tbuckley/cabot-search huggingface dataset:
Is the prognostic value of Ki-67 dependent on ER status and histological grade?.
Authors: M Klintman, P Bendahl, D Grabau, K Lövgren, P Malmström, M Fernö
Journal: Cancer Research (2009)

Abstract Abstract #1076 Purpose: Histological grade, tumor size, age, hormone receptor, and HER2 are established prognostic indicators for distant recurrences in node negative breast cancer. However, the role of the proliferation marker Ki-67 as a prognostic factor is still under debate. The aim of this study is to evaluate the additional prognostic value of Ki-67 in lymph node negative breast cancer.&amp;#x2028; Patients and methods: In 200 consecutive premenopausal women with lymph node negative breast cancer, Ki-67 was determined using the monoclonal MIB-1 antibody on tissue microarray. High Ki-67 proliferation index was defined as &amp;gt;20% positive tumor cells. Cox proportional hazards regression was used to model the impact of the prognostic factors on distant disease-free survival (DDFS). Due to non-proportional hazards, the analysis was restricted to the first 5 years after diagnosis, a time period during which 38 patients developed distant recurrences.&amp;#x2028; Results: Strong positive correlations were observed between Ki-67, histological grade, S-phase, and HER-2. In univariate analysis, Ki-67 was a prognostic factor for DDFS (HR 2.9 95%CI: 1.5-5.7, p=0.002), as well as HER2, histological grade, age and ER. Tumor size was not a significant factor. In multivariate analysis, Ki-67 was an independent prognostic factor for DDFS (HR 2.3 95% CI: 1.0-5.0, p=0.044) together with HER2 and age, whereas tumor size and ER were not significant factors. Models including both Ki-67 and histological grade were not fitted due to colinearity. When stratifying for ER status Ki-67 was a significant prognostic factor in the ER positive group only (HR 5.1 95% CI: 2.0-13, p=0.001, univariate analysis) and significant interaction between the two markers was found (p=0.02). When stratifying for histological grade, Ki-67 could divide the patients with histological grade 2 (n=69; 10 distant recurrences) into two separate groups with significant difference in DDFS (HR 15 95% CI: 3.7-57, p=0.0001). This remained significant after adjustment for age and HER2 status. In histological grade 1 and 3, Ki-67 provided no additional prognostic information.&amp;#x2028; Conclusion: This study demonstrates that Ki-67 is an independent prognostic factor for premenopausal patients with lymph node negative breast cancer. It is noteworthy that Ki-67 adds prognostic information in ER positive patients, but not in ER negative, and in patients with histological grade 2, but not in patients with histological grade 1 and 3. Taken together, Ki-67 may be clinically helpful for prognostic considerations and for selection of adjuvant treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1076.
Acute Metabolic Acidosis
Authors: Jean-Martin Wiederseiner, Juergen Muser, Thomas Lutz, Henry N. Hulter, Reto Krapf
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Despite the high incidence of acute metabolic acidosis, there are no reliable human data to enable physicians to accurately diagnose this disorder. In addition, there is uncertainty about the direction and magnitude of plasma potassium changes in acute metabolic acidosis. The systemic and renal acid-base, electrolyte, and endocrine response to acute acid loads (imposed by three timed NH(4)Cl infusions into the duodenum, 0.9 mmol of NH(4)Cl per kg of body weight over 30 min each) was characterized in six healthy male subjects in whom a metabolic steady-state had been established. Arterialized blood CO(2) tension decreased by 0.85 mmHg per mmol/L decrease in plasma bicarbonate concentration and blood hydrogen ion concentration increased by 0.45 nmol/L per mmol/L decrease in plasma bicarbonate concentration. Plasma potassium did not change significantly (+0.02 +/- 0.02 mmol/L per mmol decrease in plasma bicarbonate concentration). Plasma insulin increased and plasma glucagon levels decreased in acute metabolic acidosis, while catecholamines and aldosterone were not affected significantly. These data provide the first diagnostic criteria for the diagnosis of acute metabolic acidosis in humans. The finding of a hyperinsulinemic response in acute metabolic acidosis suggests that an insulin response counterregulates any acidemia-induced cellular potassium efflux, resulting in stable plasma potassium concentrations.
Hedgehog signalling stimulates precursor cell accumulation and impairs epithelial maturation in the murine oesophagus
Authors: Willemijn A van Dop, Sanne L Rosekrans, Anja Uhmann, Viljar Jaks, G Johan A Offerhaus, Marius A van den Bergh Weerman, Maria Kasper, Jarom Heijmans, James C H Hardwick, Hein W Verspaget, Daan W Hommes, Rune Toftgård, Heidi Hahn, Gijs R van den Brink
Journal: Gut (2012)

