tbuckley/cabot-search huggingface dataset:
Homocysteine, a thrombogenic agent, suppresses anticoagulant heparan sulfate expression in cultured porcine aortic endothelial cells.
Authors: M Nishinaga, T Ozawa, K Shimada
Journal: Journal of Clinical Investigation (1993)

Previous studies showed that homocysteine, a thrombo-atherogenic and atherogenic agent, inhibits an endothelial thrombomodulin-protein C anticoagulant pathway. We examined whether homocysteine might affect another endothelial anticoagulant mechanism; i.e., heparin-like glycosaminoglycan-antithrombin III interactions. Incubations of porcine aortic endothelial cell cultures with homocysteine reduced the amount of antithrombin III bound to the cell surface in a dose- and time-dependent fashion. The inhibitory effect was observed at a homocysteine concentration as low as 0.1 mM, and the maximal suppression occurred at 1 mM of homocysteine after 24 h. In contrast with a marked reduction in the maximal antithrombin III binding capacity (approximately 30% of control), the radioactivity of [35S]sulfate incorporated into heparan sulfate on the cell surface was minimally (< 15%) reduced. The cells remained viable after homocysteine treatment. Although neither net negative charge nor proportion in total glycosaminoglycans of cell surface heparan sulfate was altered by homocysteine treatment, a substantial reduction in antithrombin III binding capacity of heparan sulfate isolated from homocysteine-treated endothelial cells was found using both affinity chromatography and dot blot assay techniques. The antithrombin III binding activity of endothelial cells decreased after preincubation with 1 mM homocysteine, cysteine, or 2-mercaptoethanol; no reduction in binding activity was observed after preincubation with the same concentration of methionine, alanine, or valine. This sulfhydryl effect may be caused by generation of hydrogen peroxide, as incubation of catalase, but not superoxide dismutase, with homocysteine-treated endothelial cells prevented this reduction, whereas copper augmented the inhibitory effects of the metabolite. Thus, our data suggest that the inhibited expression of anticoagulant heparan sulfate may contribute to the thrombogenic property resulting from the homocysteine-induced endothelial cell perturbation, mediated by generation of hydrogen peroxide through alteration of the redox potential.
Statins and the risk of developing diabetes
Authors: R. Huupponen, J. Viikari
Journal: BMJ (2013)

Overall benefits of statins still clearly outweigh potential risks

Statins are the cornerstone of treatment for dyslipidaemia, but a recent meta-analysis of randomised trials found an association between their use and incident diabetes.1 In a linked observational study (doi:10.1136/bmj.f2610), Carter and colleagues provide an important contribution to this topic.2 Using an epidemiological approach, they analysed administrative claims data from Ontario, Canada, to retrospectively examine the comparative risk of incident diabetes for different statins in users aged over 66 years. They found that, compared with pravastatin, treatment with atorvastatin, rosuvastatin, or simvastatin—but not fluvastatin or lovastatin—was associated with an increased risk of incident diabetes in statin-naive older patients without diabetes. The risk of incident diabetes did not differ between patients with or without cardiovascular disease. Importantly, in line with a meta-analysis showing increased risk of diabetes for an intensive statin dose versus a moderate dose,3 Carter and colleagues found an association between development of overt diabetes and potency and dose of …
Abstract 700: Reduced CYLD expression is an independent prognostic factor in breast cancer: A possible link with RANKL-RANK signaling
Authors: Mitsuhiro Hayashi, Satoru Shinriki, Takuya Nakamura, Mutsuko Ibusuki, Takanao Sueyoshi, Tomoko Ota, Yutaka Yamamoto, Hirotaka Iwase, Yukio Ando
Journal: Cancer Research (2012)

