tbuckley/cabot-search huggingface dataset:
Protein Evolution with Dependence Among Codons Due to Tertiary Structure
Authors: D. M. Robinson
Journal: Molecular Biology and Evolution (2003)

Markovian models of protein evolution that relax the assumption of independent change among codons are considered. With this comparatively realistic framework, an evolutionary rate at a site can depend both on the state of the site and on the states of surrounding sites. By allowing a relatively general dependence structure among sites, models of evolution can reflect attributes of tertiary structure. To quantify the impact of protein structure on protein evolution, we analyze protein-coding DNA sequence pairs with an evolutionary model that incorporates effects of solvent accessibility and pairwise interactions among amino acid residues. By explicitly considering the relationship between nonsynonymous substitution rates and protein structure, this approach can lead to refined detection and characterization of positive selection. Analyses of simulated sequence pairs indicate that parameters in this evolutionary model can be well estimated. Analyses of lysozyme c and annexin V sequence pairs yield the biologically reasonable result that amino acid replacement rates are higher when the replacements lead to energetically favorable proteins than when they destabilize the proteins. Although the focus here is evolutionary dependence among codons that is associated with protein structure, the statistical approach is quite general and could be applied to diverse cases of evolutionary dependence where surrogates for sequence fitness can be measured or modeled.
The Foundations of Bioethics
Authors: Kenneth L. Vaux
Journal: JAMA (1986)

In a volume that will prove to be a watershed in the modern literature of bioethics, Tristram Engelhardt, perhaps the preeminent philosopher of medicine working today, argues for a public biomedical ethic that would be characterized by toleration, peace, liberty of expression, and absence of coercion of any sort. He presents his thesis with erudition and passion:  ... one might ask under what circumstances there could ever be a peaceable union of peoples of the earth, save through acquiescing in the policy that persons may do with themselves and consenting others whatever they wish, despite what others might think and feel in the matter.  The former Rosemary Kennedy Professor at Georgetown, Washington, DC, and now Professor of Medicine at Baylor College of Medicine, Houston, proceeds to elucidate this philosophical theory and operational ethic as it bears on such questions as abortion, infanticide, and euthanasia. It is a bold and provocative book,
Care commissioning process is too laborious, study concludes
Authors: N. Hawkes
Journal: BMJ (2013)

NHS commissioners of care for people with long term conditions in England put much more effort into meetings and discussions than they do into hard headed analysis of the effectiveness of that care, an investigation of three primary care trusts has found.1

The study by the Nuffield Trust concluded that the commissioning process was laborious and asked whether the outcomes for patients justified the effort involved.

The trusts—Calderdale, Somerset, and the Wirral, chosen, the report says, because they seemed to be at the forefront of commissioning practice—focused on making “small but marginal service changes, for which the …
Begone Dull Care!
Authors: Jane A. McAdams
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Your selection of the emphysematous monster Care on the cover of your Jan 23 issue to accompany a communication about dogs who died from cigarette smoking is perhaps more appropriate than you realize. Care is indeed a killer, as noted in the full text of the song from which Gillray took his cue. One version reads: Begone dull care! You'd better begone from me! Begone dull care! I tell you we'll never agree. For a long time you've been waiting here, You're trying your best to kill. So begone dull care! You never shall have your will. Oh too much care will make a young man turn gray, And too much care will turn an old man to clay. Oh my wife shall dance and I will sing, So merrily pass the day. For the wisest man will drive dull care away. The song is from an
Regeneration of the Human Heart — No Chimera?
Authors: Roberto Bolli
Journal: New England Journal of Medicine (2002)

In ancient Greece, chimeras were mythical monsters — part lion, part goat, and part snake. In addition to these interspecies animal chimeras, human–animal hybrids were common in Greek mythology; the centaurs, the sirens, and the Minotaur are famous examples. It is from this fascinating and mysterious mixture of animal and human that the scientific term originated. In biology, a chimera is an organism formed from aggregates of genetically different groups of cells derived from the same or different species. Only a few decades ago, we would have thought of these creatures exclusively as figments of our imagination. As is often . . .
THE UNBROKEN SKIN AS AN ABSORBING MEDIUM.
Authors: THOMAS F. REILLY
Journal: JAMA (1901)