<h3>Objective</h3> In the intestine Hedgehog (Hh) signalling is directed from epithelium to mesenchyme and negatively regulates epithelial precursor cell fate. The role of Hh signalling in the oesophagus has not been studied in vivo. Here the authors examined the role of Hh signalling in epithelial homeostasis of oesophagus. <h3>Design</h3> The authors used transgenic mice in which the Hh receptor <i>Patched1</i> (<i>Ptch1</i>) could be conditionally inactivated in a body-wide manner and mice in which <i>Gli1</i> could be induced specifically in the epithelium of the skin and oesophagus. Effects on epithelial homeostasis of the oesophagus were examined using immunohistochemistry, in situ hybridisation, transmission electron microscopy and real-time PCR. Hh signalling was examined in patients with oesophageal squamous cell carcinoma (SCC) by quantitative real-time PCR. <h3>Results</h3> Sonic Hh is signalled in an autocrine manner in the basal layer of the oesophagus. Activation of Hh signalling resulted in an expansion of the epithelial precursor cell compartment and failure of epithelial maturation and migration. Levels of Hh targets <i>GLI1, HHIP</i> and <i>PTCH1</i> were increased in SCC compared with normal tissue from the same patients. <h3>Conclusion</h3> Here the authors find that Hh signalling positively regulates the precursor cell compartment in the oesophageal epithelium in an autocrine manner. Since Hh signalling targets precursor cells in the oesophageal epithelium and signalling is increased in SCCs, Hh signalling may be involved in oesophageal SCC formation.
IS THERE A SMOKING GUN? THE IMPACT OF TOBACCO USE ON PERIPHERAL VASCULAR INTERVENTION INDICATIONS AND OUTCOMES; OBSERVATIONS FROM BLUE CROSS BLUE SHIELD OF MICHIGAN CARDIOVASCULAR CONSORTIUM
Authors: Shea Elizabeth Hogan, Khan Munir, Hitinder Gurm, Jeffrey Rubin, M. Ashraf Mansour, P. Michael Grossman
Journal: Journal of the American College of Cardiology (2012)
Detecting Germline <i>PTEN</i> Mutations Among At-Risk Patients With Cancer: An Age- and Sex-Specific Cost-Effectiveness Analysis
Authors: Joanne Ngeow, Chang Liu, Ke Zhou, Kevin D. Frick, David B. Matchar, Charis Eng
Journal: Journal of Clinical Oncology (2015)

Cowden syndrome (CS) is an autosomal dominant disorder characterized by benign and malignant tumors. One-quarter of patients who are diagnosed with CS have pathogenic germline PTEN mutations, which increase the risk of the development of breast, thyroid, uterine, renal, and other cancers. PTEN testing and regular, intensive cancer surveillance allow for early detection and treatment of these cancers for mutation-positive patients and their relatives. Individual CS-related features, however, occur commonly in the general population, making it challenging for clinicians to identify CS-like patients to offer PTEN testing.We calculated the cost per mutation detected and analyzed the cost-effectiveness of performing selected PTEN testing among CS-like patients using a semi-quantitative score (the PTEN Cleveland Clinic [CC] score) compared with existing diagnostic criteria. In our model, first-degree relatives of the patients with detected PTEN mutations are offered PTEN testing. All individuals with detected PTEN mutations are offered cancer surveillance.CC score at a threshold of 15 (CC15) costs from $3,720 to $4,573 to detect one PTEN mutation, which is the most inexpensive among the different strategies. At base-case, CC10 is the most cost-effective strategy for female patients who are younger than 40 years, and CC15 is the most cost-effective strategy for female patients who are between 40 and 60 years of age and male patients of all ages. In sensitivity analyses, CC15 is robustly the most cost-effective strategy for probands who are younger than 60 years.Use of the CC score as a clinical risk calculator is a cost-effective prescreening method to identify CS-like patients for PTEN germline testing.
Differential role of platelet granular mediators in angiogenesis
Authors: A BRILL
Journal: Cardiovascular Research (2004)

