tbuckley/cabot-search huggingface dataset:
Regulation of COX-2–mediated signaling by α3 type IV noncollagenous domain in tumor angiogenesis
Authors: Chandra Shekhar Boosani, Arjuna P. Mannam, Dominic Cosgrove, Rita Silva, Kairbaan M. Hodivala-Dilke, Venkateshwar G. Keshamouni, Akulapalli Sudhakar
Journal: Blood (2007)
Abstract 5148: CanDrA: Cancer-specific driver missense mutation annotation with optimized features.
Authors: Yong Mao, Han Chen, Han Liang, Funda Meric-Bernstam, Gordon Mills, Ken Chen
Journal: Cancer Research (2013)

Abstract Driver mutations are somatic mutations that provide growth advantage to tumor cells, while passenger mutations are those that are not functionally associated with oncogenesis. Distinguishing drivers from passengers is challenging because drivers occur much less frequently than passengers, they turn to have low prevalence, and their functions are multifactorial. Missense mutations are excellent candidates for driver identification, as they occur more frequently and are potentially easier to target than other types of mutations. Although several methods have been developed for predicting the functional impact of missense mutations, only a few are specifically designed for identifying driver mutations. As more mutations are being discovered, more accurate predictive models can be developed using machine learning approaches that systematically characterize the commonality and peculiarity of somatic mutations under specific cancer background. Here, we present such a Cancer Driver Annotation (CanDrA) tool that assesses the driver potential of missense somatic mutations based on a set of 95 structural and evolutionary features computed by over 10 functional prediction algorithms from SNVBOX, VEP, ANNOVAR and Mutation Assessor. Through feature optimization and supervised training, CanDrA outperforms existing tools in analysing the glioblastoma multiforme and the ovarian carcinoma data in The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia project. Citation Format: Yong Mao, Han Chen, Han Liang, Funda Meric-Bernstam, Gordon Mills, Ken Chen. CanDrA: Cancer-specific driver missense mutation annotation with optimized features. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5148. doi:10.1158/1538-7445.AM2013-5148
Antihistamines in the treatment of asthma
Authors: Alnoor Malick, J. Andrew Grant
Journal: Allergy (1997)

Antihistamines were investigated for use in asthma shortly after discovery over fifty years ago. Earlier compounds proved ineffective because of side effects: this class of drugs was not thought useful for asthma, and were actually considered contraindicated. More recent drugs have greater potency, fewer side‐effects, and no evidence of adverse effects in asthma. There are some studies showing second generation antihistamines, especially cetirizine, improve certain parameters of asthma.
407. A Single Unilateral Injection of AAV1-ASA and AAV1-FGE Vectors into the Hippocampus Results in Bilateral Expression and Widespread Distribution of ASA and Prevention of Sulfatide Storage in the Whole Brain of MLD Model Mice
Authors: Toshiyuki Kurai, Sanae Hisayasu, Yukihiko Hirai, Makoto Migita, Hidenori Suzuki, Takashi Shimada
Journal: Molecular Therapy (2006)

