tbuckley/cabot-search huggingface dataset:
Abstract B40: Methylation signatures specific to triple negative breast cancer subtypes
Authors: Jeanne Kowalski, Jeffery M. Switchenko, Bhakti Dwivedi, Dana Nickleach, Carlos S. Moreno
Journal: Cancer Research (2013)

Abstract Objective: We identify methylation signatures specific to triple negative breast cancer (TNBC) subtypes using publicly available data, and examine their association with expression. Materials and Methods: DNA methylation, RNAseq expression and clinical data from breast invasive carcinoma patients were obtained from The Cancer Genome Atlas (TCGA) Data portal. The classification of each patient sample as TNBC was defined according to a combination of FISH and/or IHC results for ER, PR and HER2 negativity. Each TNBC specimen was classified into one of the following molecular subtypes by applying the gene expression-based model of Lehman (2011): basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (MES), mesenchymal stem-like (MSL), luminal androgen receptor (LAR), and unstable (UNS). Among the 116 identified TNBC specimens, 61 had level-three data available on both methylation and RNAseq expression. For methylation, beta values were extracted based on Illumina's Infinium Human DNA Methylation 450K platform; for expression, RNAseqV2 Expectation/Maximization normalized counts (RSEM: Li and Dewey, 2011) were extracted on 20,531 genes and a logarithmic transformation applied. Data were filtered to identify methylation changes specific to each TNBC subtype based on a novel, generalized statistic (Switchenko and Kowalski, 2013) and tested for median difference between subtypes using p &amp;lt; 0.10 to define significance. Results: Among the 61 TNBC samples, the following molecular subtypes were represented: BL1 (n=6), BL2 (n=6), IM (n=12), LAR (n=5), MES (n=15), MSL (n=4), and UNS (n=13). A number of genes were determined to be hypermethylated with corresponding decreased expression by RNAseq in several subtypes. Methylated genes specific to the LAR TNBC subtype included IGF1R (61% LAR vs. 2% other) and N4BP2L1 (44% LAR vs. 3% other). Methylated genes in the MES subtype included ACSL5 (80% vs. 50%), RHOH (82% vs. 6%) and OAS2 (26% vs. 7%), and specific to the BL2 subtype were EN1 (35% vs. 8%) and TRAFIP3 (60% vs. 35%). Two hypomethylated genes, PIK3CD and CD69, associated with respective subtypes, MSL and IM, showed corresponding increased expression levels. Conclusion: Our results provide further insight into the molecular heterogeneity surrounding TNBC patients by examining methylation changes specific to molecular subtypes, which may be further examined for their effect on clinical outcome. Citation Format: Jeanne Kowalski, Jeffery M. Switchenko, Bhakti Dwivedi, Dana Nickleach, Carlos S. Moreno. Methylation signatures specific to triple negative breast cancer subtypes. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr B40.
Teaching the Competencies: Using Objective Structured Clinical Encounters for Gastroenterology Fellows
Authors: Bani Chander, Robert Kule, Peter Baiocco, Sita Chokhavatia, Don Kotler, Michael Poles, Sondra Zabar, Colleen Gillespie, Tavinder Ark, Elizabeth Weinshel
Journal: Clinical Gastroenterology and Hepatology (2008)
Giant Anterior Mediastinal Parathyroid Adenoma
Authors: Lianxi Li, Libo Chen, Yi Yang, Junfeng Han, Songhua Wu, Yuqian Bao, Weiping Jia
Journal: Clinical Nuclear Medicine (2012)

A 57-year-old woman with type 2 diabetes was admitted to our hospital presenting with generalized bone pains, hypercalcemia, and elevated parathyroid hormone level. Enhanced CT scan demonstrated a large soft tissue mass in the right anterior mediastinum. Tc-MIBI scintigraphy revealed the focal accumulation of radiotracer uptake in the anterior mediastinum. Tc-MIBI SPECT/CT imaging also corroborated the same finding. The patient underwent surgery to have a giant ectopic parathyroid adenoma (7 × 4.5 × 1.5 cm) removed. The patient has been observed for 2 years, with normal parathyroid hormone and calcium levels.
Oral Sedation for Diagnostic Upper Endoscopy
Authors: J. L. Hedenbro, M. Ekelund, T. Åberg, A. Lindblom
Journal: Endoscopy (1991)

