tbuckley/cabot-search huggingface dataset:
Arterial pressure-based cardiac output monitoring: a multicenter validation of the third-generation software in septic patients
Authors: Daniel De Backer, Gernot Marx, Andrew Tan, Christopher Junker, Marc Van Nuffelen, Lars Hüter, Willy Ching, Frédéric Michard, Jean-Louis Vincent
Journal: Intensive Care Medicine (2010)

Second-generation FloTrac software has been shown to reliably measure cardiac output (CO) in cardiac surgical patients. However, concerns have been raised regarding its accuracy in vasoplegic states. The aim of the present multicenter study was to investigate the accuracy of the third-generation software in patients with sepsis, particularly when total systemic vascular resistance (TSVR) is low.Fifty-eight septic patients were included in this prospective observational study in four university-affiliated ICUs. Reference CO was measured by bolus pulmonary thermodilution (iCO) using 3-5 cold saline boluses. Simultaneously, CO was computed from the arterial pressure curve recorded on a computer using the second-generation (CO(G2)) and third-generation (CO(G3)) FloTrac software. CO was also measured by semi-continuous pulmonary thermodilution (CCO).A total of 401 simultaneous measurements of iCO, CO(G2), CO(G3), and CCO were recorded. The mean (95%CI) biases between CO(G2) and iCO, CO(G3) and iCO, and CCO and iCO were -10 (-15 to -5)% [-0.8 (-1.1 to -0.4) L/min], 0 (-4 to 4)% [0 (-0.3 to 0.3) L/min], and 9 (6-13)% [0.7 (0.5-1.0) L/min], respectively. The percentage errors were 29 (20-37)% for CO(G2), 30 (24-37)% for CO(G3), and 28 (22-34)% for CCO. The difference between iCO and CO(G2) was significantly correlated with TSVR (r(2) = 0.37, p < 0.0001). A very weak (r(2) = 0.05) relationship was also observed for the difference between iCO and CO(G3).In patients with sepsis, the third-generation FloTrac software is more accurate, as precise, and less influenced by TSVR than the second-generation software.
Value of Flow Diagrams in Reports of Randomized Controlled Trials
Authors: Matthias Egger
Journal: JAMA (2001)

ContextDiagrams of the flow of participants through a clinical trial are recommended in the Consolidated Standards for Reporting of Trials (CONSORT) statement, but it is unclear whether such flow diagrams improve the quality of trial reports.ObjectiveTo examine the information contributed by flow diagrams and the completeness of reporting overall in reports of randomized controlled trials (RCTs) published in 5 general and internal medicine journals.Design and SettingAnalysis of 270 reports of RCTs published in 1998 in the Annals of Internal Medicine (AIM; n = 19), BMJ (n = 42), JAMA (n = 45), The Lancet (n = 81), and The New England Journal of Medicine (NEJM; n = 83).Main Outcome MeasuresProportion of reports that included a flow diagram, information provided in flow diagrams, and completeness of reporting about flow of participants overall in flow diagrams or text.ResultsA total of 139 reports (51.5%) of RCTs included a flow diagram, but this varied widely among journals (AIM, 21.0%; BMJ, 38.1%; JAMA, 80.0%; The Lancet, 93.8%; and NEJM, 8.4%). Diagrams generally provided useful information, but only 73 (52.5%) included the number of participants who received allocated interventions and only 32 (23.0%) included the number of participants included in the analysis. In logistic regression analysis, overall completeness of reporting about flow of study participants was associated with publication of a flow diagram.ConclusionsFlow diagrams are associated with improved quality of reporting of randomized controlled trials. However, the structure of current flow diagrams is less than ideal. We propose a revised flow diagram that includes all important counts through the stages of parallel group trials.
Transcription Factor NF-Y Induces Apoptosis in Cells Expressing Wild-Type p53 through E2F1 Upregulation and p53 Activation
Authors: Aymone Gurtner, Paola Fuschi, Fabio Martelli, Isabella Manni, Simona Artuso, Giacoma Simonte, Valeria Ambrosino, Annalisa Antonini, Valentina Folgiero, Rita Falcioni, Ada Sacchi, Giulia Piaggio
Journal: Cancer Research (2010)

