Wei Li Lee, Kit Leong Chui, Yayuan Liu, Ming Pin Lim, Charlotte Liwen Huang, Say Chye Joachim Loo
Journal: Advanced Healthcare Materials (2012)

A polymeric microcapsule that can house different drug-loaded particles using a simple emulsion packaging technique is presented. Compared to the neat microparticles, microcapsules simultaneously release multiple drugs in a sustained manner. These microcapsules could provide a means of controlling release of multiple drugs.
Characterization of factors associated with systemic corticosteroid use in severe asthma: Data from the Severe Asthma Research Program
Authors: Kenneth Wysocki, Seo Young Park, Eugene Bleecker, William Busse, Mario Castro, Kian Fan Chung, Benjamin Gaston, Serpil Erzurum, Elliot Israel, W. Gerald Teague, Charity G. Moore, Sally Wenzel
Journal: Journal of Allergy and Clinical Immunology (2013)