tbuckley/cabot-search huggingface dataset:
Abstract 100: Preclinical and clinical studies data consolidation and federation using an integrative data analysis system: SIMUSITETM
Authors: Meena I. Vora
Journal: Cancer Research (2010)

Abstract One of the biggest challenges of the drug development process is to secure, access the experimental work and critical communications amongst the persons involved. These are the primary assets of any organization. These challenges stem from, (i) the data generated are collected mostly over a long period of time. (ii) the fast pace of development of new laboratory technologies requires the project management and underlying data structure constantly changing. (iii) outsourcing of the project work. (iv) multiple modes of communications among the peers. Here we describe the data consolidation and federation module of BioPhase Systems’ SIMUSITETM (http://www.biophasesystems.com/simusite), a commercial software platform that allows users to integrate and analyze biological data from multiple experimental sources to uncover potentially valuable targets and guide the further drug development of therapeutic compounds. In order to ensure the accessibility to disparate knowledge bases, SIMUSITE has been architected using caBIGTM compatibility guidelines (http://cabig.nci.nih.gov). Though the software is built for the present needs of the industry, it is also designed to address the future challenges. A case study depicting the migration of various types of data generated from multiple third party data analysis applications is presented spanning from pre-clinical to clinical level studies. It also demonstrates the analysis of the consolidated data further in the context of the public domain knowledge on the fly, thus providing the environment to consolidate data, updating the projects dynamically and allowing the communications amongst the peers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 100.
Gilbert syndrome redefined: A complex genetic haplotype influences the regulation of glucuronidation
Authors: Ursula Ehmer, Sandra Kalthoff, Bastian Fakundiny, Brigitte Pabst, Nicole Freiberg, Ronald Naumann, Michael P. Manns, Christian P. Strassburg
Journal: Hepatology (2011)

Gilbert syndrome (GS) is characterized by intermittent unconjugated hyperbilirubinemia without structural liver damage, affecting about 10% of the white population. In GS the UGT1A1*28 variant reduces bilirubin conjugation by 70% and is associated with irinotecan and protease inhibitor side effects. The aim of this study was to characterize potential in vivo consequences of UGT1A gene variability in GS. Three hundred GS patients (UGT1A1*28 homozygous) and 249 healthy blood donors (HBD) were genotyped for UGT1A (UGT1A1*28, UGT1A3 - 66 T&gt;C, UGT1A6*3a, UGT1A7*3) and transporter single nucleotide polymorphisms (SNPs) ( SCLO1B1 p.V174A, SCLO1B1 p.N130D, ABCC2 p.I1324I, ABCC2 - 24 UTR) using TaqMan-5′-nuclease-assays. A humanized transgenic UGT1A - SNP and corresponding wildtype mouse model were established carrying the GS-associated UGT1A variant haplotype. UGT1A transcript and protein expression, and transcriptional activation were studied in vivo . Homozygous UGT1A1*28 GS individuals were simultaneously homozygous for UGT1A3–66 T&gt;C (91%), UGT1A6*2a (77%), and UGT1A7*3 (77%). Seventy-six percent of GS and only 9% of HBD were homozygous for the variant haplotype spanning four UGT1A genes. SCLO1B1 and ABCC2 SNPs showed no differences. In transgenic humanized UGT1A SNP and wildtype mice this UGT1A haplotype led to lower UGT1A messenger RNA (mRNA) expression and UGT1A protein synthesis. UGT1A transcriptional activation by dioxin, phenobarbital, and endotoxin was significantly reduced in SNP mice. Conclusion: Our data redefine the genetic basis behind GS. In vivo data studying the genotype present in 76% of GS individuals suggest that transcription and transcriptional activation of glucuronidation genes responsible for conjugation and detoxification is directly affected, leading to lower responsiveness. This study suggests that GS should be considered a potential risk factor for drug toxicity.
Benefits and Risks of Extended Duration Dual Antiplatelet Therapy After PCI in Patients With and Without Acute Myocardial Infarction
Authors: Robert W. Yeh, Dean J. Kereiakes, Philippe Gabriel Steg, Stephan Windecker, Michael J. Rinaldi, Anthony H. Gershlick, Donald E. Cutlip, David J. Cohen, Jean-Francois Tanguay, Alice Jacobs, Stephen D. Wiviott, Joseph M. Massaro, Adrian C. Iancu, Laura Mauri
Journal: Journal of the American College of Cardiology (2015)
Abstract 235: Desmocollin 2 (DSC2), identified by CAST method, is associated with intestinal phenotype of gastric cancer
Authors: Katsuhiro Anami, Naohide Oue, Naoya Sakamoto, Tetsutaro Hayashi, Shinya Ohara, Kazuhiro Sentani, Tsuyoshi Noguchi, Wataru Yasui
Journal: Cancer Research (2010)