The CCAAT-binding transcription factor NF-Y plays a central role in regulating cellular proliferation by controlling the expression of genes required for cell-cycle progression such as cyclin A, cyclin B1, cyclin B2, cdc25A, cdc25C, and cdk1. Here we show that unrestricted NF-Y activity leads to apoptosis in an E2F1- and wild-type p53 (wtp53)-dependent manner. Unrestricted NF-Y activity induced an increase in E2F1 mRNA and protein levels. Furthermore, NF-Y directly bound the E2F1 promoter and this correlated with the appearance of open chromatin marks. The ability of NF-Y to induce apoptosis was impaired in cells lacking E2F1 and wtp53. Moreover, NF-Y overexpression elicited phosphorylation of wt p53Ser18 in an E2F1-dependent manner. Our findings establish that NF-Y acts upstream of E2F1 in p53-mediated apoptosis.
Long Noncoding RNA, Polycomb, and the Ghosts Haunting <i>INK4b-ARF-INK4a</i> Expression
Authors: Francesca Aguilo, Ming-Ming Zhou, Martin J. Walsh
Journal: Cancer Research (2011)

Polycomb group proteins (PcG) function as transcriptional repressors of gene expression. The important role of PcG in mediating repression of the INK4b-ARF-INK4a locus, by directly binding to the long noncoding RNA (lncRNA) transcript antisense noncoding RNA in the INK4 locus (ANRIL), was recently shown. INK4b-ARF-INK4a encodes 3 tumor-suppressor proteins, p15(INK4b), p14(ARF), and p16(INK4a), and its transcription is a key requirement for replicative or oncogene-induced senescence and constitutes an important barrier for tumor growth. ANRIL gene is transcribed in the antisense orientation of the INK4b-ARF-INK4a gene cluster, and different single-nucleotide polymorphisms are associated with increased susceptibility to several diseases. Although lncRNA-mediated regulation of INK4b-ARF-INK4a gene is not restricted to ANRIL, both polycomb repressive complex-1 (PRC1) and -2 (PRC2) interact with ANRIL to form heterochromatin surrounding the INK4b-ARF-INK4a locus, leading to its repression. This mechanism would provide an increased advantage for bypassing senescence, sustaining the requirements for the proliferation of stem and/or progenitor cell populations or inappropriately leading to oncogenesis through the aberrant saturation of the INK4b-ARF-INK4a locus by PcG complexes. In this review, we summarize recent findings on the underlying epigenetic mechanisms that link PcG function with ANRIL, which impose gene silencing to control cellular homeostasis as well as cancer development.
CONTROL OF TUBERCULOSIS FROM A STRICTLY MEDICO-LEGAL STANDPOINT.
Authors: CHARLES WILSON INGRAHAM
Journal: JAMA (1896)

How far can legal measures, whether municipal, State or National, be carried to control tuberculosis? This is now one of the leading questions before the medical profession in this and in other civilized countries. That decisive legal interference will be necessary before tuberculosis can be brought under control, there is no doubt. In the minds of all, physicians, legislators and tuberculous invalids themselves, who have given the question more than ordinary thought, the necessity of legal control is realized. It is estimated by competent authorities that 450 persons die every 24 hours in the United States from tuberculosis. A disease which is responsible for a human fatality so large and so continuous should be classed with dangerous contagious affections, as one requiring the strictest hygienic management designed to minimize the infection arising from each individual case. No one expects to obtain a complete destruction of tubercular infection as it is
Dietary Factors in Oral and Pharyngeal Cancer
Authors: J. K. McLaughlin, G. Gridley, G. Block, D. M. Winn, S. Preston-Martin, J. B. Schoenberg, R. S. Greenberg, A. Stemhagen, D. F. Austin, A. G. Ershow, W. J. Blot, J. F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Dietary Factors in Oral and Pharyngeal Cancer Get access Joseph K. McLaughlin, Joseph K. McLaughlin 2Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteExecutive Plaza North, Room 415, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gloria Gridley, Gloria Gridley 2Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteExecutive Plaza North, Room 415, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gladys Block, Gladys Block 3Division of Cancer Prevention and Control, National Cancer Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar Deborah M. Winn, Deborah M. Winn 4National Center for Health StatisticsHyattsville, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar Susan Preston-Martin, Susan Preston-Martin 5University of Southern California School of MedicineLos Angeles, CA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Janet B. Schoenberg, Janet B. Schoenberg 6New Jersey Department of HealthTrenton, NJ. Search for other works by this author on: Oxford Academic PubMed Google Scholar Raymond S. Greenberg, Raymond S. Greenberg 7Emory UniversityAtlanta, GA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Annette Stemhagen, Annette Stemhagen 6New Jersey Department of HealthTrenton, NJ. Search for other works by this author on: Oxford Academic PubMed Google Scholar Donald F. Austin, Donald F. Austin 8California State Department of Health ServicesEmeryville, CA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Abby G. Ershow, Abby G. Ershow 2Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteExecutive Plaza North, Room 415, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more William J. Blot, William J. Blot 2Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteExecutive Plaza North, Room 415, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph F. Fraumeni, Jr. Joseph F. Fraumeni, Jr. 2Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteExecutive Plaza North, Room 415, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 15, 5 October 1988, Pages 1237–1243, https://doi.org/10.1093/jnci/80.15.1237 Published: 05 October 1988 Article history Received: 18 May 1988 Revision received: 18 July 1988 Accepted: 19 July 1988 Published: 05 October 1988
Regulation of the cytoplasmic accumulation of 5-methyltetrahydrofolate in MA104 cells is independent of folate receptor regulation.
Authors: B A Kamen, C A Johnson, M T Wang, R G Anderson
Journal: Journal of Clinical Investigation (1989)

