tbuckley/cabot-search huggingface dataset:
P4-02-09: Estrogen-Related Receptor a Mediates Insulin-Like Growth Factor-I Dependent Migration in Breast Cancer Cells.
Authors: LM Fettig-Anderson, AS Oh, D Yee
Journal: Cancer Research (2011)

Abstract The orphan nuclear estrogen-related receptors (ERR) have homology to steroid hormone receptors. Unlike classical steroid hormone receptors, ERRs do not have known ligands but are transcriptionally activated upon binding to nuclear receptor coregulators such as PGC1α, PGC1β, and PPRC1. ERRs regulate energy metabolism and are accordingly expressed in tissues that require high energy production. ERRs recognize their own ERRE (estrogen-related receptor response element) gene promoters, but can also activate transcription via ERE (estrogen receptor response element) promoters, representing the ability of ERRs to cross participate in ERα regulatory pathways in the absence of estrogen. Of the three family members (α,β,γ), ERRα is the most highly expressed in breast tissue. ERRα expression was found to be increased in ERα negative breast cancers and associated with poor prognoses. ERRα and its coactivators can increase the expression of a critical mediator of breast tumor angiogenesis and metastasis, VEGFA. We have previously shown that VEGFA is regulated by insulin and IGF receptor activation and hypothesized that ERRα may be a mediator of this finding. We therefore explored whether ERRα and its coactivators are necessary for IGF-I/insulin dependent regulation of VEGFA and cell migration. ERRα was expressed in breast cancer cell lines, but no correlation was observed with breast cancer subtypes. Reducing endogenous ERRα levels by shRNA reduced IGF-I dependent migration in MDA-MB-231 cells. These results were confirmed using an ERRα specific inverse agonist (XCT-790), which also inhibited MDA-MB-231 cell migration. Modulating ERRα mRNA levels via shRNA resulted in decreased VEGFA mRNA levels in MCF7L cells and increased VEGFA mRNA levels in MDA-MB-231 cells, while the inverse agonist XCT-790 caused an increase in VEGFA mRNA levels in both cell lines. Reducing ERRa levels did not affect the expression of the IGF1R, InsR, IRS-1, IRS-2, PI-3K-Akt-mTOR dependent signaling pathway. Neither ERRα protein nor mRNA levels were modulated by IGF-I or insulin. We conclude that ERRα is important for mediating IGF-I dependent migration, but have shown that ERRα is not directly regulated by the IGF signaling. We will next explore the role of ERRα's coregulators (PGC1α, PGC1β, and PPRC1) in the regulation of VEGFA by the IGF/insulin pathway given their central role in regulating ERRα's function. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-02-09.
Histopathologic Response Criteria Predict Survival of Patients with Resected Lung Cancer After Neoadjuvant Chemotherapy
Authors: Apar Pataer, Neda Kalhor, Arlene M. Correa, Maria Gabriela Raso, Jeremy J. Erasmus, Edward S. Kim, Carmen Behrens, J. Jack Lee, Jack A. Roth, David J. Stewart, Ara A. Vaporciyan, Ignacio I. Wistuba, Stephen G. Swisher
Journal: Journal of Thoracic Oncology (2012)
Irradiated food: whether we like it or not?
Authors: J. Dawson
Journal: BMJ (1987)