Abstract Background: Deubiquitinase CYLD plays an important role in tumorigenesis and immune response. RANKL-RANK system is required for osteoclast development and is also involved in bone metastasis in various malignancies while it has been also implicated in tumorigenesis, metastasis to distant organs other than bone in breast cancer through unknown mechanisms. Importantly, a recent study has reported that CYLD negatively regulated RANKL-RANK signaling in osteoclastogenesis. However, not only the role of CYLD but also its involvement in RANKL-RANK signaling in breast cancer is largely unknown. The purpose of this study was to elucidate clinical and biological significance of CYLD as well as its association with RANKL-RANK signaling in breast cancer. Materials and Methods: We assessed CYLD mRNA expression in 305 primary invasive breast cancer tissues including 26 matched-pair of tumoral and adjacent non-tumoral tissues, and 9 breast cancer cell lines as well as a nonmalignant breast epithelial cell line, HMEC by quantitative real-time RT-PCR. In addition, effect of CYLD knockdown by using siRNA on cell proliferation, migratory activity and the biological activity of RANKL in MDA-MB-231 cells. Results: Expression levels of CYLD mRNA were lower in tumoral lesion than the matched non-tumoral lesion in all of 26 cases. Our statistical analysis revealed that lower CYLD mRNA expression was significantly associated with reduced disease free survival rate (rog-rank, p = 0.025), irrespectively of breast cancer subtype. Multivariate analyses for disease free survival confirmed that low CYLD mRNA expression (Hazard ratio: HR 2.23, 95% CI 1.09 - 4.36, p = 0.029) in addition to estrogen receptor status (HR 0.15, 95% CI 0.05 - 0.44, p = 0.0003) and lymph node metastasis (HR 2.21, 95% CI 1.10 - 4.62, p = 0.026) were significant factors. Consistent with our clinical data, CYLD gene expression was reduced in all the breast cancer cell lines compared with HMEC cells. Repression of CYLD gene expression led to increased cell number in MDA-MB-231 cells. Interestingly, combination of CYLD knockdown and RANKL stimulation promoted cell migration while no change was observed in the setting of each alone. Conclusion: Downregulation of CYLD was common and an independent poor prognostic factor in invasive breast cancer. CYLD repression may promote breast cancer development and/ or progression in coordination with RANKL-RANK signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 700. doi:1538-7445.AM2012-700
New features for old: Creation or derivation?
Authors: Cyril R. Latimer
Journal: Behavioral and Brain Sciences (1998)

Schyns, Goldstone &amp; Thibaut oppose the notion of fixed feature analysis, suggesting the possibility of flexible feature creation in object recognition and categorisation. Such proposals cannot be assessed until clear definitions of the objects in question and their decompositions are formulated. Flexibility may come from the decompositions of objects rather than from feature creation.
In reference to WKA Yung (Neuro-Oncology 2012; 14:1115)
Authors: Erwin Krauskopf
Journal: Neuro-Oncology (2012)

Dear Editor:

As I am very interested in bibliometrics and editorial management, I carefully read your recently published editorial1 and I thought I could complement the information you provided, which might be of interest to your readers.

From 2007 to 2011, a total of 6055 documents were published by Neuro-Oncology according to the Web of Science. Excluding meeting abstracts (5539) and corrections (5), 83.7% of these documents had been cited at least once in their lifetime, which is very outstanding for any journal. In fact, 3 articles2–4 have been cited more than 100 times each, by articles published in journals such as Lancet Oncology (impact factor [IF]: 22.589), the Journal of the National Cancer Institute (IF: 13.753), Nature Clinical Practice Oncology (IF: 8.000), Cancer Research (IF: 7.856), Clinical Cancer Research (IF: 7.742), and Annals of Oncology (IF: 6.425). The fact that researchers publishing in the top 20 oncology journals use information extracted from Neuro-Oncology undoubtedly endorses the quality of the research being printed here.

Another important aspect to consider is the internationality of the journal. In the 5-year period, the country that contributed the most was the United States, with 46.4% of the published documents, followed by Germany (7.5%), Canada (6.5%), Japan (3.6%), and England (2.4%). This information is relevant for researchers who are interested in communicating their research to a wide-ranging audience.

Finally, an indicator of quality is reflected by the use of self-cites. Various articles have covered the topic of “impact factor manipulation” through the use of self-cites to the same journal.5,6 Well, Neuro-Oncology should be very proud that only 4% of the 1156 cites used to estimate its 2011 IF corresponded to self-citations.