Abstract Gastric cancer (GC) is one of the most common human cancers. Identification of novel genes encoding secreted or transmembrane proteins expressed specifically in GC is important for the development of ideal biomarkers for cancer diagnosis and therapeutics. In the present study, we tried to identify genes encoding cell surface and secretory proteins in GC using Escherichia coli ampicillin secretion trap (CAST) method. CAST libraries were generated from two GC cell lines, MKN-1 and MKN-28. Ampicillin-resistant 1,440 colonies from each library were sequenced and these sequences were compared to the public databases using BLAST (NCBI). Many genes encoding secreted and transmembrane proteins including some known genes were identified. Quantitative RT-PCR was performed to confirm the overexpression of the candidate genes in GC, and the expressions of several genes are narrowly restricted in GC. Among these genes, we focused on the desmosomal cadherin desmocollin 2 (DSC2). DSC2 is ubiquitously expressed in several normal tissues where desmosomes exist. In cancers, the reduction of DSC2 in sporadic colorectal cancer is reported as desmocollin switching. It is also known that the homeodomain transcription factors Cdx1 and Cdx2 regulate DSC2 expression in colon cancer cells. Quantitative RT-PCR analyses with 14 kinds of normal tissues and 9 GC cases showed that DSC2 is highly expressed in GCs. In normal tissues, the expression was seen in the heart and pancreas at the lower levels, but not in the stomach. Overexpression of DSC2 was observed in 13 (31%) of 41 GC cases. Immunohistochemical analyses revealed that DSC2 was preferentially expressed in the cases with mucosal or submucosal invasion. DSC2 expression was significantly associated with the well differentiated cases. There were no correlations between DSC2 expression and lymph node metastasis, pathological stage, or overall survival. Additionally, DSC2 was significantly associated in GCs positive for MUC2 and CDX2. Cell invasion assay and MTT assay revealed that knockdown for DSC2 of GC cell lines by siRNA did not inhibit either cell growth or invasion ability. These findings suggest that DSC2 is involved in GC with intestinal differentiation. DSC2 is a good biomarker of intestinal type GC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 235.
Understanding Health Care as a Complex System
Authors: Lewis A. Lipsitz
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Associations between Drugs Administered during Pregnancy and Congenital Abnormalities of the Fetus
Authors: M. M. Nelson, J. O. Forfar
Journal: BMJ (1971)

In a retrospective study to compare the drug consumption during pregnancy of mothers of infants with congenital abnormalities and of those without, over 97% of 1,369 mothers took prescribed drugs and 65% self-administered drugs. Significantly more mothers of infants with congenital abnormalities took aspirin, antacids, dextroamphetamine, phenobarbitone, sodium amytal, other barbiturates, cough medicines, iron, sulphonamides, and nicotinamide than mothers in the control group. However, most mothers taking analgesics, antacids, appetite suppressants, barbiturates, cough medicines, iron, sulphonamides, and vitamins produced normal infants. Any teratogenic effect of these drugs is therefore one of low potency. On the other hand, deficiencies such as those of ascorbic acid and folic acid may have a teratogenic effect. There is need for caution in presuming teratogenic effects on the basis of the associations shown here. During pregnancy, however, it would appear wise to avoid the administration of any drug which carries a suspicion of teratogenicity unless that drug is specifically indicated, and self-medication with common household remedies such as aspirin and antacids should be avoided. These recommendations would also apply to any woman of childbearing age in whom conception is likely.
High Serum Cholesterol and Risk of Suicide
Authors: Antti Tanskanen, Erkki Vartiainen, Jaakko Tuomilehto, Heimo Viinamãª©, Johannes Lehtonen, Pekka Puska
Journal: American Journal of Psychiatry (2000)

The study was conducted to estimate the association between serum total cholesterol concentration and mortality from suicide.The baseline serum total cholesterol concentration of 37,635 adults was determined in five independent population surveys conducted during 1972-1992 in Finland. Mortality from different causes of death was monitored for a mean of 14.6 years after the survey dates. The means for violent suicides (N=130) included hanging, firearms, cutting, jumping, and unspecified means. The means for nonviolent suicides (N=46) included drug overdose, poisoning with gases, and drowning.Serum total cholesterol concentration was positively related to the risk of violent suicide. Among subjects whose serum total cholesterol concentration was in the highest category, the adjusted relative risk was more than twofold compared with the lowest category. The violent/nonviolent suicide ratio increased linearly with increasing cholesterol category. No association between serum total cholesterol concentration and the risk of nonviolent suicide was found.This is the first study to demonstrate the positive relationship of high serum total cholesterol concentration with increased risk of violent suicide.
Chronic progressive eosinophilic fasciitis: report of a 20-year failure to attain remission
Authors: R. Bertken, D. Shaller
Journal: Annals of the Rheumatic Diseases (1983)

