tbuckley/cabot-search huggingface dataset:
Abstract 3769: Use of combined levels of dietary intake from FFQ and plasma biomarkers to assess association between antioxidant exposures and prostate cancer risk
Authors: So Yeon J. Kong, Michael Goodman, Roberd M. Bostick
Journal: Cancer Research (2010)

Abstract Epidemiologic studies evaluating the relation between specific nutrients and risk of disease typically rely either on questionnaire-based or on biomarker-based measures of exposure; however both of these approaches may be affected by systematic error. In this study, we aim to improve assessment of antioxidant exposure through a combined measure reflecting both plasma measurements and food frequency questionnaire (FFQ)-derived levels of intake. This combined measure of exposure is examined in relation to risk of prostate cancer. In this community-based case-control study, dietary intake was assessed through the validated Block FFQ that allowed estimating daily intakes of various antioxidants. Archived plasma samples were analyzed using high performance liquid chromatography to determine circulating levels of carotenoids (lycopene, α-carotene, β-carotene, lutine, and β-cryptoxanthin), retinol (vitamin A), and α-tocopherol (vitamin E). Cases and controls were categorized as having “high” or “low” for each antioxidant's dietary intake and plasma level based on the median value among controls. Each participant was then included into one of the following four categories: (1) low dietary intake and low plasma level; (2) low dietary intake and high plasma level; (3) high dietary intake and low plasma level; and (4) high dietary intake and high plasma level. The combined measurements of high dietary intake and high plasma levels of lycopene, β-cryptoxanthin, and α-tocopherol demonstrated a statistically significant association with prostate cancer risk with adjusted odds ratios of 0.46 (0.23-0.91), 0.43 (0.22-0.84), and 0.32 (0.14-0.72), respectively. The combined measurements of high dietary intake and low plasma levels of β-carotene also demonstrated a statistically significant association (aOR = 0.43; 95% CI=0.20-0.91) with prostate cancer risk. These results tended to be stronger than the corresponding results for each measure of exposure considered individually. These findings provide evidence that the use of combined levels of dietary intake from FFQ and plasma biomarkers can improve the assessment of antioxidant exposure compared to use of either FFQ or plasma biomarkers separately. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3769.
A Systematic Review of Neoadjuvant and Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer
Authors: Joshua J. Meeks, Joaquim Bellmunt, Bernard H. Bochner, Noel W. Clarke, Siamak Daneshmand, Matthew D. Galsky, Noah M. Hahn, Seth P. Lerner, Malcolm Mason, Thomas Powles, Cora N. Sternberg, Guru Sonpavde
Journal: European Urology (2012)
Euthanasia: can be part of good terminal care
Authors: A P M Heintz
Journal: BMJ (1994)

It makes no sense to discuss euthanasia in terms of being for or against it. The basic question is whether we accept the right of human beings to decide for themselves how their lives will end.

The backbone of ethics is respect for human life, and many doctors have interpreted their duty as being to keep patients alive at all costs and for as long as possible. Patients are sometimes treated even when the chances of success are slight, which the recent explosion in medical knowledge has made more likely.1

The request for euthanasia is in many respects a response to this. People now understand that treatment can lengthen not only life but also the suffering that may accompany treatment. They have a choice where once they had none: they can opt for treatment or, if they find …
Abstract 4226: A luminal epithelial cell line isolated from PTEN−/−;P53−/− mouse protospheres forms adenocarcinoma in vivo
Authors: Paul G. Hynes, Wassim G. Abou-Kheir, Yen-Nien Liu, Philip Martin, Kathleen Kelly
Journal: Cancer Research (2010)

