tbuckley/cabot-search huggingface dataset:
Intake of Flavonoids and Lung Cancer
Authors: Loïc Le Marchand, Suzanne P. Murphy, Jean H. Hankin, Lynne R. Wilkens, Laurence N. Kolonel
Journal: JNCI Journal of the National Cancer Institute (2000)

Background:To investigate the possible relationship between intake of flavonoids-powerful dietary antioxidants that may also inhibit P450 enzymesand lung cancer risk, we conducted a population-based, case-control study in Hawaii.Methods: An in-person interview assessed smoking history and usual intake of 242 food items for 582 patients with incident lung cancer and 582 age-, sex-, and ethnicity-matched control subjects.Subjects who donated a blood sample were genotyped for the P450 enzyme variant allele CYP1A1*2 by use of a polymerase chain reactionbased method.Logistic regression analysis was used to compute odds ratios (ORs) and 95% confidence intervals (CIs).All P values are two-sided.Results: After adjusting for smoking and intakes of saturated fat and ␤-carotene, we found statistically significant inverse associations between lung cancer risk and the main food sources of the flavonoids quercetin (onions and apples) and naringin (white grapefruit).The lung cancer OR for the highest compared with the lowest quartile of intake was 0.5 (95% CI = 0.3-0.9)for onions (P for trend = .001)and 0.6 (95% CI = 0.4-1.0)for apples (P for trend = .03).The OR for the highest compared with the lowest tertile of intake for white grapefruit was 0.5 (95% CI = 0.2-0.9)(P for trend = .02).No association was found for important food sources of other flavonoids.Using published food-composition data for flavonoids, we found an inverse association between intake of quercetin and risk of lung cancer (P for trend = .07)that appears consistent with associations for its food sources.The effect of onions was particularly strong against squamous cell carcinoma (a cell type specifically associated with CYP1A1*2 in our study) and was modified by the CYP1A1 genotype, suggesting that CYP1A1 may play a role in this association.Conclusion: If replicated, particularly in prospective studies, these findings would suggest that foods rich in certain flavonoids may protect against certain forms of lung cancer and that decreased bioactivation of carcinogens by inhibition of CYP1A1 should be explored as underlying mechanisms.
Computational Identification of Key Biological Modules and Transcription Factors in Acute Lung Injury
Authors: Sina A. Gharib, W. Conrad Liles, Gustavo Matute-Bello, Robb W. Glenny, Thomas R. Martin, William A. Altemeier
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Mechanical ventilation augments the acute lung injury (ALI) caused by bacterial products. The molecular pathogenesis of this synergistic interaction remains incompletely understood.Objective: We sought to develop a computational framework to systematically identify gene regulatory networks activated in ALI.Methods: We have developed a mouse model in which the combination of mechanical ventilation and intratracheal LPS produces significantly more injury to the lung than either insult alone. We used global gene ontology analysis to determine overrepresented biological modules and computational transcription factor analysis to identify putative regulatory factors involved in this model of ALI.Results: By integrating expression profiling with gene ontology and promoter analysis, we constructed a large-scale regulatory modular map of the important processes activated in ALI. This map assigned differentially expressed genes to highly overrepresented biological modules, including "defense response," "immune response," and "oxidoreductase activity." These modules were then systematically incorporated into a gene regulatory network that consisted of putative transcription factors, such as IFN-stimulated response element, IRF7, and Sp1, that may regulate critical processes involved in the pathogenesis of ALI.Conclusions: We present a novel, unbiased, and powerful computational approach to investigate the synergistic effects of mechanical ventilation and LPS in promoting ALI. Our methodology is applicable to any expression profiling experiment involving eukaryotic organisms.
Abstract A5: Functional role of SOX2 in hypoxia-mediated metastasis-associated functions in prostate cancer
Authors: Yao Dai, Kyung-Mi Bae, Johannes Vieweg, Dietmar W. Siemann
Journal: Cancer Research (2013)

