tbuckley/cabot-search huggingface dataset:
Cost-Effectiveness of a Conservative, Ischemia-Guided Management Strategy After Non–Q-Wave Myocardial Infarction
Authors: Paul G. Barnett, Shuo Chen, William E. Boden, Bruce Chow, Nathan R. Every, Philip W. Lavori, Mark A. Hlatky
Journal: Circulation (2002)

Background — Use of coronary angiography after myocardial infarction has been controversial, with some physicians advocating routine use and others advocating selective use only after documentation of residual myocardial ischemia. The effects of these strategies on economic outcomes have not been established. Methods and Results — We analyzed data from a randomized, controlled clinical trial conducted in 17 Department of Veterans Affairs hospitals that enrolled 876 clinically uncomplicated patients 24 to 72 hours after an acute non–Q-wave myocardial infarction. The routine invasive strategy included early coronary angiography with revascularization based on established guidelines. The conservative, ischemia-guided strategy included noninvasive testing with radionuclide ventriculography and exercise thallium scintigraphy, followed by coronary angiography in patients with objective evidence of myocardial ischemia. We measured the cost of hospitalization and outpatient visits and tests during follow-up and calculated the incremental cost-effectiveness ratio. The conservative, ischemia-guided strategy had lower costs than the routine invasive strategy, both during the initial hospitalization ($14 733 versus $19 256, P &lt;0.001) and after a mean follow-up of 1.9 years ($39 707 versus $41 893, P =0.04). The hazard ratio for death was 0.72 (confidence limits, 0.51 to 1.01) in the conservative strategy. The conservative strategy had lower costs and better outcomes in 76% of 1000 bootstrap replications, and a cost-effectiveness ratio below $50 000 per year of life added in 96% of replications. Conclusions — A conservative, ischemia-guided strategy of selective coronary angiography and revascularization for patients who develop objective evidence of recurrent ischemia is more cost-effective than a strategy of routine coronary angiography after uncomplicated non–Q-wave myocardial infarction.
Affibody Molecules for <i>In vivo</i> Characterization of HER2-Positive Tumors by Near-Infrared Imaging
Authors: Sang Bong Lee, Moinuddin Hassan, Robert Fisher, Oleg Chertov, Victor Chernomordik, Gabriela Kramer-Marek, Amir Gandjbakhche, Jacek Capala
Journal: Clinical Cancer Research (2008)

Abstract Purpose: HER2 overexpression has been associated with a poor prognosis and resistance to therapy in breast cancer patients. We are developing molecular probes for in vivo quantitative imaging of HER2 receptors using near-infrared (NIR) optical imaging. The goal is to provide probes that will minimally interfere with the studied system, that is, whose binding does not interfere with the binding of the therapeutic agents and whose effect on the target cells is minimal. Experimental Design: We used three different types of HER2-specific Affibody molecules [monomer ZHER2:342, dimer (ZHER2:477)2, and albumin-binding domain-fused-(ZHER2:342)2] as targeting agents and labeled them with Alexa Fluor dyes. Trastuzumab was also conjugated, using commercially available kits, as a standard control. The resulting conjugates were characterized in vitro by toxicity assays, Biacore affinity measurements, flow cytometry, and confocal microscopy. Semiquantitative in vivo NIR optical imaging studies were carried out using mice with s.c. xenografts of HER2-positive tumors. Results: The HER2-specific Affibody molecules were not toxic to HER2-overexpressing cells and their binding to HER2 did interfere with neither binding nor effectives of trastuzumab. The binding affinities and specificities of the Affibody-Alexa Fluor fluorescent conjugates to HER2 were unchanged or minimally affected by the modifications. Pharmacokinetics and biodistribution studies showed the albumin-binding domain-fused-(ZHER2:342)2-Alexa Fluor 750 conjugate to be an optimal probe for optical imaging of HER2 in vivo. Conclusion: Our results suggest that Affibody-Alexa Fluor conjugates may be used as a specific NIR probe for the noninvasive semiquantitative imaging of HER2 expression in vivo.
The E3 Ubiquitin Ligase GRAIL Regulates T Cell Tolerance and Regulatory T Cell Function by Mediating T Cell Receptor-CD3 Degradation
Authors: Roza I. Nurieva, Shuling Zheng, Wei Jin, Yeonseok Chung, Yongliang Zhang, Gustavo J. Martinez, Joseph M. Reynolds, Sung-Ling Wang, Xin Lin, Shao-Cong Sun, Guillermina Lozano, Chen Dong
Journal: Immunity (2010)
Stimulatory effect of hydrothermally synthesized biodegradable hydroxyapatite granules on osteogenesis and direct association with osteoclasts
Authors: Yoshinori Gonda, Koji Ioku, Yasuaki Shibata, Takatoshi Okuda, Giichiro Kawachi, Masanobu Kamitakahara, Hisashi Murayama, Katsumi Hideshima, Shimeru Kamihira, Ikuho Yonezawa, Hisashi Kurosawa, Tohru Ikeda
Journal: Biomaterials (2009)
Metastatic Sarcomatoid Renal Cell Carcinoma Treated With Vascular Endothelial Growth Factor–Targeted Therapy
Authors: Ali Reza Golshayan, Saby George, Daniel Y. Heng, Paul Elson, Laura S. Wood, Tarek M. Mekhail, Jorge A. Garcia, Hakan Aydin, Ming Zhou, Ronald M. Bukowski, Brian I. Rini
Journal: Journal of Clinical Oncology (2008)