To better understand how the folate receptor (also known as the membrane folate binder) is able to deliver 5-methyltetrahydrofolic acid to the cytoplasm of folate-depleted MA104 cells, we have examined the kinetics of movement from the cell surface into the cytoplasm. Bound 5-methyltetrahydrofolic acid was transferred into an acid-resistant membrane compartment at the rate of 0.9-1.0 pmol/10(6) cells per h. This folate appeared in the cytoplasm at the same rate. Furthermore, cytoplasmic 5-methyltetrahydrofolic acid became polyglutamated at the rate of 0.6-0.7 pmol/10(6) cells per h. As soon as intracellular 5-methyltetrahydrofolate reached 5-7 pmol/10(6) cells, however, cytoplasmic accumulation was markedly inhibited even though the folate receptor remained functional. Therefore, the acute regulation of 5-methyltetrahydrofolic acid accumulation appears to be achieved by controlling the movement of the vitamin from the receptor into the cytoplasm of the cell.
Response to Influenza Vaccine by Renal Transplant Patients
Authors: R. N. P. Carroll, S. D. Marsh, E. P. N. O'Donoghue, D. C. Breeze, R. Shackman
Journal: BMJ (1974)

Twenty-five renal transplant patients and 17 controls were vaccinated with influenza vaccine. Antibody titres were estimated before and one, three, and 12 months after vaccination. On the basis of antibody titre measurements the transplant group showed a similar qualitative and quantitative response to that of the controls. No rejection episodes occurred among the transplant patients as a result of vaccination and nobody in the trial developed influenza. We conclude that it is safe to vaccinate transplant patients with an inactivated influenza vaccine and that protection (haemagglutination-inhibiting antibody) can be induced.
Myocardial Infarction and Cigarette Smoking in Women Younger Than 50 Years of Age
Authors: Lynn Rosenberg
Journal: JAMA (1985)

The modifying influence of individual risk factors on the relation between myocardial infarction (MI) and cigarette smoking was evaluated in a case-control study of women younger than 50 years of age. Data from 555 women who survived first MIs were compared with those of 1,864 hospital controls of similar ages. The risk of MI increased with the number of cigarettes smoked, both in the presence and absence of factors that predispose to an infarction. In particular, the association was apparent at all ages, at all levels of total serum cholesterol and high-density lipoprotein cholesterol, and in the presence and absence of oral contraceptive use, hypertension, diabetes mellitus, blood group A, tendency to type A behavior, and family history of MI. The relative increase in risk was generally greater the lower the underlying predisposition to MI. There was clear evidence, however, that recent oral contraceptive use substantially augmented the increased risk for smokers, and hypercholesterolemia may have had the same effect.
VII. Impact of Training Programs on the Young Physician's Attitudes and Experiences
Authors: Patricia Kendall
Journal: JAMA (1961)