In a communication of this kind, consisting, as it largely does, of a review of the works of many observers, much condensation is necessary and many details must be omitted. In reviewing the literature of this subject from the beginning of the century, one is forcibly impressed by the ebb and flow in the popularity of the external application of medicinal agents for their constitutional effects. Early in the century this method was much in vogue. After 1860, under the inspiration of the experimental physiologists it was relegated to the rear, and for almost a quarter of a century, with the exception of treatises on the use of mercurial inunction in syphilis, there was little written on the subject. Within the past decade the pendulum, largely influenced by the French school of clinicians, has begun to swing to the opposite extreme. The experimental physiologists demonstrated that the lack of homogeneity
Complete reversibility of cat right ventricular chronic progressive pressure overload.
Authors: G Cooper, T A Marino
Journal: Circulation Research (1984)

Chronic, progressive pressure overload of the cat right ventricle produces persistent, ongoing abnormalities of contractile, energetic, and biochemical function in vitro at a time when in vivo pump function is still normal. The present study tested the reversibility of the in vitro changes in this clinically relevant hypertrophy model. Fourteen sham-operated and 14 reversal cats were studied. After banding the animals as 1-kg kittens, right ventricular pressures were normal. Before band removal (25.2 +/- 0.5 weeks later for the control group and 25.5 +/- 0.3 weeks later for the hypertrophy reversal group), systolic right ventricular pressures were 24 +/- 1 mm Hg for controls and 71 +/- 5 mm Hg for the hypertrophy reversal group (P less than 0.05). At study, 19.5 +/- 1.1 weeks after a second sham operation for controls or 18.7 +/- 0.7 weeks after band removal for the hypertrophy reversal group, these pressures were 24 +/- 1 mm Hg for controls and 23 +/- 1 mm Hg for the hypertrophy reversal group (P = NS); cardiac output was 0.18 +/- 0.01 liters/kg per min for controls and 0.19 +/- 0.01 liters/kg per min for the hypertrophy reversal group (P = NS). The ratio of right ventricle to body weight was normal in both groups, as was the right ventricular papillary muscle myocyte cross-sectional area and the myocardial collagen concentration. A right ventricular papillary muscle from each cat was studied at 29 degrees C in a polarographic myograph. Preloaded shortening velocity was 0.79 +/- 0.04 muscle lengths/sec for controls and 0.86 +/- 0.03 muscle lengths/sec for the hypertrophy reversal group (P = NS); extent of shortening was 0.15 +/- 0.01 muscle lengths for controls and 0.16 +/- 0.01 muscle lengths for the hypertrophy reversal group (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Role of calcium and calmodulin in activation of the oxyntic cell by histamine and carbamylcholine in the guinea pig.
Authors: W Walker, A Vinik, A Heldsinger, R Kaveh
Journal: Journal of Clinical Investigation (1983)

The role of calcium in stimulation of the oxyntic cell by histamine and carbamylcholine was studied using a sensitive quantitative cytochemical staining technique that measures oxyntic cell hydroxyl ion production (HIP) as an index of acid secretion. Histamine (10(-17)-10(-14) M), carbamylcholine (10(-12)-10(-9) M), and extracellular calcium (10(-7)-10(-3) M) caused a linear, dose-dependent stimulation of the oxyntic cell. EGTA (10(-6) M) inhibited carbamylcholine by 50% but not histamine-stimulated activity. Lanthanum chloride (10(-6) M) caused 100% inhibition of carbamylcholine-induced activity but did not affect histamine-stimulated activity. A maximally effective dose of calcium (10(-4) M) caused additive effects on HIP at low doses of carbamylcholine without alteration of the maximal effect of carbamylcholine. Calcium (10(-4) M) did not enhance the effects of histamine. The calmodulin antagonists, trifluoperazine (10(-5) M), pimozide (10(-5) M), and a naphthalenesulfonamide (W-7), inhibited the integrated response to histamine by 54, 56, and 53%, and that of carbamylcholine by 65, 64, and 99%, respectively. Thus, extracellular calcium per se, stimulates the oxyntic cell. The action of carbamylcholine is completely dependent upon calcium/calmodulin mediation, supporting the concept that cholinergic actions are mediated via calcium-calmodulin events. Although histamine does not require extracellular or membrane calcium events to stimulate the oxyntic cell, calmodulin appears to participate in histamine action.
Advancing Quality: Total Quality Management in the National Health Service * The Practice of Quality
Authors: P. Wilcock
Journal: BMJ (1996)

