tbuckley/cabot-search huggingface dataset:
Genome-Wide Transcriptional Response to 5-Aza-2′-Deoxycytidine and Trichostatin A in Multiple Myeloma Cells
Authors: Gerwin Heller, Wolfgang M. Schmidt, Barbara Ziegler, Sonja Holzer, Leonhard Müllauer, Martin Bilban, Christoph C. Zielinski, Johannes Drach, Sabine Zöchbauer-Müller
Journal: Cancer Research (2008)

Abstract To identify epigenetically silenced cancer-related genes and to determine molecular effects of 5-aza-2′-deoxycytidine (Aza-dC) and/or trichostatin A (TSA) in multiple myeloma (MM), we analyzed global changes in gene expression profiles of three MM cell lines by microarray analysis. We identified up-regulation of several genes whose epigenetic silencing in MM is well known. However, much more importantly, we identified a large number of epigenetically inactivated cancer-related genes that are involved in various physiologic processes and whose epigenetic regulation in MM was unknown thus far. In addition, drug treatment of MM cell lines resulted in down-regulation of several MM proliferation-associated factors (i.e., MAF, CCND1/2, MYC, FGFR3, MMSET). Ten Aza-dC and/or TSA up-regulated genes (CPEB1, CD9, GJA1, BCL7c, GADD45G, AKAP12, TFPI2, CCNA1, SPARC, and BNIP3) were selected for methylation analysis in six MM cell lines, 24 samples from patients with monoclonal gammopathy of undetermined significance (MGUS), and 111 samples from patients with MM. Methylation frequencies of these genes ranged between 0% and 17% in MGUS samples and between 5% and 50% in MM samples. Interestingly, methylation of SPARC and BNIP3 was statistically significantly associated with a poor overall survival of MM patients (P = 0.003 and P = 0.017, respectively). Moreover, SPARC methylation was associated with loss of SPARC protein expression by immunostaining in a subset of MM patients. In conclusion, we identified new targets for aberrant methylation in monoclonal gammopathies, and our results suggest that DNA methyltransferase and histone deacetylase inhibition might play an important role in the future treatment of patients with MM. [Cancer Res 2008;68(1):44–54]
Mnemonic expertise during wakefulness and sleep
Authors: Martin Dresler, Boris N. Konrad
Journal: Behavioral and Brain Sciences (2013)

Abstract We studied the world's most distinguished experts in the use of mnemonic techniques: the top participants of the World Memory Championships. They neither feel the use of mnemonics to be dreamlike, nor does their REM sleep differ from mnemonic-naive control subjects. Besides these empirical data, also theoretical considerations contradict an isomorphism between features of REM sleep dreaming and mnemonic principles.
Cost Sharing in Health Insurance — A Reexamination
Authors: M E Rasell
Journal: New England Journal of Medicine (1995)

Concern that the terms of some health insurance policies encourage overuse of medical care has led to the argument that an important element of cost containment is cost consciousness on the consumer's part. Comprehensive health care reform in the United States now appears very unlikely. Nevertheless, there is still a high degree of interest in making consumers more cost conscious.1 Two approaches are often proposed. The first is to increase the level of cost sharing specified in insurance policies by raising copayments or coinsurance rates and to make cost sharing a part of every policy. The second is to require . . .
P1-14-02: Correlation of Circulating Tumor Cells (CTC) and Circulating Endothelial Cells (CEC) with Pathological Complete Response (pCR) during Neoadjuvant Chemotherapy (CT) Combined with Bevacizumab in HER2 Negative Inflammatory Breast Cancer (IBC): Ancillary Study of Phase II Trial BEVERLY 1.
Authors: J-Y Pierga, F-C Bidard, F Andre, T Petit, F Dalenc, T Delozier, G Romieu, J Bonneterre, J-M Ferrero, P Kerbrat, J Lemonnier, P Viens
Journal: Cancer Research (2011)

