tbuckley/cabot-search huggingface dataset:
Videotape-Based Decision Aid for Colon Cancer Screening
Authors: Michael Pignone, Russell Harris, Linda Kinsinger
Journal: Annals of Internal Medicine (2000)

Background: Rates of colon cancer screening in the United States are low, in part because of poor communication between patients and providers about the availability of effective screening options. Objective: To test whether a decision aid consisting of an educational video, targeted brochure, and chart marker increased performance of colon cancer screening in primary care practices. Design: Randomized, controlled trial. Setting: Three community primary care practices in central North Carolina. Patients: 1657 consecutive adult patients 50 to 75 years of age were contacted. Of these, 651 (39%) agreed to participate; 249 of the 651 participants (38%) were eligible. Eligible patients had no personal or family history of colon cancer and had not had fecal occult blood testing in the past year or flexible sigmoidoscopy, colonoscopy, or barium enema in the past 5 years. Intervention: The 249 participants were randomly assigned to view an 11-minute video about colon cancer screening (intervention group) or a video about automobile safety (control group). After viewing the video, intervention group participants chose a color-coded educational brochure (based on stages of change) to indicate their degree of interest in screening. A chart marker of the same color was attached to their charts. Controls received a generic brochure on automobile safety, and no chart marker was attached. Measurements: Frequency of screening test ordering as reported by participants and frequency of completion of screening tests as verified by chart review. Results: Fecal occult blood testing or flexible sigmoidoscopy was ordered for 47.2% of intervention participants and 26.4% of controls (difference, 20.8 percentage points [95% CI, 8.6 to 32.9 percentage points]). Screening tests were completed by 36.8% of the intervention group and 22.6% of the control group (difference, 14.2 percentage points [CI, 3.0 to 25.4 percentage points]). Conclusion: A decision aid consisting of an educational video, brochure, and chart marker increased ordering and performance of colon cancer screening tests.
Delivery of reprogramming factors into fibroblasts for generation of non-genetic induced pluripotent stem cells using a cationic bolaamphiphile as a non-viral vector
Authors: Majad Khan, Karthikeyan Narayanan, Hongfang Lu, Yang Choo, Chan Du, Nikken Wiradharma, Yi-Yan Yang, Andrew C.A. Wan
Journal: Biomaterials (2013)
The future is already here
Authors: B. C. Brown, A. Hannan
Journal: BMJ (2011)

Light chain proximal tubulopathy (LCPT) is characterized by cytoplasmic inclusions of monoclonal LC within proximal tubular cells. The significance of crystalline versus noncrystalline LCPT and the effect of modern therapies are unknown. We reported the clinical-pathologic features of 40 crystalline and six noncrystalline LCPT patients diagnosed between 2000 and 2014. All crystalline LCPTs were <i>κ</i>-restricted and displayed acute tubular injury. One-third of noncrystalline LCPT patients displayed <i>λ</i>-restriction or acute tubular injury. Only crystalline LCPT frequently required antigen retrieval to demonstrate monoclonal LC by immunofluorescence. In five of 38 patients, crystals were not detectable by light microscopy, but they were visible by electron microscopy. Hematolymphoid neoplasms, known before biopsy in only 15% of patients, included 21 monoclonal gammopathies of renal significance; 15 multiple myelomas; seven smoldering multiple myelomas; and three other neoplasms. Biopsy indications included Fanconi syndrome (38%; all with crystalline LCPT), renal insufficiency (83%), and proteinuria (98%). Follow-up was available for 30 (75%) patients with crystalline LCPT and all six patients with noncrystalline LCPT, of whom 11 underwent stem cell transplant, 16 received chemotherapy only, and nine were untreated. Complete or very good partial hematologic remissions occurred in six of 22 treated crystalline LCPT patients. By multivariable analysis, the only independent predictor of final eGFR was initial eGFR, highlighting the importance of early detection. All patients with crystalline LCPT treated with stem cell transplant had stable or improved kidney function, indicating the effectiveness of aggressive therapy in selected patients.
Tobacco policy Combine taxation with other measures
Authors: G Waldron, J W T Chalmers, M J Harris, R Watts
Journal: BMJ (1994)

EDITOR, - The concern of Ben Walsh, of the Tobacco Manufacturers Association, for the income of poorer smokers would be touching if it did not expose the hypocrisy of his employers.1 The “antismoking world” may indeed be indirectly responsible for reducing the wealth of smokers through its advocacy of increased taxation, but Walsh ignores the fact that tobacco manufacturers are directly to blame for most of the preventable deaths and chronic ill health among their customers.

