tbuckley/cabot-search huggingface dataset:
Deregulated microRNAs in triple-negative breast cancer revealed by deep sequencing
Authors: Yao-Yin Chang, Wen-Hung Kuo, Jui-Hui Hung, Chien-Yueh Lee, Yung-Hua Lee, Ya-Chu Chang, Wen-Chun Lin, Cheng-Ying Shen, Chiun-Sheng Huang, Fon-Jou Hsieh, Liang-Chuan Lai, Mong-Hsun Tsai, King-Jen Chang, Eric Y Chuang
Journal: Molecular Cancer (2015)

MicroRNAs (miRNAs) are short, non-coding RNA molecules that play critical roles in human malignancy. However, the regulatory characteristics of miRNAs in triple-negative breast cancer, a phenotype of breast cancer that does not express the genes for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, are still poorly understood. In this study, miRNA expression profiles of 24 triple-negative breast cancers and 14 adjacent normal tissues were analyzed using deep sequencing technology. Expression levels of miRNA reads were normalized with the quantile-quantile scaling method. Deregulated miRNAs in triple-negative breast cancer were identified from the sequencing data using the Student's t-test. Quantitative reverse transcription PCR validations were carried out to examine miRNA expression levels. Potential target candidates of a miRNA were predicted using published target prediction algorithms. Luciferase reporter assay experiments were performed to verify a putative miRNA-target relationship. Validated molecular targets of the deregulated miRNAs were retrieved from curated databases and their associations with cancer progression were discussed. A novel 25-miRNA expression signature was found to effectively distinguish triple-negative breast cancers from surrounding normal tissues in a hierarchical clustering analysis. We documented the evidence of seven polycistronic miRNA clusters preferentially harboring deregulated miRNAs in triple-negative breast cancer. Two of these miRNA clusters (miR-143-145 at 5q32 and miR-497-195 at 17p13.1) were markedly down-regulated in triple-negative breast cancer, while the other five miRNA clusters (miR-17-92 at 13q31.3, miR-183-182 at 7q32.2, miR-200-429 at 1p36.33, miR-301b-130b at 22q11.21, and miR-532-502 at Xp11.23) were up-regulated in triple-negative breast cancer. Moreover, miR-130b-5p from the miR-301b-130b cluster was shown to directly repress the cyclin G2 (CCNG2) gene, a crucial cell cycle regulator, in triple-negative breast cancer cells. Luciferase reporter assays showed that miR-130b-5p-mediated repression of CCNG2 was dependent on the sequence of the 3′-untranslated region. The findings described in this study implicate a miR-130b-5p-CCNG2 axis that may be involved in the malignant progression of triple-negative breast cancer. Our work delivers a clear picture of the global miRNA regulatory characteristics in triple-negative breast cancer and extends the current knowledge of microRNA regulatory network.
Entrepreneurialism in Medicine
Authors: Robert M. Cunningham
Journal: New England Journal of Medicine (1983)

Hospitals all over the country are organizing new corporations to spin off traditional services and initiate new activities, and then joining or competing with doctors and other hospitals in new ventures such as health-maintenance organizations, preferred-provider organizations, surgicenters, emergicenters, and clinics in shopping malls. All this is grandly labeled "diversification" and seen as a cause for rejoicing that free enterprise and price competition have finally brought salvation to the health-care system.I have some misgivings about the suitability of entrepreneurial values in medical care. In some business ventures, entrepreneurs risk their own money; when it's somebody else's money, as is . . .
PTU-140 The Effect of Proton Pump Inhibitors (PPIS) on Oesophageal Acid Reflux using a Prolonged Wire-Less Bravo PH Monitoring: Abstract PTU-140 Table
Authors: G Sui, M Fox, A Anggiansah, A Vales, T Wong
Journal: Gut (2013)