Abstract Purpose: SOX2 is a typical embryonic stem cell marker that is involved in not only tumorigenesis but also metastasis in several human malignancies including prostate cancer. Hypoxia has been demonstrated as a common feature of prostate cancer that is associated with disease progression and poor prognosis. Although SOX2 has been shown to be activated by oxygen depletion in other cancer types, its functional role under hypoxic microenvironment in prostate cancer setting and its association with hypoxia inducible factors (HIFs) have not been reported. In the present study, we evaluate the role of SOX2 in hypoxia-mediated cellular behaviors associated with metastasis, including invasion and sphere formation, in prostate cancer cells. Experimental Design: A tissue microarray containing samples from 80 prostate cancer patients was employed to examine the expression of HIF-1α and its correlation with SOX2 by immunohistochemical analysis. Expression of stem cell markers and HIFs was detected by Western blot. The role of SOX2 and HIF-1/2α in the regulation of cell invasion and sphere formation with various hypoxic exposures was investigated by short hairpin RNA (shRNA) - mediated knockdown in PC-3, DU145 and LNCaP cells. Results: HIF-1α expression was significantly elevated in prostate cancer compared to non-malignant prostate tissues, and in tumors HIF-1α was strongly correlated with SOX2. In all three prostate cancer cells, while HIF-1α and HIF-2α were mainly induced under short term (acute) and long term (chronic) hypoxic conditions, respectively, SOX2 was the only one among five stem cell markers that was stimulated by both hypoxic exposures. Genetic depletion of SOX2 attenuated capacities of tumor cells to invade under acute hypoxia and form spheroids under chronic hypoxia. In addition, knockdown of HIF-1α but not HIF-2α decreased acute hypoxia-mediated cell invasion, whereas only HIF-2α gene silencing resulted in reduced sphere formation capacity mediated by long term oxygen deprivation. Conclusions: SOX2 is suggested to be correlated with hypoxia in prostate cancer. SOX2 plays an important role in acute hypoxia-induced invasiveness and chronic hypoxia-induced stemness that is associated with HIF-1α and HIF-2α activation, respectively. These results indicate that SOX2 may be a key mediator for hypoxia-induced metastasis-associated functions hence may serve as a potential target for therapeutic interventions for advanced prostate cancer. Citation Format: Yao Dai, Kyung-Mi Bae, Johannes Vieweg, Dietmar W. Siemann. Functional role of SOX2 in hypoxia-mediated metastasis-associated functions in prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A5.
Activation of Phosphatidylinositol 3-Kinase by Membrane Localization of p110α Predisposes Mammary Glands to Neoplastic Transformation
Authors: Oliver Renner, Carmen Blanco-Aparicio, Maja Grassow, Marta Cañamero, Juan F.M. Leal, Amancio Carnero
Journal: Cancer Research (2008)

Abstract Phosphatidylinositol 3-kinases (PI3K) constitute important regulators of various signaling pathways with relevance in cancer. Enhanced activation of p110α, the catalytic subunit of PI3K, was found in a high proportion of many human tumor types. We generated a mouse model in which PI3K is activated by forced recruitment of p110α to the membrane. Different transgenic lines expressing myristoylated p110α protein under the control of the epithelial-specific mouse mammary tumor virus promoter were selected according to different levels of PI3K activity and characterized. Delayed mammary gland involution and morphologic changes of the mammary ducts could be detected in young transgenic female mice. These changes were more pronounced in old animals, especially in mutiparous females, in which we observed increased ductal branching, alveolar hyperplasia, and intraductal neoplasia. We also observed a small percentage of mammary tumors. Crosses of myrp110α transgenic mice with heterozygous p53(+/−) knockout mice resulted in neither enhanced tumorigenesis nor in a stronger mammary gland phenotype. However, the CDK4 activating mutation (R24C) lead to increased tumorigenesis in transgenic myrp110α mice, emphasizing the postulated perturbation of the interaction of the CDK4/Rb/E2F cascade and the PI3K signaling in many human cancers. Interestingly, in tumors of myrp110α transgenic mice, we observed an increased phosphorylation of the estrogen receptor-α, a typical feature of human breast cancer. The model presented here will help to discover additional factors which influence the progression of preneoplastic lesions to tumors in the mammary gland and to explore antitumor therapies based on PI3K or estrogen receptor-α pathway inhibition. [Cancer Res 2008;68(23):9643–53]
Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study
Authors: R Landewé, J Braun, A Deodhar, M Dougados, W P Maksymowych, P J Mease, J D Reveille, M Rudwaleit, D van der Heijde, C Stach, B Hoepken, A Fichtner, G Coteur, M de Longueville, J Sieper
Journal: Annals of the Rheumatic Diseases (2013)

