tbuckley/cabot-search huggingface dataset:
Abstract P142: Smoking Cessation and Long-term Changes in Physical Activity Level: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Reto Auer, Eric Vittinghoff, Catharina Kiefe, Jared P Reis, Nicolas Rodondi, Yulia A Khodneva, Stefan G Kertesz, Jacques Cornuz, Mark J Pletcher
Journal: Circulation (2013)

Background Physical activity (PA) might improve health outcomes in smokers that quit smoking. However, longitudinal cohort studies have not addressed whether PA changes after smoking cessation. Aims We estimated PA trajectories for persons who quit smoking, adjusting for age trends, and relative to the expected trajectory if smoking had continued. Methods We used data from the CARDIA Study, a population-based study of African American and European American recruited at age 18-30 years in 1985/6 and followed over 25 years. Physical activity was self-reported during clinical visits at years 0 (1985/6), 2, 5, 7, 10, 15, 20 and 25 (2010/11); smoking status was reported each year (at visits or by phone, and imputed where missing). We used mixed linear models to estimate PA trajectories for persons who stopped smoking, relative to levels that would have been expected if smoking had continued. The analysis was stratified by race and sex, and controlled for fixed (education, age at smoking start) and time-varying...
PWE-196 Factors predicting mortality in acute severe gallstone pancreatitis
Authors: H Jenkins, L Ewan, Y Reddy, D Chang, A Kausar, C Harris, D Subar, S Lapsia, D Sebastian
Journal: Gut (2015)

<h3>Introduction</h3> The British Society of Gastroenterology (BSG) guidelines state that “Urgent therapeutic ERCP should be performed in patients with acute pancreatitis of suspected or proven gall stone aetiology who satisfy the criteria for predicted or actual severe pancreatitis”. The Cochrane review in 2012 suggested that ERCP does not affect morbidity and mortality and some patients with gallstones in the CBD will pass spontaneously. <h3>Aim</h3> The aim of this study was to assess predictive factors of mortality and the need for ERCP in severe gallstone pancreatitis. <h3>Method</h3> Data for patients who presented with acute severe biliary pancreatitis between January 2012 and April 2014 was collected. Data collected included predicted severity (Modified Glasgow score), liver function tests, white cell count, USS, ERCP and MRCP reports. Overall 90 day mortality was also recorded. <h3>Results</h3> 123 patients had predicted severe pancreatitis. On US 21 patients had a dilated CBD and 16 had CBD stone. 51% of patients (n = 63) had MRCP of which 22 patients had CBD stones. 60 patients had ERCP. In 17% (n = 21) no stone was found. 2 patients (3%) developed post ERCP pancreatitis.11% (n = 14)of the patients admitted with predicted severe acute pancreatitis died. On univariate analysis albumin (p = 0.003), alanine transaminase (ALT) (p= &lt;0.05) but not ERCP was significant in predicting mortality. High white cell count demonstrated a trend towards predicting mortality (p = 0.08) but did not reach statistical significance. On multivariate analysis albumin (p = 0.41) and ALT (p = 0.005) retained statistical significance. <h3>Conclusion</h3> Low serum albumin and ALT predicts mortality in severe GSP but ERCP does not and may precipitate further attacks of pancreatitis. Patients who have severe gallstone pancreatitis without deteriorating LFTs or cholangitis should have an MRCP to confirm stones in the CBD prior to ERCP. <h3>Disclosure of interest</h3> None Declared.
Second malignant neoplasms among survivors of pediatric Hodgkin disease treated with low-dose radiation (15–25.5 Gy) and chemotherapy
Authors: M. M. O'Brien, S. S. Donaldson, A. S. Whittemore, M. P. Link
Journal: Journal of Clinical Oncology (2009)

