tbuckley/cabot-search huggingface dataset:
Molecular and Cytogenetic Subgroups of Oropharyngeal Squamous Cell Carcinoma
Authors: Federica Perrone, Simona Suardi, Elisa Pastore, Paola Casieri, Marta Orsenigo, Stefano Caramuta, Gianpaolo Dagrada, Marco Losa, Lisa Licitra, Paolo Bossi, Samantha Staurengo, Maria Oggionni, Laura Locati, Giulio Cantu, Massimo Squadrelli, Antonino Carbone, Marco A. Pierotti, Silvana Pilotti
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The aim of this study was to acquire further insights into the pathogenetic pathways of head and neck squamous cell carcinomas (HNSCC) that may be useful for identifying new biomarkers instrumental in developing more specific treatment approaches. Experimental Design: Cell cycle regulators and epidermal growth factor receptor (EGFR) and BRAF genes were analyzed in a series of 90 oropharyngeal SCCs of a cohort of surgically treated patients from a single institution, and the results were matched with the presence of high-risk human papillomavirus (HR-HPV) DNA and the TP53 status. Results: At least four distinct groups of tumors were identified sharing a common histology but displaying different molecular/cytogenetic patterns: (a) 19% were HPV-positive SCCs whose lack of alterations of the investigated genes could explain their particular natural history, which requires less aggressive treatment; (b) 37% were HPV-negative SCCs carrying TP53 mutations, which may be more effectively treated by drugs acting through p53-independent apoptosis; (c) 34% were HPV-negative SCCs carrying wild-type TP53 and loss of 9p21 (p16INK4a and p15INK4b) and/or cyclin D1 overexpression that justify treatment with DNA-damaging drugs followed by cell cycle inhibitors; and (d) 10% were HPV-negative lacking tumor suppressor genes and cell cycle alterations. The second, third, and fourth groups also showed an increased copy number of EGFR and chromosome 7 (43%) that might justify the additional or alternative use of EGFR inhibitors. Conclusions: Our findings suggest that assessing HPV, TP53, 9p21, and EGFR status may be crucial to finding more tailored and beneficial treatments for oropharyngeal SCCs.
Serum Creatinine as Marker of Kidney Function in South Asians
Authors: Tazeen H. Jafar, Christopher H. Schmid, Andrew S. Levey
Journal: Journal of the American Society of Nephrology (2005)

Migrant populations of South Asian origin have a higher risk for chronic kidney disease than the native whites. Several formulas have been developed to estimate kidney function from serum creatinine concentration. However, none of these has been validated in the South Asian population, which generally has different muscle mass composition than whites. A population-based cross-sectional study was performed on 262 individuals who were aged ≥40 yr in Karachi, Pakistan. Reduced GFR was defined as creatinine clearance (Ccr) measured in 24-h urine collection of &lt;60 ml/min per 1.73 m<sup>2</sup>. Creatinine excretion was compared with age- and gender-matched white individuals by comparison of observed <i>versus</i> expected results on the basis of a formula using <i>t</i> test. The agreement among Cockcroft Gault (CG) Ccr and Modification of Diet in Renal Disease (MDRD) Study GFR equations was assessed by regression analyses, and the degree of accuracy of estimated <i>versus</i> measured GFR was determined. Mean (95% confidence interval) creatinine excretion was 1.7 (1.0 to 2.4) mg/kg per d lower than expected for age- and gender-matched white individuals (<i>P</i> &lt; 0.001). The coefficient of determination for measured Ccr on the logarithmic scale was 66.7 and 55.6% for the CG and MDRD Study equations, respectively. The proportion of estimates within 20, 30, and 50% of measured Ccr values was 47.7 <i>versus</i> 32.8% (<i>P</i> &lt; 0.001), 64.9 <i>versus</i> 49.6% (<i>P</i> &lt; 0.001), and 79.4 <i>versus</i> 72.9 (<i>P</i> = 0.07) for CG <i>versus</i> MDRD Study equations, respectively. Lower mean creatinine excretion in these individuals may explain, in part, suboptimal agreement between estimated <i>versus</i> measured GFR. Inclusion of terms for ethnic and racial groups other than white and black might improve the performance of GFR estimating equations.
Gene Expression-Based Molecular Diagnostic System for Malignant Gliomas Is Superior to Histological Diagnosis
Authors: Mitsuaki Shirahata, Kyoko Iwao-Koizumi, Sakae Saito, Noriko Ueno, Masashi Oda, Nobuo Hashimoto, Jun A. Takahashi, Kikuya Kato
Journal: Clinical Cancer Research (2007)