The only thing left to say is congratulations to the editorial team for a job well done. I have no doubt that the sustained growth observed in the past 3 years will allow this journal to reach new heights.
Tolerance induction ameliorates allograft vasculopathy in rat aortic transplants. Influence of Fas-mediated apoptosis.
Authors: L M Akyürek, C Johnsson, D Lange, P Georgii-Hemming, E Larsson, B C Fellström, K Funa, G Tufveson
Journal: Journal of Clinical Investigation (1998)

Based on successful induction of donor-specific unresponsiveness by alloantigenic stimulation in several animal models of acute rejection, we hypothesized that similar immune manipulations would also inhibit the evolution of chronic rejection and transplant vasculopathy. To induce immune tolerance, DA rats received a PVG heart allograft and were immunosuppressed with cyclosporine for 30 d. At day 100 the animals were challenged with a PVG aortic allograft after either 1 or 18 h of cold ischemia. 8 wk after the aortic transplantation, the grafts were investigated for morphological changes, infiltrating cells, apoptosis, and Fas-Fas ligand expression. Control allografts showed advanced transplant arteriosclerosis, whereas tolerance-induced aortic allografts displayed reduced neointimal formation, less medial atrophy, fewer apoptotic cells, and fewer Fas- and FasL-expressing cells. Prolonged ischemic storage time did not profoundly alter the morphological changes of the allografts. Fas expression was found in T cells, macrophages, vascular smooth muscle cells, and endothelial cells, whereas FasL was expressed mainly by T cells and macrophages. FasL mRNA expression was evident throughout the entire allograft wall. In conclusion, induction of allospecific tolerance can effectively prevent transplant arteriosclerosis. Cold ischemia damage does not abrogate the beneficial effect of tolerance, but creates a separate identity of mainly endothelial lesions. Furthermore, Fas-mediated apoptosis appears to be involved in the pathological lesions seen in chronic rejection.
Atraumatic, Nonsurgical Technic for Removal of Broken Catheters from Cardiac Cavities
Authors: R. A. Massumi, A. M. Ross
Journal: New England Journal of Medicine (1967)

THE complications of indwelling intravenous polyethylene catheters for monitoring of central venous pressure and for therapeutic infusions are well known. One of these, embolization of a severed portion or of the whole catheter, has been observed several times since it was first described in 1954.1 Reported below is such a case, with the description of a nonsurgical technic for removal of the catheter.Case ReportE.H., a 60-year-old cirrhotic man was admitted to the hospital with severe hepatic insufficiency, coma and shock. An Intracath§ was introduced into the superior vena cava by means of percutaneous subclavian puncture for the purpose . . .
Correction: Lung Transplantation and Survival in Children with Cystic Fibrosis
Authors: Theodore G. Liou, Frederick R. Adler, Barbara C. Cahill, David R. Cox
Journal: New England Journal of Medicine (2008)

To the Editor: In our article on lung transplantation and survival in children with cystic fibrosis (Nov.22 issue), 1 the recording of censoring dates, but not deaths, for 27 of the 514 patients in the final data set that we analyzed was in error.The data were inadvertently corrupted during sensitivity analyses conducted to explore the effects of different methods for censoring survival (see the Methods section of our article and the Supplementary Appendix of the article, available with the full text of this letter at www.nejm.org).The error was discovered when we repeated the entire analysis in response to published criticisms of our statistical methods 2,3 and the observation that the post-transplantation survival that we reported was at odds with the survival in other reports based on data obtained from similar patients. 4A cross-check of the data set used in our article against the original raw data obtained from the Organ Procurement and Transplantation Network showed that 27 censoring dates had been corrupted.This error led to a misreporting of median survival after transplantation.We repeated the survival analysis using corrected censoring dates.
Using the Expected Survival to Explain Differences Between the Results of Randomized Trials: A Case in Advanced Ovarian Cancer
Authors: Marc Buyse, Tomasz Burzykowski, Mahesh Parmar, Valter Torri, George Omura, Nicoletta Colombo, Chris Williams, Pierfranco Conte, Jan Vermorken
Journal: Journal of Clinical Oncology (2003)

