tbuckley/cabot-search huggingface dataset:
Abstract 1150: Genome-wide DNA methylation profiling of cell-free serum DNA in esophageal adenocarcinoma and Barrett's esophagus
Authors: Rihong Zhai, Yang Zhao, Li Su, Lauren Carssidy, Geoffrey Liu, David Christiani
Journal: Cancer Research (2012)

Abstract Aberrant DNA methylation (DNAm) is a feature of most types of cancers. Genome-wide DNAm profiling has been performed successfully on DNA extracted from many types of tumor tissues. However, the invasive procedure and the likely existence of tissue heterogeneity limit the utility of tumor tissue for epidemiological studies. While recent data indicate that cell-free circulating DNA methylation (cfDNAm) profiles reflect DNAm profiles in matched tumor tissues, no studies have examined the association of cfDNAm with cancer or precursors on a genome-wide scale. The objective of this pilot study was to evaluate the putative significance of genome-wide cfDNAm profiles in esophageal adenocarcinoma (EA) and Barrett's esophagus (BE, EA precursor). We performed genome-wide DNAm profiling in EA tissue DNA (n=8) and matched serum DNA (n=8), in serum DNAs of BE (n=12) and healthy controls (n=12), using the Infinium Humanmethylation27 Beadchip that covers 27,578 CpG loci in 14,495 genes. We found that cfDNAm profiles were highly correlated to DNAm profiles in matched tumor tissue DNAs (r=0.92) in patients with EA. We selected the most differentially methylated loci (a β-value difference of &amp;gt;0.2 and a P-value of 6 x 10 −7 between groups) to perform hierarchical clustering analysis. We found that 911 loci can perfectly discriminate between EA and control samples; 554 loci can separate EA from BE samples; and 46 loci can distinguish BE from control samples. These results suggest that genome-wide cfDNAm profiles are highly consistent with DNAm profiles detected in corresponding tumor tissues. Differential cfDNAm profiling may be a useful approach for the non-invasive screening of EA and EA premalignant lesions. Supported by grants: Flight Attendant Medical Research Institute (FAMRI) grant# 062459; NIH grants CA92824, CA74386, CA90578, and CA119650); the Kevin Jackson Memorial Fund and Alan Brown Chair of Molecular Genomics. 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 1150. doi:1538-7445.AM2012-1150
Objective assessment of technical skills in surgery
Authors: K. Moorthy
Journal: BMJ (2003)

In the past few years, considerable developments have been made in the objective assessment of technical proficiency of surgeons. Technical skills should be assessed during training, and various methods have been developed for this purpose 

Surgical competence entails a combination of knowledge, technical skills, decision making, communication skills, and leadership skills. Of these, dexterity or technical proficiency is considered to be of paramount importance among surgical trainees. The assessment of technical skills during training has been considered to be a form of quality assurance for the future.1 Typically surgical learning is based on an apprenticeship model. In this model the assessment of technical proficiency is the responsibility of the trainers. However, their assessment is largely subjective.2 Objective assessment is essential because deficiencies in training and performance are difficult to correct without objective feedback.3

The introduction of the Calman system in the United Kingdom, the implementation of the European Working Time Directive, and the financial pressures to increase productivity4 have reduced the opportunity to learn surgical skills in the operating theatre. Studies have shown that these changes have resulted in nearly halving the surgical case load that trainees are exposed to.5 Surgical proficiency must therefore be acquired in less time, with the risk that some surgeons may not be sufficiently skilled at the completion of training.6 This and increasing attention of the public and media on the performance of doctors have given rise to an interest in the development of robust methods of assessment of technical skills.7 We review the research in this field in the past decade. Our objectives are to explore all the available methods, establish their validity and reliability, and examine the possibility of using these methods on the basis of the available evidence.

We collected information for this review from …
Hypertrophic gastropathy with gastric adenocarcinoma: Menetrier's disease and lymphocytic gastritis?
Authors: J F Mosnier, J F Flejou, G Amouyal, B Gayet, G Molas, D Henin, F Potet
Journal: Gut (1991)