Advancing Quality: Total Quality Management in the National Health Service 

Richard Joss, Maurice Kogan Open University Press, £14.99, pp 215 ISBN 0 335 19395 1

The Practice of Quality 

Donald Irvine, Sally Irvine Radcliffe, £16.50, pp 206 ISBN 1 85775 073 X

Written from very different perspectives, these books come at a time when traditional paradigms of quality are being increasingly questioned. The Irvines' book is based on their extensive experience of working in primary care, while Joss and Kogan's more detailed research account analyses their three year study of a sample of the hospital and community services funded by the Department of Health to test the relevance of total quality management principles to health care.

Both books focus on the dynamic of improving health care rather than merely …
New antiepileptic drugs
Authors: M. J Brodie, A J A Elferink, B J V. Zwieten-Boot, J. J Craig, J. I Morrow, I. C Wong
Journal: BMJ (1997)

Interferon beta in multiple sclerosis Reducing frequency and severity of relapses will be of great clinical benefitEditor-Richard G Richards's editorial on interferon beta in multiple sclerosis deals with the "clinical cost effectiveness" of the drug in the disease, but it lacks a fair balance, emphasising the cost effectiveness and minimising the clinical effectiveness of the drug. 1 Richards states that "the studies showed no evidence of any reduction in the more clinically relevant endpoint-the progression of disability, which should be the goal of treatment."This is his personal judgment and does not reflect the needs and wishes of patients with multiple sclerosis and their families.Multiple sclerosis is a distressing, humiliating, and often long drawn out disease with no cure.For this reason, quality of life, for the patients and their families, is paramount.A drug that can reduce the frequency and severity of relapses, whether or not it diminishes the progression of the disease, will be of great clinical benefit to many patients, improving their situation physically, psychologically, and socially.Surely happiness, feeling better, and increased health have great value.This is what many of us believe that the practice of our profession is about.
Change of energy expenditure from physical activity is the most powerful determinant of improved insulin sensitivity in overweight patients with coronary artery disease participating in an intensive lifestyle modification program
Authors: Marie C. Audelin, Patrick D. Savage, Michael J. Toth, Jean Harvey-Berino, David J. Schneider, Janice Y. Bunn, Maryann Ludlow, Philip A. Ades
Journal: Metabolism (2011)
Abstract 2798: VDR gene polymorphism and risk of prostate cancer in African-American
Authors: Mohammad Daremipouran, Desta Beyene, Seyed-Mehdi Nouraie, Yasmine Kanaan
Journal: Cancer Research (2010)

Abstract Background: Genetics and epidemiological studies have shown that genes and environment interaction play strong roles in prostate cancer etiology. We have already shown that higher UV exposure, higher serum vitamin D, and lower skin pigmentation inversely associated with the risk of prostate cancer in African-American. Methods: In order to explore the relationship between Vitamin D receptor (VDR) polymorphisms and prostate cancer risk in African American men; 91 affected African American men with histologically diagnosed adenocarcinoma of the prostate, PSA of &amp;gt; 2.5 ng/ml and a positive digital rectal exam have been recruited. Ninety-one age and ethnicity matched controls have been also recruited. Genomic DNA was extracted from blood sample of each case and control subjects. Nine primers were designed for amplification of 9 different axons in VDR gene. DNA fragments from all samples were amplified using PCR reaction. In order to investigate the existence of heteroduplex, PCR products denatured and using denaturing high performance liquid chromatography (DHPLC) technique heteroduplex analysis on the Wave system was performed. Those samples demonstrating heteroduplex peaks were sequenced using an ABI 377 DNA sequencer. Results: Seven polymorphisms in VDR sequence were confirmed after sequencing. SNPs 132G&amp;gt;A, 332 G&amp;gt;A, 83 G&amp;gt;A, invs9-286C&amp;gt;T, 122 A&amp;gt;G, and invs10-49G&amp;gt;T are located in non-coding region. 209 T&amp;gt;C SNP is located in coding region. However this SNP is anonymous as previously reported. 332G&amp;gt;A, 83G&amp;gt;A, and invs9-286C&amp;gt;T SNPs showed strong negative association with prostate cancer risk (p&amp;lt; 0.05). 132G&amp;gt;A, 209T/C, and IVS10-49G&amp;gt;T showed direct association with risk of prostate cancer but statistically is not significant. Using Binary Logistic Regression Model confirmed that 332G&amp;gt;A, 83G&amp;gt;A, and invs9-286C&amp;gt;T SNPs are good predictor of protection against prostate cancer. Whereas having SNP 209T&amp;gt;C is strong indicator of risk of prostate cancer. Conclusion: It is possible that genetic variants may mediate prostate cancer risk via a mechanism involving availability of 1, 25(OH)2 D. Vitamin D protects against risk of prostate cancer. UV exposure, good vitamin D diet, and lighter skin along with advantageous VDR polymorphism as modulators of vitamin D can improve this protection. We are in the process of assessment of analysis the interaction between other genes involved in vitamin D metabolism and environmental factors. Our results require further corroboration in large statistically powerful sample collections. 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 2798.
THE TRANSMISSION OF TREPONEMA PALLIDUM FROM THE BRAINS OF PARETICS TO THE RABBIT
Authors: HIDEYO NOGUCHI
Journal: JAMA (1913)