A retrospective diagnosis of eosinophilic fasciitis was made in a patient with disabling contractural disease of 20 years9 duration. Chronic moderate-dose corticosteroid therapy had failed to halt either clinical or histological progression of the disease, but rapid worsening of skin thickening and contracture followed withdrawal of prednisone. Muscle wasting was severe in spite of normal serum creatine kinase levels; urinary excretion of creatinine was consistently elevated.
Are Medical Conferences Useful? And for Whom?
Authors: John P. A. Ioannidis
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cell of Origin in AML: Susceptibility to MN1-Induced Transformation Is Regulated by the MEIS1/AbdB-like HOX Protein Complex
Authors: Michael Heuser, Haiyang Yun, Tobias Berg, Eric Yung, Bob Argiropoulos, Florian Kuchenbauer, Gyeongsin Park, Iyas Hamwi, Lars Palmqvist, Courteney K. Lai, Malina Leung, Grace Lin, Anuhar Chaturvedi, Basant Kumar Thakur, Masayuki Iwasaki, Mikhail Bilenky, Nina Thiessen, Gordon Robertson, Martin Hirst, David Kent, Nicola K. Wilson, Bertie Göttgens, Connie Eaves, Michael L. Cleary, Marco Marra, Arnold Ganser, R. Keith Humphries
Journal: Cancer Cell (2011)
Metabolic Signature Identifies Novel Targets for Drug Resistance in Multiple Myeloma
Authors: Patricia Maiso, Daisy Huynh, Michele Moschetta, Antonio Sacco, Yosra Aljawai, Yuji Mishima, John M. Asara, Aldo M. Roccaro, Alec C. Kimmelman, Irene M. Ghobrial
Journal: Cancer Research (2015)

Drug resistance remains a major clinical challenge for cancer treatment. Multiple myeloma is an incurable plasma cell cancer selectively localized in the bone marrow. The main cause of resistance in myeloma is the minimal residual disease cells that are resistant to the original therapy, including bortezomib treatment and high-dose melphalan in stem cell transplant. In this study, we demonstrate that altered tumor cell metabolism is essential for the regulation of drug resistance in multiple myeloma cells. We show the unprecedented role of the metabolic phenotype in inducing drug resistance through LDHA and HIF1A in multiple myeloma, and that specific inhibition of LDHA and HIF1A can restore sensitivity to therapeutic agents such as bortezomib and can also inhibit tumor growth induced by altered metabolism. Knockdown of LDHA can restore sensitivity of bortezomib resistance cell lines while gain-of-function studies using LDHA or HIF1A induced resistance in bortezomib-sensitive cell lines. Taken together, these data suggest that HIF1A and LDHA are important targets for hypoxia-driven drug resistance. Novel drugs that regulate metabolic pathways in multiple myeloma, specifically targeting LDHA, can be beneficial to inhibit tumor growth and overcome drug resistance.
Is the concept of object still a suitable notion?
Authors: Marie-Dominique Giraudo, Andrew B. Slifkin
Journal: Behavioral and Brain Sciences (2004)

The model and framework presented in the target article by Thelen et al. is an interesting effort that is able to account for the contextual variability in the A-not-B performance of 7–12-month-old infants. In the process of developing their framework, the authors discounted the concept of object as a useful notion in discussions of A-not-B performance. For Piaget and other developmentalists, the main evidence for the acquisition of the concept of object was the disappearance of A-not-B errors after age 12 months. However, the Thelen et al. model makes predictions of A-not-B outcomes over a much shorter, trial-to-trial time scale. Given the mismatch in the time scales over which analyses in the two approaches have been based, we wonder if the challenge to the concept of object has been misplaced.
Money as tool, money as drug: The biological psychology of a strong incentive
Authors: Stephen E. G. Lea, Paul Webley
Journal: Behavioral and Brain Sciences (2006)