Platelets contain numerous substances regulating angiogenic response. However, the regulatory role of platelets in blood vessel development remains to be elucidated. We investigated the comprehensive effect of platelets as a cellular system on angiogenesis.The following approaches were applied: (a) in vitro-aortic ring assay and chemotaxis assay; (b) in vivo-injection of platelet-containing matrigel plug subcutaneously into a mouse followed by immunohistochemical analysis of angiogenic response.Platelets stimulated formation of blood vessels in vitro in the rat aortic ring model via VEGF and bFGF, while blocking of platelet factor-4 promoted this effect. Addition of platelets to the matrigel followed by its subcutaneous injection into a mouse resulted in an intensive migration of fibroblasts into the matrigel as well as formation of blood capillaries de novo. This platelet effect was mediated through bFGF, VEGF, and heparanase. Furthermore, platelet releasate was found to induce endothelial cell chemotaxis. This effect was mediated by a concerted action of intraplatelet bFGF, PDGF, VEGF, and heparanase.Platelets affect different stages of the angiogenic response with a trend to a pro-angiogenic net effect despite the presence of angiogenesis inhibitors such as platelet factor 4. While a concomitant effect of bFGF and VEGF seemed to be essential for the entire process of vessel formation (aortic ring and matrigel models), PDGF and heparanase were effective only at the migration stage.
Right Auricular and Ventricular Pressure Patterns in Constrictive Pericarditis
Authors: PAUL N. G. YU, FRANK W. LOVEJOY, HOWARD A. JOOS, ROBERT E. NYE, EARL B. MAHONEY
Journal: Circulation (1953)

The characteristic intracardiac pressure patterns of four patients with constrictive pericarditis are described. The significance of a high ratio between right ventricular end-diastolic and systolic pressure is demonstrated. Postoperative changes are described in one patient and the mechanism of the production of the pressure patterns is discussed.
Advances in allergy management
Authors: P. Van Cauwenberge
Journal: Allergy (2002)

Our understanding of the pathophysiology of allergy has moved to the molecular level, while study of epidemiology and genetics has revealed risks of developing allergies based on environmental and genetic profiles, and pharmacoeconomic data have enabled accurate measurement of the immense burden of allergic disease. These advances in allergy research have affected its management, particularly the search for new antiallergy therapies. New therapies should intervene in the systemic allergy inflammatory cascade and provide clinical efficacy that extends to multiple allergic disease states. In addition, these new therapies should present no additional safety issues, offer improvements over existing therapies, and have an impact on disease‐impaired quality of life. In vitro studies show that desloratadine, a new, once‐daily, nonsedating, selective histamine H 1 ‐receptor antagonist, blocks the systemic allergy cascade at multiple points. Desloratadine 5 mg once daily relieves the symptoms of chronic idiopathic urticaria and of both seasonal (SAR) and perennial allergic rhinitis. In patients with concomitant asthma and SAR, asthma symptoms are relieved and β 2 ‐agonist medication use is decreased by desloratadine. Unlike many other second‐generation histamine H 1 ‐receptor antagonists, desloratadine provides the added benefit of efficacy against nasal obstruction in SAR. Desloratadine improves quality of life by decreasing the impact of allergic symptoms on sleep and on daily activities.
Single-cell pharmacokinetic imaging reveals a therapeutic strategy to overcome drug resistance to the microtubule inhibitor eribulin
Authors: Ashley M. Laughney, Eunha Kim, Melissa M. Sprachman, Miles A. Miller, Rainer H. Kohler, Katy S. Yang, James D. Orth, Timothy J. Mitchison, Ralph Weissleder
Journal: Science Translational Medicine (2014)

Single-cell pharmacokinetic analysis of a fluorescent eribulin derivative in vivo revealed drug resistance mediated by MDR1-driven efflux, which was overcome by a nanoencapsulated MDR1 inhibitor.
Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor
Authors: M. Galli, T. Barbui, P. Comfurius, C. Maassen, H.C. Hemker, R.F.A. Zwaal, E.M. Bevers, M.H. de Baets, P.J.C. van Breda-Vriesman
Journal: The Lancet (1990)
Controlled trial of bowel rest and nutritional support in the management of Crohn's disease.
Authors: G R Greenberg, C R Fleming, K N Jeejeebhoy, I H Rosenberg, D Sales, W J Tremaine
Journal: Gut (1988)