The Royal Society and the Association of British Science Writers continue with their commendable efforts to improve public under? standing of science. But some responses, such as that of the Guardian's consumer affairs correspondent (Scientists open an atomic cafe), to their latest press briefing on food irradiation suggest that they may have something to learn from the recent tactics of the National History Museum when it comes to a nice resolution of scientific discord. In response to Professor Fred Hoyle's claim that their archae opteryx fossil was a fraud (concocted by a Bavarian medical officer of health from dinosaur bones, concrete, and chicken feathers) the museum dusted off their fake and mounted a display setting out in exhaustive detail the arguments and evidence of the Hoyle lobby. The result is the general conviction that the fossil is genuine. The approach of the Royal Society's panel of seven experts (four of whom were members of the Government advisory committee1 that recommended that the ban on food irradiation in Britain should be lifted) might have benefited from a touch of the archaeopteryx treatment?present the evidence and allow the punters to decide. Expert opinion on the limited use of food irradiation has been reassuring,2 but the chairman of the panel, Professor Paul Turner (Department of Clinical Pharmacology, St Bartholomew's Hospital, London) believes that food irradiation has had a bad press, and he and his fellow panelists of food scientists, toxicologists, and microbiologists set about putting the record straight with a vigour that, in the absence of representatives from the other camp, laid them open to the charge of being apologists for this pasteurisation process rather than straightforward educators. Professor D S Robinson (Department of Food Science, University of Leeds) drew attention to the fifteen million cases of food poisoning in Britain each year. Irradiation is one of the means by which the problem could be brought under control, he said. The judiciousAise of irradiation to reduce the pool of salmonellae and other enteric bacteria in poultry and seafood would make a substantial contribution to public health. Other established methods of food preservation are  without their hazards and none of them has been tested to the same extent as irradiation said Dr I F Gaunt (British Industrial Biological Research Association). Data suggest? ing that feeding freshly irradiated wheat to four or five malnourished Indian children had increased polyploidy were not enough to damn the process. This evidence has been countered by the results of trial in China, where about 400 people ate irradiated wheatflour for 15 weeks without developing any evidence of chromosomal abnormalities. Dr J C Gould (Director of the Central Microbio? logical Laboratories, Edinburgh) saw the advantages of irradiation as being reduced spoilage of food and increased microbiological safety?provided that (as with other methods of food preservation) there is careful handling after irradiation to ensure no subsequent contamination. Expected legislation
A New Laparotomy Pad.
Authors: J. HENRY BARBAT
Journal: JAMA (1901)

The ordinary Kelly pad, when used for abdominal operations, allows all the solutions used in the final preparation of the abdomen to flow under the patient's back, thus keeping it in a chemical bath during the entire operation. If the Trendelenburg position is used the pad will probably overflow and the solutions will gravitate toward the patient's neck. If irrigation is necessary, part of the irrigating material will flow on the side which has no apron, and wet the table and floor. These conditions may appear of trifling importance, but those in whose charge the patient is placed after the performance of the operation will hail with delight any device which will avoid these inconveniences. I have devised a pad which consists essentially of two Kelly pads joined back to back. The pad when in position has an apron hanging down on each side of the table. The patient's spine
International Meeting on Cancer Vaccines
Authors: Filippo Belardelli, Maria Ferrantini, Giorgio Parmiani, Jeffrey Schlom, Enrico Garaci
Journal: Cancer Research (2004)

The major aims of the International Meeting on Cancer Vaccines were to review the state-of-the-art research on cancer vaccines, to compare different experimental approaches of therapeutic vaccination and to discuss critical issues and perspectives. The results from recent clinical trials in patients treated with different types of cancer vaccines were presented. Reasons for the limited response and possible modalities for enhancing efficacy of therapeutic vaccines were subjects of major discussion. A consensus was achieved on the need of combining cancer vaccines with other anticancer treatments. Of note, evidence stemming from studies in animal models pointed out new rationales for a selective combination of cancer vaccines with chemotherapy. In addition, some main presentations focused on new adjuvants (CpG oligonucleotides) and on the role of cytokines (i.e., type I IFN, interleukin 12, and interleukin 15) in promoting an antitumor immune response to vaccines. A considerable attention was given to regulatory T cells and to strategies for suppressing their function, thus enhancing vaccine efficacy. An entire session was devoted to the use of dendritic cells for the development of cancer vaccines. The results of clinical studies and the advantages of using new modalities for preparing dendritic cell-based vaccines were discussed.
Bad medicine: the way we manage diabetes
Authors: Des Spence
Journal: BMJ (2013)

Type 2 diabetes is a modern plague largely brought on by lifestyle and is considered a progressive, non-reversible condition. The polypharmacy of chronic disease is the drug industry’s lottery win, and no more so than in diabetes, with new drugs and the increasing use of analogue insulin in type 2 diabetes worth tens of billions of pounds worldwide.1 ⇑ The drug industry’s business plan for diabetes follows a familiar pattern:
High levels of mercury contamination in multiple media of the Carson River drainage basin of Nevada: implications for risk assessment.
Authors: M S Gustin, G E Taylor, T L Leonard
Journal: Environmental Health Perspectives (1994)

