tbuckley/cabot-search huggingface dataset:
Insulin-Like Growth Factor I Suppresses Bone Morphogenetic Protein Signaling in Prostate Cancer Cells by Activating mTOR Signaling
Authors: Reema S. Wahdan-Alaswad, Kyung Song, Tracy L. Krebs, Dorjee T.N. Shola, Jose A. Gomez, Shigemi Matsuyama, David Danielpour
Journal: Cancer Research (2010)

Abstract Insulin-like growth factor (IGF) I and bone morphogenetic proteins (BMP) are critical regulators of prostate tumor cell growth. In this report, we offer evidence that a critical support of IGF-I in prostate cancer is mediated by its ability to suppress BMP4-induced apoptosis and Smad-mediated gene expression. Suppression of BMP4 signaling by IGF-I was reversed by chemical inhibitors of phosphoinositide 3-kinase (PI3K), Akt, or mTOR; by enforced expression of wild-type PTEN or dominant-negative PI3K; or by small hairpin RNA–mediated silencing of mTORC1/2 subunits Raptor or Rictor. Similarly, IGF-I suppressed BMP4-induced transcription of the Id1, Id2, and Id3 genes that are crucially involved in prostate tumor progression through PI3K-dependent and mTORC1/2-dependent mechanisms. Immunohistochemical analysis of non-malignant and malignant prostate tissues offered in vivo support for our model that IGF-I–mediated activation of mTOR suppresses phosphorylation of the BMP-activated Smad transcription factors. Our results offer the first evidence that IGF-I signaling through mTORC1/2 is a key homeostatic regulator of BMP4 function in prostate epithelial cells, acting at two levels to repress both the proapoptotic and pro-oncogenic signals of BMP-activated Smads. We suggest that deregulation of this homeostatic control may be pivotal to the development and progression of prostate cancer, providing important implications and new potential targets for the therapeutic intervention of this malignancy. Cancer Res; 70(22); 9106–17. ©2010 AACR.
An evaluation of differences in hip external rotation strength and range of motion between female dancers and non-dancers
Authors: A Gupta, B Fernihough, G Bailey, P Bombeck, A Clarke, D Hopper
Journal: British Journal of Sports Medicine (2004)

Objectives: To evaluate the differences in hip external rotation (ER) strength and inner, outer, and total hip ER range of motion (ROM) between dancers and non-dancers and between left and right sides in each group. Methods: Seventy one subjects (34 dancers and 37 non-dancers) volunteered for this study. The strength (truncated range average torque (TRAT), work, and angle specific torque (AST)) of the hip external rotator muscle group, through the full available active hip ER ROM, was evaluated using concentric isokinetic (30°/s) testing on a KinCom dynamometer. Adjustment for lean body mass (LBM) was made for comparison of strength between groups. A two way repeated analysis of covariance was used to compare strength between groups. A two way repeated analysis of variance was used to compare strength between sides and ROM between groups and sides. Bonferroni correction was made for multiple analyses, and significance was accepted at p⩽0.05. Results: AST at 0°, 20°, 30°, and 40° of hip ER was greater in the dancers than the non-dancers (p⩽0.022). TRAT, work, AST 0° , AST 20° , and AST 30° of hip ER were all greater on the right side than the left (p = 0.007) in both groups. Dancers had greater inner ER ROM (p = 0.013) and less outer ER ROM than non-dancers (p⩽0.001). There was no difference in total ER ROM between groups (p = 0.133). The right side had greater inner ER (p⩽0.001) and total ER ROM (p⩽0.001) than the left in both groups. Conclusions: Ballet dancers have greater inner range, angle specific strength and inner range ER ROM, demonstrated by a shift in the dancers’ strength curves. This shift in the strength curve towards the inner range of hip ER may be an adaptive training response.
Arsenic: a potentially useful poison for Hedgehog-driven cancers
Authors: G. Praveen Raju
Journal: Journal of Clinical Investigation (2010)

Dysregulated Hedgehog (Hh) signaling has been implicated in a growing number of human cancers. To date, most antagonists of this signaling pathway that have been developed target the Hh receptor Smoothened. However, these are predicted to have minimal effect when the pathway is activated as a result of dysregulation downstream of this receptor. In this issue of the JCI, Beauchamp and colleagues provide preclinical evidence that arsenic trioxide, a drug FDA approved for the treatment of acute promyelocytic leukemia, inhibits the growth of Ewing sarcoma and medulloblastoma cells by targeting GLI family zinc finger (GLI) proteins, which are Hh signaling pathway components downstream of Smoothened.
Incorporating Quality of Evidence into Decision Analytic Modeling
Authors: R. Scott Braithwaite, Mark S. Roberts, Amy C. Justice
Journal: Annals of Internal Medicine (2007)