Lymphocytic gastritis is a form of gastric inflammation characterised by a pronounced increase in lymphocytes in gastric surface and foveolar epithelium. Lymphocytic gastritis is often associated with endoscopic evidence of 9varioliform gastritis9. Lymphocytic gastritis has recently been reported to be associated with other forms of hypertrophic gastropathies. We present a case of hypertrophic gastropathy with gastric adenocarcinoma, with both Menetrier9s disease and lymphocyte gastritis. Immunohistochemical studies showed that the intraepithelial lymphocytes were predominantly alpha/beta T cells as in the normal stomach and not gamma/delta T cells as in coeliac sprue. This case together with the six recently published cases suggests that Menetrier9s disease and lymphocytic gastritis may be part of the same disease spectrum.
The γ-secretase inhibitor PF-03084014 combined with fludarabine antagonizes migration, invasion and angiogenesis in NOTCH1-mutated CLL cells
Authors: M López-Guerra, S Xargay-Torrent, L Rosich, A Montraveta, J Roldán, A Matas-Céspedes, N Villamor, M Aymerich, C López-Otín, P Pérez-Galán, G Roué, E Campo, D Colomer
Journal: Leukemia (2014)
EARLY INCREASE IN CIRCULATING AUTOANTIBODIES AGAINST HUMAN OXIDIZED LOW-DENSITY LIPOPROTEIN IN HYPERTENSIVE PATIENTS AFTER BLOOD PRESSURE CONTROL
Authors: Maria Cristina Izar, Sergio A. Brandao, Simone C. Fischer, Rui M. Povoa, Carlos M. Monteiro, Andrea M. Monteiro, Magnus Gidlund, Antonio M. Figueiredo Neto, Antonio C. Carvalho, Francisco A. Fonseca
Journal: Journal of the American College of Cardiology (2010)
Eleven-Year Outcome of Patients with Prostate Cancers Diagnosed During Screening After Initial Negative Sextant Biopsies
Authors: Fritz H. Schröder, Roderick C.N. van den Bergh, Tineke Wolters, Pim J. van Leeuwen, Chris H. Bangma, Theo H. van der Kwast, Monique J. Roobol
Journal: European Urology (2009)
Defective suppression in the autologous mixed lymphocyte reaction in patients with Crohn's disease.
Authors: D Kelleher, A Murphy, C A Whelan, C Feighery, D G Weir, P W Keeling
Journal: Gut (1989)

T helper and suppressor cell control of autologous immunoglobulin production was measured in 14 patients with Crohn's disease (CD) using autologous B cells or monocytes to stimulate regulatory T-cell activity. A pronounced defect in suppressor cell function was observed in the patient group but not in matched controls irrespective of whether B cells or monocytes were used as the stimulus. This defect was observed for IgG, A and M. This defect was seen both in patients with active disease and with inactive CD suggesting the possibility that a primary regulatory defect might exist in this disease. The patient group displayed normal helper cell function.
Mystique, Medical Training, and Clinical Excellence
Authors: Roger M. Cass
Journal: JAMA (1984)

<h3>To the Editor.—</h3> Dubovsky and Schrier<sup>1</sup>most properly point out in their article entitled "The Mystique of Medical Training" that attending physicians must be sensitive and perceptive to the emotional needs of their house officers. They emphasize that in this highly stressful hospital environment, comments made by the attending may be perceived as hostile attacks, and they suggest that management errors be reviewed in a spirit of comradery where the attending acknowledges that "he has found himself in similiar straits" and that "anyone could have made similiar mistakes." Unfortunately, we don't practice medicine in such a loving and forgiving atmosphere. Physicians still are held in high esteem; there are often great expectations for a good outcome, and when one is not produced, we may face the wrath of the patient and the family. To practice clinical excellence is not so much a matter of brilliant clinical insight and recall
A Bayesian Model Comparison Approach to Inferring Positive Selection
Authors: K. Scheffler, C. Seoighe
Journal: Molecular Biology and Evolution (2005)

A popular approach to detecting positive selection is to estimate the parameters of a probabilistic model of codon evolution and perform inference based on its maximum likelihood parameter values. This approach has been evaluated intensively in a number of simulation studies and found to be robust when the available data set is large. However, uncertainties in the estimated parameter values can lead to errors in the inference, especially when the data set is small or there is insufficient divergence between the sequences. We introduce a Bayesian model comparison approach to infer whether the sequence as a whole contains sites at which the rate of nonsynonymous substitution is greater than the rate of synonymous substitution. We incorporated this probabilistic model comparison into a Bayesian approach to site-specific inference of positive selection. Using simulated sequences, we compared this approach to the commonly used empirical Bayes approach and investigated the effect of tree length on the performance of both methods. We found that the Bayesian approach outperforms the empirical Bayes method when the amount of sequence divergence is small and is less prone to false-positive inference when the sequences are saturated, while the results are indistinguishable for intermediate levels of sequence divergence.
Systemic Deficiency of the MAP Kinase–Activated Protein Kinase 2 Reduces Atherosclerosis in Hypercholesterolemic Mice
Authors: Kumaravelu Jagavelu, Uwe J.F. Tietge, Matthias Gaestel, Helmut Drexler, Bernhard Schieffer, Udo Bavendiek
Journal: Circulation Research (2007)