Approximately 5.5 x 109 g (4.0 x 105) of mercury was discharged into the Carson River Drainage Basin of west-central Nevada during processing of the gold- and silver-rich Comstock ore in the late 1800s. For the past 13 decades, mercury has been redistributed throughout 500 km2 of the basin, and concentrations are some of the highest reported values in North America. This article documents the concentrations of mercury in the air, water, and substrate at both contaminated and noncontaminated sites within the basin and discusses the implications for risk assessment. At contaminated areas, the range of mercury concentrations are as follows: mill tailings, 3-1610 micrograms/g; unfiltered reservoir water, 53-591 ng/l; atmospheric vapor, 2-294 ng/m3. These values are three to five orders of magnitude greater than natural background. In all media at contaminated sites, concentrations are spatially variable, and air and water mercury concentrations vary temporally. The study are in situated in a natural mercuriferous belt, and regional background mercury concentrations in all environmental media are higher than values typically cited for natural background. As a mercury-contaminated site in North America, the Carson River Drainage Basin is unusual for a number of reasons, including its location in a natural mercuriferous belt, high and sustained levels of anthropogenic mercury inputs, long exposure time, aridity of the climate, and the riparian setting in an arid landscape, where biological activity is concentrated in the same areas that contain high levels of mercury in multiple media.
Effect of macronutrient composition of the diet on the regulation of lipolysis in adipose tissue at rest and during exercise: Microdialysis study
Authors: Hana Suljkovicova, Fabrice Marion-Latard, Jindra Hejnova, Marek Majercik, Fran[ccedil]ois Crampes, Isabelle de Glisezinski, Michel Berlan, Daniel Rivi[egrave]re, Vladimir Stich
Journal: Metabolism (2002)
Reform of undergraduate medical teaching in the United Kingdom: Unfunded reform always ends in reaction
Authors: Julian T Hart
Journal: BMJ (2004)

EDITOR—Williams and Lau seem to have overlooked an important factor common to all attempts to make education more effective by making it more humane and less industrialised.1 Humane educational methods are always far more labour intensive and always require higher teacher to pupil ratios.

I visited Albuquerque medical school in the 1980s in its first years of introducing problem based learning, modelled on experience at Case Western Reserve and McMaster. The programme was then experimental, with educational results compared in two cohorts, …
Therapeutic angiogenesis by a myoblast layer harvested by tissue transfer printing from cell-adhesive, thermosensitive hydrogels
Authors: Dong Wan Kim, Indong Jun, Tae-Jin Lee, Ji hye Lee, Young Jun Lee, Hyeon-Ki Jang, Seokyung Kang, Ki Dong Park, Seung-Woo Cho, Byung-Soo Kim, Heungsoo Shin
Journal: Biomaterials (2013)
Brain Scintigraphy of Cerebellar Infarction Secondary to Atlanto-occipital Dislocation
Authors: SHAWN D. ISAEFF, ALAN SIEGEL
Journal: Clinical Nuclear Medicine (2000)

Strict criteria for the diagnosis of entire brain death by nuclear scintigraphy requires the absence of any intracranial activity. The authors describe the case of a 22-year-old man with traumatic atlanto-occipital dislocation in whom Tc-99m HMPAO brain scintigraphy for brain death showed intact cerebral but absent cerebellar blood flow. This is an extremely rare brain scan finding, previously unreported in the setting of trauma.
[695] ADIPOKINES AND NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD): ASSOCIATION WITH METABOLIC, BIOCHEMICAL, ULTRASONOGRAPHIC AND HISTOLOGICAL FEATURES
Authors: L. Azzalini, F. Lirussi, M. Plebani, N. Vitturi, C. Poci, R. Orlando, G. Realdi
Journal: Journal of Hepatology (2007)
Severely anorexic woman should be force fed, judge rules
Authors: C. Dyer
Journal: BMJ (2012)

A severely anorexic former medical student who failed for years to respond to treatment and was being allowed to die should be force fed, a High Court judge has ruled in an unprecedented case.

The 32 year old woman, named only as E, was five weeks into an end of life care pathway when her local authority in Wales made an emergency application to the Court of Protection in London for her situation to be investigated.

Her parents and the clinicians caring for her had concluded that E, who had not taken any solid food for more than a year and whose body mass index had been between 11 and 12 for the past two years, should not have artificial feeding forced on her again.

