tbuckley/cabot-search huggingface dataset:
miR-Test: A Blood Test for Lung Cancer Early Detection
Authors: Francesca Montani, Matteo Jacopo Marzi, Fabio Dezi, Elisa Dama, Rose Mary Carletti, Giuseppina Bonizzi, Raffaella Bertolotti, Massimo Bellomi, Cristiano Rampinelli, Patrick Maisonneuve, Lorenzo Spaggiari, Giulia Veronesi, Francesco Nicassio, Pier Paolo Di Fiore, Fabrizio Bianchi
Journal: JNCI Journal of the National Cancer Institute (2015)

Lung cancer is the leading cause of cancer death worldwide. Low-dose computed tomography screening (LDCT) was recently shown to anticipate the time of diagnosis, thus reducing lung cancer mortality. However, concerns persist about the feasibility and costs of large-scale LDCT programs. Such concerns may be addressed by clearly defining the target “high-risk” population that needs to be screened by LDCT. We recently identified a serum microRNA signature (the miR-Test) that could identify the optimal target population. Here, we performed a large-scale validation study of the miR-Test in high-risk individuals (n = 1115) enrolled in the Continuous Observation of Smoking Subjects (COSMOS) lung cancer screening program. The overall accuracy, sensitivity, and specificity of the miR-Test are 74.9% (95% confidence interval [CI] = 72.2% to 77.6%), 77.8% (95% CI = 64.2% to 91.4%), and 74.8% (95% CI = 72.1% to 77.5%), respectively; the area under the curve is 0.85 (95% CI = 0.78 to 0.92). These results argue that the miR-Test might represent a useful tool for lung cancer screening in high-risk individuals.
In oesophageal squamous cells exposed to acidic bile salt medium, omeprazole inhibits IL-8 expression through effects on nuclear factor-κB and activator protein-1
Authors: Xiaofang Huo, Xi Zhang, Chunhua Yu, Qiuyang Zhang, Edaire Cheng, David H Wang, Thai H Pham, Stuart J Spechler, Rhonda F Souza
Journal: Gut (2013)

<h3>Objective</h3> Oesophagitis might result from the effects of chemokines produced by oesophageal cells in response to gastro-oesophageal reflux, and not solely from the direct, caustic effects of refluxed gastric juice. Proton pump inhibitors (PPI) can block chemokine production through mechanisms independent of their antisecretory effects. We studied omeprazole effects on chemokine production by oesophageal epithelial cells exposed to acidic bile salts. <h3>Design</h3> Human primary and telomerase-immortalised oesophageal squamous cells were exposed to acidic bile salt medium with or without omeprazole pretreatment. Interleukin (IL)-8 expression was determined by RT-PCR and ELISA. IL-8 promoter activity was measured by luciferase reporter assay. Binding of NF-κB and AP-1 subunits to the IL-8 promoter was assessed by chromatin immunoprecipitation (ChIP) assay. Immune cell migration induced by conditioned medium was determined by a double-chamber migration assay system. <h3>Results</h3> Acidic bile salt medium caused oesophageal epithelial cells to express IL-8 mRNA and protein by activating the IL-8 promoter through NF-κB and AP-1 binding. Omeprazole inhibited that acidic bile salt-stimulated IL-8 expression by blocking the nuclear translocation of p65 (an NF-κB subunit), and by blocking the binding of p65, c-jun and c-fos (AP-1 subunits) to the IL-8 promoter. Omeprazole also blocked the ability of conditioned medium from cells exposed to acidic bile salts to induce immune cell migration. <h3>Conclusions</h3> In oesophageal squamous epithelial cells, omeprazole inhibits IL-8 expression through effects on NF-κB and AP-1 that are entirely independent of effects on gastric acid secretion. These previously unrecognised PPI effects might contribute to the healing of reflux oesophagitis.
Tumor-Infiltrating Lymphocyte Grade in Primary Melanomas Is Independently Associated With Melanoma-Specific Survival in the Population-Based Genes, Environment and Melanoma Study
Authors: Nancy E. Thomas, Klaus J. Busam, Lynn From, Anne Kricker, Bruce K. Armstrong, Hoda Anton-Culver, Stephen B. Gruber, Richard P. Gallagher, Roberto Zanetti, Stefano Rosso, Terence Dwyer, Alison Venn, Peter A. Kanetsky, Pamela A. Groben, Honglin Hao, Irene Orlow, Anne S. Reiner, Li Luo, Susan Paine, David W. Ollila, Homer Wilcox, Colin B. Begg, Marianne Berwick
Journal: Journal of Clinical Oncology (2013)