Abstract Pten deletion in the mouse prostate epithelium results in the expansion of a prostatic stem/progenitor cell subpopulation, which co-fractionates with basal epithelial cells. Progenitor cells in the luminal layer of Pten null prostates also have been suggested as tumor initiating cells. Here we describe the isolation of a protosphere-derived, androgen independent cell line with a luminal epithelial phenotype that displays properties of prostate progenitor cells and forms adenocarcinoma in-vivo. The cell line was generated from Rosa26-CreERPtenfl/flP53fl/fl prostate cells. Cells were plated to form protospheres, which originate from stem/progenitor cells, and the deletion of Pten and p53 was induced by tamoxifen. After spheres were serially passaged for 3 generations, a monolayer cell line capable of growth in minimal serum-free media was established. A clonal line also was generated from the parental cell line. In order to determine the differentiated cell phenotype of the parental and the clonal cell lines, cells were stained over multiple generations for markers of epithelial (CK5, CK8, CK14) and neuroendocrine (beta 3 tubulin) cell lineages. The cell line is entirely CK8 positive with a minor component of CK8/CK14 double positive cells. Cells are capable of forming protospheres both in Matrigel and in suspension, a property of stem/progenitor cells. In addition, based on lentiviral reporter assays, a minor population of cells in the parental and the clonal cell line expressed Nanog, Oct4 and Notch dependent activity. Interestingly, Nanog and Oct4 positive cells showed higher sphere forming ability as compared to negative cells. In order to investigate their tumorigenic potential, the parental and the cloned lines were injected subcutaneously into athymic nude mice. Visible tumor formation was observed after 2 weeks, and histological analysis revealed adenocarcinoma and poorly differentiated carcinoma. In addition to CK8+ cells within the tumors, there were rare CK5+ and neuroendocrine cells, suggesting plasticity in the differentiation potential. In conclusion, we have isolated a prostate luminal epithelial cell line and derivative clones with a defined background (Pten and p53 null) that have stem-like and tumor initiating properties in vitro and in vivo. Future experiments are aimed at deciphering the molecular mechanisms regulating growth and differentiation downstream of Pten and p53 loss. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4226.
The Dueling Diagnoses of Darwin
Authors: Jeremy Adler
Journal: JAMA (1997)

To the Editor.  —In adding to the possible causes of Darwin's chronic ill health, Drs Barloon and Noyes 1 pay little attention to the proposal made by my uncle 2 that Darwin suffered from Chagas disease, a view widely accepted. Medawar 3 strongly endorsed this suggestion  being based upon the use of reasoning. The case, recently restated, 4 rests on Darwin's detailed description of an attack on March 26, 1835, by the benchuca ( Triatoma infestane ), the vector for Trypanosoma cruzi , his prior excellent health, the accordance of Darwin's symptoms with Chagas disease, and the characteristic delay between exposure and the onset of chronic ill health.  Barloon and Noyes quote selectively from Darwin's notes, creating the impression that he primarily suffered from acute episodic attacks of panic and agoraphobia. This is incorrect, and Darwin in 1845 described his condition thus:  believe I have not had one whole day, or rather night,
miR-29a maintains mouse hematopoietic stem cell self-renewal by regulating Dnmt3a
Authors: Wenhuo Hu, James Dooley, Stephen S. Chung, Dhruva Chandramohan, Luisa Cimmino, Siddhartha Mukherjee, Christopher E. Mason, Bart de Strooper, Adrian Liston, Christopher Y. Park
Journal: Blood (2015)
Compassionate use of sorafenib in FLT3-ITD–positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation
Authors: Stephan Metzelder, Ying Wang, Ellen Wollmer, Michael Wanzel, Sabine Teichler, Anuhar Chaturvedi, Martin Eilers, Erich Enghofer, Andreas Neubauer, Andreas Burchert
Journal: Blood (2009)
Acanthosis Nigricans And Pituitary Tumors
Authors: R. K. Winkelmann
Journal: JAMA (1967)

<h3>To the Editor:—</h3> My co-authors and I appreciate Dr. Curth's major contributions to the field of acanthosis nigricans, but we cannot agree entirely with her method of classification. Acanthosis nigricans is a cutaneous manifestation associated with many different conditions, and the prognosis is not associated with the acanthosis nigricans but with the associated disease or mode of inheritance. We do not use the term "pseudoacanthosis nigricans," for histologically and clinically it is in every way similar to acanthosis nigricans. It is not related to obesity, for many of our patients have lost weight without having their acanthosis nigricans involute, and acanthosis nigricans has developed in some patients without obesity. We find it difficult to separate the types II and IV in Dr. Curth's classification, seeing no difference between an inherited acanthosis nigricans which is not associated with congenital dysplasia and one which is associated with phenomena such as congenital lipodystrophy.
Exploring parent and youth perspectives of the influence of concussion on school, sport and life: a qualitative study
Authors: Christine Provvidenza, Michelle L Keightley, Nick Reed, Stephanie Green
Journal: British Journal of Sports Medicine (2013)