Our objective was to illustrate the effects of using stricter standards for the quality of evidence used in decision analytic modeling. We created a simple 10-parameter probabilistic Markov model to estimate the cost-effectiveness of directly observed therapy (DOT) for individuals with newly diagnosed HIV infection. We evaluated quality of evidence on the basis of U.S. Preventive Services Task Force methods, which specified 3 separate domains: study design, internal validity, and external validity. We varied the evidence criteria for each of these domains individually and collectively. We used published research as a source of data only if the quality of the research met specified criteria; otherwise, we specified the parameter by randomly choosing a number from a range within which every number has the same probability of being selected (a uniform distribution). When we did not eliminate poor-quality evidence, DOT improved health 99% of the time and cost less than $100 000 per additional quality-adjusted life-year (QALY) 85% of the time. The confidence ellipse was extremely narrow, suggesting high precision. When we used the most rigorous standards of evidence, we could use fewer than one fifth of the data sources, and DOT improved health only 49% of the time and cost less than $100 000 per additional QALY only 4% of the time. The confidence ellipse became much larger, showing that the results were less precise. We conclude that the results of decision modeling may vary dramatically depending on the stringency of the criteria for selecting evidence to use in the model.
Aetiology of extrahepatic portal vein thrombosis
Authors: B W M Spanier
Journal: Gut (2002)

I read with interest the article by Janssen et al (Gut 2001; 49 :720–4) regarding the aetiology and determinants of survival of extrahepatic portal vein thrombosis (EPVT). Among others, this retrospective study investigated the systemic risk factors for EPVT. We would like to add hyperhomocysteinaemia as a relatively new, not yet mentioned, risk factor.1–3 This is illustrated by a recent case in our clinic.

A 54 year old woman was hospitalised because of worsening of upper abdominal pain which started two weeks before admission and was continuously present. Her personal and family history for thromboembolic processes was uneventful and she did not smoke. She did not use vitamin supplements. One day prior to admission she was using the progesterone norethisterone (Primolut N) because of vaginal blood loss.

Combined portal-splenic vein thrombosis was diagnosed using colour Doppler ultrasonography and computed tomography. There were already some venous collaterals …
Untargeted Lipidomic Analysis in Chronic Obstructive Pulmonary Disease. Uncovering Sphingolipids
Authors: Eef D. Telenga, Roland F. Hoffmann, None Ruben t’Kindt, Susan J. M. Hoonhorst, Brigitte W. M. Willemse, Antoon J. M. van Oosterhout, Irene H. Heijink, Maarten van den Berge, Lucie Jorge, Pat Sandra, Dirkje S. Postma, Koen Sandra, Nick H. T. ten Hacken
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Cigarette smoke is the major risk factor in the development of chronic obstructive pulmonary disease (COPD). Lipidomics is a novel and emerging research field that may provide new insights in the origins of chronic inflammatory diseases, such as COPD.Objectives: To investigate whether expression of the sputum lipidome is affected by COPD or cigarette smoking.Methods: Lipid expression was investigated with liquid chromatography and high-resolution quadrupole time-of-flight mass spectrometry in induced sputum comparing smokers with and without COPD, and never-smokers. Changes in lipid expression after 2-month smoking cessation were investigated in smokers with and without COPD.Measurements and Main Results: More than 1,500 lipid compounds were identified in sputum. The class of sphingolipids was significantly higher expressed in smokers with COPD than in smokers without COPD. At single compound level, 168 sphingolipids, 36 phosphatidylethanolamine lipids, and 5 tobacco-related compounds were significantly higher expressed in smokers with COPD compared with smokers without COPD. The 13 lipids with a high fold change between smokers with and without COPD showed high correlations with lower lung function and inflammation in sputum. Twenty (glyco)sphingolipids and six tobacco-related compounds were higher expressed in smokers without COPD compared with never-smokers. Two-month smoking cessation reduced expression of 26 sphingolipids in smokers with and without COPD.Conclusions: Expression of lipids from the sphingolipid pathway is higher in smokers with COPD compared with smokers without COPD. Considering their potential biologic properties, they may play a role in the pathogenesis of COPD.
Job Performance Deficits Due to Depression
Authors: David Adler
Journal: American Journal of Psychiatry (2006)