Heavy i.v. sedation is often used in upper GI endoscopy. Sedation, however, creates the need for recovery facilities and precludes patients from returning to their normal daily activities. This is undesirable, since endoscopy is routinely performed as an out-patient procedure. Also the cost for medication and recovery facilities militate against the indiscriminate use of i.v. sedative premedication. The present study was undertaken in an attempt to establish what proportion of patients can benefit from oral premedication, and whether such an administration route can eliminate some of the disadvantages associated with i.v. sedation. Four hundred out-patients were randomized to receive orally either triazolam, 0.125 mg, or placebo. Of the patients, 359 were evaluable; 177 received placebo and 182 triazolam. All major aspects of the procedure were covered using visual analogue scale questionnaires for the endoscopist and patient. There were no differences in endoscopic experience, or sex and age distribution between the groups. Triazolam reduced patient discomfort, 38.6 +/- 25.6 vs 44.8 +/- 30.1 (p = 0.0379). Recollection of post-endoscopy information was the same in both groups. One patient complained of drowsiness following the procedure. No patient needed to stay in hospital to complete recovery. Endoscopy quality was identical in the two groups. Oral premedication has the potential to be of significant value, may optimize the use of endoscopy resources, and does not impair patient activities post-endoscopy.
To see ourselves
Authors: I. Robertson
Journal: BMJ (1996)

We are the guests from hell. Five of us descend on our dapper and meticulous relatives in a blizzard of Sainsbury's plastic bags, strewn crumbs from the journey's sandwiches, and divots of mud smeared across the hall carpet within seconds of arrival. No sooner has the mud been cleaned up, and the unloading of the car begun in earnest, than the handle of an overstuffed bag snaps and, with a wet and sickening crunch, the content of a not-quite-good-enough bottle of Bardolino spreads across the cream, deep-pile carpet with a miraculously vigorous capillary action.

Amid shrilly giggled apologies, a strangely fixed “Oh don't worry” smile from my brother …
Genetic determinants of airways' colonisation with Pseudomonas aeruginosa in cystic fibrosis
Authors: P. Kubesch, T. Dork, U. Wulbrand, N. Kälin, T. Neumann, B. Wulf, B. Tümmler, H. Geerlings, H. Weißbrodt, H. von der Hardt
Journal: The Lancet (1993)
Cleft lip and palate
Authors: R. D Holt, B F Williams
Journal: BMJ (1985)

Suite 6105 Doctor’s Office Tower 2200 Children’s Way Nashville, TN 37232-9780 Phone: 615.343.4673 Fax: 615.322.0370 / www.vanderbiltchildren’s.com Cleft Lip and Palate What are Cleft Lip and Cleft Palate? In the early weeks of fetal development, parts of the lip or palate (the roof of the mouth) usually fuse together. In some cases, however, this fusion does not occur and a cleft or separation occurs in the tissue, as seen in the diagrams below.
Inhibition of suppressor T lymphocytes by murine interferon beta.
Authors: D M Sahasrabudhe
Journal: The Journal of Experimental Medicine (1987)

We have presented data showing that IFN-beta at 1,000 U/mouse i.v. inhibits the generation of Ts-mediated tolerance to dinitrofluorobenzene (DNFB) and abrogates the transfer of suppression by Ts. We have also presented data showing that IFN-beta up to 10,000 U/mouse i.v. has no adverse effect on sensitization and elicitation. IFN-beta appears to be a suitable agent for evaluation as an adjunct in the immunotherapy of Ts inducing tumors.
418 SORAFENIB IN HCC PATIENTS WITH ADVANCED LIVER CIRRHOSIS AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION – EXPERIENCES BEYOND THE SHARP TRIAL
Authors: M. Woerns, K. Pfingst, H. Schulze-Bergkamen, M. Schuchmann, C. Dueber, G. Otto, A. Weinmann
Journal: Journal of Hepatology (2008)
Arsenic — New Life for an Old Potion
Authors: Robert E. Gallagher
Journal: New England Journal of Medicine (1998)