To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-axSpA (NCT01087762), an ongoing Phase 3 trial in patients with axial spondyloarthritis (axSpA), including patients with ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA).Patients with active axSpA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (Q4W). In total 325 patients were randomised. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society 20) response at week 12. Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Metrology Index (BASMI) linear.Baseline disease activity was similar between AS and nr-axSpA. At week 12, ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo (57.7 and 63.6 vs 38.3, p≤0.004). At week 24, combined CZP arms showed significant (p<0.001) differences in change from baseline versus placebo in BASFI (-2.28 vs -0.40), BASDAI (-3.05 vs -1.05), and BASMI (-0.52 vs -0.07). Improvements were observed as early as week 1. Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA subpopulations. Adverse events were reported in 70.4% vs 62.6%, and serious adverse events in 4.7% vs 4.7% of All CZP versus placebo groups. No deaths or malignancies were reported.CZP rapidly reduced the signs and symptoms of axSpA, with no new safety signals observed compared to the safety profile of CZP in RA. Similar improvements were observed across CZP dosing regimens, and in AS and nr-axSpA patients.
Hepatitis B immune memory in children primed with hexavalent vaccines and given monovalent booster vaccines: an open-label, randomised, controlled, multicentre study
Authors: Alessandro Remo Zanetti, Luisa Romanò, Cristina Giambi, Anna Pavan, Vito Carnelli, Guglielmino Baitelli, Giancarlo Malchiodi, Edgardo Valerio, Antonella Barale, Maria Anna Marchisio, Domenico Montù, Alberto Eugenio Tozzi, Fortunato D'Ancona
Journal: The Lancet Infectious Diseases (2010)
Mastering Medicine: Professional Socialization in Medical School
Authors: Hugh H. Hussey
Journal: JAMA (1978)

Dr Coombs's purpose was to ascertain how medical students adapt (ie, become "socialized") in the milieu of a medical school. He therefore conducted a long-term study of one class attending a school in the eastern United States. The study included preadmission questionnaires; psychological testing during orientation week and again during senior year; individual, long taped interviews at the end of each school year; and a mailed questionnaire about specialty choice. In addition, the author interviewed trainees in a West Coast school and conducted a week-long conference ("Psychosocial Aspects of Medical Training") attended by faculty members who represented 60 North American schools. The relatively small study class cooperated amazingly well throughout the entire endeavor. The results of their participation and of other aspects of the study enabled Dr Coombs to prepare an extraordinarily complete systematic report about what happens to students between the time before they start and the time after
Macrophage-specific expression of human apolipoprotein E reduces atherosclerosis in hypercholesterolemic apolipoprotein E-null mice.
Authors: S Bellosta, R W Mahley, D A Sanan, J Murata, D L Newland, J M Taylor, R E Pitas
Journal: Journal of Clinical Investigation (1995)

apoE deficiency causes hyperlipidemia and premature atherosclerosis. To determine if macrophage-specific expression of apoE would decrease the extent of atherosclerosis, we expressed human apoE in macrophages of apoE-null mice (apoE-/-) and assessed the effect on lipid accumulation in cells of the arterial wall. Macrophage-specific expression of human apoE in normal mice was obtained by use of the visna virus LTR. These animals were bred with apoE-/- mice to produce animals hemizygous for expression of human apoE in macrophages in the absence of murine apoE (apoE-/-,hTgE+/0). Low levels of human apoE mRNA were present in liver and spleen and high levels in lung and peritoneal macrophages. Human apoE was secreted by peritoneal macrophages and was detected in Kupffer cells of the liver. Human apoE in the plasma of apoE-/-,hTgE+/0 mice (n = 30) was inversely correlated (P < 0.005) with the plasma cholesterol concentration. After 15 wk on a normal chow diet, atherosclerosis was assessed in apoE-/-,hTgE+/0 animals and in apoE-/-,hTgE0/0 littermates matched for plasma cholesterol level (approximately 450 mg/dl) and lipoprotein profile. There was significantly less atherosclerosis in both the aortic sinus and in the proximal aorta (P < 0.0001) in the animals expressing the human apoE transgene. In apo-E-/-,hTgE+/0 animals, which had detectable atherosclerotic lesions, human apoE was detected in the secretory apparatus of macrophage-derived foam cells in the arterial wall. The data demonstrate that expression of apoE by macrophages is antiatherogenic even in the presence of high levels of atherogenic lipoproteins. The data suggest that apoE prevents atherosclerosis by promoting cholesterol efflux from cells of the arterial wall.
Photography or Ophthalmoscopy for Detection of Diabetic Retinopathy?
Authors: Hendrik A. van Leiden, Annette C. Moll, Jacqueline M. Dekker, Michael D. Abramoff, Bettine C.P. Polak
Journal: Diabetes Care (2003)