Objective The purpose of this qualitative study was to describe the perceived impact of sports-related concussion by youth and their parents on home, school and sport functioning. Design Semi-structured interviews were used to assess perceived changes in general academic ability, attention, learning difficulties, social performance, behaviour, mood and emotions, executive and physical function. Framework analysis was used to analyse and interpret the data. Setting Participants were purposively recruited from a longitudinal study investigating the cognitive and physical effects of sports-related concussion in children from 2007–2010. Subjects 13 child athletes (11 males and 2 females; average age=11±0.856 years) ages 10–13 years and their parents (13 parents=9 mothers and 4 fathers). Intervention None. Outcome Measures Interviews were recorded and transcribed verbatim. Framework analysis was employed to identify emerging themes. Results The theme ‘a journey of recovery from concussion across time’ was identified and encompassed: initial reaction and recovery, re-integration into sport and school, evolvement of life skills, performance related to school and sports, personality and behaviour changes, and life lessons learned. Conclusions No long term impact of concussion was reported on hockey or school performance, but higher levels of anger and frustration related to performance post-injury were found. Child athletes' comments indicated fear of being hit again when returning to play, and a return to play while symptomatic. This suggests the need for further education around the definition of concussion and recovery, and follow-up support during return to play. Acknowledgements Ontario Neurotrauma Foundation. Competing interests None.
P192Opposing effects of cAMP/PKA and cAMP/Epac signalling on in vitro angiogenesis: role of Rho gtpases
Authors: M Aslam, H Nef, C Troidl, C Hamm, D Guenduez
Journal: Cardiovascular Research (2014)

Background: cAMP signalling regulates several endothelial functions such as endothelial barrier integrity, vascular tone, and both physiological and pathological angiogenesis. cAMP mediates these effects via activation of its two well characterised effectors i.e. PKA and Epac (exchange protein directly activated by cAMP). We have previously shown that activation of both cAMP-effectors stabilises endothelial barrier via activation of different signalling pathways. The aim of the present study was to analyse the effects of these cAMP effectors on angiogenesis in vitro. Methods: The study was carried out on cultured human umbilical vein endothelial cells (HUVEC). cAMP analogues, 8-CPT-cAMP (200 μM), 6-Bnz-cAMP (50 μM) and Forskolin (FSK; 5 μM) were used to activate Epac, PKA or adenylyl cyclase, respectively. In vitro angiogenesis was analysed by wound healing, tube formation and spheroid sprouting assays. Results: Specific activation of either PKA or Epac induced HUVEC proliferation and and collective migration (wound healing) which was accompanied by enhanced phosphorylation of Akt (at Ser473) and p42/44 MAPK. Both PKA and Epac-induced HUVEC proliferation and migration was abrogated by inhibitors of both Akt and p42/44 MAPK. Accordingly, specific activation of PKA induced endothelial cell tube formation and promoted sprouting of spheroid in 3-D collagen gels. Surprisingly, specific activation of Epac abrogated endothelial cell tube formation and VEGF-induced sprouting. When both PKA and Epac were activated simultaneously (with FSK), the effect of PKA surpased the inhibitory effect of Epac. Accordingly, the inhibition of Epac resulted in enhanced effect of PKA activation. Although activtion of both PKA and Epac induced Rac1 activation, however, both have differential effects on RhoA activity. PKA antagonised RhoA activity, while Epac caused an activation of RhoA. Inhibition of either RhoA activity or downstream Rho kinase (ROCK) alone resulted in increased HUVEC tube formation and sprouting and abrogated completely the anti-angiogenic effect of Epac activation. Similarly, specific activation of RhoA abrogated PKA-induced angiogenesis. Conclusion: The data of present study demonstrate that cAMP/PKA and cAMP/Epac signalling pathways have differential effects on in vitro angiogenesis. PKA activation promotes while Epac activation antagonises angiogenesis. This differential effect is due to opposite effects of both signalling pathways on RhoA/ROCK signalling.
Methods for Nuclei Detection, Segmentation, and Classification in Digital Histopathology: A Review—Current Status and Future Potential
Authors: Humayun Irshad, Antoine Veillard, Ludovic Roux, Daniel Racoceanu
Journal: IEEE Reviews in Biomedical Engineering (2014)

