tbuckley/cabot-search huggingface dataset:
Abstract 1751: The influence of sex on prognostic markers for non-small cell lung cancer
Authors: Boutros C. Paul
Journal: Cancer Research (2010)

Abstract There are significant differences between the sexes in the incidence, presentation, and response to therapy of non-small cell lung cancer (NSCLC). This study evaluated the effects of these differences on mRNA-based prognostic markers. Several prognostic markers have been developed over the past decade by various groups, generally from microarray datasets. These markers look at the mRNA levels of specific genes and use these to determine whether a patient is likely to good or poor outcome. If such markers were successful at complementing traditional staging criteria (i.e. molecular sub-staging) then patients predicted to have poor outcome could receive additional or more intensive therapies. Surprisingly, to date, the effect of sex on such markers has not been evaluated, despite major differences in disease between males and females. To evaluate this issue, I compiled the data from nine transcriptomic studies of primary NSCLC. These studies were integrated using a novel normalization approach and then subject to meta-analysis. For each gene present in the analysis (16,391 in total), the univariate prognostic capacity was calculated separately for men and women using median dichotomization and Cox proportional hazards modeling. Of the top 100 genes in each sex, only 12 were overlapping. Novel sex-specific prognostic signatures were then derived, and shown to out-perform sex-independent signatures by a statistically significant (p &amp;lt; 0.01) margin. In summary, sex plays a major role in NSCLC etiology and response to therapy. I have demonstrate here that it also greatly effects the efficacy of transcriptomic prognostic markers. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1751.
Red cell aging in vivo
Authors: A. M. Ganzoni, R. Oakes, R. S. Hillman
Journal: Journal of Clinical Investigation (1971)

Previous studies of red cell structure and metabolism during the aging process have relied upon in vitro techniques of cell separation into various age populations. Probably the most common approach is to isolate the older red cells with the assumption that they are more dense. This may lead to a number of inconsistencies in observations, and may certainly raise questions about possible cell changes secondary to manipulative procedures. For this reason, an experimental system was devised where a normal red cell population could be studied, while aging, in an in vivo environment. The initial red cell mass of a large number of inbred rats was transferred repeatedly into an ever smaller number of animals, making it possible to follow an aging population of red cells up to 48 days while preventing contamination with newly produced cells by suppression of erythropoiesis with transfusion-induced polycythemia. During this period, samples of progressively older red cells could be obtained for measurements of red cell constant. It was noted that the normal rat red cell undergoes both volume reduction and significant hemoglobin content loss with aging. In addition, the hemoglobin concentration within the cell demonstrated an early rise after a return to nearly normal values. These findings are noteworthy in that they help to explain the characteristics of life-spans of cohort labeled red cell populations in small animals, and provide a possible example of a cell's remodeling process within the spleen.
The JAK2 V617F mutation identifies a subgroup of MDS patients with isolated deletion 5q and a proliferative bone marrow
Authors: W Ingram, N C Lea, J Cervera, U Germing, P Fenaux, B Cassinat, J J Kiladjian, J Varkonyi, P Antunovic, N B Westwood, M J Arno, A Mohamedali, J Gaken, T Kontou, B H Czepulkowski, N A Twine, J Tamaska, J Csomer, S Benedek, N Gattermann, E Zipperer, A Giagounidis, Z Garcia-Casado, G Sanz, G J Mufti
Journal: Leukemia (2006)
Effect of hypotonic expansion on sodium, water, and urea excretion in late pregnancy: the influence of posture on these results
Authors: Marshall D. Lindheimer, Peter V. Weston
Journal: Journal of Clinical Investigation (1969)