Walsh's rosy picture of a poor smoker relaxing with “a cigarette at the end of a long hard day” belies the addictive property on which the success of his product depends. Few smokers can limit themselves to one cigarette a day. If they could, tobacco would be a luxury rather tan a necessity, in which case price would be of little importance.

The tobacco industry has hitherto been relatively silent on the subject of taxation. We suspect that the real reason why it is now so concerned has more to do with the fear of loss of revenue to its counterparts in Europe than with any wish to give to poor people. The appropriate response of the government to such concerns must be to use its influence …
Protist Homologs of the Meiotic Spo11 Gene and Topoisomerase VI reveal an Evolutionary History of Gene Duplication and Lineage-Specific Loss
Authors: S.-B. Malik, M. A. Ramesh, A. M. Hulstrand, J. M. Logsdon
Journal: Molecular Biology and Evolution (2007)

Spo11 is a meiotic protein of fundamental importance as it is a conserved meiosis-specific transesterase required for meiotic recombination initiation in fungi, animals, and plants. Spo11 is homologous to the archaebacterial topoisomerase VIA (Top6A) gene, and its homologs are broadly distributed among eukaryotes, with some eukaryotes having more than one homolog. However, the evolutionary relationships among these genes are unclear, with some debate as to whether eukaryotic homologs originated by lateral gene transfer. We have identified and characterized protist Spo11 homologs by degenerate polymerase chain reaction (PCR) and sequencing and by analyses of sequences from public databases. Our phylogenetic analyses show that Spo11 homologs evolved by two ancient eukaryotic gene duplication events prior to the last common ancestor of extant eukaryotes, resulting in three eukaryotic paralogs: Spo11-1, Spo11-2, and Spo11-3. Spo11-1 orthologs encode meiosis-specific proteins and are distributed broadly among eukaryotic lineages, though Spo11-1 is absent from some protists. This absence coincides with the presence of Spo11-2 orthologs, which are meiosis-specific in Arabidopsis and are found in plants, red algae, and some protists but absent in animals and fungi. Spo11-3 encodes a Top6A subunit that interacts with topoisomerase VIB (Top6B) subunits, which together play a role in vegetative growth in Arabidopsis. We identified Spo11-3 (Top6A) and Top6B homologs in plants, red algae, and a few protists, establishing a broader distribution of these genes among eukaryotes, indicating their likely vertical descent followed by lineage-specific loss.
Perinatal period and pregnancy: intervals of high risk for chemical carcinogens.
Authors: J M Rice
Journal: Environmental Health Perspectives (1979)

Experiments in rodents indicate that during the post-embryonic period of prenatal development, the fetus is more sensitive than the adult to certain carcinogens, by several decimal orders of magnitude. Most such agents are direct-acting and independent of metabolism. To other substances, often those which require enzyme-mediated metabolic conversion to a chemically reactive derivative in order to effect carcinogenesis, the fetus may be less vulnerable than the adult. The neonate is also more susceptible than adults to some carcinogens, and may be more susceptible than the fetus to certain agents. Both rodent and primate studies indicate that gravid females are also at elevated risk for carcinogenesis, in part because of the presence in the placenta of trophoblastic tissue which may become malignant. The contributions of rapid growth rate, changing metabolic competence, and tissue differentiation to elevated perinatal susceptibility to carcinogens in rodents and primates are discussed, together with the implications of these findings for human beings subjected to industrial or environmental exposures to such chemicals.
Continued incorporation of circulating radiolabeled fibrinogen into preformed coronary artery thrombi.
Authors: A Salimi, G C Oliver, J Lee, L A Sherman
Journal: Circulation (1977)