<h3>Introduction</h3> Recently prolonged catheter-free pH monitoring (Bravo<sup>®</sup>, Given Imaging, Yoqeam, Israel) up to 96 hours has become possible which enables more physiological evaluation of oesophageal acid exposure and its response to therapeutic interventions. This study applied this technology to measure acid reflux, and reflux related symptoms in patients with proven gastro-oesophageal reflux disease on and off high-dose PPIs. The potential utility of this methodology in guiding medical therapy was assessed. <h3>Methods</h3> Patients with reflux symptoms were recruited prospectively from Mar.2012 to Oct.2012. PPI was stopped for 7 days prior to the Bravo capsule insertion. The 1st 48hr pH recording was performed off PPI and the 2nd 48hr was on twice daily PPI. The 48hr pH and symptom data for the two periods were compared, including percentages of acid exposure in total, upright and supine periods and symptom–reflux association for which heartburn (HB), chest pain (CP) and regurgitation (RG) were analysed. Data were expressed as median &amp; interquartile. Wilcoxon signed-rank and Mann Whitney tests were used for statistical analysis (*P &lt; 0.05; **P &lt; 0.01; *** &lt; 0.001). <h3>Results</h3> Data from prolonged pH monitoring up to 96 hours were available from 89patients of whom 36 (22 males, mean age 50, range 26–76 years old) with complete studies and pathological acid exposure in the 1st 48 hours were studied in detail. Acid reflux measurements on PPI therapy were greatly reduced when compared to those recorded off therapy (Table). 27/36 (75%) patients had normal acid exposure on PPI therapy. The overall number of HB and CP reported in the 2nd 48hr period was reduced by almost two thirds (13 (4–26) vs.5 (2–14)**); however the number of these symptoms that were actually associated with acid reflux events was almost completely abolished (4 (2–14) vs.1 (0–3)***). No effect on volume RG was present. <h3>Conclusion</h3> Sequential 48hrs recording off/on PPI therapy using Bravo pH test is feasible in routine clinical practise. This technique documents the physiological and clinical response to PPI therapy on acid reflux and acid reflux associated symptoms (i.e. heartburn, chest pain). These preliminary findings suggest that this methodology could be of value in distinguishing symptoms related to acid reflux that respond to acid suppression and guiding medical therapy in reflux disease. <h3>Disclosure of Interest</h3> None Declared
Claims of Equivalence in Medical Research: Are They Supported by the Evidence?
Authors: William L. Greene, John Concato, Alvan R. Feinstein
Journal: Annals of Internal Medicine (2000)

Background: Most clinical studies are done to show comparative superiority, but many reports now claim equivalence between the investigated entities. These assertions may not always be supported by the methods used and the results obtained. Purpose: To assess the justification and support for claims of clinical or therapeutic equivalence in medical journals. Data Sources: A search of MEDLINE for articles published from 1992 through 1996. Study Selection: From 1209 citations that contained the word equivalence in the title or abstract or contained the Medical Subject Heading therapeutic equivalency, we excluded 1121 studies reporting nonoriginal research, purely laboratory or other nonhuman research, and studies in which equivalence was not the main claim. The remaining 88 eligible papers were evaluated for five methodologic attributes. Data Synthesis: Only 45 (51%) of the 88 reports were specifically aimed at studying equivalence; the others either tried to show superiority or did not state a research aim. The quantitative distinctions regarded as "equivalent" ranged from 0% to 21% for direct increments and from 0% to 76% for proportionate differences. An equivalence boundary was set and confirmed with an appropriate statistical test in only 23% of reports. In 67% of reports, equivalence was declared after a failed test for comparative superiority, and in 10%, the claim of equivalence was not statistically evaluated. The sample size needed to confirm results had been calculated in advance for only 33% of reports. Sample size was 20 patients per group or fewer in 25% of reports. Conclusions: Many studies of clinical equivalence do not set boundaries for equivalence. Claims of "difference" or "similarity" are often made not by thoughtful examination of the data but by tests of statistical significance that are often misapplied or accompanied by inadequate sample sizes. These methodologic flaws can lead to false claims, inconsistencies, and harm to patients.
Role of quality measurement in inappropriate use of screening for colorectal cancer: retrospective cohort study
Authors: S. D. Saini, S. Vijan, P. Schoenfeld, A. A. Powell, S. Moser, E. A. Kerr
Journal: BMJ (2014)

