tbuckley/cabot-search huggingface dataset:
PI3K Pathway Activation in Breast Cancer Is Associated with the Basal-Like Phenotype and Cancer-Specific Mortality.
Authors: E. Lopez-Knowles, S. O'Toole, S. O'Toole, C. McNeil, C. McNeil, E. Millar, E. Millar, E. Millar, M. Qiu, M. Qiu, P. Crea, R. Daly, R. Daly, E. Musgrove, E. Musgrove, R. Sutherland, R. Sutherland
Journal: Cancer Research (2009)

Abstract Background: Current biological therapies for breast cancer are tailored to steroid hormone (ER, PR) and HER2 receptor status. Understanding the biological basis of resistance to current targeted therapies and the identification of new potential therapeutic targets is an ongoing challenge. The PI3K pathway is altered in a high proportion of breast cancers and may be associated with specific phenotypes and therapeutic resistance. We undertook an integrative study of mutational, copy number and expression analysis of key regulators of the PI3K pathway in a cohort of 292 invasive breast cancer patients with known treatment outcomes.Material and Methods: Mutations in 3 "hotspots" in exons 9 and 20 of the PIK3CA gene were determined by sequencing and PIK3CA gene copy number by qPCR. PTEN loss and Akt activation i.e. pAkt (Ser473) were assessed by immunohistochemistry using tissue microarrays. Cores were scored by 2 independent observers blinded to clinicopathological data and patient outcome and a histoscore calculated by multiplying the percent positive cells and staining intensity in a range 0-3. Standard statistical tests were applied to assess relationship between the measured parameters and patient outcome.Results: Alterations identified included PIK3CA mutations (12/168 i.e. 7%), PIK3CA copy number gain (28/209 i.e. 14%), PTEN loss (73/258 i.e. 28%) and AKT activation (62/258 i.e. 24%). Overall at least one parameter was altered in 72% i.e. 139 of 193 assessable primary breast cancers. PI3K pathway activation was significantly associated with ER negative (P=0.0008) and PR negative (P=0.006) status, high tumor grade (P=0.032) and a "basal-like" phenotype (P=0.01), where 92% (25/27) of tumors had an altered pathway. In univariate analysis PI3K pathway aberrations were associated with death from breast cancer however this relationship was not maintained in multivariate analysis. No association was identified between an activated pathway and outcome in tamoxifen- or chemotherapy-treated patients.Discussion: We conclude that &amp;gt;70% of breast cancers have an alteration in at least one component of the PI3K pathway and this might be exploited to therapeutic advantage especially in "basal-like" cancers. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2123.
CXCL12-Induced Monocyte-Endothelial Interactions Promote Lymphocyte Transmigration Across an in Vitro Blood-Brain Barrier
Authors: Shumei Man, Barbara Tucky, Anne Cotleur, Judith Drazba, Yukio Takeshita, Richard M. Ransohoff
Journal: Science Translational Medicine (2012)

An in vitro model of the human blood-brain barrier provides insights into how chemokine receptors regulate the transmigration of leukocytes into brain tissue.
The Reopened Ventricular Septal Defect
Authors: HAROLD W. MARCH, FRANK GERBODE, HERBERT N. HULTGREN
Journal: Circulation (1961)

The persistence of a left-to-right shunt due to the unsuccessful repair of a ventricular septal defect associated with infundibular stenosis has been described. A characteristic clinical picture has been reported. The main features include congestive heart failure, tricuspid insufficiency, and increased pulmonary blood flow. The severity of the symptoms appears to be due to the persistence of a left-to-right shunt at a time when the myocardium has been affected adversely by such operative insults as potassium arrest and ventriculotomy. The particular difficulties attending the repair of a ventricular septal defect with infundibular stenosis include the proximity of the defect to the hypertrophied muscle mass, the soft muscular margin of such a defect, and the tension on the suture line. Ivalon and Teflon prostheses have been disappointing in their failure to maintain the integrity of the repair. All of the patients were reoperated upon. Five survived and their defects are now closed. The second repairs were abetted by the development of a fibrous scar around the margin of the defect. The five survivors are in good health and there is no evidence of a remaining shunt. As a consequence of these experiences, surgical technics were modified. The defects are now closed by direct suture with interrupted silk, followed by the application of a crimped Dacron patch over the repair. The results have been encouraging and since the new technic has been adopted, there have been virtually no recurrences.
Effect of a Simple Deconditioning Procedure on the Diuretic and Natriuretic Response of Hypertensive Patients to a Hypertonic Salt Load
Authors: A. WELNER, J. J. GROEN
Journal: Circulation (1967)