Atherosclerosis is a chronic inflammatory disease and represents the major cause of cardiovascular morbidity and mortality. A critical regulator of inflammatory processes represents the mitogen-activated protein kinase-activated protein kinase-2 (MK2). Therefore, we investigated the functional role of MK2 in atherogenesis in hypercholesterolemic mice as well as potentially underlying mechanisms in vivo and in vitro. Activation of MK2 (phospho-MK2) was predominantly detected in the endothelium and macrophage-rich plaque areas within aortas of hypercholesterolemic LDL receptor-deficient mice (ldlr(-/-)). Systemic MK2 deficiency of hypercholesterolemic ldlr(-/-) mice (ldlr(-/-)/mk2(-/-)) significantly decreased the accumulation of lipids and macrophages in the aorta after feeding an atherogenic diet for 8 and 16 weeks despite a significant increase in proatherogenic plasma lipoproteins compared with ldlr(-/-) mice. Deficiency of MK2 significantly decreased oxLDL-induced foam cell formation in vitro, diet-induced foam cell formation in vivo, and expression of scavenger receptor A in primary macrophages. In addition, systemic MK2 deficiency of hypercholesterolemic ldlr(-/-) mice significantly decreased the aortic expression of the adhesion molecule VCAM-1 and the chemokine MCP-1, key mediators of macrophage recruitment into the vessel wall. Furthermore, silencing of MK2 in endothelial cells by siRNA reduced the IL-1beta-induced expression of VCAM-1 and MCP-1. MK2 critically promotes atherogenesis by fostering foam cell formation and recruitment of monocytes/macrophages into the vessel wall. Therefore, MK2 might represent an attractive novel target for the treatment of atherosclerotic cardiovascular disease.
THE VASCULAR BASIS OF SOME NODULAR ERUPTIONS OF THE LEGS.
Authors: D. S. WILKINSON
Journal: British Journal of Dermatology (1954)

Journal Article THE VASCULAR BASIS OF SOME NODULAR ERUPTIONS OF THE LEGS. Get access D. S. WILKINSON, M.D., M.R.C.P. D. S. WILKINSON, M.D., M.R.C.P. Dermatologist, Aylesbury and High Wycombe Hospitals Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 66, Issue 6, 1 June 1954, Pages 201–213, https://doi.org/10.1111/j.1365-2133.1954.tb12619.x Published: 01 June 1954
Discussion of risk of scuba diving in individuals with allergic and respiratory diseases
Authors: Frank Twarog, John M. Weiler, Stanley I. Wolf, Roger J. Barron, David M. Lang, James H. Wells, Myron Zitt, Frank S. Virant, Roger M. Katz, Larry W. Banyash, Melvyn H. Wolk, Nicholas Orfan, Margaret Frank Guill
Journal: Journal of Allergy and Clinical Immunology (1995)
A CONVENIENT SELF-ADMINISTERING SCALE FOR MEASURING INTELLECTUAL IMPAIRMENT IN PSYCHOTICS
Authors: WALTER C. SHIPLEY, C. CHARLES BURLINGAME
Journal: American Journal of Psychiatry (1941)