Although most hospital-based studies suggest more favorable survival with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is uncertain whether TILs provide prognostic information beyond existing melanoma staging definitions. We addressed the issue in an international population-based study of patients with single and multiple primary melanomas.On the basis of the Genes, Environment and Melanoma (GEM) study, we conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330 invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or brisk). The odds of TIL grades associated with clinicopathologic features and survival by TIL grade were examined.Independent predictors (P < .05) for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and for brisk TIL grade, they were age, site, Breslow thickness, and radial growth phase. Nonbrisk and brisk TIL grades were each associated with lower American Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (P(trend) < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex, site, and AJCC tumor stage.At the population level, higher TIL grade of primary melanoma is associated with a lower risk of death as a result of melanoma independently of tumor characteristics currently used for AJCC tumor stage. We conclude that TIL grade deserves further prospective investigation to determine whether it should be included in future AJCC staging revisions.
Determination of oestrogen-receptor status and ERBB2 status of breast carcinoma: a gene-expression profiling study
Authors: Yun Gong, Kai Yan, Feng Lin, Keith Anderson, Christos Sotiriou, Fabrice Andre, Frankie A Holmes, Vicente Valero, Daniel Booser, John E Pippen, Svetislava Vukelja, Henry Gomez, Jaime Mejia, Luis J Barajas, Kenneth R Hess, Nour Sneige, Gabriel N Hortobagyi, Lajos Pusztai, W Fraser Symmans
Journal: The Lancet Oncology (2007)
Identification of candidate predictive and surrogate molecular markers for dasatinib in prostate cancer: rationale for patient selection and efficacy monitoring
Authors: Xi-De Wang, Karen Reeves, Feng R Luo, Li-An Xu, Francis Lee, Edwin Clark, Fei Huang
Journal: Genome biology (2007)