This study measured the growth over time of experimental coronary artery (CA) thrombi by radiolabeled fibrinogen uptake. 125I-fibrinogen was injected into dogs and 24 hours later CA thrombi were induced by electrical current. Twenty-four hours after CA thrombus induction, 131I-albumin (group A) or 131I-fibrinogen (group B) was injected. At 48 hours after thrombi induction, the thrombi were removed, divided into segments, and their radioactivity measured. The 131I-fibrinogen in the group B thrombi was significantly greater than the 131I-albumin in group A thrombi (P less than 0.001). In further studies, the 131I-fibrinogen was given 48 and 72 hours post CA thrombus formation. Significant 131I was also found in these CA thrombi. 125I-fibrinogen and 131I-fibrinogen incorporation occurred in virtually all segments of the thrombi. The results suggest 1) CA thrombi growth continues for at least 72 hours after initial formation; 2) the presence of 131I in the thrombi was due to gradual fibrin deposition throughout the thrombus.
The Actin Cytoskeleton Has an Active Role in the Electrotransfer of Plasmid DNA in Mammalian Cells
Authors: Christelle Rosazza, Jean-Michel Escoffre, Andreas Zumbusch, Marie-Pierre Rols
Journal: Molecular Therapy (2011)

Electrotransfer of molecules is a well established technique which finds extensive use for gene transfer and holds great promise for anticancer treatment. Despite its widespread application, the mechanisms governing the entry of DNA into the cell and its intracellular trafficking are not yet known. The aim of this study is to unravel the role of the actin cytoskeleton during gene electrotransfer in cells. We performed single-cell level approaches to observe the organization of the actin cytoskeleton in Chinese hamster ovary (CHO) cells. In addition, we performed experiments at the multiple-cell level to evaluate the efficiency of DNA transfer after alteration of the actin cytoskeleton using the drug latrunculin B. Actin patches colocalizing with the DNA at the plasma membrane were observed with additional characteristics similar to those of the DNA aggregates in terms of time, number, and size. The disruption of the microfilaments reduces the DNA accumulation at the plasma membrane and the gene expression. This is the first direct experimental evidence of the participation of the actin cytoskeleton in DNA electrotransfer. Electrotransfer of molecules is a well established technique which finds extensive use for gene transfer and holds great promise for anticancer treatment. Despite its widespread application, the mechanisms governing the entry of DNA into the cell and its intracellular trafficking are not yet known. The aim of this study is to unravel the role of the actin cytoskeleton during gene electrotransfer in cells. We performed single-cell level approaches to observe the organization of the actin cytoskeleton in Chinese hamster ovary (CHO) cells. In addition, we performed experiments at the multiple-cell level to evaluate the efficiency of DNA transfer after alteration of the actin cytoskeleton using the drug latrunculin B. Actin patches colocalizing with the DNA at the plasma membrane were observed with additional characteristics similar to those of the DNA aggregates in terms of time, number, and size. The disruption of the microfilaments reduces the DNA accumulation at the plasma membrane and the gene expression. This is the first direct experimental evidence of the participation of the actin cytoskeleton in DNA electrotransfer.
Assessing Hospital-Associated Deaths
Authors: Douglas P. Wagner
Journal: JAMA (1989)

To the Editor.—  The comparison by Jencks et al 1 of hospital discharge death rates with 30-day postadmission death rates demonstrates the probable superiority of the longer period for hospital mortality analysis and reporting. The analysis, however, and the hospital death rate release by the Health Care Financing Administration assume throughout that the proper starting time for the 30-day period is the time of admission to the hospital. 2 I question the wisdom of that assumption.  One problem is that many patients who experience surgical misadventures or other iatrogenic mistakes die only after long attempts to recover from the mistakes. Thus, the deaths excluded from the 30-day postadmission criteria are likely to be the in-hospital deaths most attributable to poor quality of care.  The second problem is that in New York State, for diseases such as stroke, where average length of stay is quite long, the bad outcomes include some
Prevalence of Violence Against Pregnant Women
Authors: Julie A. Gazmararian
Journal: JAMA (1996)