One of our gentlemen found time to say `How delicious!'” declares Aunt Abby to a mortified Mortimer after he discovers a corpse in the 1944 movie classic Arsenic and Old Lace. The film's portrayal of rapid death after drinking arsenic-spiked elderberry wine epitomizes the public's fearful perception of this poisonous metallic element. The cognoscenti, of course, knew that rapid death was not due to the arsenic but the strychnine and cyanide that were also added to the wine, and that the manifestations of arsenic poisoning are typically not acute. Arsenic poisoning due to contaminated drinking water and industrial pollutants is . . .
Dosage Adjustment and Pharmacokinetic Profile of Irinotecan in Cancer Patients With Hepatic Dysfunction
Authors: Eric Raymond, Valérie Boige, Sandrine Faivre, Ger-Jan Sanderink, Olivier Rixe, Laurent Vernillet, Christian Jacques, Michel Gatineau, Michel Ducreux, Jean-Pierre Armand
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To determine the recommended dose (RD) and the pharmacokinetic profile of irinotecan and its metabolites in cancer patients with hyperbilirubinemia. PATIENTS AND METHODS: Patients were assigned to four treatment groups according to their baseline total bilirubin level. Patients in group I (bilirubin within normal range) and group II (bilirubin 1.0 to 1.5 times upper limit of normal [ULN]) received a dose of 350 mg/m 2 every 3 weeks. Patients in groups III (bilirubin 1.51 to 3.0 times ULN) and IV (bilirubin &gt; 3.1 times ULN) received starting doses of 175 and 100 mg/m 2 , respectively. RDs were defined according to the dose-limiting toxicity (DLT) experienced at cycle 1. RESULTS: Thirty-three patients including 21 gastrointestinal cancers were included. Grade 4 febrile neutropenia and diarrhea were common DLTs in patients with hyperbilirubinemia. At a dose of irinotecan 350 mg/m 2 , DLTs were observed in two of seven and one of five patients in groups I and II, respectively. In group III, escalated doses of irinotecan 175, 200, and 240 mg/m 2 were associated with DLTs in one of seven, one of five, and three of six patients, respectively. No DLT was observed in group IV. High bilirubin and alkaline phosphatase levels were associated with an exponential decrease in the clearance of irinotecan. Pharmacokinetic analysis showed that the relative increase in exposure was likely caused by reduced biliary excretion. CONCLUSION: We showed that baseline total bilirubin level could be used to determine the appropriate dose of irinotecan in cancer patients with hepatic dysfunction. Doses of 350 mg/m 2 and 200 mg/m 2 were considered RDs in patients with bilirubin values ≤ 1.5 times ULN and 1.51 to 3.0 times ULN, respectively.
The Health Planning Predicament: France, Quebec, England, and the United States
Authors: Lu Ann Aday
Journal: JAMA (1986)

Victor G. Rodwin, in his comparative study of health planning in France, Quebec, England, and the United States, argues that each has found itself in a considerable predicament as regards accomplishing its health planning goals.  The author offers a number of formulations of this predicament, such as, No one quite knows what the future health care sector should look like or  to gain control over the health care  (p 2) and No one knows  to assure that the right patient receives the right service at the right time and in the right place; and even when a consensus is reached on what is 'right,' critical elements... are rarely implemented (p 41). He also discusses the dilemma of how to create a reimbursement system in the health sector that encourages hospitals and physicians to pursue the interests of society as well as their own (p 59).  The solution
Subgroup Analyses in Contemporary Phase III Trials in Advanced Breast Cancer (ABC).
Authors: A. Calabrich, A. Katz, E. Saad
Journal: Cancer Research (2009)

Abstract Objective: Subgroup analyses of treatment effects according to baseline patient characteristics are often performed in phase III trials in oncology. However, the frequency and determinants of this practice in ABC have not been described in the literature.Methods: We used the medical subject headings “breast neoplasms” and “drug therapy” to search PubMed for phase III trials on systemic antineoplastic therapies published between 01/00 and 12/07 in one of 10 leading medical journals (Ann Oncol, BCRT, Br J Cancer, Cancer, Eur J Cancer, JCO, JNCI, Lancet Oncol, Lancet and NEJM). We excluded factorial trials and studies on high-dose chemotherapy. When a subgroup analysis was not reported in the main article for each trial, a PubMed search was conducted using the names of first and last authors (separately) and the experimental drug(s). All variables were analyzed as reported by the authors of trials.Results: The initial search yielded 58 trials enrolling a total of 23,371 patients in 122 trial arms. For 31 trials (53.4%), a subgroup analysis was reported in the main article. Another 7 trials reported a subgroup analysis in a companion paper, for a total of 38 out of 58 trials reporting a subgroup analysis (65.5%; 95% CI, 51.8 – 77.2%). Such analyses were reportedly pre-planned in only 11/38 cases (28.9%), and only two trials reported a formal test for interaction. The number of factors considered in subgroup analyses ranged from 1 to 14. In 21/38 cases (55.3%), none of these factors was used for stratification before randomization. The results of the subgroup analysis were mentioned in the main article abstract in 13/31 cases (41.9%), 5 of which in the conclusions. There was no difference in the proportion of positive (70.4%) and negative (61.3%) trials (regarding their primary endpoints) for which a subgroup analysis was reported (P=0.53). Likewise, financial support (pharmaceutical industry [N=36] vs others [N=22]) was not predictive of subgroup analysis (P=0.17). However, trials published between 2000 and 2003 were more likely (P=0.03) to report a subgroup analysis (79.3%) than trials published between 2004 and 2007 (51.7%).Conclusion: Our review suggests that subgroup analyses are frequently performed in phase III trials in ABC. In the vast majority of cases, no formal test for interaction is presented. There seems to be a temporal trend for decrease in reporting of subgroup analyses. Other potential predictors of subgroup analysis are currently being sought. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2107.
Trophic Skin Ulceration of Leprosy: Skin and Serum Zinc Concentrations
Authors: B. B. Oon, K. Y. Khong, M. W. Greaves, V. M. Plummer
Journal: BMJ (1974)