To examine whether the age based quality measure for screening for colorectal cancer is associated with overuse of screening in patients aged 70-75 in poor health and underuse in those aged over age 75 in good health.Retrospective cohort study utilizing electronic data from the Veterans Affairs (VA) Health Care System, the largest integrated healthcare system in the United States.VA Health Care System.Veterans aged ≥ 50 due for repeat average risk colorectal cancer screening at a primary care visit in fiscal year 2010.Completion of colonoscopy, sigmoidoscopy, or fecal occult blood testing within 24 months of the 2010 visit.399,067 veterans met inclusion/exclusion criteria (mean age 67, 97% men). Of these, 38% had electronically documented screening within 24 months. In multivariable log binomial regression adjusted for Charlson comorbidity index, sex, and number of primary care visits, screening decreased markedly after the age of 75 (the age cut off used by the quality measure) (adjusted relative risk 0.35, 95% confidence interval 0.30 to 0.40). A veteran who was aged 75 and unhealthy (in whom life expectancy might be limited and screening more likely to result in net burden or harm) was significantly more likely to undergo screening than a veteran aged 76 and healthy (unadjusted relative risk 1.64, 1.36 to 1.97).Specification of a quality measure can have important implications for clinical care. Future quality measures should focus on individual risk/benefit to ensure that patients who are likely to benefit from a service receive it (regardless of age), and that those who are likely to incur harm are spared unnecessary and costly care.
LEFT VENTRICULAR SCAR ASSESSMENT BY CONTRAST ENHANCED CARDIAC MAGNETIC RESONANCE AS PREDICTOR OF OUTCOMES IN CORONARY ARTERY BYPASS GRAFT SURGERY
Authors: Krishna Kancharla, Abdalla Elagha, Ruben Hernaez, Peter C. Hill, Steven W. Boyce, Gaby Weissman, Anthon R. Fuisz
Journal: Journal of the American College of Cardiology (2011)
What's in a Title?
Authors: Mark S. McGowan
Journal: Annals of Internal Medicine (1991)

Letters15 October 1991What's in a Title?Mark S. McGowan, MDMark S. McGowan, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-115-8-660_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editors: Short declarative sentences are being used more frequently for titles of scientific articles. This practice should be discouraged because it is misleading.One example is the otherwise well-written article by Krishna and Kapoor (1) titled "Potassium Depletion Exacerbates Essential Hypertension." Do the authors really mean to imply that the issue is now and forever settled?I suggest three alternatives, beginning with the one I prefer:1. The Effect of Potassium Depletion on Blood Pressure2. Does Potassium Depletion Elevate Blood Pressure?3. A Low Potassium Diet for Ten Days Was Associated With an Elevation of Blood Pressure...Reference1. Krishna G and Kapoor S. Potassium depletion exacerbates essential hypertension. Ann Intern Med. 1991;115:77-83. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Mark S. McGowan, MDAffiliations: University of Southern California Los Angeles, CA 90007 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 October 1991Volume 115, Issue 8Page: 660-660KeywordsBlood pressureDietHypertensionPotassium ePublished: 1 December 2008 Issue Published: 15 October 1991 PDF downloadLoading ...
Biology of the Laboratory Mouse
Authors: Mary Jane C. Showers
Journal: JAMA (1967)

For the researcher desiring a comprehensive reference concerning the laboratory mouse as a model system for observing health and disease processes, this book is an excellent choice. It contains enough literature review to allow a search forward and backward for documentation, and detail is complemented by substantial records of unpublished material.  This extensive revision of the original 1941 edition, of the same title, has been accomplished by staff of the Jackson Laboratory in Maine, where a large repository of information upon the laboratory mouse is maintained. Dominant orientation of the book concerns inbred strains of mice, with new information relevant to biochemical and hemoglobin traits, genetic factors governing transplantation of tissues, neurologic mutants. The least altered material deals with embryology, reproduction, and microscopic anatomy with minimal treatment of gross systemic anatomy.  The book, greatly expanded in scope, content, and illustrative material, is organized sequentially into sections on techniques of husbandry
Autism and DPT Vaccination in the United Kingdom
Authors: Hershel Jick, James A. Kaye
Journal: New England Journal of Medicine (2004)

To the Editor: On the basis of information recorded in the General Practice Research Database in the United Kingdom, we previously reported that the risk of receiving a diagnosis of autism between two and five years of age was four times as high among boys born in 1993 as among boys born in 1988.1 We presented evidence that this increase had no relation to the use of mumps, measles, and rubella vaccine, a finding similar to that reported by Madsen et al. in the Journal in a study based on data from Denmark.2 We recently reported on a study of . . .
CAPILLARY PERMEABILITY IN ANAPHYLAXIS
Authors: W. H. MANWARING
Journal: JAMA (1923)