Metastatic renal cell carcinoma (mRCC) with sarcomatoid differentiation is an aggressive disease that is associated with poor outcomes to chemotherapy or immunotherapy. The utility of vascular endothelial growth factor (VEGF)-targeted therapy in patients with this disease is unknown.Patients who had mRCC with sarcomatoid features in the primary tumor and who were treated with VEGF-targeted therapy were retrospectively identified. Pathology slides were reviewed to determine the percentage of sarcomatoid differentiation. Objective response rate, percentage of tumor burden shrinkage, progression-free survival (PFS), and overall survival (OS) were determined.Forty-three patients who had sarcomatoid mRCC were identified. The median percentage of sarcomatoid features was 14% (range, 3% to 90%). Patients were treated with either sunitinib (49%), sorafenib (28%), bevacizumab (19%), or sunitinib plus bevacizumab (5%). Partial responses were observed in eight patients (19%); 21 patients (49%) had stable disease; and 14 patients (33%) had progressive disease as their best response. Partial responses were limited to patients who had underlying clear-cell histology and less than 20% sarcomatoid elements. Median tumor shrinkage was -2% (range, -85% to 127%), and 53% achieved some degree of tumor shrinkage on therapy. Median PFS and OS were estimated to be 5.3 months and 11.8 months, respectively.Patients who have mRCC and sarcomatoid differentiation can demonstrate objective responses and tumor shrinkage to VEGF-targeted therapy. Patients who have clear-cell histology and a lower percentage of sarcomatoid differentiation may have better outcomes with VEGF-targeted therapy.
The standard tangential fields used for breast irradiation do not allow optimal coverage and dose distribution in axillary levels I–II and the sentinel node area
Authors: Y. Belkacemi, Q. Allab-Pan, V. Bigorie, W. Khodari, P. Beaussart, J.-L. Totobenazara, J.-P. Mège, P. Caillet, F. Pigneur, T.-H. Dao, R. Salmon, E. Calitchi, R. Bosc
Journal: Annals of Oncology (2013)
MRSA infections in patients treated with tumour necrosis factor inhibitors
Authors: N Akhmed, J Lichtenstein
Journal: Annals of the Rheumatic Diseases (2009)

Clinical experience with the three available tumour necrosis factor (TNF) inhibitors (etanercept, infliximab and adalimumab) shows improvement in inflammatory arthritis. Clinical studies have reported serious infections such as reactivation tuberculosis following treatment with TNF inhibitors. Bacterial infections with organisms such as Staphylococcus aureus (both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA)), Streptococcus and Gram-negative organisms have not been reported to be more frequent or severe. We noticed several severe MRSA infections in patients treated with TNF inhibitors and wondered whether these agents might alter the outcome of these infections. We therefore performed a retrospective analysis of patients treated in our practice.

Between August 2003 and July 2006, 430 patients with inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis) …
The Harveian Oration, Delivered at the Royal College of Physicians
Authors: J. R. Reynolds
Journal: BMJ (1884)

LIFAItNEDCOLLEGE,-Before entering on the subject which now brings us here, I must ask you to accept mny thanks for the distinction you have con- ferred on me in selecting me for the office I have the honour to fill to-day-an honour, allow me to add, which carries with it a special gratification to myself, inasmuch as,
Internet Sales of Cigarettes to Minors
Authors: Kurt M. Ribisl, Rebecca S. Williams, Annice E. Kim
Journal: JAMA (2003)