To define the role of bowel rest as an independent variable from nutritional support a prospective, randomised controlled trial was undertaken in 51 patients with active Crohn9s disease unresponsive to other medical management. Nutritional support for 21 days was randomised to total parenteral nutrition and nil by mouth (n = 17), defined formula diet administered through a nasogastric tube (n = 19), or partial parenteral nutrition and oral food (n = 15). Nutrient input in the first two groups provided 40 non-protein kcal/kg ideal body weight /d and 1g/ kg/d protein respectively, while the third group received 15 non-protein kcal/kg/d and 0.3 g/kg/d protein intravenously and ate unrestricted food. Clinical remissions occurred in 71% of patients on parenteral nutrition, in 58% on the defined formula diet and in 60% on partial parenteral nutrition; the probability for each group of being in remission at one year, after successful therapy was 42%, 55%, and 56% respectively. These differences were not significant. In patients with active Crohn9s disease bowel rest was not a major factor in achieving a remission during nutritional support and did not influence outcome during one year9s follow-up.
Treating low back pain: Alexander technique and exercise, antibiotics (!) and Paul Hodges on dynamic stability
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2008)

I am delighted that major luminaries including Professors Frank Booth and Paul Hodges have agreed to share their wisdom in this issue of BJSM . Professor Booth’s millennium review, “Waging war on modern chronic diseases”,1 is compulsory reading. It clearly trumps Machiavelli’s The Prince for top spot among the Great Literature; Macca never made it onto PubMed nor did he get cited 187 times for 1 paper in 8 short years. In his magnum opus, Professor Booth provides incontrovertible evidence that physical inactivity causes medical costs of $US 1 trillion (yes, trillion, that’s a thousand billion) annually in the USA alone. Don’t just skip over that number—it happens to equal the estimate for the projected deficit of the USA in 2009. So with just a 12.5% reduction in the cost of physical inactivity, President Obama could have it all paid off by the time he leaves the White House in 2016. Not bad. My point? If you are having trouble justifying the importance of physical activity to a patient, government representative, Dean or President/Vice Chancellor, just slap Professor Booth’s paper on the desk and remind the person that a trillion is 16 times the current population of the planet. …
Angiopoietin-1 Reduces VEGF-Stimulated Leukocyte Adhesion to Endothelial Cells by Reducing ICAM-1, VCAM-1, and E-Selectin Expression
Authors: Injune Kim, Sang-Ok Moon, Sung Kwang Park, Soo Wan Chae, Gou Young Koh
Journal: Circulation Research (2001)

Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) are potent vasculogenic and angiogenic factors that hold promise as a means to produce therapeutic vascularization and angiogenesis. However, VEGF also acts as a proinflammatory cytokine by inducing adhesion molecules that bind leukocytes to endothelial cells, an initial and essential step toward inflammation. In the present study, we used human umbilical vascular endothelial cells (HUVECs) to examine the effect of Ang1 on VEGF-induced expression of three adhesion molecules: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Interestingly, Ang1 suppressed VEGF-induced expression of these adhesion molecules. Furthermore, Ang1 reduced VEGF-induced leukocyte adhesion to HUVECs. These results demonstrate that Ang1 counteracts VEGF-induced inflammation by reducing VEGF-induced endothelial adhesiveness.
Effect of Granulocyte Colony–Stimulating Factor on Circulating Immune and Stem Cells in Septic Shock: Revisit the Basics and Consider Giving It Another Chance
Authors: Tomasz Skirecki, Jerzy Kawiak, Grażyna Hoser, Wiesław Tarnowski, Małgorzata Złotorowicz, Urszula Zielińska-Borkowska
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
Randomized Phase III Trial of Paclitaxel/Carboplatin With or Without PF-3512676 (Toll-Like Receptor 9 Agonist) As First-Line Treatment for Advanced Non–Small-Cell Lung Cancer
Authors: Vera Hirsh, Luis Paz-Ares, Michael Boyer, Rafael Rosell, Gary Middleton, Wilfried E.E. Eberhardt, Aleksandra Szczesna, Pavel Reiterer, Mansoor Saleh, Oscar Arrieta, Emilio Bajetta, Roy T. Webb, Johannes Raats, Rebecca J. Benner, Camilla Fowst, Sandra J. Meech, David Readett, Joan H. Schiller
Journal: Journal of Clinical Oncology (2011)