Dasatinib is a potent, multi-targeted kinase inhibitor that was recently approved for treatment of chronic myelogenous leukemia resistant to imatinib. To aid the clinical development of dasatinib in prostate cancer, we utilized preclinical models to identify potential molecular markers for patient stratification and efficacy monitoring.Using gene expression profiling, we first identified 174 genes whose expression was highly correlated with in vitro sensitivity of 16 cell lines and, thus, considered as candidate efficacy predictive markers. Among these are important prostatic cell lineage markers, cytokeratin 5, androgen receptor and prostate specific antigen. Our results indicate that 'basal type' cell lines with high expression of cytokeratin 5 and low expression of androgen receptor or prostate specific antigen are sensitive to dasatinib. To identify markers as surrogates for biological activity, we treated cell lines with dasatinib and identified genes whose expression was significantly modulated by the drug. Ten genes, including that encoding urokinase-type plasminogen activator (uPA), were found to not only be potential efficacy markers but also to have reduced expression upon dasatinib treatment. The down-regulation of uPA by dasatinib was drug-specific and correlated with the sensitivity of cell lines to dasatinib. Furthermore, EphA2, a target of dasatinib, was found to be a sensitivity biomarker.Using the gene expression profiling approach and preclinical models, we have identified prostatic biomarkers that are associated with sensitivity to dasatinib. This study has provided a basis for clinical evaluation of a potential dasatinib efficacy signature in prostate cancer.
Views of American Oncologists About the Purposes of Clinical Trials
Authors: S. Joffe, J. C. Weeks
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Many research subjects believe incorrectly that the primary purpose of clinical trials is to benefit the participants rather than to improve therapy for future patients. However, few data are available about how physicians view trials. Methods: We mailed surveys to a stratified random sample (n = 1120) of U.S. medical, pediatric, and other oncology specialists who were selected from the American Society of Clinical Oncology Membership Directory. Respondents were asked to select, from a list of options, their reasons for enrolling individual patients in trials and what they thought the main societal purposes of clinical trials are. We used logistic regression models to evaluate which demographic and clinical practice characteristics were associated with responses to these questions. All statistical tests were two-sided. Results: Of the 547 physicians (48.8%) who responded, 40.5% of the medical oncologists, 32.3% of the pediatric oncologists, and 62.6% of the other oncology subspecialists reported enrolling individual patients in clinical trials to improve future therapy. Most of the other respondents reported enrolling patients to ensure that they received state-of-the-art treatment. When asked about the main societal purpose of clinical trials, 72.7% of the medical oncologists, 59.4% of the pediatric oncologists, and 81.9% of the other oncology subspecialists cited improving future therapy; most of the other respondents cited ensuring state-of-the-art treatment for participants. In multivariable analysis, medical oncologists (odds ratio [OR] = 0.6, 95% confidence interval [CI] = 0.3 to 0.9) and pediatric oncologists (OR = 0.3, 95% CI = 0.2 to 0.5) were less likely than other oncologists to identify improving future therapy as the main societal purpose of clinical trials, whereas industry physicians (OR = 4.6, 95% CI = 1.1 to 20.5) chose this option more often than physicians who did not work for industry. Conclusions: Many respondents viewed the main societal purpose of clinical trials as benefiting the participants rather than as creating generalizable knowledge to advance future therapy. This view, which was more prevalent among specialists such as pediatric oncologists that enrolled greater proportions of patients in trials, conflicts with established principles of research ethics.
Electrocardiographic evolutionary changes and left ventricular remodeling after acute myocardial infarction11The Investigators and Institutions participating in the GISSI-3 Echo Substudy are listed in the Appendix.
Authors: Enzo Bosimini, Pantaleo Giannuzzi, Pier L Temporelli, Francesco Gentile, Donata Lucci, Aldo P Maggioni, Luigi Tavazzi, Luigi Badano, Ioanna Stoian, Rita Piazza, Ioanna Heyman, Giacomo Levantesi, Eugenio Cervesato, Enrico Geraci, Gian L Nicolosi
Journal: Journal of the American College of Cardiology (2000)
Oxidative Stress in Uremia
Authors: Vicente Lahera, Marian Goicoechea, Soledad García de Vinuesa, Pilar Oubiña, Victoria Cachofeiro, Francisco Gómez-Campderá, Raquel Amann, José Luño
Journal: Journal of the American Society of Nephrology (2006)

Patients with chronic kidney disease (CKD) are prone to develop cardiovascular disorders. Numerous reports have shown the association between uremia and oxidative stress, which increases patients' risk for cumulative injury to multiple organs. Anemia is a common and disabling feature of CKD and seems to be a main cause of oxidative stress; correction of anemia represents an effective approach to reduce oxidative stress and, consequently, cardiovascular risk. There is increasing evidence that correction of anemia with erythropoiesis-stimulating agents could protect from oxidative stress in patients with CKD and ESRD. However, iron deficiency frequently complicates anemia in patients with CKD, and ferrous iron cation is a co-factor that is needed for hydroxyl radical production, which can promote cytotoxicity and tissue injury. This has raised a justifiable concern that prescription of intravenous iron may exacerbate oxidative stress and, hence, endothelial dysfunction, inflammation, and progression of cardiovascular disease, which are widely known consequences of CKD. Correction of anemia represents an effective approach to reduce oxidative stress and, consequently, cardiovascular risk. Iron deficiency is a common cause of resistance to erythropoiesis-stimulating agents, and the overall risk-benefit ratio favors use of intravenous iron to treat iron deficiency in patients with CKD. Consecutive or combined treatment with intravenous iron and erythropoiesis-stimulating agents clearly is beneficial for patients with CKD and iron deficiency, and anemia and could contribute to prevent the risk for cardiovascular events in these patients.
Indications of vascular endothelial cell dysfunction in systemic lupus erythematosus.
Authors: M A Byron, M J Allington, H M Chapel, A G Mowat, S A Cederholm-Williams
Journal: Annals of the Rheumatic Diseases (1987)