The acute anaphylactic shock in dogs is characterized by a sudden pronounced fall in arterial blood pressure. This fall usually begins about forty seconds after the beginning of the intravenous protein injection. The pressure usually reaches a minimum of about 25 mm. of mercury by the end of ninety seconds. In shocks of moderate severity, the pressure remains at this low level for about twenty minutes, and then gradually increases, reaching normal in from one to two hours, depending on the severity of the reaction. With highly sensitized dogs, injected with relatively large doses of the specific foreign protein, little or no recovery takes place, the pressure remaining at a low level till the death of the animal, which usually occurs in about forty minutes. This characteristic fall in arterial blood pressure does not take place in dehepatized (Eck-fistula) dogs. This is true, not only for the mildly sensitized dogs
Shear-dependent Eosinophil Transmigration on Interleukin 4–stimulated Endothelial Cells
Authors: Susan L. Cuvelier, Kamala D. Patel
Journal: The Journal of Experimental Medicine (2001)

Leukocyte infiltration into inflammatory sites is regulated by the expression of adhesion and activation proteins, yet the role of these proteins in shear-dependent transmigration is poorly understood. We examined eosinophil recruitment on cytokine-stimulated human umbilical vein endothelial cells (HUVECs) under laminar flow conditions. Eosinophils rapidly transmigrated on interleukin (IL)-4–, but not TNF-stimulated HUVECs. Transmigration was shear dependent, with up to 90% of eosinophils transmigrating in the presence of shear and less than 25% of cells transmigrating under static conditions. Eosinophils express CC chemokine receptor CCR3 and are responsive to various CC chemokines. The effects of chemokines are mediated primarily through Gαi, which is pertussis toxin sensitive. Greater than 65% of shear-dependent eosinophil transmigration on IL-4–stimulated HUVECs was blocked by either pertussis toxin or by an anti-CCR3 monoclonal antibody. Using reverse transcription polymerase chain reaction (RT-PCR) and Western blots, we found that IL-4–stimulated HUVECs produce both mRNA and protein for eotaxin-3. Eotaxin-3 was both released by HUVECs and expressed on the endothelial cell surface. Pretreatment of HUVECs with an anti–eotaxin-3 antibody blocked eosinophil transmigration to the same extent as an anti-CCR3 antibody. These results indicate that IL-4–stimulated HUVECs support shear-dependent eosinophil transmigration by upregulating eotaxin-3, and that surface association is critical for the role of eotaxin-3 in transmigration.
ANTISERUM TO LEUCOCYTE LYSOSOMES
Authors: Paul G. Quie, James G. Hirsch
Journal: The Journal of Experimental Medicine (1964)

Antisera to rabbit polymorph granules and to rabbit erythrocytes have been prepared in guinea pigs. Both antigranule and antierythrocyte sera are hemolytic and both exhibit striking cytotoxicity on leucocytes. The sequence of toxic events, as observed by phase contrast cinemicrophotography and electron microscopy, consists of explosive granule lysis, cell swelling, cytoplasmic liquifaction, and nuclear fusion. Other rabbit cells are also susceptible to these cytotoxic effects, but cells, including polymorphs, of other mammals are not. Cytotoxic action of the antisera requires, in addition to the antibody, heat-labile serum factors and divalent cations, suggesting that the action is a combined one of antibody and complement. The morphologic observations have been supported by biochemical studies demonstrating release into the medium of granule-bound hydrolases following exposure of polymorphs or of isolated granules to the antigranule or antierythrocyte sera. Granulolytic activity of the antisera can be reduced or removed by absorption with either rabbit leucocyte granules or with erythrocytes, indicating that leucocyte granules and erythrocytes have an identical or similar membrane constituent. The observations lend support to the notion that lysosomal hydrolases may exert autolytic effects in some situations.
Primary prevention of skin cancer
Authors: R Marks
Journal: BMJ (1994)

should avoid reinventing the wheel.5More worrying is the offer of fellowship by assessment leading to recertification.This is bound to cause serious confusion within the profession as the General Medical Services Committee has already proposed a promising model of reaccreditation.6Is it possible that, despite public shows of unity, each arm of general practice will continue to develop its own system of reaccreditation?This consultative document contains several excellent and long overdue proposals.It also makes a blatant attempt to bring the college into the forefront of education.These should be welcomed: it is time for the college to discard the political shackles of the past and become Britain's supreme educational body in general practice.Only then can the college's aspirations be turned into reality.
A New JAMA Feature for Resident Physicians
Authors: Joseph K. Lim, Stephen J. Lurie
Journal: JAMA (2000)