Abstract Background: Prognostic value of CTC detection in blood has been reported in primary breast cancer with a rate around 20% in the neoadjuvant setting. No correlation between CTC and pCR to neoadjuvant CT in operable breast cancer has been reported (Pierga CCR 2008, Riethdorf CCR 2010). Predictive value of CEC for response to anti-angiogenic agents is unclear. Methods: CTC and CEC were detected in 7.5 ml and 4 ml of blood respectively with CellSearch™ System in the neoadjuvant setting of HER2 negative IBC (T4d) patients (pts) enrolled in the phase II multicentre trial BEVERLY 1, evaluating bevacizumab (15mg/kg q3w) in combination with sequential neoadjuvant CT of 4 cycles of FEC followed by 4 cycles of Docetaxel. Patients received postoperatively 10 cycles of bevacizumab and hormonotherapy if tumor was ER+. Results: From 12/08 to 09/10, 101 pts were included, 96 were evaluable for pCR and 92 for CTC and CEC. Out of 96 pts, 51 (53%) had triple negative breast cancer (TNBC). At baseline, 37 pts out of 92 had ≥ 1 detectable CTC (40%, 95%CI 30–50%). At baseline, CTC level was not correlated with CEC level, neither with TNBC nor pCR. A drop in CTC incidence was observed from baseline to the 1st follow-up analysis after 4 cycles (p&amp;lt;0.0001). Out of 6 pts with detectable CTC at the end of adjuvant bevacizumab (8 months post surgery) none had pCR (p=0.05 Yates test). There was a significant increase of CEC from baseline to presurgery sample (p &amp;lt;0.001) and a decrease (p=0.04) after tumor removal and end of CT. A higher level of CEC (&amp;gt;20/4ml) before C5 could be associated with a higher probability of pCR (Khi2 test, p=0.003). Conclusions: We observed a high CTC detection rate of 40% in HER2− IBC, including TNBC. CEC levels increased progressively during neoadjuvant treatment and decreased after its interruption. Baseline CTC and CEC levels were not predictive of pCR. Detection of CTC at 8 months of follow-up was associated with the absence of response to neoadjuvant chemotherapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-14-02.
Pacemaker Therapy for Prevention of Syncope in Patients With Recurrent Severe Vasovagal Syncope
Authors: Stuart J. Connolly, Robert Sheldon, Kevin E. Thorpe, Robin S. Roberts, Kenneth A. Ellenbogen, Bruce L. Wilkoff, Carlos Morillo, Michael Gent, None for the VPS II Investigators
Journal: JAMA (2003)

Three previous small randomized trials have reported that pacemaker therapy is beneficial for patients with severe recurrent vasovagal syncope. However, because these trials were not double blind, they may have been biased in their assessment of outcomes and had a placebo effect of surgery.To determine if pacing therapy reduces the risk of syncope in patients with vasovagal syncope.A randomized double-blind trial of pacemaker therapy in outpatients referred to syncope specialists at 15 centers from September 1998 to April 2002. In the year prior to randomization, patients had had a median of 4 episodes of syncope. Patients were followed up for up to 6 months.After implantation of a dual chamber pacemaker, 100 patients were randomly assigned to receive dual-chamber pacing (DDD) with rate drop response or to have only sensing without pacing (ODO).Time to first recurrence of syncope.No patients were lost to follow-up. Of the 52 patients randomized to ODO, 22 (42%) had recurrent syncope within 6 months compared with 16 (33%) of 48 patients in the DDD group. The cumulative risk of syncope at 6 months was 40% (95% confidence interval [CI], 25%-52%) for the ODO group and 31% (95% CI, 17%-43%) for the DDD group. The relative risk reduction in time to syncope with DDD pacing was 30% (95% CI, -33% to 63%; 1-sided P =.14). Lead dislodgement or repositioning occurred in 7 patients. One patient had vein thrombosis, another had pericardial tamponade leading to removal of the pacemaker system, and a third had infection involving the pacemaker generator.In this double-blind randomized trial, pacing therapy did not reduce the risk of recurrent syncope in patients with vasovagal syncope. Because of the weak evidence of efficacy of pacemaker therapy and the risk of complications, pacemaker therapy should not be recommended as first-line therapy for patients with recurrent vasovagal syncope.
Prognostic value of enhanced bone marrow angiogenesis in early B-cell chronic lymphocytic leukemia
Authors: Stefano Molica, Angelo Vacca, Domenico Ribatti, Antonio Cuneo, Francesco Cavazzini, Domenico Levato, Gaetano Vitelli, Luigi Tucci, Aldo M. Roccaro, Franco Dammacco
Journal: Blood (2002)
1040-71 Interhospital transfers are costly, cause delays and do not address the imbalance of access to revascularization: The case for more angiographic facilities? Results from the global registry of acute coronary events
Authors: Ameet Bakhai, Omar H Dabbous, David J Cohen, Marcus D Flather, Dan Greenberg, Frederick A Anderson, Enrique P Gurfinkel, Kami White, Keith A.A Fox
Journal: Journal of the American College of Cardiology (2004)
Neurodegeneration caused by intronic expansions of C9ORF72 is a clinically heterogeneous but pathologically distinct disease
Authors: Johnathan Cooper-Knock, J Robin Highley, Judith Hartley, Antonio Milano, Stephen Sawcer, Alistair Compston, Antonina Frolov, Gavin Charlesworth, Nicholas Wood, Oliver Bandmann, Christopher J McDermott, Janine Kirby, Paul Ince, Pamela Shaw
Journal: The Lancet (2013)
Bile formation: Do not ignore the role of plasma membrane-cytoskeleton linking proteins
Authors: Konstantinos N. Lazaridis, Nicholas F. LaRusso
Journal: Hepatology (2003)