A quick, objective, self-administering scale for measuring intellectual impairment has been described. It requires but 20 minutes to give and 2 minutes to score, and is adapted to group, as well as individual use. It consists of a vocabulary and an abstract-thinking test which are used together. Impairment is measured in terms of the abstract-thinking deficit taken in relation to vocabulary level. For convenience, a special impairment index, the C. Q. ( conceptual quotient), is employed; it represents the ratio of the patient's abstract-thinking ability to that of the average normal individual at his vocabulary level. The scale was standardized on over a thousand normals for whom I. Q.'s were available; mental-age equivalents were established for the vocabulary and abstract-thinking tests, as well as for the two tests combined. This method of standardization rendered [SEE GRAPH IN SOURCE PDF] FIG. 4.mGraph showing median C. Q.'s and interquartile ranges (middle 50 per cent of cases) for the private hospital diagnostic sub-groups. the scale useful as a measure of intelligence, as well as of intellectual impairment. To test its efficacy the scale was given to several hundred mental patients from both private and state hospitals. Comparison of the [SEE FIG.5 IN SOURCE PDF] FIG.5.mGraph showing median C. Q.'s and interquartile ranges (middle 50 per cent of cases) for the state hospital diagnostic sub-groups. C. Q.'s thus obtained with those of normals yielded the following significant findings. (1) Only 5 per cent of the state hospital cases reached the median of the normals, while less than 1 per cent of the normals fell as low as the state hospital median. (2) The private hospital median fell midway between that of the normals and state hospital cases. Analysis by diagnostic groups showed the psychoneurotics and other non-psychotics to approach the normals, with the functional psychotics falling lower, and the organic psychotics lowest of all. This trend was both striking and consistent. [SEE FIG.6 IN SOURCE PDF] FIG. 6.mPrivate and state hospital data combined. The dots represent midpoints between the private and state hospital median C. Q.'s The evidence confirms the original tenets; the scale has been found useful in measuring intellectual impairment. It is best suited for work with relatively early cases of average or superior intelligence. It is not suited for use with markedly deteriorated cases, and its use with subnormals must await the establishment of further norms.
Abstract OT2-6-13: A randomized phase 2 study of the triplet combination of ridaforolimus (RIDA), dalotuzumab (DALO) and exemestane (EX) compared to the ridaforolimus, exemestane doublet in high proliferation, estrogen receptor positive (ER+) advanced breast cancer
Authors: HS Rugo, O Tredan, J Ro, SM Morales, A Musolina, N Afonso, M Ferreira, KH Park, J Cortes, AR Tan, JL Blum, L Eaton, D Mauro, C Gause, E Im, J Baselga
Journal: Cancer Research (2013)

Abstract Background: The clinical benefit of combination of mTOR inhibition and anti-hormonal therapy has been previously established and represents a new standard of care for patients with hormone receptor positive (HR+) advanced breast cancer (ABC). Preclinical evaluation of the mTOR pathway demonstrates that dual inhibition of IGFR and mTOR may be additive or synergistic and abrogates the feedback activation of AKT due to rapamycin analog mTOR inhibitors. A completed phase 1 study of the combination of the mTOR inhibitor, RIDA and the anti-IGFR antibody, DALO demonstrated preliminary signals of anti-tumor activity. This was further evaluated in a recently completed phase 2 study of RIDA-DALO compared to exemestane in ER+ ABC. Final safety and efficacy results from that phase 2 study will be reported at this meeting (see Baselga et al). Building upon the clinical synergies of mTOR and EX as well as the biologic relationship of the mTOR and IGFR pathways, a clinical study has been initiated to evaluate the triplet combination of RIDA-DALO-EX compared to RIDA-EX. Methods: This is a multicenter, international, randomized phase 2 study of the triplet combination of RIDA (10 mg by mouth daily for 5 out of every 7 days), DALO (10 mg/kg IV weekly), and EX (25 mg QD) compared to RIDA (30 mg by mouth daily for 5 out of every 7 days) and EX (25 mg QD) in high KI67 (≥15%) expressing ER+, ABC. Approximately 84 patients will be randomized 1:1 to either triplet or doublet therapy. Key eligibility criteria include: HR+ and HER-2 negative measurable ABC, prior therapy with a non-steroidal aromatase inhibitor, and KI67 labeling index ≥15%. The primary endpoint of the study is progression free survival (PFS). Key secondary endpoints include evaluation of percent (%) reduction from baseline in the sum of imaging measurements (target lesion diameters or volumes) at 16 weeks between the two arms, and overall response rates. The sample size is event driven with a target of 38 PFS events, which provides approximately 80% power, at 1-sided alpha of 0.1, to detect a HR of 0.5, corresponding to an approximate 100% improvement in median PFS, from 10.6 to 21.2 months. Safety parameters or adverse experiences of special interest include hyperglycemia, stomatitis, mucosal inflammation, pneumonitis and hearing loss. Accrual has been completed with results expected in May 2014. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-6-13.
Myocardial Connective Tissue Metabolism in Response to Injury
Authors: JOSEPH T. JUDD, BERNARD C. WEXLER, George Williamson, Jacob Boyer
Journal: Circulation Research (1970)