For nearly 9 years, the Bureau of Applied Social Research has been conducting studies in the sociology of medical education. At the beginning, this research was focused on the students in 3 medical schools. We traced the changes in attitudes and orientations which these students underwent as their training progressed, and tried to relate such changes to typical experiences in medical school.<sup>1</sup> The initial decision to concentrate on the 4 years of medical school was dictated by the desire to keep our study within manageable bounds. But we were well aware from the very outset that medical education does not end abruptly with graduation from medical school. After a considerable body of information about medical students had been assembled, we then felt free to turn our attention to the period of graduate medical education. This was done primarily in order to obtain a more complete picture of the process
Massive Infarction of Spinal Cord and Vertebral Bodies as a Complication of Dissecting Aneurysm of the Aorta
Authors: C. STRATTON HILL, JESUS M. VASQUEZ
Journal: Circulation (1962)

A case of spinal cord and vertebral body necrosis as a complication of dissecting aneurysm of the aorta has been presented. Previous report of vertebral body necrosis complicating this entity could not be found. The incidence of intercostal and lumbar artery involvement in this condition is not known; a disparity appears between the incidence of involvement and necrosis of structures supplied by them. Factors believed to be important in assessing the significance of involvement of these vessels are mentioned. All cases of dissecting aneurysm in which there are neurologic signs should have thorough study of the spinal cord and vertebral bodies if they come to autopsy.
868 EFFICACY OF EZETIMIBE FOR THE TREATMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE: A RANDOMIZED, CONTROLLED TRIAL
Authors: Y. Takeshita, T. Takamura, Y. Kita, H. Misu, K. Arai, T. Yamashita, E. Mizukoshi, S. Kaneko
Journal: Journal of Hepatology (2011)
Phospholipase A2 activating protein and idiopathic inflammatory bowel disease.
Authors: J W Peterson, W D Dickey, S S Saini, W Gourley, G R Klimpel, A K Chopra
Journal: Gut (1996)

BACKGROUND: Crohn9s disease and ulcerative colitis are idiopathic inflammatory bowel diseases (IBD) involving synthesis of eicosanoids from arachidonic acid (AA), which is released from membrane phospholipids by phospholipase A2 (PLA2). A potentially important regulator of the production of these mediators is a protein activator of PLA2, referred to as PLA2 activating protein (PLAP). AIMS: The purpose of this investigation was to discover if PLAP values might be increased in the inflamed intestinal tissue of patients with IBD and in intestinal tissue of mice with colitis. PATIENTS: Biopsy specimens were taken from patients with ulcerative colitis and Crohn9s disease undergoing diagnostic colonoscopy, and normal colonic mucosa was obtained from patients without IBD after surgical resection. METHODS: Immunocytochemistry with affinity purified antibodies to PLAP synthetic peptides was used to locate PLAP antigen in sections of intestinal biopsy specimens from IBD patients compared with that of normal intestinal tissue. Northern blot analysis with a murine [32P] labelled plap cDNA probe was performed on RNA extracted from the colons of mice fed dextran sulphate sodium (DSS) and cultured HT-29 cells exposed to lipopolysaccharide (LPS). RESULTS: PLAP antigen was localised predominantly within monocytes and granulocytes in intestinal tissue sections from IBD patients, and additional deposition of extracellular PLAP antigen was associated with blood vessels and oedema fluid in the inflamed tissues. In contrast, tissue sections from normal human intestine were devoid of PLAP reactive antigen, except for some weak cytoplasmic reaction of luminal intestinal epithelial cells. Similarly, colonic tissue from DSS treated mice contained an increased amount of PLAP antigen compared with controls. The stroma of the lamina propria of the colonic mucosa from the DSS treated mice reacted intensely with antibodies to PLAP synthetic peptides, while no reaction was observed with control mouse colons. These data were supported by northern analysis which showed that PLAP mRNA was increased in the colons of DSS treated mice and cultured HT-29 cells exposed to LPS. CONCLUSIONS: As PLAP values were increased in the intestinal mucosa of IBD patients and mice with colitis, as well as in LPS treated cultured HT-29 cells, a role was postulated for PLAP in increasing PLA2 activity, which leads to the increased synthesis of eicosanoids in intestinal tissues of patients with these inflammatory diseases.
Natriuretic Peptide Receptor A as a Novel Anticancer Target
Authors: Xiaoyuan Kong, Xiaoqin Wang, Weidong Xu, Sumita Behera, Gary Hellermann, Arun Kumar, Richard F. Lockey, Subhra Mohapatra, Shyam S. Mohapatra
Journal: Cancer Research (2008)