The ezrin-radixin-moesin (ERM) family of proteins crosslink ac-tin filaments and integral membrane proteins. Radixin (encoded by Rdx) is the dominant ERM protein in the liver of wildtype mice and is concentrated at bile canalicular membranes (BCMs). Here we show that Rdx(-/-) mice are normal at birth, but their serum concentrations of conjugated bilirubin begin to increase gradually around 4 weeks, and they show mild liver injury after 8 weeks. This phenotype is similar to human conjugated hyperbiliru-binemia in Dubin-Johnson syndrome, which is caused by mutations in the multidrug resistance protein 2 (MRP2, gene symbol ABCC2), although this syndrome is not associated with overt liver injury. In wildtype mice, Mrp2 concentrates at BCMs to secrete conjugated bilirubin into bile. In the BCMs of Rdx / mice, Mrp2 is decreased compared with other BCM proteins such as dipeptidyl peptidase IV (CD26) and P-glycoproteins. In vitro binding studies show that radixin associates directly with the car-boxy-terminal cytoplasmic domain of human MRP2. These findings indicate that radixin is required for secretion of conjugated bilirubin through its support of Mrp2 localization at BCMs.
Genetic counseling throughout the life cycle
Authors: Leslie J. Ciarleglio, Robin L. Bennett, Jennifer Williamson, Jessica B. Mandell, Joan H. Marks
Journal: Journal of Clinical Investigation (2003)

As the definition of genetic counseling continues to evolve, so does the application of genetic counseling services in all areas of medicine and throughout the human life cycle. While governmental policy, economics, ethics, and religion continue to influence society's views regarding the necessity of testing germ cells for mutations to prevent the birth of an affected child or predicting whether healthy adults will develop future life-threatening illness, patient autonomy in the choice of whether to know, or not know, one's genetic make-up remains a core principle of genetic counseling.
Empathy is important for enablement
Authors: S. W Mercer
Journal: BMJ (2001)

Using patient identifiable data without consent Obtaining individual consent may hinder studiesEditor-The editorial by Al-Shahi and Warlow is timely and well argued. 1 The implications of a strict requirement for written consent from patients in observational and epidemiological research are extremely serious.Research in histopathology would be particularly severely affected.It is essential that patients' consent is obtained in interventional studies or where information, or, in the case of pathology, tissue, is collected solely for the purpose of research.However, applying this requirement for every study of archived biopsy, surgical or necropsy tissue blocks, or review of patient records, where diagnosis has been made and where patient management will not be affected, is impracticable.Studies of archival material have been the core of research in histopathology.A glance at the methods section of the papers of any pathology journal reveals that most have used archival tissue with no indication that specific patient consent has been obtained.For recent issues of the Journal of Pathology, Histopathology, and the Journal of Clinical Pathology the proportions of archi-val, non-consented research were 9/16, 9/9, and 11/13 papers, respectively.Until now, this form of research has been simple and cheap to undertake, and has provided valuable information on the causes and pathology of many human diseases.It is unlikely that any of the large studies of gastric biopsies, cancers, etc would have been conducted had every patient or their relatives had to be contacted to obtain consent.We would be left with only anecdotal information on which to base prognosis and treatment for many common cancers and we would know much less about many common diseases.Despite considerable problems in obtaining funding for research in histopathology, authors in the United Kingdom continue to produce papers of high quality, but it is doubtful that this will continue if individual consent for each study becomes a legal requirement.Either a general consent for use of residual tissues for research should be allowed or alternatively the NHS needs to fund the staff necessary to obtain the consent from central or regional research and development budgets, which could be accessed by researchers wishing to undertake archival studies.This would, however, be both cumbersome and costly.If observational research in pathology or other subjects and epidemiological studies are to be outlawed, the public interest will be damaged and patients in the future will be the losers.
TUMOR MARKER CARBOHYDRATE ANTIGEN 125 PREDICTS ADVERSE OUTCOME AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Oliver Husser, Julio Nunez, Eduardo Nunez, Andreas Holzamer, Günter Riegger, Christof Schmid, Michael Hilker, Christian Hengstenberg
Journal: Journal of the American College of Cardiology (2013)
Potassium channel openers are likely to be proarrhythmic in the diseased human heart
Authors: S. C Black, B. R Lucchesi
Journal: Cardiovascular Research (1994)