Current morphology-based glioma classification methods do not adequately reflect the complex biology of gliomas, thus limiting their prognostic ability. In this study, we focused on anaplastic oligodendroglioma and glioblastoma, which typically follow distinct clinical courses. Our goal was to construct a clinically useful molecular diagnostic system based on gene expression profiling.The expression of 3,456 genes in 32 patients, 12 and 20 of whom had prognostically distinct anaplastic oligodendroglioma and glioblastoma, respectively, was measured by PCR array. Next to unsupervised methods, we did supervised analysis using a weighted voting algorithm to construct a diagnostic system discriminating anaplastic oligodendroglioma from glioblastoma. The diagnostic accuracy of this system was evaluated by leave-one-out cross-validation. The clinical utility was tested on a microarray-based data set of 50 malignant gliomas from a previous study.Unsupervised analysis showed divergent global gene expression patterns between the two tumor classes. A supervised binary classification model showed 100% (95% confidence interval, 89.4-100%) diagnostic accuracy by leave-one-out cross-validation using 168 diagnostic genes. Applied to a gene expression data set from a previous study, our model correlated better with outcome than histologic diagnosis, and also displayed 96.6% (28 of 29) consistency with the molecular classification scheme used for these histologically controversial gliomas in the original article. Furthermore, we observed that histologically diagnosed glioblastoma samples that shared anaplastic oligodendroglioma molecular characteristics tended to be associated with longer survival.Our molecular diagnostic system showed reproducible clinical utility and prognostic ability superior to traditional histopathologic diagnosis for malignant glioma.
Tissue culture of epithelium derived from Barrett's oesophagus.
Authors: K Washington, M R Gottfried, M J Telen
Journal: Gut (1994)

Barrett9s oesophagus is a preneoplastic condition in which the squamous mucosa of the oesophagus is replaced by columnar epithelium. Epithelial cells of Barrett9s oesophagus were isolated from resected oesophagus specimens by two methods not previously applied to the culture of Barrett9s oesophagus cells. These techniques included trypsinisation of small fragments of mucosa, followed by plating in tissue culture dishes, and a direct tissue explant technique. A modified MCDB-153 growth medium was used. Primary trypsin technique cultures were plated on uncoated plastic, or plastic coated with type I collagen, type IV collagen, or fibronectin. Growth on type IV collagen and fibronectin plates was slower but produced less contamination from fibroblasts. By 20-40 days most cultures formed confluent monolayers made up of cells with epithelial morphology. The cells were cytokeratin positive, vimentin negative, and contained alcian blue positive vacuoles, confirming their epithelial origin and suggesting their derivation from Barrett9s oesophagus. Electron microscopy showed tonofilaments, microvilli, and desmosomes. Cells proliferated through up to eight subcultures before growth slowed and cells showed senescent changes. This study shows that epithelial cells from Barrett9s oesophagus can be grown by comparatively simple tissue culture techniques. These methods can provide sufficient material for a variety of molecular biology and biochemical studies of epithelial cells from Barrett9s oesophagus.
Symptoms of Diabetes and Their Association With the Risk and Presence of Diabetes
Authors: Nathaniel G. Clark, Kathleen M. Fox, Susan Grandy
Journal: Diabetes Care (2007)

OBJECTIVE—The American Diabetes Association (ADA) lists seven symptoms of diabetes; however, it is not known how specific these symptoms are for initial diagnosis of type 2 diabetes. The Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) examined prevalence of ADA symptoms and their association with diabetes diagnosis. RESEARCH DESIGN AND METHODS—SHIELD is a 5-year observational study of individuals with or at risk for diabetes diagnosis. Following an initial screening phase, follow-up questionnaires were mailed to a stratified random sample of individuals (n = 22,001) with type 1 or type 2 diabetes or at high (three to five risk factors) or low (zero to two risk factors) risk for diabetes. Individuals reported whether they experienced each ADA symptom, as well as symptoms unrelated to diabetes. RESULTS—A total of 15,794 questionnaires were returned (response rate 71.8%). All ADA symptoms were reported more frequently in type 2 diabetes than in low- and high-risk groups (P &amp;lt; 0.0001 for each). Multivariable logistic regression analyses found that each ADA symptom other than irritability was significantly associated with type 2 diabetes, as was erectile/sexual dysfunction. However, 48% of type 1 diabetic and 44% of type 2 diabetic respondents reported no ADA symptom in the previous year. CONCLUSIONS—Occurrence of ADA symptoms alone may not adequately identify those who should be evaluated for type 2 diabetes. Longitudinal data from SHIELD will evaluate whether combinations of symptoms or addition of other symptoms can better identify individuals for evaluation.
Dexrazoxane-Associated Risk for Secondary Malignancies in Pediatric Hodgkin's Disease: A Claim Without Compelling Evidence
Authors: Steven E. Lipshultz, Stuart R. Lipsitz, Endel John Orav
Journal: Journal of Clinical Oncology (2007)