Purpose: A meta-analysis of randomized trials in advanced ovarian cancer showed a longer survival with cyclophosphamide, doxorubicin, and cisplatin (CAP) than with cyclophosphamide and cisplatin (CP; P = .009). In contrast, the results of the large International Collaborative Ovarian Neoplasm Study (ICON2) showed no survival difference between CAP and carboplatin (P = .98). In this article, we show how these discrepant results can be reconciled through the estimation of expected survival curves. Materials and Methods: A proportional hazards model, fitted to the meta-analysis data, was used to construct the expected survival curve for each treatment arm of the ICON2 trial. Expected survival curves were compared with observed survival curves in the ICON2 trial at all time points using a nonparametric test. Results: The prognostic model for survival obtained in the meta-analysis included extent of residual disease, age, histologic grade, and International Federation of Gynecology and Obstetrics stage. When this model was applied to the ICON2 data, there was no difference between the expected and observed curves in the CAP arm. In contrast, the observed survival curve for carboplatin was far superior to the expected survival curve for CP (P &lt; .01). Conclusion: These analyses provide indirect evidence that better results are achieved with carboplatin alone at an optimally tolerated dose, compared with the CP combination at a cisplatin dose of 50 to 60 mg/m 2 . The expected survival may provide valuable insight when direct comparisons between randomized groups yield discrepant results across different studies.
Therapeutic effects of the artemisinin analog SM934 on lupus-prone MRL/lpr mice via inhibition of TLR-triggered B-cell activation and plasma cell formation
Authors: Yanwei Wu, Shijun He, Bingxin Bai, Luyao Zhang, Lu Xue, Zemin Lin, Xiaoqian Yang, Fenghua Zhu, Peilan He, Wei Tang, Jianping Zuo
Journal: Cellular and Molecular Immunology (2015)
Hemoperfusion in the Management of Digoxin Toxic Reaction
Authors: Teut Risler
Journal: JAMA (1979)

To the Editor.—  Smiley and associates (240:2736,1978) recommend hemoperfusion as a standard treatment of digoxin intoxication. According to our own investigations 1 and those of others, 2,3 we agree with these results as far as high clearance rates for digoxin are concerned. But in our opinion, plasma clearance is only one factor attributing to the efficiency of hemoperfusion. At least as important is the plasma-tissue distribution of the drug that is to be eliminated. Less than 1% of the total body pool of digoxin (normal range, 1 to 2 mg) is accumulated in the plasma (normal concentration, 1 to 2 ng—L).  In our experimental model, we used dogs because their digoxin pharmacokinetics are comparable with those in humans. 4,5 In 12 dogs (body weight, 20 to 25 kg) chronically digitalized with 0.05 mg/kg of digoxin intravenously for three days before the hemoperfusion experiment, we tested the influence of the absorbent
Intravenously Given Ethacrynic Acid and Gastrointestinal Bleeding
Authors: Dennis Slone
Journal: JAMA (1969)

An association (<i>P</i>&lt; 0.0001) between the administration of ethacrynic acid and the occurrence of gastrointestinal bleeding was observed during routine computer monitoring of data obtained in a drug-surveillance program. This prompted a detailed analysis wherein diagnosis, age, sex, blood urea nitrogen levels, the presence or absence of heparin sodium therapy, and the severity of illness were controlled. Even after these adjustments, the frequency of gastrointestinal bleeding among patients receiving ethacrynic acid was higher than in those patients who received furosemide, meralluride sodium and/or hydrochlorothiazide and/or chlorothiazide orally, or in those who received none of these diuretics (<i>P</i>&lt; 0.02). The difference noted with ethacrynic acid was confined to the subgroup of patients who received the drug intravenously.
SURVIVAL IN OCTOGENARIANS UNDERGOING CARDIAC RESYNCHRONIZATION THERAPY COMPARED TO THE GENERAL POPULATION
Authors: Jack Rickard, Rayan Yousefzai, David O. Martin, Richard A. Grimm, Dan Sraow, Bruce A. Lindsay, Bruce L. Wilkoff, Mina K. Chung, Patrick Tchou
Journal: Journal of the American College of Cardiology (2011)
Diphtheria as a model. Introduction of serums and vaccines for scarlet fever and pneumococcal pneumonia
Authors: H. F. Dowling
Journal: JAMA (1973)

Although the investigations of Pasteur and Koch opened a new world to the scientists of their day, in the beginning they contributed nothing to the therapy of disease. The first clear-cut demonstration that the science of bacteriology could lead to the cure of disease came when Behring announced, in 1890, that the serum of animals immunized with diphtheria toxin protected other animals against infection with the diphtheria bacillus.<sup>1</sup>A year later clinicians began to use this antiserum to check the course of diphtheria in patients.<sup>2(p261)</sup>Research on diphtheria took a second practical step forward when Behring showed in 1913 that the toxin could be used to immunize humans against the disease.<sup>3</sup> Thus, the pattern was laid down for others to follow: Find a toxin for each bacterium being investigated, use it to immunize animals and humans against the disease, and obtain an antiserum from animals that will
Pre-Columbian Medical Sculpture
Authors: ABNER I. WEISMAN
Journal: JAMA (1966)