Mineralocorticoid-treated, normotensive third trimester subjects positioned in lateral recumbency were studied before and during the infusion of 300 mEq of hypotonic saline. Urinary sodium excretion increased in all subjects from a mean value of 199 to 416 muEq/min. In 12 maximally hydrated subjects free water clearance (C(H2O)) and urine flow (V) increased from means of 7.54 and 9.50 to 11.6 and 14.5 ml/100 ml of glomerular filtrate (GFR) Also the ratio of urea to inulin clearance (C(urea)/C(inulin)) increased from 0.59 to 0.64. The changes in the renal handling of water and urea suggest that fractional sodium reabsorption decreased at proximal nephron sites. The subjects then assumed a supine position, and the results were compared to those obtained during the lateral recumbent control periods. Filtered sodium decreased in 11 experiments, but in five studies it remained up to 2.6 mEq/min above control values. There was only one instance in which a significant increase in sodium excretion occurred. It was concluded that supine recumbency blunts natriuresis despite volume expansion or an increase in the filtered load of sodium.Finally, in the 12 hydrated subjects supine recumbency reduced C(H2O) and V from a mean of 11.6 and 14.5 to 6.2 and 8.2 ml/100 ml of GFR. In eight of these experiments urine osmolality fell or did not change. Simultaneously, C(urea)/C(inulin) fell from 0.64 to 0.57. These data suggest that the antinatriuresis, which occurred when the volume-expanded subjects were positioned in supine recumbency, was accompanied by a decrease in the fractional reabsorption of sodium at proximal nephron sites.
Britain's National Health Service Revisited
Authors: Rudolf Klein
Journal: New England Journal of Medicine (2004)

This Health Policy Report reviews recent policy changes in Britain's National Health Service (NHS). The government plans to increase spending on health to 8 percent of the gross domestic product, which is the average level of spending across the European Union. The report discusses the implications of new initiatives to decentralize management of the NHS, improve the quality of health care, reduce patients' waiting times, and make the NHS more consumer-oriented.
Exposure Assessment Implications for the Design and Implementation of the National Children’s Study
Authors: Halûk Özkaynak, Robin M. Whyatt, Larry L. Needham, Gerry Akland, James Quackenboss
Journal: Environmental Health Perspectives (2005)

Examining the influence of environmental exposures on various health indices is a critical component of the planned National Children's Study (NCS). An ideal strategy for the exposure monitoring component of the NCS is to measure indoor and outdoor concentrations and personal exposures of children to a variety of pollutants, including ambient particulate and gaseous pollutants, biologic agents, persistent organics, nonpersistent organics (e.g., pesticides), inorganic chemicals (e.g., metals), and others. However, because of the large sample size of the study (approximately 100,000 children), it is not feasible to assess every possible exposure of each child. We envision that cost-effective strategies for gathering the necessary exposure-related information with minimum burden to participants, such as broad administration of product-use questionnaires and diaries, would likely be considered in designing the exposure component of the NCS. In general a biologic (e.g., blood, urine, hair, saliva) measure could be the dosimeter of choice for many of the persistent and for some of the nonpersistent organic pollutants. Biologic specimens, such as blood, can also indicate long-term internal dose to various metals, including lead and mercury. Environmental measures, on the other hand, provide pathway/source-specific exposure estimates to many of the environmental agents, including those where biologic measurements are not currently feasible (e.g., for particulate matter and for some gaseous criteria pollutants). However, these may be burdensome and costly to either collect or analyze and may not actually indicate the absorbed dose. Thus, an important technical and logistical challenge for the NCS is to develop an appropriate study design with adequate statistical power that will permit detection of exposure-related health effects, based on an optimum set of exposure measurement methods. We anticipate that low-cost, low-burden methods such as questionnaires and screening type assessments of environmental and biologic samples could be employed, when exposures at different critical life stages of vulnerability can be reliably estimated by these simpler methods. However, when reliability and statistical power considerations dictate the need for collecting more specific exposure information, more extensive environmental, biologic, and personal exposure measurements should be obtained from various "validation" subsets of the NCS population that include children who are in different life stages. This strategy of differential exposure measurement design may allow the exposure-response relationships to be tested on the whole cohort by incorporating the information on the relationship between different types of exposure measures (i.e., ranging from simple to more complex) derived from the detailed validation subsamples.
A Standard of Knowledge for the Professional Practice of Toxicology
Authors: Janis E. Hulla, Lewis B. Kinter, Bruce Kelman
Journal: Environmental Health Perspectives (2015)

