tbuckley/cabot-search huggingface dataset:
A Unified Model Explaining the Offsets of Overlapping and Near-Overlapping Prokaryotic Genes
Authors: Carl Kingsford, Arthur L. Delcher, Steven L. Salzberg
Journal: Molecular Biology and Evolution (2007)

Overlapping genes are a common phenomenon. Among sequenced prokaryotes, more than 29% of all annotated genes overlap at least 1 of their 2 flanking genes. We present a unified model for the creation and repair of overlaps among adjacent genes where the 3' ends either overlap or nearly overlap. Our model, derived from a comprehensive analysis of complete prokaryotic genomes in GenBank, explains the nonuniform distribution of the lengths of such overlap regions far more simply than previously proposed models. Specifically, we explain the distribution of overlap lengths based on random extensions of genes to the next occurring downstream stop codon. Our model also provides an explanation for a newly observed (here) pattern in the distribution of the separation distances of closely spaced nonoverlapping genes. We provide evidence that the newly described biased distribution of separation distances is driven by the same phenomenon that creates the uneven distribution of overlap lengths. This suggests a dynamic picture of continual overlap creation and elimination.
Genomics-Driven Oncology: Framework for an Emerging Paradigm
Authors: Levi A. Garraway
Journal: Journal of Clinical Oncology (2013)

A majority of cancers are driven by genomic alterations that dysregulate key oncogenic pathways influencing cell growth and survival. However, the ability to harness tumor genetic information for its full clinical potential has only recently become manifest. Over the past several years, the convergence of discovery, technology, and therapeutic development has created an unparalleled opportunity to test the hypothesis that systematic knowledge of genomic information from individual tumors can improve clinical outcomes for many patients with cancer. Rigorous evaluation of this genomics-driven cancer medicine hypothesis will require many logistic innovations that are guided by overarching conceptual advances in tumor genomic profiling, data interpretation, clinical trial design, and the ethical return of genetic results to oncologists and their patients. The results of these efforts and the rigor with which they are implemented will determine whether and how comprehensive tumor genomic information may become incorporated into the routine care of patients with cancer.
Abstract 5308: Targeting the Cox2 pathway prostaglandin EP receptors to regulate NK cell functions
Authors: Dawn M. Holt, Xinrong Ma, Namita Kundu, Amy M. Fulton
Journal: Cancer Research (2010)

Abstract Breast malignancies often have high levels of Cox-2. The Cox-2 product prostaglandin E2 (PGE2) contributes to the high metastatic capacity of breast tumors. Our published data indicates that inhibiting either PGE2 production or PGE2-mediated signaling through the PGE2 receptor (EP4) reduces metastasis by a mechanism that requires Natural Killer (NK) cells. In order to better understand the mechanism by which inhibiting PGE2 production or signaling reduces metastatic disease, we examined the role of PGE2 in regulating protective host effector cells. It is known that NK cell function is compromised by PGE2, but very little is known about the mechanism by which PGE2 affects NK effector activity. NK effector function is regulated by complex interactions of recognition receptors expressed on NK cells and cognate ligands expressed on target cells. Both stimulatory and inhibitory signals are delivered through these receptor-ligand interactions. We have previously shown that both Cox inhibitors and antagonists of the EP4 receptor modulate the expression of NK cell stimulatory (H60) and inhibitory (MHC class I) ligands on the tumor target cell in favor of NK recognition and killing. We now report the direct effects of PGE2 on the NK cell. Murine splenic NK cells express all four PGE2 receptors (EP1-4). We examined the role of EP receptors in three NK cell functions; cytokine release, cytotoxicity, and migration. Activating all four NK-EP receptors with PGE2 leads to inhibited IFNγ secretion, induced TNFα production, less migration of NK cells and reduced ability to lyse tumor target cells. Using agonists and antagonists of individual EP receptors, we showed that only certain EP receptors contribute to loss of function. Next, we showed that all NK-EP receptor expression is downregulated during progressive tumor growth, which produced an environment that induced a less mature NK phenotype. EP2 and EP4 are linked to protein kinase A and elevations in intracellular cAMP. NK cells from tumor bearing mice respond poorly to stimulation with 10µM PGE2 and intracellular cAMP levels were increased by only 1.45-1.78 fold. In contrast, cAMP was induced by 6.08-10.58-fold in NK cells from normal mice. Thus, the tumor milieu results in changes in both NK-EP expression levels and EP receptor functions. NK mediated cytotoxicity, cytokine release, and migration were also compromised in tumor bearing mice. These results taken together support a mechanism whereby inhibiting PGE2 production or preventing signaling through some, but not all EP receptors may prevent suppression of NK functions that are critical to control breast cancer metastasis. 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 5308.
Lessons From the Avandia Controversy
Authors: Robert I. Misbin
Journal: Diabetes Care (2007)