There is growing concern that the Internet might become a source of tobacco products for minors. Although researchers have studied tobacco sales to minors at retail outlets for more than a decade, there are no published studies of tobacco sales to minors via the Internet.To determine the proportion of Internet cigarette vendors that will sell cigarettes to minors.Cross-sectional study conducted in April-July 2001. Under adult supervision, 4 adolescents aged 11 to 15 years attempted to purchase cigarettes via 55 Internet cigarette vendors located in 12 states. These minors made a total of 83 purchase attempts, paying by credit card (n = 47) and by money order (n = 36).Proportion of Internet cigarette vendors that sold cigarettes to minors.Minors successfully received cigarettes for 93.6% of credit card purchase attempts and for 88.9% of money order purchase attempts. Age was never verified for any of these deliveries. Internet vendors sent a total of 1650 packs of cigarettes to the underage adolescents in this study.Minors appear to have easy access to cigarettes via the Internet because many Internet vendors have weak or nonexistent age verification procedures.
God, the devil, and the details: Fleshing out the predictive processing framework
Authors: Daniel Rasmussen, Chris Eliasmith
Journal: Behavioral and Brain Sciences (2013)

Abstract The predictive processing framework lacks many of the architectural and implementational details needed to fully investigate or evaluate the ideas it presents. One way to begin to fill in these details is by turning to standard control-theoretic descriptions of these types of systems (e.g., Kalman filters), and by building complex, unified computational models in biologically realistic neural simulations. God is in the details — Mies van der Rohe The devil is in the details — Anonymous
Receptor Antibodies as Novel Therapeutics for Diabetes
Authors: Siegfried Ussar, Sara G. Vienberg, C. Ronald Kahn
Journal: Science Translational Medicine (2011)

Antibodies to receptors can block or mimic hormone action. Taking advantage of receptor isoforms, co-receptors, and other receptor modulating proteins, antibodies and other designer ligands can enhance tissue specificity and provide new approaches to the therapy of diabetes and other diseases.
Prediction of Colorectal Neoplasia by Quantitative Methylation Analysis of <i>Estrogen Receptor</i> Gene in Nonneoplastic Epithelium from Patients with Ulcerative Colitis
Authors: Keiichi Tominaga, Shigehiko Fujii, Kenichiroh Mukawa, Mikio Fujita, Kazuhito Ichikawa, Shigeki Tomita, Yasuo Imai, Kazunari Kanke, Yuko Ono, Akira Terano, Hideyuki Hiraishi, Takahiro Fujimori
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The incidence of colorectal neoplasia has increased among patients with longstanding and extensive ulcerative colitis (UC). Therefore, surveillance colonoscopy has been widely recommended. However, there is controversy about the impact of cancer surveillance, and ways to improve its effectiveness are being sought. The estrogen receptor (ER) gene shows age-related methylation in the colorectal epithelium and is frequently methylated in colorectal neoplasia, suggesting that ER methylation occurs early in the process of colorectal tumorigenesis. Experimental Design: To clarify whether methylation analysis of the ER gene in nonneoplastic epithelium can help predict an increased risk for UC-associated neoplasia, a total of 105 nonneoplastic colorectal epithelia from 18 patients with longstanding and extensive UC, including 8 patients with neoplasia and 10 patients without neoplasia, were analyzed. In all patients, multiple samples were taken from six regions of the colorectum. The combined bisulfite restriction analysis method was used to determine the methylation status of the ER gene. Results: The mean methylation level of the ER gene was 25.4% in the nonneoplastic epithelia from UC patients with neoplasia, whereas it was only 4.0% in those without neoplasia (P &amp;lt; 0.001). The methylation level of the ER gene in UC patients with neoplasia was significantly higher than in UC patients without neoplasia throughout the colorectum except for the cecum. In UC patients with neoplasia, the mean ER methylation level in the distal colon (36.1%) was significantly higher than in the proximal colon (14.6%; P &amp;lt; 0.001). Conclusions: These results suggest that the analysis of ER gene methylation in nonneoplastic colorectal epithelium could have the potential to be a useful adjunct for identifying individuals with longstanding and extensive UC who are at increased risk of neoplasia and contribute to more effective cancer surveillance.
Genomic and Transcriptional Alterations in Lung Adenocarcinoma in Relation to Smoking History
Authors: Anna Karlsson, Markus Ringnér, Martin Lauss, Johan Botling, Patrick Micke, Maria Planck, Johan Staaf
Journal: Clinical Cancer Research (2014)