Why are people interested in money? Specifically, what could be the biological basis for the extraordinary incentive and reinforcing power of money, which seems to be unique to the human species? We identify two ways in which a commodity which is of no biological significance in itself can become a strong motivator. The first is if it is used as a tool, and by a metaphorical extension this is often applied to money: it is used instrumentally, in order to obtain biologically relevant incentives. Second, substances can be strong motivators because they imitate the action of natural incentives but do not produce the fitness gains for which those incentives are instinctively sought. The classic examples of this process are psychoactive drugs, but we argue that the drug concept can also be extended metaphorically to provide an account of money motivation. From a review of theoretical and empirical literature about money, we conclude that (i) there are a number of phenomena that cannot be accounted for by a pure Tool Theory of money motivation; (ii) supplementing Tool Theory with a Drug Theory enables the anomalous phenomena to be explained; and (iii) the human instincts that, according to a Drug Theory, money parasitizes include trading (derived from reciprocal altruism) and object play.
Prolonged Remission of Diabetes by Regeneration of β Cells in Diabetic Mice Treated with Recombinant Adenoviral Vector Expressing Glucagon-like Peptide-1
Authors: Meng-Ju Liu, Seungjin Shin, Na Li, Toshikatsu Shigihara, Young-Sun Lee, Ji-Won Yoon, Hee-Sook Jun
Journal: Molecular Therapy (2006)

Type 1 diabetes results from insulin deficiency caused by destruction of pancreatic β cells. Glucagon-like peptide (GLP)-1 stimulates β cell growth and differentiation. To determine whether continuous expression of GLP-1 in vivo can regenerate β cells and remit type 1 diabetes in mice for a prolonged time, we constructed an adenoviral vector containing the cytomegalovirus promoter/enhancer and albumin leader sequence followed by GLP-1 cDNA (rAd-GLP-1). A single administration of rAd-GLP-1 via the tail vein into streptozotocin (STZ)-induced diabetic non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice resulted in remission of diabetes within 10 days; normoglycemia remained until the experiment was terminated. The number of insulin-positive cells in the pancreas and insulin secretion significantly increased in rAd-GLP-1-treated mice compared with STZ-induced diabetic mice treated with rAd-β-galactosidase. Glucose tolerance tests in mice that achieved normoglycemia after treatment with rAd-GLP-1 showed that the kinetics of glucose clearance was similar to normal NOD/SCID mice. Treatment of autoimmune diabetic mice with rAd-GLP-1 restored normoglycemia, which was maintained for 1 year when mice were also treated with an immunoregulator to halt the autoimmune response to β cells. We suggest that regeneration of insulin-producing cells by GLP-1 gene therapy may be a potential method for prolonged control of type 1 diabetes in humans.
Review: Varenicline is better than bupropion but not nicotine patch for smoking abstinence in adults
Authors: Allan V. Prochazka, Tanner J. Caverly
Journal: Annals of Internal Medicine (2012)

ACP Journal Club18 September 2012Review: Varenicline is better than bupropion but not nicotine patch for smoking abstinence in adultsAllan V. Prochazka, MD, Tanner J. Caverly, MDAllan V. Prochazka, MDDenver VA Medical Center, Denver, Colorado, USA (A.V.P., T.J.C.)Search for more papers by this author, Tanner J. Caverly, MDDenver VA Medical Center, Denver, Colorado, USA (A.V.P., T.J.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-6-201209180-02007 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationCahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2012(4):CD006103. https://pubmed.ncbi.nlm.nih.gov/22513936Clinical Impact RatingsGIM/FP/GP: Mental Health: Pulmonology: References1 Etter JF. Cytisine for smoking cessation: a literature review and a meta-analysis. Arch Intern Med. 2006;166:1553-9. [PMID: 16908787] Google Scholar2 Vickers A, Goyal N, Harland R, Rees R. Do certain countries produce only positive results? A systematic review of controlled trials. Control Clin Trials. 1998;19:159-66. [PMID: 9551280] Google Scholar3 Singh S, Loke YK, Spangler JG, Furberg CD. Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ. 2011;183:1359-66. [PMID: 21727225] Google Scholar4 Prochaska JJ, Hilton JF. Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis. BMJ. 2012;344:e2856. [PMID: 22563098] Google Scholar Author, Article, and Disclosure InformationAuthors: Allan V. Prochazka, MD; Tanner J. Caverly, MDAffiliations: Denver VA Medical Center, Denver, Colorado, USA (A.V.P., T.J.C.)This article was published at Annals.org on 4 September 2012. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCan an index of smokers’ emotional status predict the chances of success in attempts to quit smoking? 18 September 2012Volume 157, Issue 6Page: JC3-7KeywordsDrugsNicotineResearch fundingResearch quality assessmentSafetySerious adverse eventsSmoking cessationSuicideSystematic reviews ePublished: 18 September 2012 Issue Published: 18 September 2012 Copyright & PermissionsCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...