This phase III study examined efficacy of the synthetic Toll-like receptor 9-activating oligodeoxynucleotide PF-3512676 in combination with standard paclitaxel/carboplatin chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomly assigned (1:1) to receive up to six courses of paclitaxel/carboplatin (intravenous paclitaxel 200 mg/m(2) and carboplatin at area under the [concentration-time] curve 6 on day 1 of a 3-week cycle) alone (control arm) or in combination with 0.2 mg/kg subcutaneous PF-3512676 on days 8 and 15 (investigational arm). Primary end point was overall survival (OS).Baseline demographics were similar across arms (N = 828). Most patients (88%) had stage IV disease. Median OS and median progression-free survival (PFS) were similar (OS: investigational arm, 10.0 months v control arm, 9.8 months; P = .56; PFS: investigational arm, 4.8 months v control arm, 4.7 months; P = .79). Most commonly reported PF-3512676-related adverse events (AEs) were mild-to-moderate local injection site reactions, pyrexia, and flu-like symptoms. In the investigational arm, grades 3 to 4 AEs, including neutropenia, thrombocytopenia, and anemia, were more frequent, and more patients had one or more sepsis-related AEs versus controls (17 v 3). At first interim analysis, the Data Safety Monitoring Committee recommended study discontinuation because of lack of incremental efficacy and more sepsis-related serious AEs in the PF-3512676 arm. Administration of PF-3512676, but not chemotherapy, was halted.Addition of PF-3512676 to paclitaxel/carboplatin did not improve OS or PFS versus paclitaxel/carboplatin alone for first-line treatment of patients with advanced NSCLC but did increase toxicity. This regimen cannot be recommended for treating patients with advanced NSCLC.
Curtailment of higher surgical training in the UK
Authors: D. Bray
Journal: Journal of the Royal Society of Medicine (2005)

Examining the potential impact of the proposed two-year cut in otology training, Jaydip Ray and colleagues conclude that intensification of training would be necessary to eradicate the significant difference in specialist surgical experience between current year-four and year-six otology trainees (June 2005 JRSM 1 ).In our opinion their article misses the point regarding the changes.The proposed model of four years' general training followed by two years of specialist training will not require future year-four trainees to have comparable operative experience to today's year-six trainees, as implied.The Specialist Advisory Committee for Otolaryngology has set stage-specific criteria of required operative competencies for higher surgical trainees. 2Georgalas et al., 3 in a recent survey of otolaryngology trainees, concluded that all stage-specific criteria were currently being met, and that training standards were satisfactory across the UK.They concluded that current training is adequate and that a system of twotier trainees, with four years of general training and two years devoted to the subspecialties, would be an adequate option for the vast majority of specialist registrars, provided that current standards are maintained. 2 Training in specialist otological surgery will not be offered or assessed in the new four-year 'generalist' higher surgical rotations, since specialist experience will be gained in accredited otology fellowships for prospective otologists.
How biologically relevant are interaction-based modules in protein networks?
Authors: Juan F Poyatos, Laurence D Hurst
Journal: Genome biology (2004)

Abstract By applying a graph-based algorithm to yeast protein-interaction networks we have extracted modular structures and show that they can be validated using information from the phylogenetic conservation of the network components. We show that the module cores, the parts with the highest intramodular connectivity, are biologically relevant components of the networks. These constituents correlate only weakly with other levels of organization. We also discuss how such structures could be used for finding targets for antimicrobial drugs.
The "Ripple Effect" Following Adjunct Hypnosis in Analytic Psychotherapy
Authors: HERBERT SPIEGEL, LOUIS LINN
Journal: American Journal of Psychiatry (1969)

Treatment of several patients in analysis seemed obstructed by a single persisting symptom; in each case a consultant psychiatrist removed the symptom through hypnosis and the patients were returned to their referring psychotherapist. The authors note that not only were there no unfortunate sequelae but that a "ripple effect" occurred that resulted in genuine emotional growth by the patients.
Age at menarche in Nigerian athletes.
Authors: D. N. Mathur, A. L. Toriola
Journal: British Journal of Sports Medicine (1982)

The subjects of the study were 418 highly successful female athletes and 512 female non-athletes drawn from all over Nigeria. Recall procedures were used to ascertain the age at menarche. The study gave the following results: In general, over-all mean menarcheal age of athletes (14.13 years) was significantly higher (p less than .05) than that of non-athletes (13.57 years). Menarche was significantly (p less than .05) delayed (14.41 years) in those athletes (n = 272) who started physical activities before the onset of menstruation. The mean menarcheal age of non-athletes i.e. general population was significantly lower (p less than .05) than that established thirty years ago in Nigerian women.
Language as an emergent group-level trait
Authors: Lan Shuai, Tao Gong
Journal: Behavioral and Brain Sciences (2014)

Abstract Following Smaldino's definition, we claim that language is also an emergent group-level trait, and propose two facets (human groups tend to organize in a way to efficiently trigger language and linguistic interactions can render formation of certain social organization) to verify this statement, both of which also provide a general framework to address the future work about group-level traits.