E had been seriously sexually …
Extreme Lipoprotein(a) Levels and Risk of Myocardial Infarction in the General Population
Authors: Pia R. Kamstrup, Marianne Benn, Anne Tybjærg-Hansen, Børge G. Nordestgaard
Journal: Circulation (2007)

Background— Elevated lipoprotein(a) levels are associated with myocardial infarction (MI) in some but not all studies. Limitations of previous studies include lack of risk estimates for extreme lipoprotein(a) levels, measurements in long-term frozen samples, no correction for regression dilution bias, and lack of absolute risk estimates in the general population. We tested the hypothesis that extreme lipoprotein(a) levels predict MI in the general population, measuring levels shortly after sampling, correcting for regression dilution bias, and calculating hazard ratios and absolute risk estimates. Methods and Results— We examined 9330 men and women from the general population in the Copenhagen City Heart Study. During 10 years of follow-up, 498 participants developed MI. In women, multifactorially adjusted hazard ratios for MI for elevated lipoprotein(a) levels were 1.1 (95% CI, 0.6 to 1.9) for 5 to 29 mg/dL (22nd to 66th percentile), 1.7 (1.0 to 3.1) for 30 to 84 mg/dL (67th to 89th percentile), 2.6 (1.2 to 5.9) for 85 to 119 mg/dL (90th to 95th percentile), and 3.6 (1.7 to 7.7) for ≥120 mg/dL (&gt;95th percentile) versus levels &lt;5 mg/dL (&lt;22nd percentile). Equivalent values in men were 1.5 (0.9 to 2.3), 1.6 (1.0 to 2.6), 2.6 (1.2 to 5.5), and 3.7 (1.7 to 8.0). Absolute 10-year risks of MI were 10% and 20% in smoking, hypertensive women aged &gt;60 years with lipoprotein(a) levels of &lt;5 and ≥120 mg/dL, respectively. Equivalent values in men were 19% and 35%. Conclusions— We observed a stepwise increase in risk of MI with increasing levels of lipoprotein(a), with no evidence of a threshold effect. Extreme lipoprotein(a) levels predict a 3- to 4-fold increase in risk of MI in the general population and absolute 10-year risks of 20% and 35% in high-risk women and men.
403 VITAMIN A DEFICIENCY NEGATIVELY AFFECTS THE RESPONSE TO ANTIVIRAL TREATMENT IN PATIENTS WITH CHRONIC HEPATITIS C
Authors: P. Bitetto, N. Bortolotti, S. Vescovo, G. Fattovich, E. Ceriani, M. Pasino, C. Cristofori, A. Cussigh, C. Fabris, E. Fornasiere, S. Cmet, E. Fontanini, E. Falleti, M. Pirisi, P. Toniutto
Journal: Journal of Hepatology (2011)
Who Has Seen a Blood Sugar? Reflections on a Medical Education
Authors: Eugene V. Boisaubin
Journal: JAMA (1997)

Excitement was not the emotion I experienced when first contemplating this new book. The title is catchy, but the subtitle—"Reflections on Medical Education"—gave me pause and a sense of ambivalence. Was this yet another work from a senior academician, now entering the "philosopause," lamenting the decline in the morality and practices of modern medicine in general, and education in particular, wrought by the evil empire of entrepreneurial medicine and managed care? But my hopes were buoyed by the author's name, well recognized by internists as a writer and editor of the<i>Annals of Internal Medicine</i>. In fact, the 41 essays were largely culled from a series appearing in the American College of Physician's monthly newsletter,<i>ACP Observer</i>, from 1992 to 1995. Many have been revised and expanded, partly after feedback from readers. The essays are brief and erudite and cover diverse elements from the wide landscape of medical
Skin cancer in renal transplant recipients is associated with increased concentrations of 6-thioguanine nucleotide in red blood cells
Authors: L. LENNARD, S. THOMAS, C.I. HARRINGTON, J.L. MADDOCKS
Journal: British Journal of Dermatology (1985)

Of 108 renal transplant recipients (53 men and 55 women) treated with azathioprine (0.8-2.9 mg/kg/day) and prednisolone (10 mg daily), 10 men had actinic keratoses, and five of these had squamous cell carcinoma, on light-exposed areas of skin. The time from transplantation to diagnosis of these skin lesions varied from 1.2 to 9.0 (mean 5.1) years. The concentration of the active azathioprine metabolite 6-thioguanine nucleotide was 120-425 (mean 276) pmol per 8 X 10(8) red blood cells in the transplant patients who developed skin lesions and 54-203 (mean 130) pmol per 8 X 10(8) red blood cells in a matched control group of renal transplant recipients. This difference was statistically significant (P = 0.005). There was no statistically significant difference between patients and controls in azathioprine dosage, clinical features of immunosuppression, sunlight exposure or infection with human papilloma virus. The association of raised 6-thioguanine nucleotide concentrations in red blood cells with actinic keratoses and malignant skin tumours in these patients supports chemical carcinogenesis as a possible cause.
Management of patients with congenital hypothyroidism.
Authors: G J Frost, J M Parkin
Journal: BMJ (1985)