Sulfonylureas used to be the only oral agents available in the U.S. to treat patients with type 2 diabetes. The biguanide phenformin had been used widely in the 1950s and 1960s but was removed from the market in 1977 because of lactic acidosis (1). Other biguanides, including metformin, were felt to be safer and had been used extensively elsewhere in the world. But a biguanide did not become available in the U.S. until 1995 (2).

The year 1995 marked a sea change in availablilty of drugs to treat type 2 diabetes. The approval of metformin, a biguanide, was followed by the approval of acarbose, a galactosidase inhibitor that, like metformin, had been widely used in Europe. A new drug application for acarbose had been rejected by the Food and Drug Administration (FDA) 3 years earlier, but in 1995 the regulatory environment had become friendlier, owing in large part to the finding of the Diabetes Control and Complications Trial (DCCT) that aggressive treatment of hyperglycemia prevented or delayed complications of diabetes (3). Approval of the thiazolidinedione (TZD) troglitazone and the non-sulfonylurea insulin secretagog repaglinide followed soon after, along with additional members of the newly approved classes.

In 2005, the uninterrupted succession of new drug approvals came to an end. Muraglitazar was a dual peroxisome proliferator–activated receptor agonist. It was different chemically from the TZDs and fibrates but was believed to combine the desirable pharmacological effects of both. Muraglitazar was highly effective in lowering A1C and had favorable effects on serum lipids. But contrary to what one might expect, muraglitazar appeared to increase the risk of adverse events related to cardiac ischemia (4). This might have been considered an isolated event were it not for the recent brouhaha that rosiglitazone (Avandia) also increased the risk of cardiac ischemia.

The Avandia affair …
Antibiotic Sensitivity of Klebsiella
Authors: T. D. M. Martin
Journal: BMJ (1973)

Riot Control Agent SIR,-In your leading article (7 July, p. 5) it vws reported that an improvement on the riot control CS gas is on the way.It is code-named CR and, being of low toxicity but extremely irritant to skin, eyes, nose and throat, only very little would cause con- siderable pain and discomfort.In the article there was no expression of concern or disgust that oral LD 5 tests were done on animals to test the toxicity of the compound.If a dose of very low toxicity can cause such acute symptoms when applied to the skin and mucous membranes it seems quite possible that doses of high, lethal, toxicity, even when given by other routes, will cause severe pain and distress.Does medical ethics approve the use of animals in this way in testing substances which only our own folly have made necessary?-Iam, etc., J. D. WHITTALL Rye, Sussex Haemolytic-Uraemic Syndrome with Pericarditis SIR,-We were interested in the case re- ported by Drs.J. A. Utting and D. R. Shreeve (9 June, p. 591) of a patient with haemolytic-uraemic syndrome and pericarditis.Their statement that "no cases with prominent friction rubs due to the micro- angiopathy have previously been described" is not correct.In 1972 we reported1 a case of haemolytic-uraemic syndrome and nmicroan- giepathy in a woman with a hydatidiform mole who had a strong pericardial rub and who recovered with heparin therapy.This rub also was unrelated to uraemia.-Weare, etc.,
The Mode in which Direction is Ascertained by Migratory Animals
Authors: F. J. Brown
Journal: BMJ (1870)

Median operations, 57; with 3 deaths, or I in I9; of these, 9 were adults, or above 17 years of age ; the deaths were, 2 adults and I juvenile.Lateral operations, I2 ; of which iI were cured, and I adult died, aged 67.'The grand total is 69, with 4 deaths, or I in 17.The result is, in * Read before the West Kent District Meeting.+ Whether by swirmming or in a boat, I do not recollect.
Abstract 3772: Lifestyle factors and global methylation in peripheral leukocyte DNA
Authors: Fang Fang Zhang, Alfredo Morabia, Joan Carroll, Karina Gonzalez, Kimberly Fulda, Manleen Kaur, Regina M. Santella, Roberto Cardarelli
Journal: Cancer Research (2010)

