tbuckley/cabot-search huggingface dataset:
ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression
Authors: Young-Ho Ahn, Don L. Gibbons, Deepavali Chakravarti, Chad J. Creighton, Zain H. Rizvi, Henry P. Adams, Alexander Pertsemlidis, Philip A. Gregory, Josephine A. Wright, Gregory J. Goodall, Elsa R. Flores, Jonathan M. Kurie
Journal: Journal of Clinical Investigation (2012)

Metastatic cancer is extremely difficult to treat, and the presence of metastases greatly reduces a cancer patient's likelihood of long-term survival. The ZEB1 transcriptional repressor promotes metastasis through downregulation of microRNAs (miRs) that are strong inducers of epithelial differentiation and inhibitors of stem cell factors. Given that each miR can target multiple genes with diverse functions, we posited that the prometastatic network controlled by ZEB1 extends beyond these processes. We tested this hypothesis using a mouse model of human lung adenocarcinoma metastasis driven by ZEB1, human lung carcinoma cells, and human breast carcinoma cells. Transcriptional profiling studies revealed that ZEB1 controls the expression of numerous oncogenic and tumor-suppressive miRs, including miR-34a. Ectopic expression of miR-34a decreased tumor cell invasion and metastasis, inhibited the formation of promigratory cytoskeletal structures, suppressed activation of the RHO GTPase family, and regulated a gene expression signature enriched in cytoskeletal functions and predictive of outcome in human lung adenocarcinomas. We identified several miR-34a target genes, including Arhgap1, which encodes a RHO GTPase activating protein that was required for tumor cell invasion. These findings demonstrate that ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression and provide a compelling rationale to develop miR-34a as a therapeutic agent in lung cancer patients.
A CASE OF HEMORRHAGIC TYPHOID.
Authors: J. R. DURHAM
Journal: JAMA (1904)

<h3>History</h3> J. O., aged 28, single, occupation woodsman, was admitted to the hospital on the evening of Sept. 3, 1903, with a history of having been ill one week, and of coming from a camp where typhoid fever was present. Temperature, 104.6; pulse, 94; respiration, 34; urinary analysis negative. <h3>Course of the Disease.</h3> The next morning the temperature was 105; pulse, 100; respiration, 42; considerable bronchial cough, severe headache and delirium. The pulse becoming weaker, he was placed on strychnia, gr. 1/60 every four hours, while the nervous symptoms and pyrexia were treated by the icebag to the head and ice-water sponges every two hours. September 5. Temperature ranged from 102 to 105; pulse from 90 to 100; respiration varied between 40 at 8 a. m., 22 at 2 p. m., and back to 40 at 6 p. m.; abdominal symptoms were now more pronounced, there being considerable tympanitis and diarrhea; for these turpentine stupes and turpentine inunctions were used, with salol and bismuth betanaphtholate internally and later turpentine emulsion; large quantities of gas were expelled.
Injectable PLGA porous beads cellularized by hAFSCs for cellular cardiomyoplasty
Authors: Chieh-Cheng Huang, Hao-Ji Wei, Yi-Chun Yeh, Jiun-Jie Wang, Wei-Wen Lin, Ting-Yin Lee, Shiaw-Min Hwang, Sung-Wook Choi, Younan Xia, Yen Chang, Hsing-Wen Sung
Journal: Biomaterials (2012)
American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy
Authors: Barry J. Maron, William J. McKenna, Gordon K. Danielson, Lukas J. Kappenberger, Horst J. Kuhn, Christine E. Seidman, Pravin M. Shah, William H. Spencer, Paolo Spirito, Folkert J. Ten Cate, E.Douglas Wigle, Robert A. Vogel, Jonathan Abrams, Eric R. Bates, Bruce R. Brodie, Peter G. Danias, Gabriel Gregoratos, Mark A. Hlatky, Judith S. Hochman, Sanjiv Kaul, Robert C. Lichtenberg, Jonathan R. Lindner, Robert A. O’rourke, Gerald M. Pohost, Richard S. Schofield, Cynthia M. Tracy, William L. Winters, Werner W. Klein, Silvia G. Priori, Angeles Alonso-Garcia, Carina Blomström-Lundqvist, Guy De Backer, Jaap Deckers, Markus Flather, Jaromir Hradec, Ali Oto, Alexander Parkhomenko, Sigmund Silber, Adam Torbicki
Journal: Journal of the American College of Cardiology (2003)
The Quality of Mercy
Authors: Marcia Angell
Journal: New England Journal of Medicine (1982)