The biochemical state and treatment of 73 children and 44 adults up to the age of 40 with proved congenital hypothyroidism were assessed in a regional study in the north of England. The findings showed that a substantial proportion of the patients were having inappropriate treatment or were not taking their treatment regularly and that in some of these there were clinical effects.
Royal colleges call for more staff on maternity wards
Authors: Andrew Cole
Journal: BMJ (2007)

The four royal colleges that represent UK doctors and nurses involved in childbirth are calling for urgent increases in the number of staff to ensure safe levels of care on maternity wards.

In their report Safer Childbirth the royal colleges for obstetricians and gynaecologists, anaesthetists, midwives, and paediatrics and child health list the minimum standards required for safe childbirth. These include one to one midwifery care for women in established labour and the presence of a consultant obstetrician on the ward at least 40 hours a week.

At the moment, says the report, only 27% of maternity units in England and Wales have enough …
THE CHARACTER OF CHROMATOPHORES.
Authors: LEO LOEB
Journal: JAMA (1904)

In regard to the origin of the cell masses characteristic of pigmented moles and in regard to the origin of the melanotic tumors of the skin, different views are still held. A number of pathologists believe in the epithelial origin of nevi and of melanotic tumors; others assume a mesodermal origin. The latter view is especially represented in the work of Ribbert.<sup>1</sup>He believes the melanotic tumors to be composed of in part modified chromatophores. All chromatophores he regards as of common mesoblastic origin, in accordance with the previously formulated theory of Ehrmann.<sup>2</sup>In view of this divergence of opinion, it might not be without interest to inquire what the actual stand of our present knowledge of the chromatophores is, and if it supports the view of Ehrmann and Ribbert. Without attempting to give a complete review of the literature on this subject, I shall limit myself to a brief
Response to Letter Regarding Article, “Validation of the Bleeding Academic Research Consortium Definition of Bleeding in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention”
Authors: Gjin Ndrepepa, Martin Hadamitzky, Robert A. Byrne, Julinda Mehilli, Stefanie Schulz, Steffen Massberg, Albert Schömig, Adnan Kastrati, Tibor Schuster, Franz-Josef Neumann, Gert Richardt, Karl-Ludwig Laugwitz
Journal: Circulation (2012)

We thank Drs Vranckx and Valgimigli for their interest in our article 1 related to validation of the Bleeding Academic Research Consortium (BARC) definition of bleeding in patients with coronary artery disease undergoing percutaneous coronary intervention. 2In the article, and in this response, we share the same opinion with Drs Vranckx and Valgimigli regarding the need to validate the BARCproposed bleeding definition criteria in prospective studies.Although compiled and proposed by a highly experienced group of researchers in investigating bleeding complications (as an end point in various trials of anticoagulant /antithrombotic therapy), the BARC proposal was a consensus-based rather than a data-based document, and the need to validate it was felt concomitantly with its publication. 3Moreover, at the time we undertook the validation study, there were signals that BARC bleeding criteria were included in the end point assessment of new studies. 4Considering these facts and the well-documented importance of bleeding complications, and the emergence of new anticoagulant/antiaggregant agents with a poorly known safety profile (including the risk for bleeding), we validated the BARC bleeding criteria using existing data, although recognizing the need for future prospectively designed validation studies.Because the quality of event adjudication was also one of our main concerns, we have clarified that all data used for characterization of bleeding events according to the BARC criteria were derived from randomized prospective studies, which means that every bleeding complication was sought actively, quantified accurately, and recorded.As emphasized in our article, 1 for every case with bleeding, source documentation-including patients' charts for those treated with coronary artery bypass surgery-was available and was reevaluated.A BARC class Ն2 bleeding quantifies overt actionable signs of hemorrhage, and as such is an important and quantifiable clinical event; thus, we do believe that the individual components of BARC class Ն2 bleeding were assessed properly.Retrospectively, we only categorized these components into the appropriate BARC classes.We acknowledge that prospective adjudication of bleeding increases the diagnostic power for BARC class 1 events.We have certainly missed a number of BARC class 1 events in our patient records and believe that future prospective studies might enable a better definition of the prognostic role of this class of bleeding.