Employers, courts, and the general public judge the credibility of professionals based on credentials such as academic degrees, publications, memberships in professional organizations, board certifications, and professional registrations. However, the relevance and merit of these credentials can be difficult to determine objectively. Board certification can be a reliable indicator of proficiency if the certifying organization demonstrates, through regularly scheduled independent review, that its processes meet established standards and when a certificate holder is required to periodically demonstrate command of a body of knowledge that is essential to current professional practice.We report herein a current Standard of Knowledge in general toxicology compiled from the experience and opinions of 889 certified practicing professional toxicologists.An examination is the most commonly used instrument for testing a certification candidate's command of the body of knowledge. However, an examination-based certification is only creditable when the body of knowledge, to which a certification examination tests, is representative of the current knowledge, skills, and capabilities needed to effectively practice at the professional level. Thus, that body of knowledge must be the current "Standard of Knowledge" for the profession, compiled in a transparent fashion from current practitioners of the profession.This work was conducted toward ensuring the scientific integrity of the products produced by professional toxicologists.
U.S. Drug Laws -- An Introduction
Authors: Rachel Hart
Journal: New England Journal of Medicine (1994)

The two Sounding Board articles that follow address substance abuse. The first, by Lester Grinspoon and James Bakalar, argues for relaxing the laws against drug use; the second, by Herbert Kleber, favors retaining them. Because these laws are confusing and may not be widely understood by our readers, Rachel Hart, research assistant at the Journal, prepared the following summary.Drug-control laws, which are established by both federal and state statutes, generally regulate three activities: the manufacture, distribution, and possession of drugs. Other illegal drug-related activities, such as possessing drug-related paraphernalia, laundering money, and driving while intoxicated, are regulated by a . . .
Prognosis of Physicians Treated for Alcoholism and Drug Dependence
Authors: Robert M. Morse
Journal: JAMA (1984)

Data on 73 physicians are compared with data on 185 middle-class patients similarly treated for alcoholism or drug dependence in a hospital-based inpatient program. General patients were contacted on year after treatment and physicians, one to five years later. The prognosis was more favorable for physicians than for general patients. When the groups were selected for study on the basis of completion of inpatient treatment, availability at time of contact, and not having died, 83% of physicians and 62% of the general group were noted to have favorable outcomes. Close monitoring may account, in part, for the better prognosis for physicians.
US trade agreement threatens to increase drug prices and withhold safety data
Authors: D. Cohen
Journal: BMJ (2013)

Campaign groups have criticized the US government of “shameful bullying on behalf of the giant drug companies” during trade negotiations between the United States and 11 Asian and Latin American countries in the so called Trans-Pacific Partnership.

Draft text from the secretive trade rounds published on WikiLeaks focus on intellectual property, an area of law affecting areas as diverse as pharmaceuticals and civil liberties.1 The leak came ahead of another meeting on the agreement in Salt Lake City next week.

The trade agreement includes proposals for more than a dozen measures that would limit competition and raise drug prices.

The US watchdog group Public Citizen said that the text showed that a US representative was pressing the other negotiating countries “to expand pharmaceutical monopoly protections and trade away …
Abstract 4200: EXO1 is required for normal SN1 methylator-induced DNA damage response
Authors: Eugene Izumchenko
Journal: Cancer Research (2011)