Few things a doctor does are more important than relieving pain. Yet the treatment of severe pain in hospitalized patients is regularly and systematically inadequate.1 2 3 4 5 One study showed that 73 per cent of patients undergoing treatment for pain continued to experience moderate to severe discomfort.2 This is not for want of tools. It is generally agreed that most pain, no matter how severe, can be effectively relieved by narcotic analgesics.4 , 6 , 7 Why this inconsistency between what is practiced and what is possible?One consideration that limits the use of narcotics is the possibility of a variety of side effects, including drowsiness, . . .
Infiltration of Stellate Ganglion for Apoplexy
Authors: W. A. Mackey, L. D. W. Scott
Journal: BMJ (1938)

Dispenisai(ryT Physician to the lVestern Inifir-mary of GlasgowA paper by Leriche and Fontaine (1936) suggests the use in cases of apoplexy of a method of treatment which may be dramatic in its immediate effects.It consists essentially in the temporary anaesthesia of the stellate ganglion by means of novocain.These authors submit that in any case of apoplexy the vascular lesion, be it haemorrhage or softening, acts as an irritant on the sur- rounding vessels and produces a "halo" of irritative vasospasm.If this be true, then vasospasm, by rendering anoxaemic an area of cerebral tissue around the organic lesion, may play an important part in determining the scope of the initial symptoms, and, if persistent, may contribute to the ultimate neuronic degeneration.Leriche and Fontaine claim that vasospasm can be abolished by interrupting the sympathetic outflow to the head by infiltration of the stellate ganglion-with novocain, and suggest that such treatment, by sparing neurons that woLild otherwise perish, may in certafn cases save life and also aid many pat'ients to 'make the most complete recovery.
Comparing introduction to Europe of highly pathogenic avian influenza viruses A(H5N8) in 2014 and A(H5N1) in 2005
Authors: C Adlhoch, C Gossner, G Koch, I Brown, R Bouwstra, F Verdonck, P Penttinen, T Harder
Journal: Eurosurveillance (2014)

Since the beginning of November 2014, nine outbreaks of highly pathogenic avian influenza virus (HPAIV) A(H5N8) in poultry have been detected in four European countries. In this report, similarities and differences between the modes of introduction of HPAIV A(H5N1) and A(H5N8) into Europe are described. Experiences from outbreaks of A(H5N1) in Europe demonstrated that early detection to control HPAIV in poultry has proven pivotal to minimise the risk of zoonotic transmission and prevention of human cases.
Crystals of cadmium, zinc metallothionein.
Authors: K A Melis, D C Carter, C D Stout, D R Winge
Journal: Environmental Health Perspectives (1984)

Single crystals have been grown of Cd,Zn metallothionein isoform II from rat liver. The space group is P41212(P43212) with unit cell dimensions a = b = 31.0 A and c = 120.0 A, and one molecule in the crystallographic asymmetric unit. The crystals are square bipyramids elongated on the tetragonal c-axis and are grown by repetitive seeding. The crystals are suitable for high resolution structure analysis. Assays of dissolved crystals show that the crystals have the same Cd and Zn content and amino acid composition as the native, as-isolated protein.
Experimental infection of the respiratory tract with Mycoplasma pneumoniae.
Authors: P C Hu, J M Kirtz, D E Gardner, D A Powell
Journal: Environmental Health Perspectives (1980)

M. pneumoniae, a common human respiratory pathogen, has been studied experimentally for years using intranasal inoculation of the golden Syrian hamster. Because of recent evidence outlining the role in pulmonary immune development of particle size and depth of mycoplasma deposition in the hamster lung, we developed an aerosol chamber for the reproducible aerosolization of radiolabeled M. pneumoniae. Organisms were labeled to high specific activity by the incorporation of 3H-oleic acid and aerosolized under airflow and humidity conditions creating a mean particle diameter of 2.0 micrometers. Under these conditions, viable mycoplasmas were reproducibly and evenly distributed to all major lobes of the lung. Examination of radioactive clearance and organism viability within the lung during the first 48 hr after aerosolization have suggested a minimal role for macrophage mycoplasmacidal activity and a more prominent role for ciliary clearance. Data from aerosol infections of hamsters with radio-labeled M. pneumoniae should provide a unique opportunity to examine in a highly controlled manner the effects of air pollutants on the initial stages of infection as well as effects on the development of pulmonary immunity and histologic alterations.
Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation
Authors: Katia De Filippo, Anne Dudeck, Mike Hasenberg, Emma Nye, Nico van Rooijen, Karin Hartmann, Matthias Gunzer, Axel Roers, Nancy Hogg
Journal: Blood (2013)
New X wave in electrocardiographic complex.
Authors: B L Agarwal, G B Gupta
Journal: BMJ (1967)