Abstract Global hypomethylation is associated with genomic instability and may mediate the association between environmental and lifestyle factors and cancer risk. We examined the association between lifestyle factors and levels of genomic DNA methylation in the peripheral blood leukocytes of 160 participants in the North Texas Healthy Heart Study aged 45-75. We used in-person interviews for demographics and lifestyle factors, a self-administrated Block food frequency questionnaire for dietary data, bioelectrical impedance analysis (BIA) and CT-scan for body composition including fat mass % and areas of visceral and truncal subcutaneous adipose tissues at the L4L5 level. We measured genomic DNA methylation using bisulfite conversion of DNA and real time PCR (MethyLight) for SAT2-M1. The median level of global methylation was 61.3% in this cancer-free population. Male gender was positively associated with global hypomethylation (i.e. &amp;lt; median) (OR=3.7, 95%CI: 1.4-9.7). Compared to Hispanics (n=58), non-Hispanic whites (n=33) and non-Hispanics blacks (n=68) had a significantly higher level of global hypomethylation (OR=8.4, 95%CI: 2.4-29.6 and OR=4.1, 95%CI: 1.5-11.2 respectively). Although the area of L4L5 subcutaneous adipose tissue was positively associated with DNA methylation in the univariate model (342 cm2 among subjects with methylation &amp;lt; median vs. 395 cm2 among subjects with methylation ≥ median, p=0.04), none of the body composition measures were associated with DNA methylation in the multivariate model after adjusting for age, gender and ethnicity, nor were cigarette smoking, alcohol drinking, dietary folate intake and perceived stress. Although there was no association of lifestyle factors with genomic methylation in the peripheral leukocyte DNA, the strong association with gender and race/ethnicity indicates that interactions between these variables and lifestyle factors need to be explored in a larger sample before firm conclusions can be reached. 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 3772.
Amodiaquine-lnduced Hepatitis
Authors: DOMINIQUE LARREY
Journal: Annals of Internal Medicine (1986)

Seven patients developed hepatitis after receiving amodiaquine for malaria prophylaxis for 4 to 15 weeks. Four patients had a minor form of hepatitis: jaundice was mild or absent, serum aminotransferase levels were moderately increased, and recovery was prompt. Three patients had a severe form: jaundice was intense, serum aminotransferase levels were markedly increased, jaundice persisted for 3 to 6 months, and liver tests were still abnormal 7 to 27 months after the onset of hepatitis. In two patients, serum aminotransferase levels increased promptly after readministration of the drug, which is consistent with an immunoallergic mechanism for amodiaquine-induced hepatitis.
Is there a relationship between symptoms of the irritable bowel syndrome and objective measurements of large bowel function? A longitudinal study.
Authors: G J Oettle, K W Heaton
Journal: Gut (1987)