Journal Article Potassium channel openers are likely to be proarrhythmic in the diseased human heart Get access Shawn C Black, Shawn C Black Department of Pharmacology, University of Michigan Medical School, M6322 Medical Science Building 1, Ann Arbor, MI 48109-0626, USA: S C Black, B R Lucchesi. Correspondence to Dr Lucchesi. Search for other works by this author on: Oxford Academic PubMed Google Scholar Benedict R Lucchesi Benedict R Lucchesi Department of Pharmacology, University of Michigan Medical School, M6322 Medical Science Building 1, Ann Arbor, MI 48109-0626, USA: S C Black, B R Lucchesi. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 6, June 1994, Pages 923–924, https://doi.org/10.1093/cvr/28.6.923 Published: 01 June 1994
Mechanism of Late In-Stent Restenosis After Implantation of a Paclitaxel Derivate–Eluting Polymer Stent System in Humans
Authors: Renu Virmani, Francesco Liistro, Goran Stankovic, Carlo Di Mario, Matteo Montorfano, Andrew Farb, Frank D. Kolodgie, Antonio Colombo
Journal: Circulation (2002)

We recently reported delayed angiographic restenosis in 15 patients who received 7-hexanoyltaxol (QP2)-eluting polymer stents (QuaDS) for the treatment of in-stent restenosis. This study presents the histological findings of atherectomy specimens from a subset of these patients receiving implants.Between October and December 2001, 5 patients treated with QuaDS-QP2 stents underwent directional coronary atherectomy at 11.2+/-1.0 months for recurrent in-stent restenosis. Restenotic lesion composition was assessed with special stains, immunohistochemistry with quantitative image analysis, and, in one specimen, transmission electron microscopy. Atherectomy specimens contained fibrin interspersed in a smooth muscle cell-rich neointima with proteoglycan matrix. In 2 of 5 specimens, large aggregates of macrophages and T-lymphocytes were noted. These areas of active inflammation demonstrated a relatively high proliferation index by Ki-67 antibody staining, whereas the proliferation index in smooth muscle cell-rich restenotic areas was low.Restenotic lesions from QuaDS-QP2-eluting stents at 12 months show persistent fibrin deposition with varying degrees of inflammation. These pathological changes, representing delayed healing, are usually observed up to only 3 months in human coronary arteries with stainless steel balloon-expandable stents. The nonreabsorbable polymer alone may have induced chronic inflammation.
A Most Satisfactory Man: The Story of Theodore Brevard Hayne, Last Martyr of Yellow Fever
Authors: Henry Wilde
Journal: JAMA (1997)

This book deserves praise as a fascinating, well-written, historical study of a little-known great "young Turk" of American medicine: Theodore B. Hayne. Here is a man of average high school and college achievements but with a burning curiosity that ranged from entomology, epidemiology, and clinical infectious disease to automobile mechanics. Would such a young man even make it into a respected medical college or postgraduate science faculty today? Indeed, Hayne could serve as an example that motivation, a wide range of interests, perseverance, and the ability to improvise and think creatively combined with good intellect can be predictors for achievement in science. What held my attention most, however, as an infectious disease physician in a tropical environment, was the discussion of the direct, technology-poor approaches to problem solving—now almost unknown—in field research some six decades ago. This was the age when enzyme-linked immunosrobent assays, radioisotope studies, and most other sophisticated
Performance Characteristics of a Rapid HIV Antibody Assay in a Hospital with a High Prevalence of HIV Infection
Authors: Kathleen Irwin
Journal: Annals of Internal Medicine (1996)