Digital pathology represents one of the major evolutions in modern medicine. Pathological examinations constitute the gold standard in many medical protocols, and also play a critical and legal role in the diagnosis process. In the conventional cancer diagnosis, pathologists analyze biopsies to make diagnostic and prognostic assessments, mainly based on the cell morphology and architecture distribution. Recently, computerized methods have been rapidly evolving in the area of digital pathology, with growing applications related to nuclei detection, segmentation, and classification. In cancer research, these approaches have played, and will continue to play a key (often bottleneck) role in minimizing human intervention, consolidating pertinent second opinions, and providing traceable clinical information. Pathological studies have been conducted for numerous cancer detection and grading applications, including brain, breast, cervix, lung, and prostate cancer grading. Our study presents, discusses, and extracts the major trends from an exhaustive overview of various nuclei detection, segmentation, feature computation, and classification techniques used in histopathology imagery, specifically in hematoxylin–eosin and immunohistochemical staining protocols. This study also enables us to measure the challenges that remain, in order to reach robust analysis of whole slide images, essential high content imaging with diagnostic biomarkers and prognosis support in digital pathology.
The genetic jigsaw of inflammatory bowel disease
Authors: D A Watts, J Satsangi
Journal: Gut (2002)

Following a prolonged period of relative inertia, real progress has been made in the past few years in understanding the pathogenesis of the chronic inflammatory bowel diseases, Crohn9s disease and ulcerative colitis. Clinical experience, epidemiological studies, and molecular genetics have provided strong evidence that both genetic and environmental factors are important in disease pathogenesis, and gene–environmental interaction determines disease susceptibility and behaviour.
Foreign Body Granuloma Simulating Gastric Carcinoma – Therapeutic Fiberendoscopy
Authors: L. Domján, A. Bruncsák, E. Frank, G. Garay
Journal: Endoscopy (1974)

A case of foreign body granuloma with close clinical and radiological resemblance to gastric carcinoma is presented. Correct diagnosis was obtained by endoscopy and succesful fiberscopic foreign body removal spared the patient the risk of laparotomy. With this report both the diagnostic and therapeutic value of fiberoptic instruments are emphasized.
A specific DNA methylation profile correlates with a high risk of disease progression in stage I classical (Alibert-Bazin type) mycosis fungoides
Authors: G. Ferrara, M. Pancione, C. Votino, P. Quaglino, C. Tomasini, M. Santucci, N. Pimpinelli, F. Cusano, L. Sabatino, V. Colantuoni
Journal: British Journal of Dermatology (2013)

Background Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma; in its classical presentation it evolves slowly, but it can have an aggressive course in a subset of patients. Objectives To investigate the impact of epigenetic mechanisms on the progression of early stage MF. Methods We analysed DNA methylation at 12 different loci and long interspersed nucleotide elements-1 (LINE-1), as a surrogate marker of global methylation, on tissue samples from 41 patients with stage I MF followed up for at least 12 years or until disease progression. The methylation profiles were also analysed in two T-cell lymphoma cell lines and correlated with gene expression. Results The selected loci were methylated in a tumour-specific manner; concomitant hypermethylation of at least four loci was more frequent in cases progressing within 1–3 and 3–6 years than in late-progressive or non-progressive cases. LINE-1 methylation was significantly lower in rapidly progressive MF at 3 years (61%, P < 0·001) than in those at 12 years (67%). PPARG, SOCS1 and NEUROG1 methylation showed remarkable differences among the prognostic groups, but only PPARG was a significant predictor of disease progression within 6 years, after adjustment for patients' age or gender. Strikingly, a methylation profile similar to progressive cases was found in highly proliferative Sézary-derived HUT78 cells but not in MF-derived HUT102 cells. Exposure to a DNA demethylating agent restored sensitivity to apoptosis and cell cycle arrest. Conclusions Epigenetic silencing of specific biomarkers can predict the risk of disease progression in early-stage MF, providing insights into its pathogenesis, prognosis and therapy.
Survival Analysis of Patients Undergoing Dialysis
Authors: Philip J. Held
Journal: JAMA (1987)