Abstract The receptor for atrial natriuretic peptide (ANP), natriuretic peptide receptor A (NPRA), is expressed in cancer cells, and natriuretic peptides have been implicated in cancers. However, the direct role of NPRA signaling in tumorigenesis remains elusive. Here, we report that NPRA expression and signaling is important for tumor growth. NPRA-deficient mice showed significantly reduced antigen-induced pulmonary inflammation. NPRA deficiency also substantially protected C57BL/6 mice from lung, skin, and ovarian cancers. Furthermore, a nanoparticle-formulated interfering RNA for NPRA attenuated B16 melanoma tumors in mice. Ectopic expression of a plasmid encoding NP73-102, the NH2-terminal peptide of the ANP prohormone, which down-regulates NPRA expression, also suppressed lung metastasis of A549 cells in nude mice and tumorigenesis of Line 1 cells in immunocompetent BALB/c mice. The antitumor activity of NP73-102 was in part attributed to apoptosis of tumor cells. Western blot and immunohistochemistry staining indicated that the transcription factor, nuclear factor-κB, was inactivated, whereas the level of tumor suppressor retinoblastoma protein was up-regulated in the lungs of NPRA-deficient mice. Furthermore, expression of vascular endothelial growth factor was down-regulated in the lungs of NPRA-deficient mice compared with that in wild-type mice. These results suggest that NPRA is involved in tumor angiogenesis and represents a new target for cancer therapy. [Cancer Res 2008;68(1):249–56]
Tetrahydrobiopterin Determines Vascular Remodeling Through Enhanced Endothelial Cell Survival and Regeneration
Authors: Ziad A. Ali, Ruth Rinze, Gillian Douglas, Yanhua Hu, Qingzhong Xiao, Wei Qi, Eileen McNeill, Christina Bursill, Isaac George, David R. Greaves, Qingbo Xu, Keith M. Channon
Journal: Circulation (2013)

Background— Endothelial cell (EC) survival and regeneration are important determinants of the response to vascular injury that leads to neointimal hyperplasia and accelerated atherosclerosis. Nitric oxide (NO) is a key regulator of EC and endothelial progenitor cell function, but the pathophysiological mechanisms that regulate endothelial NO synthase in endothelial regeneration remain unclear. Methods and Results— Endothelium-targeted overexpression of GTP cyclohydrolase (GCH) I increased levels of the endothelial NO synthase cofactor, tetrahydrobiopterin, in an EC-specific manner and reduced neointimal hyperplasia in experimental vein grafts in GCH/apolipoprotein E-knockout mice. These effects were mediated through enhanced donor-derived survival and recipient-derived repopulation of GCH transgenic ECs, revealed by tracking studies in Tie2-LacZ/GCH-Tg/apolipoprotein E-knockout recipient mice or donor grafts, respectively. Endothelial GCH overexpression increased endothelial NO synthase coupling and enhanced the proliferative capacity of ECs and circulating endothelial progenitor cell numbers after vascular injury. Conclusions— These observations indicate that endothelial tetrahydrobiopterin availability modulates neointimal hyperplasia after vascular injury via accelerated EC repopulation and growth. Targeting tetrahydrobiopterin-dependent endothelial NO synthase regulation in the endothelium is a rational therapeutic target to enhance endothelial regeneration and reduce neointimal hyperplasia in vascular injury states.
Prescription for Leadership: Training for the Medical Elite
Authors: E. James Potchen
Journal: JAMA (1971)

The medical elite, defined as the leaders of medical thought, obtain their position largely through the addition of research and teaching responsibilities to patient care. Professor Miller, a sociologist, spent 18 months with the interns at Boston City Hospital to "clarify the processes by which new members of the medical profession are recruited for training, what they must do to satisfactorily complete their training, and the implication of that training for their subsequent medical careers." He appraises the effects of medical students, paramedical personnel, teaching methods and patient population on the successful attainment of power, prestige, and reputation in the medical community. The author has probed into the complexities of the internship year and how they influence a career. This internship is not so much "an educational experience, approximating the work of full-fledged physicians, as it is a particular kind of job at the Boston City Hospital." By comparing the