The finding of<i>Treponema pallidum</i><sup>1</sup>in the substance of the brains of paretics has now been confirmed by several investigators in this country and abroad. Since the first report in which the<i>pallidum</i>was described as having been discovered in twelve of the seventy brains from which sections had been studied, I have now found the spirochetes in thirty-six of one hundred and thirty additional brains, from which sections stained by the modified Levaditi method<sup>2</sup>were examined. Thus, in two hundred cases of paresis so far studied the<i>pallidum</i>has been seen by me in forty-eight, or in nearly 25 per cent. of the specimens. I have, moreover, also succeeded in finding the micro-organism in one of twelve specimens of the spinal column, studied from cases of tabes dorsalis. A spiral organism morphologically identical with the<i>pallidum</i>was in this instance found in the posterior columns of the
Report Focuses on Global Patterns of Violence Against Children
Authors: M. J. Friedrich
Journal: JAMA (2014)

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Prospective Phase II Trial of Neoadjuvant Chemotherapy With Gemcitabine and Cisplatin for Resectable Adenocarcinoma of the Pancreatic Head
Authors: Stefan Heinrich, Bernhard C. Pestalozzi, Markus Schäfer, Achim Weber, Peter Bauerfeind, Alexander Knuth, Pierre-Alain Clavien
Journal: Journal of Clinical Oncology (2008)

To test the safety of neoadjuvant chemotherapy for resectable pancreatic cancer.Patients with cytologically proven resectable adenocarcinoma of the pancreatic head were eligible for this prospective phase II trial. After confirmation of resectability by contrast-enhanced computed tomography (ceCT), positron emission tomography/CT, laparoscopy, and endoscopic ultrasound, patients received four biweekly cycles of gemcitabine 1,000 mg/m(2) and cisplatin 50 mg/m(2). Thereafter, staging was repeated and patients underwent surgery. Quality of life (QoL) and prealbumin serum levels were determined pre- and postchemotherapy. Follow-up included 3-month CA 19-9 measurements and ceCT after 6, 12, 18, and 24 months. Histologic tumor response was assessed by two scoring systems.Twenty-eight patients entered this study. Adverse effects were mainly gastrointestinal and hematologic, most often mild, and never of grade 4. Twenty-six patients (93%) had resectable cancer on restaging examinations, and the R0 resection rate was 80%. Histologic tumor response and cytopathic effects were documented in 54% and 83% of patients, respectively. On intention-to-treat analysis, disease-free and overall survival were 9.2 months (95% CI, 5.6 to 12.9 months) and 26.5 months (95% CI, 11.4 to 41.5 months) and 9 months (95% CI, 6.99 to 10.1 months) and 19.1 months (95% CI, 15 to 23.1 months) for ductal adenocarcinoma, respectively. QoL improved in two items and was unchanged in all other items. Moreover, prealbumin serum levels significantly improved during chemotherapy (P = .008). CONCLUSION Neoadjuvant chemotherapy with gemcitabine and cisplatin is well tolerated and does not impair resectability of pancreatic cancer. Furthermore, it improves the QoL and the nutritional status of affected patients with favorable overall and disease-free survival.
Small-Bowel Obstruction During Enzymatic Treatment of Gastric Bezoar
Authors: H. Nomura, T. Kitamura, Y. Takahashi, M. Mai
Journal: Endoscopy (1997)