Skin and serum zinc measurements have been made in patients with leprosy with and without trophic skin ulceration and in several other groups. Serum zinc concentrations were decreased in leprosy irrespective of the presence or absence of skin ulceration. Serum zinc concentrations in leprosy were also unrelated to smears positive for Mycobacterium leprae and to the clinical type of leprosy. Since a decrease of the serum zinc was also found in patients with dermatitis herpetiformis and pulmonary tuberculosis it seems likely that the decreased serum zinc in leprosy is a nonspecific metabolic consequence of chronic skin and internal disease. The mean skin zinc concentration in leprosy did not differ significantly from the corresponding value in control subjects, the lack of agreement between serum and skin concentrations being possibly related to the presence of nonexchangeable keratin-bound zinc in skin. Though the clinical significance of lowered serum zinc concentrations in leprosy is uncertain therapeutic trials of zinc treatment in leprosy with trophic skin ulceration seem justifiable.
A SERIES OF APPARENTLY WELL ESTABLISHED FACTS IN THERAPEUTICS ON WHICH ARE BASED SOME QUESTIONS OF GREAT PRACTICAL IMPORTANCE.
Authors: N. S. DAVIS
Journal: JAMA (1894)

1. The three well-known anesthetics in common use—ether, chloroform and alcohol each and all, when received into the blood, either by inhalation, hypodermic injection, or by the stomach, first suspend the sensibility of the cerebral hemispheres (unconsciousness or anesthesia), and next they suspend in succession or simultaneously the functions of the respiratory, vasomotor and cardiac nerve centers or ganglia, thereby suspending life. It is hardly necessary to adduce proof of this proposition, as it is familiar to every practitioner of medicine and surgery. 2. Each of these three anesthetics act on the nervous centers in the same direction, and consequently each intensifies the action of the others, whether given together by inhalation as in the A. C. E. mixture, or separately by different methods, provided they are present in the blood at the same time. The correctness of this proposition is demonstrated by the experiments of Dubois in 1883, and
Epitopes of apolipoprotein B-100 and B-48 in both liver and intestine. Expression and evidence for local synthesis in recessive abetalipoproteinemia.
Authors: R P Dullaart, B Speelberg, H J Schuurman, R W Milne, L M Havekes, Y L Marcel, H J Geuze, M M Hulshof, D W Erkelens
Journal: Journal of Clinical Investigation (1986)

The presence of apolipoprotein (apo) B in liver and intestine from a patient with abetalipoproteinemia was evaluated by immunohistochemistry with a polyclonal and six monoclonal antibodies to different apo B-48 and B-100 epitopes. In normal liver, apo B was present inside and outside hepatocytes. The patients liver exhibited staining in the cytoplasm with the polyclonal and three monoclonal antibodies. By immunoelectron-microscopy, apo B was found to be present in the smooth endoplasmatic reticulum and the Golgi complex. Normal intestinal epithelium was labeled with polyclonal and all monoclonal antibodies, including those specific for apo B-100. The patients epithelium stained with polyclonal and six monoclonals, and apo B was present in the Golgi complex. Thus, normal intestinal mucosa expressed apo B-48 and B-100 epitopes, which indicates apo B-100 synthesis in the gut. The synthesis of the apo B molecule in the patient seems to be retained in both liver and gut, which suggests a posttranslational defect.
Gene Transfer of a Synthetic Pacemaker Channel Into the Heart
Authors: Yuji Kashiwakura, Hee Cheol Cho, Andreas S. Barth, Ezana Azene, Eduardo Marbán
Journal: Circulation (2006)