Myocardial necrosis was produced in rats by administering isoproterenol, and the increase in hexosamine-containing materials in the injured myocardium was investigated. Total hexosamine, galactosamine, neutral sugars, and uronic acids were determined on various fractions isolated from the hearts. Mucopolysaccharides were precipitated as the cetyl pyridinium chloride complex and fractionated according to their solubility in NaCl solutions. Of the hexosamine in the heart, approximately 50% was retained after proteolytic digestion and dialysis. Approximately one-fourth to one-third of the nondialyzable hexosamine was in mucopolysaccharides. The hyaluronic acid fraction of the mucopolysaccharides increased during the early edematous reaction observed in the hearts. The chondroitin sulfate fraction increased in conjunction with the beginning fibrinogenic processes and remained elevated during repair. There was evidence that the glycoproteins may be involved in the myocardial necrosis and repair.
Human connexin43 gap junction channels. Regulation of unitary conductances by phosphorylation.
Authors: A P Moreno, J C Sáez, G I Fishman, D C Spray
Journal: Circulation Research (1994)

Connexin43 is the major gap protein in the heart and cardiovascular system. Single channel recordings of human connexin43 gap junction channels exogenously expressed in transfected SKHep1 cells demonstrate two discrete classes of channel events, with unitary conductances of predominantly 60 to 70 and 90 to 100 pS when recorded with an internal solution containing CsCl as the major current-carrying ionic species and at moderate transjunctional voltages (&lt; 60 mV). Human connexin43 expressed in SKHep1 cells displays multiple electrophoretic mobilities (apparent M(r), approximately 41 to 45 kD) when resolved in Western blots. Treatment of connexin43 from these cells with alkaline phosphatase collapses the bands into a single 41-kD species; application of alkaline phosphatase to the cell interior through patch pipettes yields channels that are predominantly of the larger unitary conductance. The smaller 60- to 70-pS unitary conductance values correspond to the most common channel size seen in cultured rat cardiac myocytes; these channels were more frequently observed after treatment with the phosphatase inhibitor okadaic acid, which was shown to increase phosphorylation of human connexin43 in these cells under similar conditions. Exposure to the protein kinase inhibitor staurosporine shifted the proportion of events toward the largest unitary conductance and resulted in decreased phosphorylation of human connexin43 in seryl residues in these cells. Thus, the unitary conductance of human connexin43 gap junction channels covaries with the phosphorylation state of the protein. This change in unitary conductance appears to be a unique effect of phosphorylation on gap junction channels, since it has not been observed for other ion channels that have thus far been evaluated.
Mirk/Dyrk1b Mediates Cell Survival in Rhabdomyosarcomas
Authors: Stephen E. Mercer, Daina Z. Ewton, Sejal Shah, Asghar Naqvi, Eileen Friedman
Journal: Cancer Research (2006)

Abstract Rhabdomyosarcoma is the most common sarcoma in children and is difficult to treat if the primary tumor is nonresectable or if the disease presents with metastases. The function of the serine/threonine kinase Mirk was investigated in this cancer. Mirk has both growth arrest and survival functions in terminally differentiating skeletal myoblasts. Maintenance of Mirk growth arrest properties would cause down-regulation of Mirk in transformed myoblasts. Alternatively, Mirk expression would be retained if rhabdomyosarcoma cells used Mirk survival capability. Mirk expression was significant in 12 of 16 clinical cases of rhabdomyosarcoma. Mirk was detected in each rhabdomyosarcoma cell line examined. Mirk was a functional kinase in each of three rhabdomyosarcoma cell lines, where it proved to be more active than in C2C12 skeletal myoblasts. Mirk mediated survival of the majority of clonogenic rhabdomyosarcoma cells. Knockdown of Mirk by RNA interference reduced the fraction of RD and of Rh30 rhabdomyosarcoma cells capable of colony formation 3- to 4-fold in multiple experiments. Depletion of Mirk induced cell death by apoptosis, as shown by increased numbers of terminal deoxynucleotidyl transferase–mediated nick-end labeling–positive cells and by increased binding of Annexin V. Mirk is a stress-activated kinase that mediates expression of contractile proteins in differentiating myoblasts, but Mirk is not essential for muscle formation in the embryo. It is likely that Mirk also facilitates survival of satellite cell–derived rhabdomyoblasts in regenerating skeletal muscle and aids their differentiation. This survival function is maintained in rhabdomyosarcoma, where Mirk may be a novel therapeutic target. (Cancer Res 2006; 66(10): 5143-50)