Fibrinolytic and other factors have been measured in 73 patients with systemic lupus erythematosus or related conditions to determine whether clinical thrombosis, a common feature of these disorders, is associated with defective fibrinolysis. Twenty five of 72 (35%) patients, compared with two of 22 (9%) controls, showed a low level of plasminogen activator activity in response to venous occlusion, suggesting decreased fibrinolytic potential. In addition, mean plasma levels of von Willebrand factor antigen and fibronectin were markedly raised in the patients (mean (SD) 384.5 (277)% and 727 (436) mg/l respectively) compared with healthy controls (100 (50)% and 306 (65) mg/l). These data suggest a degree of endothelial cell dysfunction. No clear correlation was found between a history of thrombosis and any plasma factor measured, except for prolongation of clotting tests suggestive of the 9lupus anticoagulant9.
Decoding the Cardiac Message
Authors: Gerald W. Dorn
Journal: Circulation Research (2012)

This review reflects and expands on the contents of my presentation at the Thomas W. Smith Memorial Lecture at American Heart Association Scientific Sessions, 2011. “Decoding the cardiac message” refers to accumulating results from ongoing microRNA research that is altering longstanding concepts of the mechanisms for, and consequences of, messenger RNA (mRNA) regulation in the heart. First, I provide a brief historical perspective of the field of molecular genetics, touching on seminal research that paved the way for modern molecular cardiovascular research and helped establish the foundation for current concepts of mRNA regulation in the heart. I follow with some interesting details about the specific research that led to the discovery and appreciation of microRNAs as highly conserved pivotal regulators of RNA expression and translation. Finally, I provide a personal viewpoint as to how agnostic genome-wide techniques for measuring microRNAs, their mRNA targets, and their protein products can be applied in an integrated multisystems approach to uncover direct and indirect effects of microRNAs. Experimental designs integrating next-generation sequencing and global proteomics have the potential to address unanswered questions regarding microRNA–mRNA interactions in cardiac disease, how disease alters mRNA targeting by specific microRNAs, and how mutational and polymorphic nucleotide variation in microRNAs can affect end-organ function and stress response.
THE PREVENTION OF RICKETS IN PREMATURE INFANTS BY THE USE OF VIOSTEROL 100 D
Authors: EARL W. MAY
Journal: JAMA (1931)

The results of comprehensive study of vitamins during the last two decades are reflected in the more efficient methods being used at present for the control of deficiency diseases. The final word may not have been said in respect to rickets, but the investigations of Tanret, Rosenheim and Webster, Hess and Windaus, and Steenbock on the production and action of vitamin D has contributed materially to our knowledge of the etiology, prophylaxis and treatment of the disease. The process of imparting the antirachitic factor to sterols by ultraviolet emanations from a mercury vapor lamp is too familiar to need elaboration in this report. The name viosterol was assigned by the Council on Pharmacy and Chemistry of the American Medical Association to irradiated ergosterol when adjusted to a potency of 100 times the vitamin D strength of standardized cod liver oil. Since Oct. 1, 1930, the strength of these preparations has
A Simple Flow-Driven Method for Online Measurement of Exhaled NO Starting at the Age of 4 to 5 Years
Authors: EUGENIO BARALDI, MASSIMO SCOLLO, CRISTINA ZARAMELLA, STEFANIA ZANCONATO, FRANCO ZACCHELLO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