Objective: This study assessed the relationship between depression severity and job performance among employed primary care patients. Method: In a 2001–2004 longitudinal observational study of depression’s affect on work productivity, 286 patients with DSM-IV major depressive disorder and/or dysthymia were compared to 93 individuals with rheumatoid arthritis, a condition associated with work disability, and 193 depression-free healthy control subjects. Participants were employed at least 15 hours per week, did not plan to stop working, and had no major medical comorbidities. Measures at baseline, six, 12, and 18 months included the Work Limitations Questionnaire for work outcomes, and the Patient Health Questionnaire-9 for depression. Results: At baseline and each follow-up, the depression group had significantly greater deficits in managing mental-interpersonal, time, and output tasks, as measured by the Work Limitations Questionnaire: The rheumatoid arthritis group’s deficits in managing physical job demands surpassed those of either the depression or comparison groups. Improvements in job performance were predicted by symptom severity. However, the job performance of even the “clinically improved” subset of depressed patients remained consistently worse than the control groups. Conclusions: Multiple dimensions of job performance are impaired by depression. This impact persisted after symptoms have improved. Efforts to reduce work-impairment secondary to depression are needed.
The role of social experience in advanced social understanding
Authors: Robin Banerjee
Journal: Behavioral and Brain Sciences (2004)

Carpendale & Lewis (C&L) rightly emphasise the central role of social interaction in the development of children's understanding of mind. Further support and justification for their theoretical focus are provided by research on advanced reasoning about socio-emotional and socio-motivational processes. Variability in social experience can explain both developmental change and within-age-group differences in such social understanding.
Impaired microRNA processing causes corpus luteum insufficiency and infertility in mice
Authors: Motoyuki Otsuka, Min Zheng, Masaaki Hayashi, Jing-Dwan Lee, Osamu Yoshino, Shengcai Lin, Jiahuai Han
Journal: Journal of Clinical Investigation (2008)

The microRNA (miRNA) processing enzyme Dicer1 is required for zygotic and embryonic development, but the early embryonic lethality of Dicer1 null alleles in mice has limited our ability to address the role of Dicer1 in normal mouse growth and development. To address this question, we used a mouse mutant with a hypomorphic Dicer1 allele (Dicer(d/d)) and found that Dicer1 deficiency resulted in female infertility. This defect in female Dicer(d/d) mice was caused by corpus luteum (CL) insufficiency and resulted, at least in part, from the impaired growth of new capillary vessels in the ovary. We found that the impaired CL angiogenesis in Dicer(d/d) mice was associated with a lack of miR17-5p and let7b, 2 miRNAs that participate in angiogenesis by regulating the expression of the antiangiogenic factor tissue inhibitor of metalloproteinase 1. Furthermore, injection of miR17-5p and let7b into the ovaries of Dicer(d/d) mice partially normalized tissue inhibitor of metalloproteinase 1 expression and CL angiogenesis. Our data indicate that the development and function of the ovarian CL is a physiological process that appears to be regulated by miRNAs and requires Dicer1 function.
Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis
Authors: Mark T. Gladwin
Journal: JAMA (2011)