Cigarette smoking is the major pathogenic factor for lung cancer. The precise mechanisms of tobacco-related carcinogenesis and its effect on the genomic and transcriptional landscape in lung cancer are not fully understood.A total of 1,398 (277 never-smokers and 1,121 smokers) genomic and 1,449 (370 never-smokers and 1,079 smokers) transcriptional profiles were assembled from public lung adenocarcinoma cohorts, including matched next-generation DNA-sequencing data (n = 423). Unsupervised and supervised methods were used to identify smoking-related copy-number alterations (CNAs), predictors of smoking status, and molecular subgroups.Genomic meta-analyses showed that never-smokers and smokers harbored a similar frequency of total CNAs, although specific regions (5q, 8q, 16p, 19p, and 22q) displayed a 20% to 30% frequency difference between the two groups. Importantly, supervised classification analyses based on CNAs or gene expression could not accurately predict smoking status (balanced accuracies ∼60% to 80%). However, unsupervised multicohort transcriptional profiling stratified adenocarcinomas into distinct molecular subgroups with specific patterns of CNAs, oncogenic mutations, and mutation transversion frequencies that were independent of the smoking status. One subgroup included approximately 55% to 90% of never-smokers and approximately 20% to 40% of smokers (both current and former) with molecular and clinical features of a less aggressive and smoking-unrelated disease. Given the considerable intragroup heterogeneity in smoking-defined subgroups, especially among former smokers, our results emphasize the clinical importance of accurate molecular characterization of lung adenocarcinoma.The landscape of smoking-related CNAs and transcriptional alterations in adenocarcinomas is complex, heterogeneous, and with moderate differences. Our results support a molecularly distinct less aggressive adenocarcinoma entity, arising in never-smokers and a subset of smokers.
Maspin: The New Frontier
Authors: Zhila Khalkhali-Ellis
Journal: Clinical Cancer Research (2006)

Abstract Maspin (mammary serine protease inhibitor) was identified in 1994 by subtractive hybridization analysis of normal mammary tissue and breast cancer cell lines. Subsequently, emerging evidence portrays maspin as a multifaceted protein, interacting with diverse group of intercellular and extracellular proteins, regulating cell adhesion, motility, apoptosis, and angiogenesis and critically involved in mammary gland development. The tissue-specific expression of maspin is epigenetically controlled, and aberrant methylation of maspin promoter is closely associated with maspin gene silencing. Identification of new tissue sites expressing maspin and novel maspin-binding partners has expanded the horizon for maspin research and promises maspin-based therapeutic approaches for combating cancer. This perspective briefly outlines the past and present strides in deciphering this unique molecule and speculates on new frontiers in maspin research and prospects of maspin as a diagnostic/prognostic indicator in cancer.
Predominance of fetal type DJH joining in young children with B precursor lymphoblastic leukemia as evidence for an in utero transforming event.
Authors: R Wasserman, N Galili, Y Ito, B A Reichard, S Shane, G Rovera
Journal: The Journal of Experimental Medicine (1992)

The presence of N sequences in the complementarity determining region 3 (CDR3) of the rearranged immunoglobulin H chain is developmentally regulated: N regions are generally present in the DJH joinings of adult B cells but are often absent in fetal B cells. Analysis of the CDR3 in 61 B precursor acute lymphoblastic leukemias indicated that 87.5% of the leukemias obtained from children &amp;lt; or = 3 yr old lacked N regions at the DJH junction. In contrast, in children &amp;gt; 3 yr old, only 11.1% of the leukemias lacked N regions at this junction, a frequency similar to what we have observed in B cells from children and adults. These findings suggest that the majority of leukemias presenting within the first 3 yr of age arise from an in utero transforming event.
Hair density, hair diameter and the prevalence of female pattern hair loss
Authors: M.P. Birch, J.F. Messenger, A.G. Messenger
Journal: British Journal of Dermatology (2001)

Journal Article Hair density, hair diameter and the prevalence of female pattern hair loss Get access M.P. Birch, M.P. Birch Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.F. Messenger, J.F. Messenger Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.G. Messenger A.G. Messenger Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 144, Issue 2, 1 February 2001, Pages 297–304, https://doi.org/10.1046/j.1365-2133.2001.04018.x Published: 01 February 2001
Pulmonary 99mTc-DTPA aerosol clearance and survival in usual interstitial pneumonia (UIP)
Authors: N Mogulkoc
Journal: Thorax (2001)