Changes in the electric potentials during a cardiac cycle producing positive or negative deflections in an electrocardiographic tracing have been designated by the well-known PQRSTU (including R' or r' and S' or s').All these waves can be individually recognized in most of the leads.An addi- tional upright deflection after U is described below which so far as we are aware has not been reported in English literature.This was encountered during routine electrocardiographic recordings of cases of cerebrovascular accidents.
Sequence Gaps Join Mice and Men: Phylogenetic Evidence from Deletions in Two Proteins
Authors: Celine Poux, Teun van Rheede, Ole Madsen, Wilfried W. de Jong
Journal: Molecular Biology and Evolution (2002)

Recent nuclear sequence analyses have provided evidence that primates and rodents are more closely related than previously believed (Madsen et al. 2001; Murphy et al. 2001a, 2001b). This proposal is difficult to reconcile with morphological insights (Liu et al. 2001; Novacek 2001) and is not generally supported by current mitochondrial sequence data (Reyes, Pesole, and Saccone 2000; Nikaido et al. 2001; Arnason et al. 2002; Janke et al. 2002). Moreover, the supporting data and analyses have been criticized on methodological grounds (Rosenberg and Kumar 2001). Here we report deletions in two nuclear protein-coding genes that lend independent support to this contested grouping. Some 18 orders of placental mammals are currently recognized, but their phylogenetic relationships remain highly controversial. Extensive sequence comparisons of mainly nuclear genes support a basal division into four major clades (Xenarthra, Afrotheria, Laurasiatheria, and Euarchontoglires), which has far-reaching implications for early mammalian biogeography and morphological diversification (Murphy et al. 2001b). Euarchontoglires is composed of the orders Primates, Rodentia, Lagomorpha (rabbits, hares, and pikas), Scandentia (tree shrews), and Dermoptera (flying lemurs). In contrast, morphology groups Primates, Scandentia, and Dermoptera with Chiroptera (bats) in the clade Archonta, whereas Rodentia and Lagomorpha (jointly called Glires) are in a distant clade with Macroscelidea (elephant shrews) (Liu et al. 2001; Novacek 2001). Also, sequence data from 12 proteins encoded by the mitochondrial genome generally do not support Euarchontoglires (e.g., Nikaido et al. 2001) or even maintain rodent polyphyly in many cases (Reyes, Pesole, and Saccone 2000; Arnason et al. 2002; Janke et al. 2002). Only by excluding some taxa with high or atypical substitution rates (or both) can sound mitochondrial support be obtained (Waddell, Kishino, and Ota 2001). Establishing the monophyly of the most speciose eutherian order, Rodentia, and finding its sister group has indeed been most difficult to solve on the basis of sequence evidence (e.g., Graur, Hide, and Li 1991; Adkins et al. 2001; Huchon et al. 2002). As for the molecular data sets giving support to Euarchontoglires, it has been questioned whether these are actu-
Inhibition of gastric secretion in treatment of pancreatic insufficiency.
Authors: J H Saunders, S Drummond, K G Wormsley
Journal: BMJ (1977)

The content of pancreatic enzymes in the duodenum was studied in two patients with pancreatic achylia after a standard meal supplemented with commercial pancreatic extract. Gastric transit of the enzymes, with appearance of near-normal amounts in the duodenal contents, occurred only after inhibition of gastric secretion and buffering of residual gastric acid with antacids. Gastric inhibition and neutralisation of acid are therefore necessary for the satisfactory treatment of patients with pancreatic exocrine insufficiency but normal gastric function.
BLASTING EYE INJURIES.
Authors: JOHN A. DONOVAN
Journal: JAMA (1905)

"Frenzied Finance," pro and con, of late has so filled the air that to many the question arises: Does mining really exist? With all her disadvantages, Butte still demonstrates mining as a reality. With her annual production of 250,000,000 pounds of copper, not to mention her silver and gold, her many miles of underground tunnels extending nearly half a mile below the surface, and her thousands of miners using tons of powder daily, Butte offers for our study a subject worthy of consideration. Eissler<sup>1</sup>says: In no department of human industry has more rapid progress been made of late years than in explosives. The ablest chemists and the best engineers have found in the study of explosives a fruitful field, and the results of their labors are to be seen in the perfected explosives of to-day—explosives which are marvels of chemical perfection; which are so modified and varied in
NHS scores well on access, out of hours care, and patient engagement but not on outcomes, conference hears
Authors: N. Hawkes
Journal: BMJ (2013)

The paradox of a service that seems to do all the right things but does not always deliver the right results was never quite resolved at a conference in London on primary care on 11 March. 