Four patients with the irritable bowel syndrome completed 28 day continuous stool collections and concurrent symptom diaries. The diaries revealed that three patients had multiple pains. When the diaries were compared with objective measurements, no relationship could be detected between the occurrence of pain or any other symptom on the one hand and stool weight, stool form or consistency, mean whole gut transit time, or interdefecatory transit on the other. Patients9 descriptions of urgency, looseness and frequency of defecation give little guide to intestinal events, at least using currently available techniques.
Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity
Authors: Yoichi Maekawa, Yoshiaki Minato, Chieko Ishifune, Takeshi Kurihara, Akiko Kitamura, Hidefumi Kojima, Hideo Yagita, Mamiko Sakata-Yanagimoto, Toshiki Saito, Ichiro Taniuchi, Shigeru Chiba, Saburo Sone, Koji Yasutomo
Journal: Nature Immunology (2008)
Prevalence, risk factors and consequences of severe burnout syndrome in ICU
Authors: Gastón Burghi, Jerome Lambert, Marine Chaize, Katerin Goinheix, Carlos Quiroga, Gerardo Fariña, Mario Godino, Gustavo Pittini, Sebastián Pereda, Carolina Fregossi, Silvia Mareque, Homero Bagnulo, Elie Azoulay
Journal: Intensive Care Medicine (2014)
Varicella-Zoster Virus Infection
Authors: SAM J. SUGAR
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 June 1988Varicella-Zoster Virus InfectionSAM J. SUGAR, M.D.SAM J. SUGAR, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-108-6-907_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The conference on varicella zoster by Strauss and colleagues (1) may indeed reflect one viewpoint on using medications for treating zoster, but it certainly does not reflect current clinical practices.Acyclovir, which is being marketed by its manufacturer (Zovirax, Burroughs Wellcome, Research Triangle Park, North Carolina) to be used extensively in primary care settings at the first evidence of an outbreak of zoster, appears to reduce the length of the illness from several weeks to several days when used in doses of 2 g per day for 5 days. In addition, the treatment of postherpetic neuralgia has...Reference1. SAWYER M. Treatment and prevention of varicella-zoster virus infeetions, pp 229-34. In: STRAUS SE, moderator. Varicella-zoster virus infeetions: biology, natural history, treatment, and prevention. Ann Intern Med. 1988;108:221-37. LinkGoogle Scholar1. SAWYER M. Treatment and prevention of varicella-zoster virus infections, pp 229-34. In: STRAUS SE, moderator. Varicella-zoster virus infections: biology, natural history, treatment, and prevention. Ann Intern Med. 1988;108:221-37. LinkGoogle Scholar2. BERNSTEINBICKERSDAHLROSHAL JDMJ. Treatment of chronic postherpetic neuralgia with topical capsaicin. J Am Acad Dermatol. 1987;17:93-6. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: SAM J. SUGAR, M.D.Affiliations: Glenbrook Medical Associates Evanston, IL 60201 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1988Volume 108, Issue 6Page: 907-907KeywordsVaricella zoster virus ePublished: 1 December 2008 Issue Published: 1 June 1988 PDF downloadLoading ...
High-fat nutrition reduces hepatic damage following exposure to bacterial DNA and hemorrhagic shock
Authors: Misha D.P. Luyer, Joep P.M. Derikx, Rudi Beyaert, M’hamed Hadfoune, Toin H. van Kuppevelt, Cornelis H.C. Dejong, Erik Heineman, Wim A. Buurman, Jan Willem M. Greve
Journal: Journal of Hepatology (2008)
Measuring Coverage in MNCH: Evaluation of Community-Based Treatment of Childhood Illnesses through Household Surveys
Authors: Elizabeth Hazel, Jennifer Requejo, Julia David, Jennifer Bryce
Journal: PLoS Medicine (2013)

Community case management (CCM) is a strategy for training and supporting workers at the community level to provide treatment for the three major childhood diseases—diarrhea, fever (indicative of malaria), and pneumonia—as a complement to facility-based care. Many low- and middle-income countries are now implementing CCM and need to evaluate whether adoption of the strategy is associated with increases in treatment coverage. In this review, we assess the extent to which large-scale, national household surveys can serve as sources of baseline data for evaluating trends in community-based treatment coverage for childhood illnesses. Our examination of the questionnaires used in Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) conducted between 2005 and 2010 in five sub-Saharan African countries shows that questions on care seeking that included a locally adapted option for a community-based provider were present in all the DHS surveys and in some MICS surveys. Most of the surveys also assessed whether appropriate treatments were available, but only one survey collected information on the place of treatment for all three illnesses. This absence of baseline data on treatment source in household surveys will limit efforts to evaluate the effects of the introduction of CCM strategies in the study countries. We recommend alternative analysis plans for assessing CCM programs using household survey data that depend on baseline data availability and on the timing of CCM policy implementation.
HISTOCHEMICAL COMPARISON OF THE EFFECTS OF A CARCINO-GENIC AND A NON-CARCINOGENIC DERIVATIVE OF TRI-CYCLOQTINAZOLINE
Authors: J. V. DIENGDOH, R. W. BALDWIN, J. CHAYEN
Journal: British Journal of Dermatology (1970)