<h3>BACKGROUND</h3> Clearance of inhaled technetium 99m-labelled diethylenetriamine penta-acetic acid (<sup>99m</sup>Tc-DTPA) from the lungs is a potential indicator of disease progression in patients with idiopathic pulmonary fibrosis (IPF). <h3>METHODS</h3> We prospectively analysed the usefulness of this technique for predicting survival in 106 non-smoking patients with usual interstitial pneumonia (UIP) pattern IPF diagnosed by high resolution CT (HRCT) scanning or histological examination (M/F 65/41, mean (SD) age 61 (11) years). DTPA clearance was analysed according to both mono-exponential and bi-exponential models. Half times for the fast (<i>t</i><sub>0.5</sub><i>F</i>) and slow (<i>t</i><sub>0.5</sub><i>S</i>) components of clearance, the percentage contribution of the fast component (<i>f</i><i>F</i>), and half time for mono-exponential approximation to the early part of the clearance curve (<i>t</i><sub>0.5</sub>) were calculated. <h3>RESULTS</h3> The patients had substantially faster <i>t</i><sub>0.5</sub>(mean 23.9 (9.6) minutes) than normal values (&gt;45 minutes). Thirty seven patients (35%) died during follow up (median 15 months). Univariate Cox regression analysis identified significant predictors of survival as age, forced expiratory volume in 1 second (FEV<sub>1</sub>), forced vital capacity (FVC), total lung capacity (TLC), % predicted TLC, carbon monoxide transfer factor (Tlco), % predicted Tlco, arterial oxygen tension (Pao<sub>2</sub>), oxygen saturation,<i>t</i><sub>0.5</sub><i>F</i>, and HRCT fibrosis score. Multiple stepwise Cox regression analysis identified<i>t</i><sub>0.5</sub><i>F</i>(p=0.03, hazard ratio 0.747, 95% CI 0.578 to 0.964), % predicted TLC (p=0.02, hazard ratio 0.976, 95% CI 0.956 to 0.995), % predicted Tlco (p=0.003, hazard ratio 0.960, 95% CI 0.935 to 0.986), and age (p=0.003, hazard ratio 1.062, 95% CI 1.021 to 1.104) as independent predictors of survival. <h3>CONCLUSION</h3> These data suggest that <sup>99m</sup>Tc-DTPA clearance<i>t</i><sub>0.5</sub><i>F</i>measurement may predict survival in patients with UIP pattern IPF.
Epigenetic Changes in Cancer
Authors: Christine A. Iacobuzio-Donahue
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Cancer is as much an epigenetic disease as it is a genetic disease, and epigenetic alterations in cancer often serve as potent surrogates for genetic mutations. Normal epigenetic modifications of DNA encompass three types of changes: chromatin modifications, DNA methylation, and genomic imprinting, each of which is altered in cancer cells. This review addresses the various epigenetic modifications that are pervasive among human tumors and traces the history of cancer epigenetics from the first observations of altered global methylation content to the recently proposed epigenetic progenitor model, which provides a common unifying mechanism for cancer development.
Evaluation of acute bronchodilator reversibility in patients with symptoms of GOLD stage I COPD
Authors: D E O'Donnell, P Laveneziana, J Ora, K A Webb, Y-M Lam, D Ofir
Journal: Thorax (2008)

Patients with symptoms of GOLD stage I chronic obstructive pulmonary disease (COPD) can have significant abnormalities of ventilatory mechanics with greater exertional symptoms and exercise limitation than age-matched healthy subjects. In such patients the impact of bronchodilator therapy remains unknown and is difficult to evaluate.The acute effects of nebulised ipratropium bromide 500 microg (IB) on resting pulmonary function and on dyspnoea and ventilatory parameters during symptom-limited constant work rate cycle exercise were measured. In a randomised double-blind crossover study, 16 patients with COPD (mean (SD) post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 90 (7)% predicted, FEV(1)/forced vital capacity (FVC) 59 (7)%) with a significant smoking history (mean (SD) 44 (16) pack-years) inhaled either IB or placebo on each of two separate visits. Pulmonary function tests and cycle exercise at 80-85% of each subject's maximal work capacity were performed 2 h after dosing.Compared with placebo, FEV(1) increased 5 (9)% predicted, residual volume decreased 12 (20)% predicted and specific airway resistance decreased 81 (93)% predicted (all p<0.05) after IB. At a standardised time during exercise, dynamic inspiratory capacity and tidal volume significantly increased in tandem by 0.12 and 0.16 litres, respectively (each p<0.05), dyspnoea fell by 0.9 (1.8) Borg units (p = 0.07) and dyspnoea/ventilation ratios fell significantly (p<0.05). The fall in dyspnoea intensity at higher submaximal ventilations correlated with the concurrent decrease in end-expiratory lung volume (p<0.05).In patients with symptoms of GOLD stage I COPD, IB treatment is associated with modest but consistent improvements in airway function, operating lung volumes and dyspnoea intensity during exercise. These results provide a physiological rationale for a trial of bronchodilator therapy in selected patients with milder but symptomatic COPD.