We analyzed the five-year survival of 4661 patients with end-stage renal disease whose first dialysis occurred in 1977. The analysis incorporated characteristics of patients and dialysis institutions. Results showed that mortality was positively correlated with patient age, initial conditions leading to renal failure, being male and white, open staffing, and the number of staff physicians. In addition, lower death rates were observed for patients treated in larger dialysis units and units that had been long-term reusers of dialyzers. Patients treated in for-profit and not-for-profit units appeared to have the same mortality, although patients treated in freestanding units had lower mortality. The direction of causation was not always clear in these results. (<i>JAMA</i>1987;257:645-650)
Optical Immunoassay Test for Group A β-Hemolytic Streptococcal Pharyngitis
Authors: Michael A. Gerber, Robert R. Tanz, William Kabat, Elizabeth Dennis, Gillian L. Bell, Edward L. Kaplan, Stanford T. Shulman
Journal: JAMA (1997)

To compare the accuracy of an optical immunoassay (OIA) for the rapid diagnosis of group A streptococcal pharyngitis with blood agar plate (BAP) culture.Blinded comparison with criterion standard.A total of 6 private pediatricians' offices, 3 in Connecticut and 3 in Chicago, III.A total of 2113 consecutive patients with acute pharyngitis, 983 in Connecticut and 1130 in Chicago.The sensitivities and specificities of OIA and BAP culture (both performed and interpreted in the office) were determined using a research laboratory's interpretation of a combination of BAP culture and Todd-Hewitt broth (THB) culture of transport tube pledget as criterion standard.Among patients in Connecticut, the sensitivities of the OIA and BAP culture were 94% and 89%, respectively (P=.004), while the specificities were 96% and 99%, respectively (P=.001). Among patients in Chicago, the sensitivities of the OIA and BAP culture were 79% and 72%, respectively (P<.001), while the specificities were 89% and 99%, respectively (P<.001). In each of the 6 pediatricians' offices, the OIA was more sensitive than the BAP culture. Combining the data from Connecticut and Chicago, the overall sensitivities of the OIA and BAP culture were 84% and 78%, respectively (P<.001), while the specificities were 93% and 99%, respectively (P<.001).The results of this comprehensive office-based investigation suggest that with adequately trained personnel, negative OIA test results may not always need to be routinely confirmed with BAP cultures.
Dystrophic epidermolysis bullosa presenting with congenital localized absence of skin: report of four cases
Authors: FENELLA T. WOJNAROWSKA, R.A.J. EADY, R.S. WELLS
Journal: British Journal of Dermatology (1983)

Four cases of epidermolysis bullosa presenting with congenital absence of skin are described. These cases were shown to be dystrophic epidermolysis bullosa on clinical and ultrastructural findings. They demonstrate that congenital localized absence of skin (Bart's syndrome) may be the presenting sign of epidermolysis bullosa.
Revisiting “Freely Given Informed Consent” in Relation to the Developing World: Role of an Ombudsman
Authors: Athula Sumathipala, Sisira Siribaddana
Journal: The American Journal of Bioethics (2004)

Establishment of Sri Lankan Twin Registry demanded development of ethical guidelines, as an effective ethical framework was not available in Sri Lanka.Objectives were to find out whether the ombudsman concept exists in current informed consent practices and to investigate opinion about ombudsmen. We searched Pub Med, conducted a postal survey, and monitored Internet discussion.The responses were categorized into current practices and existing models in informed consent process, reservations expressed about current practices, arguments supporting the concept, concerns and issues, alternatives, and how to implement the proposal. The concept of a third person is not entirely novel. How to find a truly independent person, the financial implication, confidentiality, obligations, and liabilities of ombudsmen, also emerged.The concept of an ombudsman is conceptually and ethically sound and acceptable but the challenges posed by this very same solution to creating a better process of informed consent will have to be faced.
Spring-loaded dissecting clamp.
Authors: L Tinckler
Journal: BMJ (1969)

We publish below a selection of questions and answers of general interest.Sensitivity to Vitamin Bu Q.-Is hydroxocobalamin more likely than cyanocobalamin to cause hypersensitivity in a patient or vice versa ?If a patient is sensitive to one can he tolerate the other?A.-Sensitivity reactions were a common complication of parenteral liver extracts but are extremely rare with vitamin B12.The reactions may be severe, with peripheral circulatory collapse, shivering, generalized itching,' and even death.'Less severe