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by a deficiency of arylsulfatase A (ASA). The disease is characterized by progressive demyelination and widespread deposition of sulfatide in both the central and peripheral nervous systems. Therefore, direct injection of viral vector through the blood brain barrier is a possible approach for gene therapy of MLD. Lysosomal enzymes including ASA are known to be secreted and recaptured by surrounding cells through the mannose-6 phosphate receptor mediated pathway. Despite of this unique property, to treat the whole brain, it is likely that a large number of vector particles should be repeatedly injected into multiple sites. High efficient gene transfer and expression are critical for direct gene therapy of the brain of MLD. We have previously reported that co-expression of formylglycine generating enzyme (FGE), which is a post-translational modifying enzyme essential for activating all sulfatases, is essential for over-expression of functional ASA both in vitro and in vivo. In this study, we examined the utility of FGE co-expression in AAV1 mediated gene therapy of ASA knockout (MLD) mice. A preliminary experiment showed that stereotactic injection of AAV1-GFP into the CA3 region of the hippocampus resulted in strong GFP expression in both ipsilateral and contralateral hippocampi, suggesting that AAV1 vector is efficiently transported through axons to distal cell bodies. In a treatment experiment, AAV1-ASA alone or AAV1- ASA plus AAV1-FGE (total 7.5×109particles) were injected into the right hippocampus CA3 region of 8 month-old ASA knockout mice. The treated mice were analyzed 7 months after injection. Colorimetric assay of brain homogenates showed that injection of AAV1-ASA alone increased ASA activity in the injected hemisphere along with a slight increase in ASA in the non-injected hemisphere. Co-introduction of AAV1-ASA and AAV1-FGE significantly increased ASA activity in both sides. Widespread distribution of ASA was also confirmed by immunohistochemical analysis using anti-ASA antibody. Alcian blue staining and chemical analysis showed that sulfatide in the injected hemisphere was decreased after AAV1- ASA injection. Remarkably, reduction of sulfatide in the whole brain was observed when AAV1-ASA and AAV1-FGE were co-introduced. Rotarod test and walking pattern revealed significant improvement of neurological functions. These results indicate that AAV1 mediated expression of ASA and FGE is highly efficient for long-term expression and secretion of functional ASA in the brain. Unexpectedly, ASA could be distributed to the brain areas distant from the site of gene transfer by axonal transfer and diffusion. Extensive distribution of ASA in the brain may rationalize direct gene therapy of MLD.
Diagnostic performance of T-SPOT.TB for extrapulmonary tuberculosis according to the site of infection
Authors: Oh-Hyun Cho, Ki-Ho Park, Sun-Mi Kim, Su-Jin Park, Song Mi Moon, Yong Phil Chong, Heungsup Sung, Mi-Na Kim, Jin-Yong Jeong, Sang-Oh Lee, Sang-Ho Choi, Jun Hee Woo, Yang Soo Kim, Sung-Han Kim
Journal: Journal of Infection (2011)
Explicitness and nonconnectionist vehicle theories of consciousness
Authors: Fernando Martínez-Manrique
Journal: Behavioral and Brain Sciences (2004)

O'Brien & Opie's connectionist vehicle theory of consciousness is heavily dependent on their notion of explicitness as (1) structural and (2) necessary and sufficient for consciousness. These assumptions unnecessarily constrain their position: the authors are forced to find an intrinsic property of patterns that accounts for the distinction between conscious and unconscious states. Their candidate property, stability, does not capture this distinction. Yet, I show that we can drop assumptions (1) and (2) and still develop a vehicle theory of consciousness. This alternative is better served by models that incorporate both connectionist and symbolic representations.
Blood Oxygen Level–Dependent Magnetic Resonance Imaging in Patients with Stress-Induced Angina
Authors: Matthias G. Friedrich, Thoralf Niendorf, Jeanette Schulz-Menger, C. Michael Gross, Rainer Dietz
Journal: Circulation (2003)

Blood oxygen level-dependent (BOLD) MRI reflects tissue oxygenation and may be useful for the detection of myocardial ischemia in patients with suspected coronary artery disease.We studied 25 patients with stress-induced angina using a T2*-sensitive echo planar imaging sequence before and during adenosine in a single-slice approach. BOLD-MRI results were compared with quantitative angiography and adenosine thallium single-photon emission computed tomography (SPECT). Although image quality was variable because of artifacts, no data were excluded from the analysis. During adenosine, a mean signal intensity decrease was observed for myocardial segments related to coronary stenoses >75%. On average, a nonsignificant increase was observed in the other segments. The angiographically determined stenosis was correlated with BOLD-MRI results. Including all segments and using BOLD-MRI signal intensity increase cutoff value of 1.2%, BOLD-MRI had a sensitivity of 88% and a specificity of 47% to correctly classify severe stenoses. Adenosine thallium SPECT data from distal segments of the same coronary territory were also correlated with BOLD-MRI. However, variability was substantial.In patients with stress-induced angina, adenosine BOLD-MRI detects myocardial ischemia in myocardial segments related to severe coronary stenoses. Its potential will increase with additional improvement of spatial coverage and image quality.
Book: The Bewitching of Anne Gunter: A Horrible and True Story of Football, Witchcraft, Murder and the King of England
Authors: J. Cayley
Journal: BMJ (2000)