Abstract The mismatch repair (MMR) system plays an important role in mutation avoidance and its inactivation, which is commonly seen in both hereditary and sporadic cancers, results in genomic instability and increased cancer risk. SN1 DNA methylating agents are potent chemotherapeutics that can methylate the O6 position of guanine. This O6meG adduct subsequently mispairs with thymine during DNA replication, MMR recognizes these O6meG/T mispairs, and consequently activates DNA damage response (DDR). While the exact mechanism by which MMR activates DDR signaling remains unresolved, the DNA repair activity of MMR has been implicated as important in this process. Exonuclease I (EXO1) plays a crucial role in eukaryotic MMR by removing the strand containing the mismatched base. Several studies describe direct association between EXO1 and several MMR proteins (ie, MSH2, MLH1) and that EXO1 is activated during MMR processing of O6meG lesions. However, whether EXO1 is required to activate MMR-dependent response to O6meG remains unknown. Here we show that Lentiviral shRNA-mediated EXO1 knockdown in mouse embryonic fibroblasts (MEFs) results in decreased G2/M arrest in response to treatment with the SN1 methylator MNNG. Accordingly, we observed reduced phosphorylation of the checkpoint proteins Cdc2 and Chk1, consistent with reduced MMR-dependent signaling in response to MNNG. We also found that EXO1 knockdown resulted in a limited effect on cell proliferation and loss of viability while MEFs transduced with control virus displayed clear growth arrest and a heightened cytotoxic response following MNNG exposure. Taken together, these data support our interpretation that reduced EXO1 activity results in an alkylation-tolerant phenotype similar to documented defects stemming from loss of MMR. Moreover, these findings seemingly strengthen the hypothesis that MMR-associated DNA repair activity is required for response to O6meG lesions. However, several lines of evidence suggest that EXO1 may function in both a catalytic and a structural manner during MMR-mediated mutation avoidance. Therefore, we are currently testing if EXO1 is required for MMR complex assembly at sites of mismatches within duplex DNA, and if exonuclease activity is required for normal response to SN1 methylators. Our long-term goal is to better understand the mechanisms that guide response to SN1 alkylators since deducing MMR-mediated DNA damage response will yield essential insights for designing drugs targeting these pathways, and predicting drug response in cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4200. doi:10.1158/1538-7445.AM2011-4200
The role of Epstein–Barr virus in acute and chronic hepatitis
Authors: Uta Drebber, Hans U. Kasper, Joanna Krupacz, Katharina Haferkamp, Michael A. Kern, Hans M. Steffen, Maria Quasdorff, Axel zur Hausen, Margarete Odenthal, Hans P. Dienes
Journal: Journal of Hepatology (2006)
Multicenter Randomized Controlled Trial of Terlipressin Versus Sclerotherapy in the Treatment of Acute Variceal Bleeding: The TEST Study
Authors: Àngels Escorsell, Luis Ruiz Del Arbol, Ramon Planas, Agustín Albillos, Rafael Bañares, Paul Calès, Dominique Pateron, Brigitte Bernard, Jean-Pierre Vinel, Jaume Bosch
Journal: Hepatology (2000)

Failure to control bleeding and early rebleeding account for the high mortality associated with variceal hemorrhage in cirrhosis. We compared endoscopic sclerotherapy to terlipressin, a drug that effectively controls acute bleeding while reducing in-hospital mortality. This multicenter randomized controlled trial included 219 cirrhotic patients admitted for endoscopy-proven acute variceal bleeding and randomized to receive repeated injections of terlipressin during 6 days (n = 105) or emergency sclerotherapy (n = 114). Success was defined as obtaining control of bleeding (24-hour bleeding-free period during the first 48 hours) and lack of early rebleeding (any further bleeding from initial control to 5 days later) and survival during the study. Both groups were similar at inclusion. Failure rate for terlipressin was 33% and 32% for sclerotherapy (not significant [NS]). Early rebleeding was responsible for 43% and 44% of failures, respectively. This high efficacy was observed in both Child-Pugh class A + B and Child-Pugh class C patients. Both treatments were similar regarding transfusion requirements, in-hospital stay, and 6-week mortality (26 vs. 19 patients). Side effects appeared in 20% of patients receiving terlipressin and in 30% of those on sclerotherapy ( P = .06); being serious in 4% and 7%, respectively (NS). In conclusion, terlipressin and sclerotherapy are equally highly effective therapies achieving the initial control of variceal bleeding and preventing early rebleeding. Both treatments are safe, but terlipressin is better tolerated. Therefore, terlipressin may represent a first-line treatment in acute variceal bleeding until the administration of elective therapy, especially in hospitals where a skilled endoscopist is not available 24 hours a day.
Patients With Prolonged Ischemic Chest Pain and Presumed-New Left Bundle Branch Block Have Heterogeneous Outcomes Depending on the Presence of ST-Segment Changes
Authors: Cheuk-Kit Wong, John K. French, Philip E.G. Aylward, Ralph A.H. Stewart, Wanzhen Gao, Paul W. Armstrong, Frans J.J. Van De Werf, R. John Simes, O. Christopher Raffel, Christopher B. Granger, Robert M. Califf, Harvey D. White
Journal: Journal of the American College of Cardiology (2005)
The role of fat and cholecystokinin in functional dyspepsia
Authors: M Fried, C Feinle
Journal: Gut (2002)