Ara Darzi, the former Labour health minister and now co-director of the Centre for Health Policy at Imperial College London, organised the conference with the aim of harnessing international experience to raise the quality of primary care in the NHS.

He called primary care the “rock” of the NHS. David Nicholson, chief executive of the NHS in England, added that it was its cornerstone. And the conference watched a slide presentation by Robin Osborn, vice president of the New York based Commonwealth Fund, who extolled the NHS as the exemplar of what a health service should be. 

On almost every slide Osborn showed (except the one on outcomes) the NHS came out best or nearly best in an international comparison of 11 advanced countries: on access, out of hours care, patient engagement, shared care plans, electronic medical records, and patients’ and doctors’ opinions. 

She …
Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study
Authors: P Lahdenne, P Vähäsalo, V Honkanen
Journal: Annals of the Rheumatic Diseases (2003)

To study infliximab and etanercept in the treatment of refractory juvenile idiopathic arthritis (JIA).In a non-randomised, prospective, open label study, 24 patients (mean age 10.2 years, range 3.3-16.3) with polyarticular JIA were treated with either infliximab (n=14) or etanercept (n=10). The patients had had active polyarthritis for at least one year and standard treatment had failed. Anti-tumour necrosis factor (TNF) treatment was added to the current drug treatment. Infliximab (3-4 mg/kg) was given intravenously at weeks 0, 2, and 6, and thereafter at 4 to 8 week intervals. Etanercept (0.4 mg/kg) was given subcutaneously twice a week. Improvement of the patients was assessed at 3, 6, and 12 months according to established JIA response criteria.In intention to treat analyses, patients in both treatment groups improved significantly. ACR Paediatric 50 was achieved at 3, 6, and 12 months by 9/10 (90%), 8/9 (89%), and 8/9 (89%) patients with etanercept and by 8/12 (67%), 10/12 (83%), and 7/9 (78%) with infliximab, respectively. At 12 months, ACR Paediatric 75 was achieved by 67% of patients in both treatment groups. Five withdrawals due to adverse effects or lack of efficacy occurred in the infliximab group and one due to lack of compliance in the etanercept group.In this open label clinical study of active JIA, both infliximab and etanercept provided a significant rapid and sustained reduction in disease activity. Adequately powered randomised controlled trials are needed to elucidate the long term safety and efficacy of TNF modulators in the treatment of JIA.
E2 transacylase-deficient (type II) maple syrup urine disease. Aberrant splicing of E2 mRNA caused by internal intronic deletions and association with thiamine-responsive phenotype.
Authors: J L Chuang, R P Cox, D T Chuang
Journal: Journal of Clinical Investigation (1997)

Maple syrup urine disease (MSUD) or branched-chain alpha-ketoaciduria is an autosomally inherited disorder in the catabolism of branched-chain amino acids leucine, isoleucine, and valine. The disease is characterized by severe ketoacidosis, mental retardation, and neurological impairments. MSUD can be classified into genetic subtypes according to the genes of the branched-chain alpha-ketoacid dehydrogenase (BCKD) complex which are affected in patients. We describe here four intronic deletions and an intronic nucleotide substitution in the E2 transacylase gene of type II MSUD, in which the E2 subunit of the BCKD complex is deficient. These new E2 mutations comprise an internal 3.2-kb deletion in intron 4 (causing a 17-bp insertion in mRNA), an internal 12-bp (ttaccttgttac) deletion in intron 4 (creating a 10-bp insertion), a 10-bp (catttctaG) deletion in intron 10/ exon 11 junction (leading to a 21-bp deletion), a 2-bp deletion in the exon 5/intron 5 junction (ATgt--> A-t) (resulting in the skipping of exon 5), and a G to A transition at nucleotide -7 of intron 9 (causing a 6-bp insertion). These intronic mutations were initially detected by secondary alterations in the mutant E2 mRNA, as a result of aberrant splicing. The 3.2-kb deletion in intron 4 was determined by the amplification of the entire intron from both a normal subject (11.2 kb) and a homozygous patient (8 kb) by long PCR, followed by subcloning and sequencing of regions flanking the deletion. Similar methods were used to identify and characterize the other intronic alterations. Our results depict heretofore undescribed splicing errors caused by the deletion of internal intronic segments, and provide an approach for detecting this class of novel and rare human mutation. The association of the thiamine-responsive phenotype with a subset of the type II MSUD patients studied is also discussed.
1010 OPTIB – A MULTICENTER PROSPECTIVE OPEN LABEL STUDY ON TENOFOVIR (TDF) FOR CHRONIC HEPATITIS B PATIENTS WITH SUBOPTIMAL RESPONSE TO ADV OR ADV/LAM TREATMENT
Authors: M. Levrero, L. Cimino, P. Lampertico, M. Vigano', G. Gaeta, G. Brancaccio, E. Sagnelli, V. Messina, G. Raimondo, A. Marzano, S. Fagiuoli, G. Niro, T. Santantonio, V. Di Marco, G. Mazzella, G. Di Costanzo, M. Angelico, S. Pierconti, C. Sava'
Journal: Journal of Hepatology (2010)
Telomeres, Cancer, and Aging
Authors: Dwayne A. Banks
Journal: JAMA (1997)