The increased diuretic and natriuretic response of hypertensive patients to an intravenous salt load was modified toward normal by a deconditioning procedure which consisted in repeated exposure to the external situation of the test without, however, infusing any fluid into the vein. After this deconditioning, ratios between amounts of urine and sodium excreted in the first and the second 90-minute period of the test and the total 3-hour quantity of urine excreted were significantly reduced, but blood pressure was not changed. The response of normotensive patients to the same deconditioning was modified in the same direction but to a much smaller extent. It is suggested that the increased diuretic and natriuretic responses of hypertensive patients to an intravenous salt load are similar to the hyperreactive pressor and diuretic responses of these patients when exposed to stimuli that seem threatening to them, and that these responses are caused (at least in part) by hyperreactivity of the central nervous system to the external situation of the test.
Historical footnote on the treatment of mild hypertension
Authors: J. T. Hart
Journal: BMJ (2012)

The Cochrane review of randomised trials of treatment for “mild” hypertension, which found no benefit in drug treatment, prompts two important questions.1 Why has it taken more than 30 years to reach a conclusion that was evident from critical reading of the original trials that claimed to justify interventions in the diastolic range 90-100 mm Hg? And how can we get practice on to a more rational footing?

In 1983 I was invited to a symposium …
Phthalate Exposure and Early Thelarche
Authors: Richard H. McKee
Journal: Environmental Health Perspectives (2004)

The main objective of the Endosulfan Manufacturers and Formulators Welfare Association in India is disseminating scientific facts concerning the use of endosulfan.Because endosulfan is used in several countries, the association watches for global news and information relevant to endosulfan.Members of the Endosulfan Manufacturers and Formulators Welfare Association are of the strong opinion that Saiyed et al. (2003) omitted significant information in their published report "Effect of Endosulfan on Male Reproductive Development."Consequently, to uninitiated readers the article presented an alarming picture of endosulfan, a pesticide registered for use in over 70 countries for more than 40 years.Saiyed et al. (2003) failed to mention the origin of their study.In fact, their study is an integral part of an epidemiologic study submitted to the government of India in 2003, "Report of the Investigation of Unusual Illnesses Allegedly Produced by Endosulfan Exposure in Padre Village of Kasargod District" [National Institute of Occupational Health (NIOH) 2003].After studying this report and other related studies, an expert group appointed by the government of India categorically concluded in February 2003 that "there is no link established between use of endosulfan in PCK [Plantation Corporation of Kerala] plantations and health problems reported in Padre village" (Central Insecticides Board and Registration Committee 2003).The government of India has since accepted this conclusion.Epidemiology is a science of proving association and not causation.Therefore, we consider the conclusion of Saiyed et al. (2003) that their "study results suggest that endosulfan exposure may delay sexual maturity and interfere with hormone synthesis in male children" to be unscientific, uncalled for, and objectionable.Saiyed et al. (2003) failed to mention the fact that, besides endosulfan, a host of other pesticides were also used in both exposed and control study areas.The comment by EHP's Science Editor, Jim Burkhart, in the press release dated 1 December 2003 (EHP 2003) that "decades of spraying this pesticide [endosulfan], and only this pesticide" is therefore erroneous.The authors failed to mention the actual quantity of endosulfan aerially applied in the cashew plantation block closest to Vaninagar school (exposed group), which was 105 g active ingredient (ai)/acre/year.This rate should be compared with the permissible seasonal application rates elsewhere, including the United States, where 1,000 g ai/acre/year is often exceeded.
Risk of recurrence after venous thromboembolism in men and women: patient level meta-analysis
Authors: J. Douketis, A. Tosetto, M. Marcucci, T. Baglin, B. Cosmi, M. Cushman, P. Kyrle, D. Poli, R. C. Tait, A. Iorio
Journal: BMJ (2011)