NO is increased in exhaled air of asthmatic patients, and may be used as a marker of airway inflammation. The online method is a standardized technique for measuring exhaled nitric oxide (ENO). However, this method has proven difficult for some children, who may have trouble maintaining a constant expiratory flow. The aim of this study was to validate a modified technique for online ENO measurement that utilizes a flow regulator to overcome the patient problem of having to actively maintain a constant expiratory flow. We measured ENO levels with two methods in 105 asthmatic and 10 healthy subjects, comparing the standardized (ST) single-breath method with a modified single-breath, flow-driven (FD) method. With the ST method and visual monitoring, the subjects inhaled NO-free air to TLC, and exhaled with a target flow of 50 ml/s. With the FD method, the subjects exhaled from TLC and flow was kept constant (50 ml/s) by the operator, using a flow regulator. The subjects were divided into two groups, one consisting of children aged 4 to 8 yr (n = 74) and the other of children aged 9 to 16 yr (n = 41). In the group aged 4 to 8 yr, 38 children (51%) were unable to perform the ST method, whereas only five children (7%) failed to perform the FD technique. In the group aged 9 to 16 yr, only four children (10%) were unable to perform the ST maneuver, and all successfully performed the FD maneuver. The mean concentrations of ENO in the 73 children who performed both types of maneuver were similar (36.1 ± 3.4 [mean ± SEM] ppb with the ST method and 33.8 ± 3.3 ppb with the FD technique, p = NS) and were highly correlated with one another (r = 0.99, p < 0.0001). ENO values were significantly higher in steroid-naive than in steroid-treated asthmatic children. In conclusion, we describe a modified online method for measuring ENO that is simple, does not require active cooperation to maintain a constant expiratory flow, and can be easily performed by children from 4 to 5 yr of age onward.
Clinical Utility of a Rapid Whole-Blood<scp>d</scp>-Dimer Assay in Patients with Cancer Who Present with Suspected Acute Deep Venous Thrombosis
Authors: Agnes Y.Y. Lee, Jim A. Julian, Mark N. Levine, Jeffrey I. Weitz, Clive Kearon, Philip S. Wells, Jeffrey S. Ginsberg
Journal: Annals of Internal Medicine (1999)

Although D-dimer assays have high negative predictive values for the diagnosis of deep venous thrombosis, their accuracy in patients with cancer is uncertain.To compare the clinical utility of a whole-blood D-dimer assay for the diagnosis of deep venous thrombosis in patients with and those without cancer.Retrospective analysis of three prospective studies.Two tertiary care hospitals.1068 consecutive outpatients with suspected deep venous thrombosis.All patients underwent D-dimer testing and assessment with a priori diagnostic strategies that incorporated impedance plethysmography, compression ultrasonography, or contrast venography. Patients in whom deep venous thrombosis was not diagnosed initially were followed for 3 months for the development of thrombosis. Results of D-dimer testing were assessed according to the final diagnosis based on objective testing and clinical follow-up. Cancer status was identified at presentation.The prevalence of deep venous thrombosis was 48.8% in 121 patients with cancer and 14.6% in 947 patients without cancer. Although the sensitivity of the D-dimer assay was similar in patients with and those without cancer (86.4% [95% CI, 75.0% to 94.0%] and 82.6% [CI, 75.2% to 88.5%], respectively), the specificity was significantly lower in patients with cancer (48.4% [CI, 35.5% to 61.4%] and 82.2% [CI, 79.4% to 84.8%]), as was the negative predictive value (78.9% [CI, 62.7% to 90.4%] and 96.5% [CI, 94.9% to 97.8%]). In contrast, the likelihood ratios of a negative test result (0.28 [CI, 0.14 to 0.56] and 0.21 [CI, 0.15 to 0.31]) did not differ significantly.A negative D-dimer test result in patients with cancer does not reliably exclude deep venous thrombosis because the negative predictive value of the test is significantly lower in these patients than in patients without cancer.
Pulmonary Ventilation-Perfusion Relations after Heart Valve Replacement or Repair in Man*
Authors: J. Hedley-Whyte, H. Corning, M. B. Laver, W. G. Austen, H. H. Bendixen
Journal: Journal of Clinical Investigation (1965)

The anatomical shunt may be larger than 2% in cer- tain diseased states ( 12).An anatomic shunt of 2% of the cardiac output is our estimate of the average ana-
Preparation and characterization of protein loaded microspheres based on a hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid)
Authors: A.H. Ghassemi, M.J. van Steenbergen, H. Talsma, C.F. van Nostrum, W. Jiskoot, D.J.A. Crommelin, W.E. Hennink
Journal: Journal of Controlled Release (2009)