Population projections of the aging global society and its fiscal and social impact have depended on assumptions regarding the human life span. Until now, the assumption that the maximum human life span is fixed has been justified. Recent advances in cell biology, genetics, and our understanding of the cellular processes that underlie aging, however, have shown that this assumption is invalid in a number of animal models and suggest that this assumption may become invalid for humans as well. In vitro alteration of telomeres affects cellular senescence, and in vivo manipulation of genes and diet can increase maximum life span in animal models if these discoveries are extended to humans. We may soon be able to extend the maximum human life span and postpone or prevent the onset of diseases associated with aging. Such a possibility requires that we recognize a growing uncertainty in any attempt to project international health care costs into the next few decades. The costs may be significantly lower than projections, if life span increases and age-related disabilities are postponed or less severe, or perhaps higher, if life span increases without altering the onset and severity of disability. An appropriate uncertainty regarding the human life span undermines any attempt to accurately predict health costs in the next century.
Random measurement error and regression dilution bias
Authors: J. A. Hutcheon, A. Chiolero, J. A. Hanley
Journal: BMJ (2010)

Random measurement error is a pervasive problem in medical research, which can introduce bias to an estimate of the association between a risk factor and a disease or make a true association statistically non-significant. <b>Hutcheon and colleagues</b> explain when, why, and how random measurement error introduces bias and provides strategies for researchers to minimise the problem
Functional Organization of a Neural Network for Aversive Olfactory Learning in Caenorhabditis elegans
Authors: Heon-ick Ha, Michael Hendricks, Yu Shen, Christopher V. Gabel, Christopher Fang-Yen, Yuqi Qin, Daniel Colón-Ramos, Kang Shen, Aravinthan D.T. Samuel, Yun Zhang
Journal: Neuron (2010)
Genotoxicity of N-acetylarylamines in the Salmonella/hepatocyte system
Authors: Snorri S. Thorgeirsson, Leonard C. Erickson, Carole L. Smith, Irene B. Glowinski
Journal: Environmental Health Perspectives (1983)

Coincubation of isolated, intact rat hepatocytes with Salmonella typhimurium tester strain TA 98 (Salmonella/hepatocyte system) has been employed to determine both bacterial mutagenicity and DNA damage in the hepatocytes following treatment with 2-acetylaminofluorene (AAF) and other AAF derivatives. In vivo pretreatment of rats with either 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) or 3-methylcholanthrene (MC) markedly increased both DNA damage and bacterial mutation frequency upon incubation of AAF or 2-aminofluorene (AF), in this system. The increase in damage to the hepatocyte-DNA was more pronounced after AAF treatment than by that for AF, while the increase in bacterial mutation frequency was greater after AF treatment. Hepatocytes treated with paraoxon prior to exposure to N-hydroxy-2-acetylaminofluorene (N-OH-AAF) or N-acetoxy-2-acetylaminofluorene (N-OAc-AAF) partially inhibited the DNA damage caused by these agents, as well as inhibiting the bacterial mutagenicity of N-OAc-AAF (50% inhibition) and N-OH-AAF (80% inhibition). These data indicate that metabolic processes other than those involved in activating AAF and its derivatives into a bacterial mutagen(s) may contribute to the genotoxic effects of these compounds. Thus, the Salmonella/hepatocyte system may provide a useful model in which to study the relative role of the various metabolic processes associated with the carcinogenic effects of N-acetylarylamines.