TO THEEDITOR: The title of a recent article by Tebbi et al 1 claims that dexrazoxane poses a risk, and that it is responsible for a higher incidence of secondary acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and other second malignant neoplasms (SMNs) in children with Hodgkin’s disease (HD) treated with dexrazoxane plus doxorubicin, bleomycin, vincristine, and etoposide (ABVE) or dose-intensified ABVE with prednisone and cyclophosphamide (ABVE-PC) as well as radiotherapy (POG 9426 [low-stage HD] and 9425 [advanced-stage HD]). This claim is based on 10 SMNs (including eight AML/MDS) in 478 patients. Differences in the incidence of SMNs between children randomly assigned to receive dexrazoxane versus no dexrazoxane concomitantly with chemotherapy to evaluate its efficacy as a cardiopulmonary protectant show no statistical significance by simple Fisher’s exact tests (of 239 patients, eight [3.35%] v two [0.84%] with SMNs, respectively, and P .11; six [2.51%] v two [0.84%] with AML/ MDS, respectively, and P .24), nor by the more conventional and appropriate time-to-event analysis used by the authors (P .06 for SMNs;P .16 for AML/MDS). Only after adjusting for race, age, and sex in a different analysis using a Poisson regression model were the authors able to achieve aP value below .05 for any type of SMN (P .02 for SMNs; P .10 for AML/MDS), even though the authors demonstrated no imbalance between arms for race, age, or sex. We would regard this as scant statistical evidence, particularly in a trial that, as the authors observe, was not “designed for statistical comparison of leukemia and SMN risk.” 1 Dexrazoxane is a US Food and Drug Administration–approved, established protectant against doxorubicin-induced cardiotoxicity in patients with breast cancer 2 and is also cardioprotective in acute lymphoblastic leukemia of childhood, 3 as well as with other malignancies. 4 No evidence shows that this protection has impaired the effectiveness (survival) of doxorubicin-treated patients or that it has caused any new or clinically relevant sequelae (infection, hemorrhage, deaths, or necessity for change of dosage). Some 16 clinical trials in seven different countries over the past 10 years involving more than 500 patients have not reported a single case of AML as a result of combining dexrazoxane with doxorubicin plus fluorouracil and cyclophosphamide (the FAC regime). 4
Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study
Authors: Mark S Pearce, Jane A Salotti, Mark P Little, Kieran McHugh, Choonsik Lee, Kwang Pyo Kim, Nicola L Howe, Cecile M Ronckers, Preetha Rajaraman, Alan W Craft, Louise Parker, Amy Berrington de González
Journal: The Lancet (2012)

Although CT scans are very useful clinically, potential cancer risks exist from associated ionising radiation, in particular for children who are more radiosensitive than adults. We aimed to assess the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young adults.In our retrospective cohort study, we included patients without previous cancer diagnoses who were first examined with CT in National Health Service (NHS) centres in England, Wales, or Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age. We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer diagnosis, follow-up for leukaemia began 2 years after the first CT and for brain tumours 5 years after the first CT.During follow-up, 74 of 178,604 patients were diagnosed with leukaemia and 135 of 176,587 patients were diagnosed with brain tumours. We noted a positive association between radiation dose from CT scans and leukaemia (excess relative risk [ERR] per mGy 0·036, 95% CI 0·005-0·120; p=0·0097) and brain tumours (0·023, 0·010-0·049; p<0·0001). Compared with patients who received a dose of less than 5 mGy, the relative risk of leukaemia for patients who received a cumulative dose of at least 30 mGy (mean dose 51·13 mGy) was 3·18 (95% CI 1·46-6·94) and the relative risk of brain cancer for patients who received a cumulative dose of 50-74 mGy (mean dose 60·42 mGy) was 2·82 (1·33-6·03).Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer. Because these cancers are relatively rare, the cumulative absolute risks are small: in the 10 years after the first scan for patients younger than 10 years, one excess case of leukaemia and one excess case of brain tumour per 10,000 head CT scans is estimated to occur. Nevertheless, although clinical benefits should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate.US National Cancer Institute and UK Department of Health.
The Molecular Basis of Synergism between Carboplatin and ABT-737 Therapy Targeting Ovarian Carcinomas
Authors: Harsh Vardhan Jain, Michael Meyer-Hermann
Journal: Cancer Research (2010)