The U.K. National Screening Committee recommended digital fundus photography as the screening method of choice for diabetic retinopathy (DR). However, concerns have been expressed about replacing ophthalmoscopy with slit-lamp biomicroscopy by digital photography. These concerns included the possibility of missing peripheral and stereoscopic visible retinal lesions; increased chance of a technical failure compared with ophthalmoscopy, resulting in more reexaminations; and higher cost (1). New data from our study of 453 patients with diabetes, aged 31–86 years, highlight the need for a careful consideration of the retinal area photographed and the minimal resolution of …
Molecular epidemiology of hepatitis B virus in Iran
Authors: S.R. Mohebbi, S. Amini-Bavil-Olyaee, N. Zali, B. Noorinayer, F. Derakhshan, M. Chiani, M. Rostami Nejad, M.H. Antikchi, F. Sabahi, M.R. Zali
Journal: Clinical Microbiology and Infection (2008)
Abnormal metabolism of secondary bile acids in patients with cirrhosis
Authors: Z. R. Vlahcevic, I. Buhac, C. C. Bell, L. Swell
Journal: Gut (1970)

The composition of bile acids in human bile was determined in bile-rich duodenal fluid on four consecutive days in a group of seven patients with cirrhosis and eight control patients with no liver disease. There was a marked reduction of secondary biliary bile acids in cirrhotic patients. Possible mechanisms for these changes are discussed.
Expression of prostaglandin H2-mediated mechanism of vascular contraction in hypertensive rats. Relation to lipoxygenase and prostacyclin synthase activities.
Authors: L Lin, M Balazy, P J Pagano, A Nasjletti
Journal: Circulation Research (1994)

We tested the hypothesis that a prostanoid-mediated mechanism of vascular contraction is expressed in rats with aortic coarctation-induced hypertension. Rings of descending thoracic aorta taken from normotensive and hypertensive rats were contrasted in terms of constrictor responsiveness to arachidonic acid (AA), AA-induced release of eicosanoids, and ability to convert exogenous prostaglandin (PG) H2 to PGI2. AA (10(-8) to 10(-5) mol/L) increased isometric tension in aortic rings (bathed in Krebs' bicarbonate buffer) of hypertensive but not normotensive rats. AA (10(-5) mol/L) also elicited the release of PGI2, PGE2, thromboxane (TX) A2, and monohydroxyeicosatetraenoic acids (HETEs); this release from the aortic rings of hypertensive rats exceeded the corresponding release from the aortic rings of normotensive rats. However, the rate of conversion of exogenous PGH2 to PGI2 by aortic rings of hypertensive rats was &lt; 50% the rate of conversion by aortic rings of normotensive rats. The constrictor effect of AA in aortic rings of hypertensive rats was abolished by an inhibitor of cyclooxygenase (indomethacin, 10 mumol/L) and a blocker of TXA2-PGH2 receptors (SQ29548, 1 mumol/L) but was not affected by an inhibitor of TXA2 synthesis (CGS13080, 10 mumol/L), suggesting mediation by PGH2. The lipoxygenase inhibitor baicalein (75 mumol/L) also attenuated the constrictor effect of AA in aortic rings of hypertensive rats while decreasing the associated release of HETEs and correcting the impairment in the conversion of PGH2 to PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)
Serial assessment of pulmonary microvascular permeability in a patient developing the adult respiratory distress syndrome
Authors: S Braude, S Baudouin, TW Evans
Journal: European Respiratory Journal (1992)

Serial measurements of lung extravascular accumulation of 113mIndium-transferrin were made in a patient with acute respiratory failure during the development of the adult respiratory distress syndrome (ARDS). Abnormality of this index of pulmonary microvascular permeability antedated radiological change and appeared to predict the onset of frank ARDS.
Association Between American Board of Surgery In-Training Examination Scores and Resident Performance
Authors: Juliet J. Ray, Joshua A. Sznol, Laura F. Teisch, Jonathan P. Meizoso, Casey J. Allen, Nicholas Namias, Louis R. Pizano, Danny Sleeman, Seth A. Spector, Carl I. Schulman
Journal: JAMA Surgery (2015)