<h3>To the Editor:</h3> Working in subtropical Central America, Dr. Peña Chavarría must be familiar with many dermatological lesions rarely seen in the United States. I had previously shown these sculptures at a meeting of the Greater New York Dermatological Society, attended by Drs. Dominique Verut and Fernando Ortiz-Monasterio of Mexico. On this occasion this illustrious group of skin specialists substituted ancient American sculptured figures with dermatological lesions for living patients in the study. A number of specimens of leishmaniasis from the Mohica tribe of northern Peru were exhibited. There was no disagreement on these, although Virchow many years earlier had insisted they represented leprosy. There was little difference of opinion regarding the statues illustrated on the cover ofThe Journal. Dr. Verut showed similar reproductions of a figure which he thought might represent secondary syphilis. There was no indication from any of the participants that these two figures portrayed leishmaniasis,
Cancer of the Prostate
Authors: William J. Catalona
Journal: JAMA (1992)

To the Editor.  —The study by Johansson et al 1 is of limited relevance because their selection criteria resulted in a study group that is not representative of the patient population with early prostate cancer. Their study group included an inordinately high proportion of men over the age of 75 years, most of whom had low-grade tumors too small to be detected on rectal examination. Nearly half of the tumors were discovered at the time of an operation for presumed benign hyperplasia. Because such tumors progress slowly and most patients were elderly to begin with, it is not surprising that most patients died of other causes. The patient selection process was a self-fulfilling prophesy.  During the first 2 years of their study, only patients with grade 1 tumors were accepted for the untreated group, which enriched the group with low-grade tumors. During the last 5 years, some patients under the
TCT-429 Fetal Pulmonary Valvuloplasty. In-Utero and Post-Natal Outcomes
Authors: Carlos Pedra, Fabio Peralta, Rodrigo Costa, Marcelo Ribeiro, Jose C. Fernandes, Carlos R. Ferreiro, Solange C. Gimenez, Ieda Jatene, Simone Pedra
Journal: Journal of the American College of Cardiology (2014)
Do women develop alcoholic liver disease more readily than men?
Authors: J B Saunders, M Davis, R Williams
Journal: BMJ (1981)

The sudden increase in alcoholic liver disease among women in the past 10 years has caused much speculation that they may be more susceptible to the hepatotoxic effects of alcohol than men. Women tend to present with more severe liver disease, particularly alcoholic hepatitis, and do so after a shorter period of excessive drinking and at a lower daily alcohol intake. Differences in body size and composition are partly responsible for the greater susceptibility of women, but differences in immune reactivity between the sexes may also play a part. Greater emphasis must be placed on designing abstinence programmes specifically for female patients, on earlier detection of liver disease, and on educating women about hazardous drinking levels.
Dehydroepiandrosterone and its Sulfate Predict the 5-Year Risk of Coronary Heart Disease Events in Elderly Men
Authors: Åsa Tivesten, Liesbeth Vandenput, Daniel Carlzon, Maria Nilsson, Magnus K. Karlsson, Östen Ljunggren, Elizabeth Barrett-Connor, Dan Mellström, Claes Ohlsson
Journal: Journal of the American College of Cardiology (2014)
Comparison of Endobronchial Ultrasound and/or Endoesophageal Ultrasound with Transcervical Extended Mediastinal Lymphadenectomy for Staging and Restaging of Non–Small-Cell Lung Cancer
Authors: Marcin Zielinski, Artur Szlubowski, Marcin Kołodziej, Stanislaw Orzechowski, Ewa Laczynska, Juliusz Pankowski, Magdalena Jakubiak, Anna Obrochta
Journal: Journal of Thoracic Oncology (2013)
Extent of Dutch psychologist's research fraud was "unprecedented"
Authors: J. Wise
Journal: BMJ (2011)

A well known Dutch psychologist falsified data in dozens of studies in one of the biggest cases of scientific fraud on record, an investigative committee has found.

Diederik Stapel, a professor of cognitive social psychology and dean of the Tilburg School of Social and Behaviour Sciences, committed academic fraud in “several dozen” publications since at least 2004. Much of his research, which covered topics such as stereotyping and discrimination and the effectiveness of advertising, received widespread publicity.

Mr Stapel was suspended from his post in September pending an investigation. On 31 October an interim report released by the three Dutch institutions where Mr Stapel worked—the University of Tilburg, the University of Groningen, and the University of Amsterdam—concluded that the extent of his fraud was very substantial. Mr Stapel has published about 150 papers. A full list of the fraudulent publications will be presented in the committee’s final report, expected to be in a few months. …