James Sharpe Profile Books, £16.99, pp 256 ISBN: 186197048X Rating: ![Graphic][1]</img>![Graphic][2]</img> Some eminent 17th century doctors gathered at the bedside of Anne Gunter. They included the regius professor of medicine at Oxford and John Hall, almost certainly the Dr Hall who married Shakespeare's daughter. All were agreed that the bizarre fits from which Anne suffered could not be due to illness but must have some supernatural cause. Other physicians who examined Anne later, notably the famous Edward Jorden, were sceptical. The matter was eventually brought before King James I himself. … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
LIMITATIONS OF THE AGGLUTINATION REACTION IN THE DIAGNOSIS OF BACILLARY DYSENTERY
Authors: J. Menton
Journal: BMJ (1928)

Microscopically the intestine showed nothing beyond intense congestion and catarrh.Death was therefore due to an intense intoxication, there being 'no time for structural changes to be produced.Cultures from the contents of the large intestine an.d from the ileo-caecal lymphatic glands yielded abundant and almost pure growths of the Sonne bacillus, but cultures from the contents of the ileum, spleen, and heart blood were negative.The bacillus had the following characters.On the MacConkey plate it formed rather large, opaque, rounded colonies, which at first remained colourless.Subcultures into the fluid sugar media gave the results tabulated below: Lactose ... ... ... ...
Performance related pay for general practitioners
Authors: P. Bower
Journal: BMJ (1990)

They are quite correct to point out that an accurate diagnosis cannot be reached on the basis of one completion of the mental status question- nalre.Cognitive impairment can indeed be misdiagnosed in patients with a low intelligence quotient who are depressed and those who are in an acute confusional state.This lack of diagnostic specificity was partly offset by the large number concerned in the screening investigation, and the test was selected on the basis of its brevitv and acceptability.'rhere are two misconceptions, however, in their letter.Firstly, the mental status questionnaire does not entail tests of calculation or short term memory.Secondly, their reference to our earlier study' implies that the diagnosis of dementia was reached in a similar fashion therein.In fact, the subjects in the earlier study were diagnosed after an interview, the use of several cognitive tests, and the collection of information from a relative whenever this was possible.Dr McRorie and colleagues mention that it may be illuminating to establish the acutal causes of death in our sample.This we are seeking to do at the same time as we investigate whether admitting patients into an institution conferred a protective effect against early death.
Dengue Fever: A Thrombocytopenic Disease?
Authors: Ethel R. Nelson, Howard R. Bierman
Journal: JAMA (1964)

In a study of dengue fever in Thailand, bone-marrow examinations showed hypocellularity early in the disease, followed by hypercullarity during recovery and normocellularity in convalescence. Thrombocytopenia due to megakaryocytic suppression was a characteristic. In 18 patients with early dengue, thrombocytopenia lasted one to four days; platelet counts in 8 were less than 50,000/cu cm. Petechiae or other bleeding manifestations were noted in 15 patients. Intensive hematologic studies of dengue infections in other geographic areas are suggested, to determine if thrombocytopenia is a universal characteristic of this and related virus diseases.
Effect of Procaine Amide, Quinidine, and Ajmaline in the Wolff-Parkinson-White Syndrome
Authors: HEIN J.J. WELLENS, DIRK DURRER
Journal: Circulation (1974)