and approved by JAMA editors for release to the news media the week before the embargo is released. This advance information and the news embargo are intended to provide journalists from various competitive news media equal access to news sources and an equal amount of time to prepare their news stories. Authors may cooperate with reporters for interviews or to discuss other information related to the study during the week before publication but only on the condition that the information will be released in accordance with THE JOURNAL’s embargo policy. Authors should resist pressure from their institutions, sponsors, the news media, or others to release information before the embargo. Authors, their institutional representatives, sponsors, and the news media who have questions about THE JOURNAL’s policies regarding release of information should contact the editorial office. REFERENCES
AXIS TRACTION HANDLE FOR OBSTETRIC FORCEPS
Authors: W. P. MEGRAIL
Journal: JAMA (1910)

during loading or shoveling, and, as every physician knows, the most efficacious way of administering nitro¬ glycerin is to dissolve the triturate in the mouth.An- oiher way of absorbing this poison is through the skin.Hence, these miners complain of headache, palpitation
Extracranial–Intracranial Arterial Bypass and Cerebral Vascular Disease
Authors: Fred Plum
Journal: New England Journal of Medicine (1985)

IN this issue of the Journal, Barnett and his co-workers1 report the results of a remarkable piece of clinical investigation, comparing in a controlled, prospective study the neurologic effects of surgical extracranial—intracranial arterial bypass (EC—IC bypass) in 1377 randomly assigned patients with known ischemic cerebral vascular disease. Despite great technical success on the part of the surgeons in creating patency in 96 per cent of the bypassing arteries, the data demonstrate a lack of benefit of surgical treatment. With all the patients receiving equivalent appropriate medical therapy, there was no reduction in transient ischemic attacks, major strokes, or death . . .
Theophylline Toxicity and the Beta-Adrenergic System
Authors: THOMAS E. KEARNEY
Journal: Annals of Internal Medicine (1985)

After ingestion of 12g of theophylline caused severe toxicity in a young woman, we developed an experimental canine model to study human theophylline toxicity. Our study involved four anesthetized dogs given theophylline in a continuous intravenous drip for 180 minutes in one of four protocols. The protocols included a low-dose infusion (400 mg/h) a high-dose infusion (1000 mg/h), a high-dose infusion with beta-blockade induced by propranolol at 125 minutes after infusion, and a high-dose infusion while maintaining beta-blockade with propranolol throughout the experiment. Toxic levels of theophylline were associated with hypokalemia, hypophosphatemia, hyperglycemia, metabolic acidosis, and hypotension in both the patient and the experimental series. These effects were either prevented or partially reversed after induction of beta-blockade with propranolol. Very high levels of theophylline were associated with elevated levels of norepinephrine and epinephrine in the animals.
Decreased fibrinolytic activity in juvenile chronic arthritis.
Authors: L Mussoni, G Pintucci, G Romano, F De Benedetti, M Massa, A Martini
Journal: Annals of the Rheumatic Diseases (1990)

The basal fibrinolytic activity in 17 children with active juvenile chronic arthritis (JCA) was investigated. It was found that patients with JCA, and particularly those with the systemic form, show decreased plasma fibrinolytic activity and a marked increase in plasminogen activator inhibitor. Additionally, it was found that patients with systemic JCA, but not those with the polyarticular or pauciarticular form, have increased circulating levels of tissue-type plasminogen activator, and endothelial cell protein, suggesting possible endothelial cell participation in systemic JCA.
Endoscopic Clipping of Perforation Following Pneumatic Dilation of Esophagojejunal Anastomotic Strictures
Authors: L. Cipolletta, M. A. Bianco, G. Rotondano, R. Marmo, R. Piscopo, C. Meucci
Journal: Endoscopy (2000)

Two patients with small perforations occurring after endoscopic balloon dilation of esophagojejunal anastomotic strictures were treated conservatively using metal clips. Closure of the perforation was achieved in both cases, using one and two clips in a single session. There was no procedure-related morbidity and no patient developed complications. Patients were discharged from hospital on days 4 and 5, respectively. In patients with esophagojejunal anastomotic stictures, endoscopic treatment of postdilation perforation by metal clips is safe and effective.