To determine the effect of sex on the risk of recurrent venous thromboembolism in all patients and in patients with venous thromboembolism that was unprovoked or provoked (by non-hormonal factors). Data source Comprehensive search of electronic databases (Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials) until July 2010, supplemented by review of conference abstracts and contact with content experts.Seven prospective studies investigating an association between D-dimer, measured after anticoagulation was stopped, and disease recurrence in patients with venous thromboembolism.Patient level databases were obtained, transferred to a central database, checked, and completed with further information provided by authors.2554 patients with a first venous thromboembolism had follow-up for a mean of 27.1 (SD 19.6) months. The one year incidence of recurrent venous thromboembolism was 5.3% (95% confidence interval 4.1% to 6.7%) in women and 9.5% (7.9% to 11.4%) in men, and the three year incidence of recurrence was 9.1% (7.3% to 11.3%) in women and 19.7% (16.5% to 23.4%) in men. Among patients with unprovoked venous thromboembolism, men had a higher risk of recurrence than did women (hazard ratio 2.2, 95% confidence interval 1.7 to 2.8). After adjustment for women with hormone associated initial venous thromboembolism, the risk of recurrence remained higher in men (hazard ratio 1.8, 1.4 to 2.5). In patients with provoked venous thromboembolism, occurring after exposure to a major risk factor, recurrence of disease did not differ between men and women (hazard ratio 1.2, 0.6 to 2.4). In women with hormone associated venous thromboembolism and no other risk factors, recurrence was lower than that in women with unprovoked venous thromboembolism and no previous hormone use (hazard ratio 0.5, 0.3 to 0.8).In patients with a first unprovoked venous thromboembolism, men have a 2.2-fold higher risk of recurrent venous thromboembolism than do women, which remained 1.8-fold higher in men after adjustment for previous hormone associated venous thromboembolism in women. In patients with a first provoked venous thromboembolism, risk of recurrence does not differ between men and women with or without hormone associated venous thromboembolism. Indefinite anticoagulation may be given greater consideration in men than in women after a first venous thromboembolism.
Association Between Disease-Free Survival and Overall Survival When Survival Is Prolonged After Recurrence in Patients Receiving Cytotoxic Adjuvant Therapy for Colon Cancer: Simulations Based on the 20,800 Patient ACCENT Data Set
Authors: Aimery de Gramont, Joleen Hubbard, Qian Shi, Michael J. O'Connell, Marc Buyse, Jacqueline Benedetti, Brian Bot, Chris O'Callaghan, Greg Yothers, Richard M. Goldberg, Charles D. Blanke, Al Benson, Qiqi Deng, Steven R. Alberts, Thierry Andre, Norman Wolmark, Axel Grothey, Daniel Sargent
Journal: Journal of Clinical Oncology (2009)

Purpose We previously validated disease-free survival (DFS) as a surrogate for overall survival (OS) in fluorouracil-based adjuvant colon cancer clinical trials. New therapies have extended survival after recurrence from 1 to approximately 2 years. We examined the possible impact of this improvement on the DFS/OS association. Methods The Adjuvant Colon Cancer Endpoints (ACCENT) data set of 20,898 patients was analyzed. In an exploratory fashion, time from recurrence to death in patients experiencing recurrence was extended using several algorithms, and the association of DFS after 3 years of median follow-up and OS after varying lengths of follow-up (median of 5, 6, and 7 years) was assessed. Results Seven thousand four hundred two patients (35%) experienced recurrence. Median time from recurrence to death was 24 months in the hypothetical data sets. When times from recurrence to death were doubled, the association between treatment effects on DFS and 5-year OS was modest (R 2 = 0.51 for both 2- and 3-year DFS) but remained strong for DFS and 6-year OS (R 2 = 0.67 for both 2- and 3-year DFS) and 7-year OS (R 2 = 0.70 for both 2- and 3-year DFS). The reduced DFS/OS association with extended survival after recurrence was greater in stage II than stage III patients. Multiple simulations provided consistent findings. Conclusion Extended survival after recurrence reduces the association between treatment effects on 3-year DFS and 5-year OS, particularly in stage II patients; longer follow-up strengthens the association. In modern adjuvant trials, 6 or 7 years may be required to demonstrate OS improvements, further supporting DFS as the preferred primary end point for future adjuvant colon cancer clinical trials.
A Single Subset of Dendritic Cells Controls the Cytokine Bias of Natural Killer T Cell Responses to Diverse Glycolipid Antigens
Authors: Pooja Arora, Andres Baena, Karl O.A. Yu, Neeraj K. Saini, Shalu S. Kharkwal, Michael F. Goldberg, Shajo Kunnath-Velayudhan, Leandro J. Carreño, Manjunatha M. Venkataswamy, John Kim, Eszter Lazar-Molnar, Gregoire Lauvau, Young-tae Chang, Zheng Liu, Robert Bittman, Aymen Al-Shamkhani, Liam R. Cox, Peter J. Jervis, Natacha Veerapen, Gurdyal S. Besra, Steven A. Porcelli
Journal: Immunity (2014)

Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending on the structure of a particular glycolipid antigen. Here we have shown that a single type of cell, the CD8α+ DEC-205+ dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. After glycolipid presentation, these dendritic cells rapidly altered their expression of various costimulatory and coinhibitory molecules in a manner that was dependent on the structure of the antigen. These findings show flexibility in the outcome of two-way communication between CD8α+ dendritic cells and iNKT cells, providing a mechanism for biasing toward either proinflammatory or anti-inflammatory responses.
Short term increase in risk of breast cancer associated with full term pregnancy.
Authors: E M Williams, L Jones, M P Vessey, K McPherson
Journal: BMJ (1990)

determine which statements described them and were related to their health.The patient could answer only yes or no to each question.An example of a question about sleep and rest is, "I spend much of the day lying down in order to rest." TIME TRADE OFF TECHNIQUEThe time trade off technique is used to derive a "utility," a score between 0 and 1, in which 1 represents perfect health and 0 a state in which the patient is indifferent between life and death."With the help of visual aids patients were asked how many years of their current health they would be willing to forgo to achieve perfect health.For example, if a 36 year old patient stated that she was unable to choose between four years of perfect health and 40 years of her current health the utility of her current health state was 4/40=0 10 (she would be willing to give up 36 years of her current health to achieve four years of perfect health).
Cancer in Elderly Blacks
Authors: J. M. Miller
Journal: CA A Cancer Journal for Clinicians (1986)

noticed the Editor's Note on page 325.That note says that al though the authors of the article recom mend annual Pap smears, the American Cancer Society guidelines state that â€oe¿ all asymptomatic women age 20 and over, and those under 20 who are sexually active, shouldhave a Pap test atleast everythree years, after two initial negative tests a year apart.â€•Apparently you forgot toadd:â€oe¿ Unless there are some increased risk factors.â€•If someone who was not an informedphy sician were to read this, the result could be that patients would come in for a Pap smear only every three years and that high risk patients could develop invasive can cer.In my own practice, I have had two women who failed tocome infortheir Pap smearsand endedup withinvasive cancer.In each case, when I asked them why
Combined Therapy of Malignant Stenoses of the Upper Gastrointestinal Tract by Means of Laser Beam and Bougienage
Authors: J.F. Riemann, Ch. Ell, G. Lux, L. Demling
Journal: Endoscopy (1985)

Eighteen patients with malignant inoperable stenoses of the upper digestive tract were treated with a combination of laser (neodymium-YAG) coagulation and bougienage. Following treatment, 14 out of 18 patients (78%) were able to eat solid food again; the width of the lumen was greater than 11 mm in every case. Between 1 and 5 laser sessions (median 3.5) and between 1 and 2 (median 1) bougienages were required; per session, between 1,017 and 9,096 joules (median 3,362) were required, and a total of between 4,770 and 36,244 joules (median 8,763) were utilized per patient treated. To date, 6 patients remain free of dysphagia (at between 3 and 24 weeks), 1 patient has in the meantime been submitted to surgery. In 7 patients, recurrent stenosis occurred, which was again treated with the laser (3) or with an endoscopically implanted prosthetic tube (4). In 4 patients, the result was unsatisfactory. By way of major complications, merely one perforation occurred. We conclude that the combined use of laser coagulation and bougienage represents an effective and largely complication-free palliative treatment for malignant stenoses in the upper digestive tract.
Intracoronary adenosine administered after reperfusion limits vascular injury after prolonged ischemia in the canine model.
Authors: D G Babbitt, R Virmani, M B Forman
Journal: Circulation (1989)