Using the single test stimulus method, atrioventricular (A-V) conduction, ventriculo-atrial conduction, the refractory period of right atrium and right ventricle, and the mechanism of tachycardia were studied in 16 patients with the Wolff-Parkinson-White syndrome. The same studies were repeated at least four times during the hour following intra-atrial administration of 10 mg procaine amide/kg body weight (six patients), 4 mg quinidine gluconate/kg body weight (six patients), or 50 mg ajmaline (four patients). Following procaine amide the refractory period of the accessory pathway increased in all patients, with temporary complete block of the accessory pathway in four patients. There was an increase in H-V interval during antegrade conduction through the A-V node-His pathway. The effective refractory period of the A-V node showed no appreciable change. In three of four patients tachycardia could not be produced by pacing in contrast to the pacing effect found prior to procaine amide. Quinidine gluconate increased the refractory period of the accessory pathway in four patients, causing temporary complete block in two patients. The H-V interval increased in three patients. The refractory period of the A-V node showed no change in three patients, lengthened in one, and shortened in the other two. Quinidine gluconate prevented pacing-induced initiation of tachycardia in two out of four patients. Ajmaline * increased the refractory period of the accessory pathway in all four patients, with temporary complete block in three patients. The H-V interval also lengthened. No change was observed in the refractory period of the A-V node. Ajmaline prevented initiation of tachycardia in one out of two patients. In the other patient tachycardias could still be initiated despite disappearance of pre-excitation during atrial pacing. In one patient in each group tachycardia could be produced during pacing following drug administration where no tachycardia could be produced under control conditions. In two patients re-entry in the A-V node during ventricular pacing caused this phenomenon. In the other patient administration of the drug prevented atrial re-entry during atrial pacing. This re-entrant beat had previously created refractoriness in the atrial part of the tachycardia pathway. The changes following procaine amide, quinidine gluconate, and ajmaline were clearly short term; their effects disappeared after one hour in 15 of the 16 patients studied.
A False-negative Xenon-133 Study in Focal Fatty Infiltration of the Liver
Authors: MICHAEL F. HARTSHORNE, LIDA A. CROOKS, WILLIAM BENNETT, HECTOR RAMIREZ, STEPHEN R. BUNKER, MICHAEL A. CAWTHON, ROBERT D. KARL, JOHN M. BAUMAN
Journal: Clinical Nuclear Medicine (1985)

A Xe-133 hepatic study was misleading when the absence of Xe-133 localization in an area of low CT numbers was considered to be negative for a diagnosis of focal fatty infiltration.
Unsuspected exposure to asbestos and bronchogenic carcinoma.
Authors: K M Martischnig, D J Newell, W C Barnsley, W K Cowan, E L Feinmann, E Oliver
Journal: BMJ (1977)

Two hundred and fifty men admitted to a thoracic surgical centre and matched controls were questioned in detail about their occupations after leaving school and their smoking habits. Of 201 men with confirmed bronchial carcinoma 58 gave a history of occupational exposure to asbestos, whereas only 29 out of 201 men matched for age and residential area who were admitted with other diseases gave such a history. This difference was statistically highly significant. The usual association of bronchial carcinoma with heavy smoking was observed, but asbestos exposure increased the risk of carcinoma whatever the level of smoking. These results are consistent with the hypothesis that asbestos exposure and the level of smoking act independently in causing bronchial carcinoma. The patients with carcinoma who had been exposed to asbestos presented on average three years earlier than those who had not been exposed. Asbestos regulations have eliminated the risk of exposure to workers in scheduled industries, so asbestos-induced diseases will probably be increasingly found among the many workers who have had incidental exposure to asbestos. It is therefore important to take a full occupational history.
A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy
Authors: A K Stewart, P L Bergsagel, P R Greipp, A Dispenzieri, M A Gertz, S R Hayman, S Kumar, M Q Lacy, J A Lust, S J Russell, T E Witzig, S R Zeldenrust, D Dingli, C B Reeder, V Roy, R A Kyle, S V Rajkumar, R Fonseca
Journal: Leukemia (2007)
Human autoantibodies to poly(adenosine diphosphate-ribose) polymerase recognize cross-reactive epitopes associated with the catalytic site of the enzyme.
Authors: H Yamanaka, E H Willis, D A Carson
Journal: Journal of Clinical Investigation (1989)