Background: The delay between collection of blood samples and availability of test results may be as long as 3 weeks and is one barrier to the acceptance of voluntary testing for human immunodeficiency virus (HIV) infection. Serologic tests that provide results rapidly could overcome this barrier, but the accuracy and reliability of rapid tests have not been well characterized in the United States. Objective: To evaluate, in a "real world" setting, the performance characteristics of a rapid HIV assay that reduces the need for patients to return for counseling after the test. Design: Testing of HIV antibodies by rapid and nonrapid assays and survey about risk behaviors for HIV. Setting: A hospital in Bronx, New York, with a high prevalence of HIV-seropositive patients. Patients: 837 patients who were not known to be infected with HIV, had not been admitted for conditions related to the acquired immunodeficiency syndrome, and agreed to participate in HIV testing and an interview. Measurements: Sensitivity and specificity of a rapid HIV antibody assay based on comparisons with nonrapid assay and Western blot assay. Results: According to nonrapid assays, 5.4% of patients were infected with HIV. The rapid assay was highly accurate in this sample overall: Its sensitivity was 1.00, its specificity was 0.991, its positive predictive value was 0.865, and its negative predictive value was 1.00. The assay was also highly accurate in various subgroups. Conclusions: Accurate, rapid tests for HIV infection may enhance testing programs by preventing the need for delayed counseling of seronegative patients and by providing preliminary results to seropositive patients. These preliminary results may encourage patients to return for confirmatory test results and to adopt risk-reducing behaviors sooner. *For additional members of the CDC-Bronx-Lebanon HIV Serosurvey Team, see the Appendix.
Hormone therapy and loss of kidney function
Authors: Aniruddha V. Palya, Bulent Cuhaci, Karthik M. Ranganna
Journal: Kidney International (2009)

To the Editor: We read with interest the stimulating article by Ahmed et al.1.Ahmed S.B. Culleton B.F. Tonelli M. et al.Oral estrogen therapy in postmenopausal women is associated with loss of kidney function.Kidney Int. 2008; 74: 370-376Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar on the association of oral hormone replacement therapy and kidney function in postmenopausal women. The authors reported the baseline characteristics of the groups by categorical hormone therapy use. There was a significant difference in terms of the use of nonsteroidal anti-inflammatory drugs and diuretics. The groups namely ‘Estrogen only’ (46.8%) and ‘Progestin only’ (52.5%) had a higher percentage of patients on diuretics. The percentage of patients on nonsteroidal anti-inflammatory drugs was higher (45.3%) in the ‘Estrogen only’ group. The elderly (all 66 years old or older) made up the entire data population. This makes the subjects more vulnerable to the effects of both nonsteroidal anti-inflammatory drugs and diuretics on the renal function. Although other factors were analyzed in multivariate analysis, we are surprised that the authors did not include diuretics in the analysis. These drugs are known to affect effective circulating volume and renal function.2.Hawkins R.G. Houston M.C. Is population-wide diuretic use directly associated with the incidence of end-stage renal disease in the United States?.AJH. 2005; 18: 744-749Google Scholar, 3.Choudhury D. Ahmed Z. Drug-associated renal dysfunction and injury.Nat Clin Pract Nephrol. 2006; 2: 80-91Crossref PubMed Scopus (238) Google Scholar Logistic regression analysis has shown the greatest decline of glomerular filtration rate in the ‘Progestin only’ group (Δ, 3.98; confidence interval: -0.30, 8.26) followed by the ‘Estrogen only’ group (Δ, 1.21; confidence interval: 0.28, 2.14), but the ‘Combined group’ had the least decline in glomerular filtration rate (Δ, 0.99; confidence interval: -0.56, 2.54) with large confidence intervals.1.Ahmed S.B. Culleton B.F. Tonelli M. et al.Oral estrogen therapy in postmenopausal women is associated with loss of kidney function.Kidney Int. 2008; 74: 370-376Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar They did not offer a plausible explanation for this discrepancy. We hope that they have a reasonable explanation for this, or is this just a statistical finding? It will be interesting to see their results with the inclusion of diuretic use in the analysis.