<h3>Context</h3>Inhaled nitric oxide has shown evidence of efficacy in mouse models of sickle cell disease (SCD), case series of patients with acute chest syndrome, and 2 small placebo-controlled trials for treatment of vaso-occlusive pain crisis (VOC).<h3>Objective</h3>To determine whether inhaled nitric oxide gas reduces the duration of painful crisis in patients with SCD who present to the emergency department or hospital for care.<h3>Design, Setting, and Participants</h3>Prospective, multicenter, double-blind, randomized, placebo-controlled clinical trial for up to 72 hours of inhaled nitric oxide gas vs inhaled nitrogen placebo in 150 participants presenting with VOC of SCD at 11 centers between October 5, 2004, and December 22, 2008.<h3>Intervention</h3>Inhaled nitric oxide gas vs inhaled nitrogen placebo.<h3>Main Outcome Measures</h3>The primary end point was the time to resolution of painful crisis, defined by (1) freedom from parenteral opioid use for 5 hours; (2) pain relief as assessed by visual analog pain scale scores of 6 cm or lower (on 0-10 scale); (3) ability to walk; and (4) patient's and family's decision, with physician consensus, that the remaining pain could be managed at home.<h3>Results</h3>There was no significant change in the primary end point between the nitric oxide and placebo groups, with a median time to resolution of crisis of 73.0 hours (95% confidence interval [CI], 46.0-91.0) and 65.5 hours (95% CI, 48.1-84.0), respectively (P = .87). There were no significant differences in secondary outcome measures, including length of hospitalization, visual analog pain scale scores, cumulative opioid usage, and rate of acute chest syndrome. Inhaled nitric oxide was well tolerated, with no increase in serious adverse events. Increases in venous methemoglobin concentration confirmed adherence and randomization but did not exceed 5% in any study participant. Significant increases in plasma nitrate occurred in the treatment group, but there were no observed increases in plasma or whole blood nitrite.<h3>Conclusion</h3>Among patients with SCD hospitalized with VOC, the use of inhaled nitric oxide compared with placebo did not improve time to crisis resolution.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00094887
CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease
Authors: Nicolas Barnich, Frédéric A. Carvalho, Anne-Lise Glasser, Claude Darcha, Peter Jantscheff, Matthieu Allez, Harald Peeters, Gilles Bommelaer, Pierre Desreumaux, Jean-Frédéric Colombel, Arlette Darfeuille-Michaud
Journal: Journal of Clinical Investigation (2007)

The ileal mucosa of Crohn disease (CD) patients is abnormally colonized by adherent-invasive E. coli (AIEC) that are able to adhere to and invade intestinal epithelial cells. Here, we show that CD-associated AIEC strains adhere to the brush border of primary ileal enterocytes isolated from CD patients but not controls without inflammatory bowel disease. AIEC adhesion is dependent on type 1 pili expression on the bacterial surface and on carcinoembryonic antigen–related cell adhesion molecule 6 (CEACAM6) expression on the apical surface of ileal epithelial cells. We report also that CEACAM6 acts as a receptor for AIEC adhesion and is abnormally expressed by ileal epithelial cells in CD patients. In addition, our in vitro studies show that there is increased CEACAM6 expression in cultured intestinal epithelial cells after IFN-γ or TNF-α stimulation and after infection with AIEC bacteria, indicating that AIEC can promote its own colonization in CD patients.
Allergic bronchopulmonary aspergillosis in lung allograft recipients
Authors: JJ Egan, N Yonan, KB Carroll, AK Deiraniya, AK Webb, AA Woodcock
Journal: European Respiratory Journal (1996)

Following lung transplantation for end-stage cystic fibrosis, two male patients presented with shortness of breath, peripheral blood eosinophilia and segmental lung collapse. At bronchoscopy, each had bronchial mucous plugging containing Aspergillus fumigatus. This finding was associated with a systemic eosinophilia and skin test positivity to Aspergillus. Augmented steroid therapy resulted in the successful resolution of the symptoms. We believe that these are the first reported cases of allergic bronchopulmonary aspergillosis in lung allograft recipients.
Effect of perfusion pressure distal to a coronary stenosis on transmural myocardial blood flow.
Authors: R J Bache, J S Schwartz
Journal: Circulation (1982)

We tested the hypothesis that reductions of perfusion pressure distal to a flow-limiting coronary artery stenosis can directly impair perfusion of the subendocardial myocardium. Dogs were instrumented with an electromagnetic flowmeter probe and a variable occluder on the proximal left circumflex coronary artery. Coronary perfusion pressure was measured with a catheter distal to the occluder. Coronary autoregulation was abolished by intraarterial infusion of adenosine to produce maximal coronary vasodilation. The transmural distribution of myocardial blood flow was measured with radioactive microspheres during unimpeded arterial inflow, when the occluder was progressively narrowed to reduce distal coronary pressure to approximately 70%, 50% and 35% of the control coronary perfusion pressure, and during total coronary occlusion. Heart rate, left ventricular diastolic pressure and the fraction of coronary artery flow during systole remained constant throughout the study. Progressive reductions of coronary perfusion pressure were accompanied by direct reductions of the subendocardial/subepicardial blood flow ratio (r = 0.83). Examination of the relationship between myocardial blood flow and coronary perfusion pressure showed that blood flow decreased linearly with perfusion pressure, with flow ceasing at a positive pressure (zero-flow pressure). Blood flow data from four transmural myocardial layers from epicardium to endocardium showed that this zero-flow pressure increased progressively from 10 +/- 2.1 mm Hg in the subepicardium to 18 +/- 2.3 mm Hg in the subendocardium (p less than -.01). Consequently, as coronary pressure was reduced, the zero-flow pressure represented a progressively greater fraction of coronary pressure in the subendocardium than in the subepicardium. This effect appeared to account for the progressive redistribution of blood flow away from the subendocardium that occurred as coronary pressure was decreased. Myocardial vascular resistance did not change as a result of changes in coronary perfusion pressure.
Tick bite and early Lyme borreliosis
Authors: C. J. A. Duncan, G. Carle, R. A. Seaton
Journal: BMJ (2012)