The factors responsible for the production of autoantibodies against self-components are not well understood. We have identified monospecific human autoantibodies to poly(ADP-ribose) polymerase (ADPRP) in the sera of rheumatic patients. Since this nuclear enzyme has been extensively characterized, and its entire structure is known, we could investigate in detail the epitope specificity of the human autoantibodies, and their effects on the biological functions of the enzyme. All sera with autoantibodies to ADPRP recognized the NAD-binding domain of the enzyme, as demonstrated by either immunoblotting or immunoprecipitation of partially proteolyzed ADPRP. The autoantibodies also inhibited the catalytic activity of the purified enzyme, as measured by the transfer of ADP-ribose from [32P]NAD to either histones or to ADPRP itself. Because comparative structural analyses have shown that the active sites of enzymes are often conserved during evolution, we tested the ability of the autoantibodies to react with ADPRP from lower eukaryotes. The human autoantibodies reacted with ADPRP in cellular extracts from mammalian, avian, amphibian, arthropod, and protozoan cells, and also inhibited the catalytic activity of the various enzymes. Collectively, these experiments indicate that the human autoantibodies to ADPRP recognize a distinct group of evolutionarily conserved antigenic determinants that are closely related to the catalytic site of the enzyme. The results are consistent with the hypothesis that the epitope selectivity of human autoantibodies to ADPRP is influenced by cross-reactive antigens in the external environment.
Best books on anaesthesia: a personal choice
Authors: N Goodman
Journal: BMJ (1994)

Anaesthesia is applied physiology, pharmacology, and physics; their application depends on knowledge of medicine and surgery. General textbooks of anaesthesia should move from the scientific principles to clinical practice and will never include enough detail for someone especially interested in particular topics.

(Fig Omitted)

I guess that the large textbooks are bought mostly by libraries and by candidates for the FRCA examinations who want something more than spoon feeding, though my advice to them is to use the contents pages of a large textbook as a list of topics to be covered and to write their own textbook of notes from reviews and editorials. These are written by the same people who write the chapter in the textbooks but are more up to date.

Contributors to textbooks must give readers perspective, not merely regurgitated fact. The editors must have done more than collect the manuscripts and send them to the publisher. No textbook is going to be glaringly incorrect for even a chapter or two, so probably the most important consideration is whether it is easy to read. Is the text a sensible size and laid out well? Are the diagrams clear, and are they to a uniform style? Will the pages dissolve or stick together when the inevitable coffee or propofol gets spilled on them? Textbooks …
Systole has little effect on diastolic coronary artery blood flow.
Authors: S A Katz, E O Feigl
Journal: Circulation Research (1988)

The hypothesis that myocardial systolic contraction attenuates diastolic coronary flow was tested by comparing flow during diastole to flow during a prolonged asystole. The circumflex coronary artery was cannulated and perfused at constant pressure in closed-chest, morphine- and alpha-chloralose-anesthetized dogs. The heart was paced at 80, 120, 160, or 200 beats/min after atrioventricular heart block under control, intracoronary adenosine, and intravenous norepinephrine treatment conditions. Cessation of pacing while holding coronary pressure constant at the previous diastolic pressure resulted in asystolic circumflex flow that initially equaled the previous diastolic flow during heart rates of 80, 120, and 160 in all treatment groups. Initial asystolic circumflex flow was approximately 5% higher than the previous diastolic flow at a heart rate of 200 beats/min, but this was probably due to an artifact. It is concluded that systolic contraction does not limit diastolic coronary flow at heart rates less than 160 beats/min and probably does not at higher heart rates.
The Big Blue
Authors: P McCrory
Journal: British Journal of Sports Medicine (2003)

In October 2002, Audrey Mestre both set a world record for free diving and died in an attempt to extend it further.This extreme sport is fascinating for sports physicians as it represents a very practical demonstration of pulmonary physiology.Free diving was made popular by the 1988 French film, The Big Blue, which was inspired by real events and featured spectacular underwater cinematography.Currently there are more than 20 000 free divers worldwide and the numbers are growing.The International Association of Free Divers (IAFD) based in Miami, USA oversees the sport and certifies world records.Most free divers use the "constant ballast" technique in which divers use fins but no extra weights to dive as deep as possible before coming up for air."No limit" free divers take it further by using a metal sled (weighing 90kg) that slides down a vinyl coated steel cable.When the diver wishes to ascend, he or she releases an airbag at the top of the sled that shoots the diver back to the surface.Due to the relatively short submersion time, decompression sickness is not normally a problem although the effects of rapid pressure changes on air-fluid interfaces in the body may result in the same spectrum of problems seen in compressed air divers.Fewer than two dozen elite athletes compete in the "no limit" extreme category attempting to push the boundary of human performance ever further.