One key element of natural pacemakers is the pacemaker current encoded by the hyperpolarization-activated nucleotide-gated channel (HCN) gene family. Although HCN gene transfer has been used to engineer biological pacemakers, this strategy may be confounded by unpredictable consequences of heteromultimerization with endogenous HCN family members and limited flexibility with regard to frequency tuning of the engineered pacemaker.To circumvent these limitations, we converted a depolarization-activated potassium-selective channel, Kv1.4, into a hyperpolarization-activated nonselective channel by site-directed mutagenesis (R447N, L448A, and R453I in S4 and G528S in the pore). Gene transfer into ventricular myocardium demonstrated the ability of this construct to induce pacemaker activity with spontaneous action potential oscillations in adult ventricular myocytes and idioventricular rhythms by in vivo electrocardiography.Given the sparse expression of Kv1 family channels in the human ventricle, gene transfer of a synthetic pacemaker channel based on the Kv1 family has novel therapeutic potential as a biological alternative to electronic pacemakers.
Hedgehog Signaling Blockade Delays Hepatocarcinogenesis Induced by Hepatitis B Virus X Protein
Authors: Alla Arzumanyan, Vaishnavi Sambandam, Marcia M. Clayton, Steve S. Choi, Guanhua Xie, Anna Mae Diehl, Dae-Yeul Yu, Mark A. Feitelson
Journal: Cancer Research (2012)

The hepatitis B virus (HBV) encoded X protein (HBx) contributes centrally to the pathogenesis of hepatocellular carcinoma (HCC). Aberrant activation of the Hedgehog (Hh) pathway has been linked to many tumor types including HCC. Thus, experiments were designed to test the hypothesis that HBx promotes HCC via activation of Hh signaling. HBx expression correlated with an upregulation of Hh markers in human liver cancer cell lines, in liver samples from HBV infected patients with HCC, and in the livers of HBx transgenic mice (HBxTg) that develop hepatitis, steatosis, and dysplasia, culminating in the appearance of HCC. The findings in human samples provide clinical validation for the in vitro results and those in the HBxTg. Blockade of Hh signaling inhibited HBx stimulation of cell migration, anchorage-independent growth, tumor development in HBxTg, and xenograft growth in nude mice. Results suggest that the ability of HBx to promote cancer is at least partially dependent upon the activation of the Hh pathway. This study provides biologic evidence for the role of Hh signaling in the pathogenesis of HBV-mediated HCC and suggests cause and effect for the first time. The observation that inhibition of Hh signaling partially blocked the ability of HBx to promote growth and migration in vitro and tumorigenesis in two animal models implies that Hh signaling may represent an "oncogene addiction" pathway for HBV-associated HCC. This work could be central to designing specific treatments that target early development and progression of HBx-mediated HCC.
Physicians' Attitudes Toward Using Deception-Reply
Authors: Dennis H. Novack
Journal: JAMA (1989)

In Reply.—  Baker and colleagues misrepresent us and seem to misunderstand the point of our study. We did not analyze half of our scenarios in terms of  deception. We did not label as deceivers physicians who would allow the wife of a patient with gonorrhea to be misled about his diagnosis. In our construction of the case of the pregnant teen, we did not consider nondisclosure to be deception. In this vignette, the only choices we categorized as deceptive were Sherry has a gastroenteritis... or ... something common that's going around. We did not assert that because one can deceive by nondisclosure, that all nondisclosure is therefore deception. Our intent was to study the degree to which physicians are willing to accept  as a part of ethical medical practice. We did not presume to measure physicians' integrity by passive deception or other yardsticks.  We agree with Baker et al
SMALLPOX STUDIES IN MADRAS CITY, INDIA
Authors: T. N. S. RAGHAVACHARI
Journal: Annals of Internal Medicine (1968)

Letters and Comments1 March 1968SMALLPOX STUDIES IN MADRAS CITY, INDIAT. N. S. RAGHAVACHARIT. N. S. RAGHAVACHARISearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-3-710_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: I am writing in the context of the editorial note on smallpox that appeared in the June 1967 issue of the ANNALS.During the past 5 years a number of health officers of air- and seaports of Europe, Asia, and Australia were trained in the detection of smallpox cases at the Infectious Diseases Hospital, Madras City, which was chosen for the training because it led the country in the prevalence of smallpox, with an annual average of 4,000 cases in an epidemic year and 1,000 cases in a nonepidemic year. In 1967 the first batch of Australian... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 61 Lloyd's Rd., Royapettah, Madras-14, PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1968Volume 68, Issue 3Page: 710-710KeywordsInfectious diseases Issue Published: 1 March 1968 PDF DownloadLoading ...