A 48 year old man removed two ticks attached to his leg while walking in the Scottish Highlands. A week later he develops a rash and consults you worried about Lyme disease.

Epidemiology— Lyme borreliosis is the commonest tick-borne infection in the northern hemisphere. It is relatively uncommon in the UK overall (about 1200 cases in 2009), but marked geographical variation is observed. Risk is highest in rural forested areas and heathland such as the Highlands (incidence 56.35/100 000 in 2009-101), Lake District, and New Forest. Some 15–20% of infections are acquired in Europe or the US. There has been a steady rise in cases diagnosed in the UK over the past decade.2 3

Risk assessment— Ask about duration of hard bodied ( Ixodes ) tick attachment, with or without engorgement (fig 1⇓). Transmission of pathogenic Borrelia species is unlikely if ticks are attached for <24 hours and unengorged.2 4



Fig 1 Fully engorged female Ixodes ricinus (courtesy of Dr Alan S Bowman, University of Aberdeen)



Clinical features— Erythema migrans (fig 2 …
Specialist dermatology clinics for organ transplant recipients significantly improve compliance with photoprotection and levels of skin cancer awareness
Authors: F. Ismail, L. Mitchell, D. Casabonne, A. Gulati, R. Newton, C.M. Proby, C.A. Harwood
Journal: British Journal of Dermatology (2006)

Organ transplant recipients (OTRs) have 100-fold increased risk of developing squamous cell carcinomas. Cumulative exposure to ultraviolet radiation is the main risk factor and there is evidence that lack of dermatological surveillance may be responsible for poor levels of knowledge and photoprotection among OTRs.
Comparative Mortality Risk of Anemia Management Practices in Incident Hemodialysis Patients
Authors: M. Alan Brookhart
Journal: JAMA (2010)

Controversy exists about optimal management of anemia in end-stage renal disease.To compare the mortality risk of different dialysis center-level patterns of anemia management.Using data from Medicare's end-stage renal disease program (1999-2007), we characterized each US dialysis center's annual anemia management practice by estimating its typical use of erythropoiesis-stimulating agents (ESAs) and intravenous iron in hemodialysis patients within 4 hematocrit categories. We used Cox proportional hazards regression to correlate center-level patterns of ESA and iron use with 1-year mortality risk in 269,717 incident hemodialysis patients.One-year all-cause mortality.Monthly mortality rates were highest in patients with hematocrit less than 30% (mortality, 2.1%) and lowest for those with hematocrit of 36% or higher (mortality, 0.7%). After adjustment for baseline case-mix differences, dialysis centers that used larger ESA doses in patients with hematocrit less than 30% had lower mortality rates than centers that used smaller doses (highest vs lowest dose group: hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.90-0.97). Centers that administered iron more frequently to patients with hematocrit less than 33% also had lower mortality rates (highest vs lowest quintile, HR, 0.95; 95% CI, 0.91-0.98). However, centers that used larger ESA doses in patients with hematocrit between 33% and 35.9% had higher mortality rates (highest vs lowest quintile, HR, 1.07; 95% CI, 1.03-1.12). More intensive use of both ESAs and iron was associated with increased mortality risk in patients with hematocrit of 36% or higher. These findings persisted across a range of secondary analyses.Greater ESA and iron use were associated with decreased mortality risk at lower hematocrit levels, in which mortality rates are the highest. Although the overall mortality rate was lower at higher hematocrit levels, elevated mortality risk was associated with greater use of ESAs and iron in these patients.