Resistance to standard chemotherapy (carboplatin + paclitaxel) is one of the leading causes of therapeutic failure in ovarian carcinomas. Emergence of chemoresistance has been shown to be mediated in part by members of the Bcl family of proteins including the antiapoptotic protein Bcl-x(L), whose expression is correlated with shorter disease-free intervals in recurrent disease. ABT-737 is an example of one of the first small-molecule inhibitors of Bcl-2/Bcl-x(L) that has been shown to increase the sensitivity of ovarian cancer cells to carboplatin. To exploit the therapeutic potential of these two drugs and predict optimal doses and dose scheduling, it is essential to understand the molecular basis of their synergistic action. Here, we build and calibrate a mathematical model of ABT-737 and carboplatin action on an ovarian cancer cell line (IGROV-1). The model suggests that carboplatin treatment primes cells for ABT-737 therapy because of an increased dependence of cells with DNA damage on Bcl-x(L) for survival. Numerical simulations predict the existence of a threshold of Bcl-x(L) below which these cells are unable to recover. Furthermore, co- plus posttreatment of ABT-737 with carboplatin is predicted to be the best strategy to maximize synergism between these two drugs. A critical challenge in chemotherapy is to strike a balance between maximizing cell-kill while minimizing patient drug load. We show that the model can be used to compute minimal doses required for any desired fraction of cell kill. These results underscore the potential of the modeling work presented here as a valuable quantitative tool to aid in the translation of novel drugs such as ABT-737 from the experimental to clinical setting and highlight the need for close collaboration between modelers and experimental scientists.
Pharmacological Stress Myocardial Perfusion Imaging With the Potent and Selective A <sub>2A</sub> Adenosine Receptor Agonists ATL193 and ATL146e Administered by Either Intravenous Infusion or Bolus Injection
Authors: David K. Glover, Mirta Ruiz, Kazuya Takehana, Frank D. Petruzella, Laurent M. Riou, Jayson M. Rieger, Timothy L. Macdonald, Denny D. Watson, Joel Linden, George A. Beller
Journal: Circulation (2001)

Adenosine (Ado) and dipyridamole are alternatives to exercise stress for myocardial perfusion imaging. Though generally safe, side effects frequently occur that cause patient discomfort and sometimes lead to premature termination of the study or require aminophylline administration. Recently, a new class of A(2A) Ado receptor agonists was synthesized. ATL193 and ATL146e are 2-propynylcyclohexyl-5'-N-ethylcarboxamido derivatives of Ado. The study goals were to evaluate the potency and selectivity of these new compounds on recombinant canine Ado receptors and to evaluate their hemodynamic properties in dogs to assess their usefulness as vasodilators for myocardial perfusion imaging.In assays of recombinant canine Ado receptors, ATL-193 and ATL-146e were highly selective for the A(2A) over the A(1) and A(3) receptors and were more potent than MRE-0470 and CGS-21680. In 16 anesthetized dogs, the agonists were administered by infusion (ATL-193; n=7 normal) or bolus injection (ATL-146e; n=9 critical left anterior descending coronary artery stenosis), and hemodynamic responses were compared with those of Ado. Both agonists produced dose-dependent coronary flow (CF) elevation without provoking the hypotension observed with Ado. After an ATL-146e bolus, the CF increase was sustained for several minutes, providing ample time for injection and myocardial uptake of (99m)Tc-sestamibi, and CF returned to baseline within 20 minutes. The CF increase was completely blocked by the selective A(2A) antagonist ZM241385 (3 microgram. kg(-1). min(-1)).ATL-193 and ATL-146e are highly potent and selective Ado A(2A) receptor agonists with excellent potential for use as vasodilators for myocardial perfusion imaging. An important advantage of ATL-146e is the ability to administer it by bolus injection.
NCAA concussion education in ice hockey: an ineffective mandate
Authors: Emily Kroshus, Daniel H Daneshvar, Christine M Baugh, Christopher J Nowinski, Robert C Cantu
Journal: British Journal of Sports Medicine (2013)