The main factors involved in the pathophysiology of fat induced dyspepsia were investigated by reviewing a series of controlled double blind randomised studies which sought to determine the role of nutrient fat and the postprandial release of cholecystokinin (CCK) in the development of dyspeptic symptoms in healthy volunteers and in patients with functional dyspepsia. The studies showed that during distension of the stomach, lipids are a major trigger of dyspeptic symptoms such as nausea, bloating, pain, and fullness, and that they modulate upper gastrointestinal sensations and symptoms in a dose related fashion. CCK is a major mediator of the sensitisation of gastric perception by lipids in patients with functional dyspepsia as the CCK-A receptor antagonist dexloxiglumide markedly diminishes this effect. The studies provide important insights into the mechanisms underlying gastrointestinal perception in response to fat and the role of CCK in patients with functional dyspepsia.
Peruvian mummy shows that TB preceded Columbus
Authors: F. B Charatan
Journal: BMJ (1994)

A study of the naturally mummified remains of a Peruvian woman shows conclusively that pulmonary tuberculosis was present centuries before Columbus discovered the New World. The mummy of the middle aged woman was exhumed in 1990, and radio-carbon studies have indicated that she died about 1000 years ago. …
NEUROSIS AND THE MEXICAN FAMILY STRUCTURE
Authors: ROGELIO DIAZ-GUERRERO
Journal: American Journal of Psychiatry (1955)

A presentation is made of the cultural assumptions which it is believed underlie a great deal of the role playing in the Mexican family. Examples are given to demonstrate the effect of the assumptions in actual role playing. Remarks are made regarding (1) the areas where neurotic difficulty would be expected from the assumptions and the role playing, and ( 2) some evidence which seems to verify such expectations. It is proposed that opinion polls may serve the purpose of identifying the degree of variation of a given group from the dominant pattern.
Edwin James Essex Parker
Authors: P J Ward
Journal: BMJ (2003)

Former general practitioner Moira, County Armagh (b Castledawson, County Tyrone, 1923; q Queen's University, Belfast, 1948; FRCGP), d 1 January 2003.

After qualification, Edwin Parker was a house surgeon at Lurgan and Portadown Hospital. In 1950 he set up in general practice in Moira, where he said that for the first two years he earnt more money from hens. He became staff medical officer at Lurgan Hospital in 1954 and GP geriatrician to Moira Hospital in 1956. He was also a police surgeon and, from 1969 to 1975, medical officer at the Maze prison. He was an active member of the BMA and his local medical committee. He leaves a wife, Saide; three children; and four grandchildren.
Detection and Treatment of Ductal Carcinoma In Situ of the Breast
Authors: Alan B. Hollingsworth
Journal: JAMA (1996)

<h3>To the Editor.</h3> —In their description of trends for ductal carcinoma in situ (DCIS), Dr Ernster and colleagues<sup>1</sup>provide a realistic assessment of this controversial area. However, their caution concerning the "potential risk of screening mammography in the face of questionable value of the test" for women younger than 50 years seems to demonstrate circular logic via faulty deductive reasoning. In using the deductive process, it is best to be certain that the premises in a syllogism are axiomatic, or else the conclusion will be in error. The first premise is stated in the article as "efficacy of screening mammography for women younger than 50 years has not been clearly demonstrated." Actually, an updated meta-analysis of the 7 non-Canadian trials now reveals a 24% reduction in mortality in the group aged 40 to 49 years.<sup>2</sup>The authors would likely reply that if it takes so long to assure mortality reduction, "a