Myocardial salvage after reperfusion may be limited by deleterious vascular changes in the previously ischemic microcirculatory bed. This could result in a progressive decrease in blood flow in the capillary bed to potentially viable myocytes (no-reflow phenomenon). The effect of intracoronary adenosine on these changes was assessed in 15 closed-chest dogs subjected to 2 hours of proximal left anterior descending artery (LAD) occlusion followed by 3 hours of reperfusion. Animals randomly received adenosine (n = 8) 3.75 mg/min into the proximal LAD or an equivalent volume of saline (control) (n = 7) for 1 hour after reperfusion. Endothelial-dependent and independent coronary vasodilator reserve was determined using a chronically implanted volume-flowmeter on the mid-LAD at baseline and 1 and 3 hours after reperfusion with acetylcholine and papaverine infusions, respectively, into the proximal vessel. Regional myocardial blood flow was measured serially with radioactive microspheres and regional contractile function with contrast ventriculography. Both agonists produced a significant increase in LAD flow before occlusion. Endothelial-dependent and independent vasodilatory reserve was significantly reduced (p less than 0.05) at 1 and 3 hours after reperfusion in control animals compared with adenosine treatment. A progressive decrease in mid-LAD flow and increase in coronary vascular resistance after reperfusion was observed in control animals (p less than 0.05). The treated group manifested improved regional myocardial blood flow in endocardial regions from the central (0.73 +/- 0.15 versus 0.24 +/- 0.11 ml/g/min; p less than 0.02) and lateral ischemic zones (0.80 +/- 0.15 versus 0.34 +/- 0.12 ml/g/min; p less than 0.05) 3 hours after reperfusion. A significant reduction (p less than 0.05) in endocardial and midmyocardial flow compared with baseline was seen in control animals at 3 hours. Intravascular and interstitial neutrophil infiltration was reduced in adenosine animals and this was associated with relative ultrastructural preservation of endothelial cells. Regional ventricular function in the ischemic zone was improved in the adenosine group 3 hours after reperfusion (13.4 +/- 3.9% versus -5.3 +/- 1.6%; p less than 0.001). This study demonstrates that selective administration of adenosine after reperfusion significantly attenuates functional and structural abnormalities in the microvasculature after prolonged (2 hours) regional ischemia in the canine model. Prevention of microvascular injury and the non-reflow phenomenon by adenosine may preserve reversibly injured myocytes following restoration of blood flow to previously ischemic myocardium.
Somatic symptoms in women 11 years after the Chornobyl accident: prevalence and risk factors.
Authors: Evelyn J Bromet, Semyon Gluzman, Joseph E Schwartz, Dmitry Goldgaber
Journal: Environmental Health Perspectives (2002)

Exposure to the Chornobyl nuclear power plant explosion resulted in widespread, persistent somatic complaints, but little is known about the nature and risk factors for these conditions. This study compares the health reports of 300 women evacuated to Kyiv from the contamination zone around the plant and 300 controls with a child in the same homeroom as the evacuees in 1997. The interview addressed somatic concerns, risk factors for poor health, and Chornobyl-related stress. Compared with controls, evacuees reported significantly more health problems and rated their health more poorly overall. These differences remained significant after controlling for demographic and clinical risk factors, including the tendency to amplify physical symptoms. Significantly more evacuees received a diagnosis of a Chornobyl-related illness by a local physician, believed that their health and their children's health had been adversely affected, and were positive for Chornobyl-induced post-traumatic stress disorder. After controlling for these Chornobyl stress variables, the differences in number of health problems commonly attributed to Chornobyl remained significant but differences in general health ratings did not. The perceptions of controls were similar to those of women in a national sample. The relationship between Chornobyl stress and illness was twice as strong in evacuees (odds ratio = 6.95) as in Kyiv controls (odds ratio = 3.34) and weakest in the national sample (odds ratio = 1.64). The results confirm the persistence and nonspecificity of the subjective medical consequences of Chornobyl and are consistent with the hypothesis that traumatic events exert their greatest negative impacts on health in vulnerable or disadvantaged groups.
46 IN AUTOSOMAL DOMINANT POLYCYSTIC LIVER DISEASE (PCLD) CYSTS DEVELOP THROUGH A CELLULAR RECESSIVE MECHANISM INVOLVING LOSS OF HETEROZYGOSITY AND SOMATIC MUTATIONS
Authors: M.J. Janssen, E. Waanders, H.B.P.M. Dijkman, R.H.M. te Morsche, J. Woudenberg, J.P.H. Drenth
Journal: Journal of Hepatology (2010)