The American Board of Surgery In-Training Examination (ABSITE) is designed to measure progress, applied medical knowledge, and clinical management; results may determine promotion and fellowship candidacy for general surgery residents. Evaluations are mandated by the Accreditation Council for Graduate Medical Education but are administered at the discretion of individual institutions and are not standardized. It is unclear whether the ABSITE and evaluations form a reasonable assessment of resident performance.To determine whether favorable evaluations are associated with ABSITE performance.Cross-sectional analysis of preliminary and categorical residents in postgraduate years (PGYs) 1 through 5 training in a single university-based general surgery program from July 1, 2011, through June 30, 2014, who took the ABSITE.Evaluation overall performance and subset evaluation performance in the following categories: patient care, technical skills, problem-based learning, interpersonal and communication skills, professionalism, systems-based practice, and medical knowledge.Passing the ABSITE (≥30th percentile) and ranking in the top 30% of scores at our institution.The study population comprised residents in PGY 1 (n = 44), PGY 2 (n = 31), PGY 3 (n = 26), PGY 4 (n = 25), and PGY 5 (n = 24) during the 4-year study period (N = 150). Evaluations had less variation than the ABSITE percentile (SD = 5.06 vs 28.82, respectively). Neither annual nor subset evaluation scores were significantly associated with passing the ABSITE (n = 102; for annual evaluation, odds ratio = 0.949; 95% CI, 0.884-1.019; P = .15) or receiving a top 30% score (n = 45; for annual evaluation, odds ratio = 1.036; 95% CI, 0.964-1.113; P = .33). There was no difference in mean evaluation score between those who passed vs failed the ABSITE (mean [SD] evaluation score, 91.77 [5.10] vs 93.04 [4.80], respectively; P = .14) or between those who received a top 30% score vs those who did not (mean [SD] evaluation score, 92.78 [4.83] vs 91.92 [5.11], respectively; P = .33). There was no correlation between annual evaluation score and ABSITE percentile (r(2) = 0.014; P = .15), percentage correct unadjusted for PGY level (r(2) = 0.019; P = .09), or percentage correct adjusted for PGY level (r(2) = 0.429; P = .91).Favorable evaluations do not correlate with ABSITE scores, nor do they predict passing. Evaluations do not show much discriminatory ability. It is unclear whether individual resident evaluations and ABSITE scores fully assess competency in residents or allow comparisons to be made across programs. Creation of a uniform evaluation system that encompasses the necessary subjective feedback from faculty with the objective measure of the ABSITE is warranted.
Deep breathing and awake apnoea in a patient who had recurrent hypoxaemia and hypercapnia without sleep apnoea
Authors: K Chin, Y Oku, K Nishimura, M Ohi
Journal: European Respiratory Journal (1998)

A 21 yr old with deep breathing and awake apnoea, who had recurrent hypoxaemia and hypercapnia without sleep apnoea, was presented. Although the organic abnormality responsible for the breathing disturbance was not found, administration of acetazolamide facilitated several breaths between sighs, and the patient's hypoxaemia with hypercapnia improved. Some patients who have abnormalities in the cortical control of breathing that cannot be detected by present methods of examination may experience some improvement in breathing with the administration of chemical stimulants such as acetazolamide.
Post-infarct remodelling: contribution of wound healing and inflammation
Authors: S. Frantz, J. Bauersachs, G. Ertl
Journal: Cardiovascular Research (2008)

In human and experimental myocardial infarction (MI), cessation of blood supply leads to rapid necrosis of cardiac myocytes in the ischaemic heart. Immediately after injury, various intra- and intercellular pathways contribute to healing the myocardial wound in order to achieve tissue integrity and function. MI and the consequent loss of myocardium are the major aetiology for heart failure. Despite aggressive primary therapy, prognosis remains poor in patients with large infarction and severe left ventricular dysfunction. Thus, it would be highly desirable to improve healing of the cardiac wound to maintain structure and function of the heart. Healing in the heart occurs in overlapping phases. Herein, we review the inflammatory phase as a trigger of tissue formation.
Hereditary angioedema caused by the p.Thr309Lys mutation in the F12 gene: A multifactorial disease
Authors: Carmen Gómez-Traseira, Alberto López-Lera, Christian Drouet, Margarita López-Trascasa, Elia Pérez-Fernández, Bertrand Favier, Nieves Prior, Teresa Caballero
Journal: Journal of Allergy and Clinical Immunology (2013)