To summarize the methods and findings of studies examining the prevalence of violence against pregnant women and to synthesize these findings by comparing study characteristics for studies with similar and dissimilar results.MEDLINE, POPLINE, Psychological Abstracts, and Sociological Abstracts databases were searched for all articles pertaining to violence during pregnancy for the period 1963 through August 1995.Thirteen studies were selected on the basis of specific criteria: a sample with initially unknown violence status; a clear statement of research question(s), with focus on measuring the prevalence of violence; descriptions of the sample, data source, and data collection methods; and data from the United States or another developed country.Relevant data were extracted to compare studies by study description, methods, and results.Evidence from the studies we reviewed indicates that the prevalence of violence during pregnancy ranges from 0.9% to 20.1%. Measures of violence, populations sampled, and study methods varied considerably across studies, and these factors may affect prevalence estimates. Studies that asked about violence more than once during detailed in-person interviews or asked later in pregnancy (during the third trimester) reported higher prevalence rates (7.4%-20.1%). The lowest estimate was reported by women who attended a private clinic and responded to a self-administered questionnaire provided to them by a person who was not a health care provider.Violence may be a more common problem for pregnant women than some conditions for which they are routinely screened and evaluated. Future research that more accurately measures physical violence during pregnancy would contribute to more effective design and implementation of prevention and intervention strategies.
Urinary Excretion of Cocaine
Authors: William M. Burke, Narsipur V. Ravi
Journal: Annals of Internal Medicine (1990)

Letters and Corrections1 April 1990Urinary Excretion of CocaineWilliam M. Burke, MD, Narsipur V. Ravi, MDWilliam M. Burke, MD, Narsipur V. Ravi, MDAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-112-7-548 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:Nademanee and colleagues (1) present an important finding in their article on myocardial ischemia during cocaine withdrawal. In discussing the possible mechanism, however, they do not consider the possibility that cocaine is a two-compartment drug that is slowly released after cessation of use so that there may be significant levels of drug present in patients for 2 or more weeks after last use. The fact that there were "negligible" levels of benzoylecgonine in the urine at the time of the first Holter does not eliminate this possibility. It has been recently shown that regular cocaine users who...References1. NademaneeGorelickJosephson KDM. Myocardial ischemia during cocaine withdrawal. Ann Intern Med. 1989;111:876-80. LinkGoogle Scholar2. ConeDarwinDickerson EWS. Prolonged excretion of cocaine and metabolite in human urine after chronic use. Proceedings of the International Association of Forensic Toxicology, 1989, Glasgow, Scotland. 1990; (In press). Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCocaineRecent applications of mass spectrometry in forensic toxicologyRecent applications of mass spectrometry in forensic toxicologyEmbolic stroke after smoking "crack" cocaine. 1 April 1990Volume 112, Issue 7Page: 548-549KeywordsCocaineDrugsExcretionIschemiaUrine Issue Published: 1 April 1990 PDF DownloadLoading ...
Norrie's Disease — An X-Linked Syndrome of Retinal Malformation, Mental Retardation and Deafness
Authors: Lewis B. Holmes
Journal: New England Journal of Medicine (1971)

WE have recently evaluated a family in which six males in four generations were affected with Norrie's disease, an X-linked syndrome of retinal malformation, mental retardation and deafness. In spite of the positive family history, alternate diagnoses, such as retrolental fibroplasia, pseudoglioma, and congenital taxoplasmosis were suggested for these patients. A general lack of awareness of this syndrome was probably responsible for these incorrect diagnoses. Only one family1 in the United States has been reported as having Norrie's disease; a second family2 with X-linked recessive microphthalmia probably had Norrie's disease. This can be contrasted to Denmark and Sweden, where Warburg . . .
Abstract 4761: The iCD40. MyD88 combo-vector: A new platform for enhanced DC tumor immunotherapy
Authors: Priyadharshini Narayanan, Natalia Lapteva, Jan O. Kemnade, Kevin M. Slawin, David M. Spencer
Journal: Cancer Research (2010)