A 66-year-old woman had a sudden onset of small-bowel obstruction during enzymatic treatment for gastric persimmon bezoar. Oral enzymatic therapy is the most effective method of treatment for large phytobezoars when endoscopic extraction is not possible. However, this report suggests that a further endoscopic intervention may be necessary in case the dissolved bezoars cause small-bowel obstruction during this form of therapy.
Benchmarking framework for myocardial tracking and deformation algorithms: An open access database
Authors: C. Tobon-Gomez, M. De Craene, K. McLeod, L. Tautz, W. Shi, A. Hennemuth, A. Prakosa, H. Wang, G. Carr-White, S. Kapetanakis, A. Lutz, V. Rasche, T. Schaeffter, C. Butakoff, O. Friman, T. Mansi, M. Sermesant, X. Zhuang, S. Ourselin, H-O. Peitgen, X. Pennec, R. Razavi, D. Rueckert, A.F. Frangi, K.S. Rhode
Journal: Medical Image Analysis (2013)
Copeptin as a marker of relative arginine vasopressin deficiency after pediatric cardiac surgery
Authors: Christopher W. Mastropietro, Meredith Mahan, Kevin M. Valentine, Jeff A. Clark, Patrick C. Hines, Henry L. Walters, Ralph E. Delius, Ashok P. Sarnaik, Noreen F. Rossi
Journal: Intensive Care Medicine (2012)
THE NATURE OF “PREFORMED WATER”
Authors: John P. Peters, Paul H. Lavietes
Journal: Journal of Clinical Investigation (1933)

In the method which Newburgh and Johnston (1, 2) have proposed for the calculation of water exchange, they define the latter as consisting of three components: 1, preexisting water from the external environment; 2, water formed de novo by the oxidation of food stuffs; 3, " preformed water."This last term is applied to water which already existed as such in the tissues, presumably acting as a solvent for protoplasmic substances in the cells and as both solvent and vehicle in the circulating fluids and extracellular (or interstitial) fluids.This fluid or some fraction of it, they postulate, is intimately associated with protein, fat and carbohydrate (glycogen) in the tissues and is liberated when the latter are burned.Con- versely it may be presumed that a fraction of the extraneous water be- comes bound when the body content of these substances increases.It has been pointed out (3) in a simple analysis of the form of their mathematical calculations that it may be advisable, for certain purposes, at least, to dis- tinguish this third fraction of water from the others because it belongs in a different category.For this reason two equations were proposed, based on Newburgh and Johnston's methods of calculation.The first of these expresses the change in the total quantity of water in the body:1. WB= (W2 W1) + (Se-Sr) + (Pb + Cb + 0.49Pb), in which WB represents water balance; W1 and W2 initial and final body
Autoantibodies to an epidermal protease inhibitor in skin diseases
Authors: V.K. HOPSU-HAVU, KIRSTI KALIMO, M. JARVINEN
Journal: British Journal of Dermatology (1981)

Solid phase radioimmunoassay for measurement of autoantibodies in human sera to an epidermal protein is presented. The protein purified from normal human epidermis is inhibitory to SH-dependent protease and its molecular weight is about 13,000. Antibodies were detected in 139 of the 4,400 sera collected from dermatological patients. Most of the patients suffered from wide-spread eczematous conditions. It is suggested that the antibodies are secondary to the inflammatory conditions, but they may exacerbate or delay the course of the disease.
Endolyn (CD164) modulates the CXCL12-mediated migration of umbilical cord blood CD133+ cells
Authors: Sinead Forde, Britt Jorgensen Tye, Sarah E. Newey, Maria Roubelakis, Jon Smythe, Colin P. McGuckin, Ruth Pettengell, Suzanne M. Watt
Journal: Blood (2006)
Prevalence and Socioeconomic Impact of Upper Gastrointestinal Disorders in the United States: Results of the US Upper Gastrointestinal Study
Authors: M CAMILLERI, D DUBOIS, B COULIE, M JONES, P KAHRILAS, A RENTZ, A SONNENBERG, V STANGHELLINI, W STEWART, J TACK
Journal: Clinical Gastroenterology and Hepatology (2005)