<h3>Background/aim</h3> Despite concussion education being increasingly mandated by states and sports leagues, there has been limited evaluation of what education is in fact effective. The National Collegiate Athletic Association (NCAA) currently mandates that institutions provide concussion education, without specifying content or delivery. The present study evaluated the effectiveness of this general mandate, as enacted for male collegiate ice hockey teams within one conference of competition. <h3>Methods</h3> In a prospective cohort design, 146 players from 6 male collegiate ice hockey teams in one Division 1 conference completed written surveys before and after receiving their institution-determined concussion education. Knowledge, attitudes, perceived norms and behavioural intention were assessed using validated measures. Education content and delivery was assessed by open-ended responses and consultation with team athletic trainers. <h3>Results</h3> All teams received concussion education material; however, content and delivery varied. Rates of material recall differed by delivery format. Considering all teams together, there were no significant improvements in knowledge and only a very small decrease in intention to continue playing while experiencing symptoms of a concussion. Pre-education and post-education, there were significant between-team differences in attitudes towards concussion reporting and behavioural intention. <h3>Conclusions</h3> The NCAA9s general education mandate was divergently enacted; it did not significantly change the constructs of interest nor did it mitigate the pre-education team differences in these constructs. Existing educational materials should be evaluated, theory and evidence-driven materials developed, and mandates extended to, at a minimum, recommend materials found to be effective in changing concussion-reporting behaviour.
Differentiation between aberrant ventricular conduction and ventricular ectopy in atrial fibrillation using RR interval scattergram.
Authors: A C Suyama, K Sunagawa, M Sugimachi, T Anan, K Egashira, A Takeshita
Journal: Circulation (1993)

Differentiation between aberrant ventricular conduction and ventricular ectopy during atrial fibrillation (AF) is of etiologic, prognostic, and therapeutic importance. We developed a noninvasive technique to diagnose aberrant ventricular conduction and ventricular ectopy in AF.We studied the Holter ECGs of 34 patients with paroxysmal AF and 62 patients with chronic AF. In all the patients, frequent wide QRS complexes were observed, and 32 patients were shown by electrophysiological examination to have ventricular ectopies or aberrant ventricular conductions. We obtained the RR interval scattergrams by plotting sequential pairs of RR intervals. Each point has the (n)th RR interval as its x value and the (n + 1)th RR interval as its y value. The irregularity of the RR intervals in AF resulted in widely scattered points delineated by the envelope along the axes. The y value of the envelope along the x axis indicates the shortest coupling interval to the preceding RR interval. Therefore, this curve defines the functional refractory period of atrioventricular conduction. The scattergram of the RR interval pairs immediately preceding the aberrant conduction (coupling points of aberrant conduction) specifically distributed along the envelope. In contrast, the coupling points of ventricular ectopies showed different distributions that had no relation to the envelope. That is, it included three typical patterns, ie, linear distribution below the envelope, linear distribution partially overlapped in the area of normal AF conduction, and chaotic distribution in the AF area. None of the scattergrams of ventricular ectopies showed curvilinear distribution along the envelope as aberrant conduction did. The specific distribution of the aberrant conduction on the RR interval scattergram suggested that aberrant conduction in AF could result from the difference of refractory periods between the AV node and bundle branch block.We conclude that the RR interval scattergram makes it possible to differentiate between aberrant ventricular conduction and ventricular ectopy in atrial fibrillation, and thus, it is a useful noninvasive clinical tool.
Intraoperative versus extended antimicrobial prophylaxis after gastric cancer surgery: a phase 3, open-label, randomised controlled, non-inferiority trial
Authors: Hiroshi Imamura, Yukinori Kurokawa, Toshimasa Tsujinaka, Kentaro Inoue, Yutaka Kimura, Shohei Iijima, Toshio Shimokawa, Hiroshi Furukawa
Journal: The Lancet Infectious Diseases (2012)