Abstract Introduction: Given the pre-eminent role of dendritic cells (DCs) as antigen-presenting cells, their exploitation as natural adjuvants in vaccination protocols for the treatment of various malignancies and infectious diseases is not surprising. Nevertheless, inadequate or unsustained activation has likely limited response rates in clinical trials. We previously reported a potent synthetic dimerizer drug-inducible CD40 (iCD40) receptor that permits temporally controlled DC-specific activation within the context of an immunological synapse (Hanks et al, Nat Med, 2005). We showed that when combined with Toll-like Receptor (TLR) adjuvants, iCD40-modified DCs (iCD40-DCs) have enhanced survival, co-stimulatory marker expression, migration, IL-12 production, antigen (Ag)-specific T cell stimulatory capacity and anti-tumor responses (Lapteva et al, Cancer Res, 2007). A phase I/II clinical trial based on iCD40-DCs to treat castration-resistant, metastatic prostate cancer began enrolling patients in August 2009. Procedures: To simplify this approach, we have developed a unified, inducible DC switch, called “iCD40. MyD88”, which combines signaling elements from costimulatory molecule, CD40, and TLR adapter, MyD88, fused to tandem FK506-binding binding proteins (FKBP12v36). Activation is initiated in vitro or in vivo by lipid-permeable dimerizing ligands (i.e. AP1903 or AP20187). Results: Both murine and human iCD40. MyD88-DCs secrete high (ng) levels of IL-12 and maturation markers in a ligand-dependent fashion without the need for exogenous adjuvants. iCD40. MyD88 activation is associated with synergistic activation of IKK&amp;#945;/&amp;#946; and p38. Moreover, tumor-bearing mice treated with antigen-pulsed, iCD40. MyD88-DCs show a potent anti-tumor immune response, consistent with expansion of antigen-specific CTLs in vivo. Bicistronic vectors combining iCD40. MyD88 along with tumor-associated antigens are underway. Conclusion: This “combo-switch” permits potent, targeted activation of antigen-pulsed DCs in vivo, leading to improved anti-tumor immunity with a high likelihood for reduced side effects. Production of a single vector that combines a potent DC switch with tumor antigen is the first requisite step leading to economically viable, “off-the-shelf”, vaccine therapies for cancer. 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 4761.
Abstract 3028: A multiplexed, bioluminescent HDAC assay for determining target-specific, anti-cancer potency
Authors: Nathan Evans, Andrew L. Niles, Thomas A. Kirkland
Journal: Cancer Research (2011)

Abstract Histone deacetylase (HDAC) class I and II enzymes are zinc dependent protein deacetylases. They play many roles in normal gene regulation events of development and homeostasis, but their dysregulation has been linked to a variety of solid tumors and hematological malignancies. We have recently developed a one-step, homogeneous, luminescent assay for activity detection from multiple HDAC Class I and II isoforms, thereby providing a useful tool for cell culture, enriched or recombinant sources of lysine deacetylases. This luciferase-containing, “glow-type” assay reagent is cell-permeable and can directly measure HDAC activity in living attachment-dependent and suspension cells. Furthermore, this luminescent HDAC assay can be paired in same well multiplex formats with fluorescent assays that measure biomarkers associated with changes in viability and cytotoxicity. Here we correlate HDAC inhibition with cellular fate using representative inhibitors from the hydroxamate, short-chain fatty acid, benzamide and cyclic peptide classes. We will also demonstrate relative on-target anti-cancer efficacies and off-target safety using transformed, primary or iPS-derived cell lineages. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3028. doi:10.1158/1538-7445.AM2011-3028
Status of Clinical Research in Academic Health Centers
Authors: Eric G. Campbell, Joel S. Weissman, Ernest Moy, David Blumenthal
Journal: JAMA (2001)

research that involves living humans as subjects, is composed of a wide spectrum of research types such as clinical trials, translational research, epidemiological research, health services research, and outcomes research and is critical to translating the results of basic science into useable health care products and services. 1The challenges facing the clinical research enterprise in the United States have become major concerns of the academic medical community.One reason is that these challenges could eventually reduce the flow of future medical knowledge by inhibiting the amount or reducing the quality of the research conducted. 2,3Realizing this potential, the Institute of Medicine recommended the establishment of a US $1 billion fund to incorporate, rapidly and appropriately, the results of scientific research into clinical practice-one of the causes of low-quality health care. 46][7] First, insurers are less willing to pay the higher costs of patient care at academic health centers (AHCs).