SUMMARY.— Mouse skin is highly sensitive to irritants and to carcinogenic agents. Histochemistry has been used to demonstrate that the pattern in malignant growths is distinctively different from that in hyperplasia produced by irritants. Evidence is given to indicate that the altered pattern of metabolism can be discerned after a single application of the carcinogenic 3‐methyl‐TCQ (tricycloquinazoline) but that no significant alteration is induced by the non‐carcinogenic 2‐methyl‐TCQ.
Electronic Endoscopy - The Latest Technology
Authors: M. Classen, K. Knyrim, H. K. Seidlitz, F. Hagenmüller
Journal: Endoscopy (1987)

At present, video endoscopic systems (VE) are available from four companies. We have had an opportunity to test these instruments in clinical practice. In principle, all the VE's are similar in that they employ charge coupling devices (CCD-chips) as image sensors, but they differ significantly in CCD chip technology and in the color acquisition technique. The basic aspects of CCD chip and transmission technology of relevance to the endoscopist are discussed. The mechanical properties of the endoscopes are listed. Finally, we provide an outlook on the determinants of the optical performance of VE's. The optical performance of a VE can be characterized by its resolution and color performance.
Effect of Age and Sex on Human Drug Metabolism
Authors: K. O'Malley, J. Crooks, E. Duke, I. H. Stevenson
Journal: BMJ (1971)

The capacity of inpatients in a geriatric hospital to metabolize drugs was measured. The mean plasma half-life values with antipyrine and with phenylbutazone were found to be 45% and 29% greater respectively in patients than in young controls. When women alone were considered the half-life of antipyrine was 78% longer in the elderly group. In a number of elderly individuals the rate of metabolism of these two drugs was found to be extremely slow. This decreased ability to metabolize drugs may contribute to the known high incidence of adverse drug reactions in the elderly.Within the control group a significant sex difference in the rate of antipyrine metabolism was found, the mean half-life being 30% longer in the males. It is clear from these results that the age and sex of subjects must be taken into account in studies of human drug metabolism.
JAMA as an International Public Health Journal Transcending Geographic and Political Boundaries
Authors: Annette Flanagin, Irving G. Thomas, George D. Lundberg
Journal: JAMA (1991)

Seventy-two years ago, physicians in Central and South America read about the latest advances in the diagnosis and treatment of yellow fever and influenza in the pages of<i>JAMA</i>—but in their own language. Until the turn of the century, these physicians had sought information and education in the medical literature of France and Germany.<sup>1</sup>However,<i>JAMA</i>'s entry into the international publishing arena, reflecting the rise of early 20th-century US medicine, gave these physicians another reason to look north for new medical information. The<i>Edición en Español</i>, first published on January 1, 1919, looked much like a regular issue of<i>JAMA</i>.<sup>2</sup>The first issue featured 11 articles originally published in the Englishlanguage<i>JAMA</i>on such topics as blood transfusions, pasteurian methods of prophylaxis, the value of blood chemistry, and scabies in the military. In fact, four of the articles selected for inclusion in the Spanish edition were
Effects of n-3 Polyunsaturated Fatty Acids on Left Ventricular Function and Functional Capacity in Patients With Dilated Cardiomyopathy
Authors: Savina Nodari, Marco Triggiani, Umberto Campia, Alessandra Manerba, Giuseppe Milesi, Bruno M. Cesana, Mihai Gheorghiade, Livio Dei Cas
Journal: Journal of the American College of Cardiology (2011)
Doctors should stop supporting unethical screening
Authors: Margaret McCartney
Journal: BMJ (2011)

We are in serious trouble over screening. For all that medicine has cringed at paternalism and “doctor knows best,” has wrung its collective hands, and promised to do better, screening is still the last great preserve of unethical practice. 

If you are about to have a small skin tag removed, a quick procedure with low risk of hazards and complications, you have to give your written consent. The doctor must explain the procedure and potential hazards; the patient must understand and agree before anything is done. You are an adult, properly informed by your personal doctor, and free …
The delta-lambda model: “Yes” for simple movement trajectories; “no” for speed/accuracy tradeoffs
Authors: Charles E. Wright, David E. Meyer
Journal: Behavioral and Brain Sciences (1997)

Although it provides a useful description of elementary movement trajectories, we argue that the delta-lognormal model is deficient as an account of speed/accuracy tradeoffs in aimed movements. It fails in this regard because (1) it is deterministic, (2) its formulation ignores critical task elements, and (3) it fails to account for the corrective role of submovements.