10003 Background: Second malignant neoplasms (SMN) are a known complication of Hodgkin disease (HD) treatment. While it is theorized that lower radiation doses may be associated with lower SMN risk, long-term follow-up of children treated with low-dose radiation is lacking. We report the occurrence of SMN among pediatric HD survivors treated at Stanford with chemotherapy and low-dose radiation from 1970 to 1990. Methods: Patients received 6 cycles of MOPP (mechlorethamine, vincristine, prednisone, procarbazine) with 15–25.5 Gy radiation ± 10 Gy boost or 3 MOPP and 3 ABVD cycles (doxorubicin, bleomycin, vinblastine, dacarbazine) with 15 Gy radiation ± 10 Gy boost. Follow-up was obtained through 9/1/2007. Standardized incidence ratios (SIRs) and absolute excess risk (AER) for SMN were calculated using the SEER9 database (1973–2004). Cumulative SMN incidence was determined by the Kaplan-Meier method. Univariate associations were evaluated with the chi-square test or t-test. Multivariate analysis was performed with Cox proportional hazards regression using chronological age as the time scale. Results: One hundred ten of 112 patients achieved remission; median follow-up is 20.6 years. Four patients developed secondary leukemia. Fifteen patients developed 17 secondary solid tumors (5 thyroid carcinomas, 6 breast carcinomas, 4 sarcomas, 1 bladder paraganglioma, 1 melanoma) at a median of 15.4 years. All solid tumors except the melanoma occurred within or at the margin of radiation fields, ranging in dose from 15–26.5 Gy. There were no cases of lung, gastric, or colorectal carcinoma. Cumulative incidence of any SMN is 17% (95%CI 10.5–26.7) at 20 years following HD diagnosis. The SIR for any SMN is 22.9 (95%CI 14.2–35) with an AER of 93.7 cases per 10,000 person-years. In univariate analysis, older age at HD diagnosis (&gt;11 years) and female gender were associated with SMN (p&lt;0.05). In multivariate analysis, there were no statistically significant associations. Conclusions: The incidence of SMN in pediatric HD survivors is elevated following treatment with chemotherapy and low-dose radiation. Sarcomas, breast, and thyroid carcinomas occurred with similar frequency and latency as found in studies of HD survivors who received high-dose radiation. No significant financial relationships to disclose.
Abstract 13600: RNAseq Analysis of Pulmonary Arterial Endothelial Cells from Patients with Idiopathic Pulmonary Arterial Hypertension Reveals Dysregulation of Angiogenic Factors
Authors: Christopher J Rhodes, Hogune Im, Rui Chen, Nancy Ferreira Tojais, Lingli Wang, Michael Snyder, Marlene Rabinovitch
Journal: Circulation (2012)

Pulmonary arterial (PA) endothelial cell (EC) dysfunction is a pathological feature in idiopathic PA hypertension (IPAH) reflected both in vulnerability to apoptosis and dysregulation of angiogenes...
BMJ introduces a fast track system for papers
Authors: J. McConnell, R. Smith
Journal: BMJ (1999)

Performance indicators for primary care groups Current indicators have been chosen for ease of collection rather than scientific validityEditor-McColl et al provide a welcome alternative 1 to performance indicators proposed by the NHS Executive and the Department of Health. 2 They have suggested a range of evidence based interventions which are likely to produce behaviour change at practice level.The proposed indicators are very different from the performance indicators in current use, which seem to have a political role at health authority level, often being used simply to search for poorly performing doctors.I have looked at the performance indicators that have been described in the literature, and in particular the scientific evidence underpinning them.Little evidence exists for the validity of using the common indicators in current use. 3 A consistent finding is that indicators are often chosen for their ease of collection rather than their scientific validity.The most commonly used indicators include uptake of cervical cytology, immunisation rates, and various prescribing indicators.I have found little published research showing the importance of a high or low indicator.This applies particularly when the indicators have been accepted as proxy measures of individual general practitioners' clinical competence.Others have also reviewed performance indicators and have identified additional areas that raise doubts about their validity. 4 5 The new indicators will need to be differentiated from the non-clinical indicators that are currently popular markers of clinical competence.In practice these often reflect historic support that has been provided for the practice rather than the competence of the individual general practitioner.Thus the proposed introduction of evidence based clinical indicators for primary care groups provides a more acceptable way forward.Although McColl et al's paper refers to cost effectiveness of proposed interventions, the likely timescale over which they will operate requires consideration, as it has an important implication for the primary care groups at which they are targeted.Although secondary and tertiary prevention may reduce morbidity and mortality over decades, the short term effects of the implementation of interventions will create upward pressure on costs, particularly prescribing costs.This issue should not present obstacles to the promotion of evidence based interventions at the level of primary care groups but must be taken into account when these groups and health authorities are funding health improvement plans.
Loss of heterozygosity in the chromosomal region 12p12-13 is very common in childhood acute lymphoblastic leukemia and permits the precise localization of a tumor-suppressor gene distinct from p27KIP1
Authors: H Cave, B Gerard, E Martin, C Guidal, I Devaux, J Weissenbach, J Elion, E Vilmer, B Grandchamp
Journal: Blood (1995)
STUDIES OF MOUSE POLYOMA VIRUS INFECTION
Authors: Wallace P. Rowe, Janet W. Hartley, Lloyd W. Law, Robert J. Huebner
Journal: The Journal of Experimental Medicine (1959)

Eight mouse colonies were surveyed for prevalence of antibody to mouse polyoma virus. Frequency of HI antibody varied from 0 to 84 per cent in adult mice in different colonies. Antibody was infrequent in mice less than 3 months of age, and increased in frequency with age. There was no evidence that infection was specific for particular mouse strains. The highest frequency of infection was found in colonies in which breeding mice are housed in proximity to mice inoculated with polyoma virus or passage tumors, and within an infected colony, the incidence of infection was greatest in rooms housing mice inoculated with polyoma virus. Mice from a colony free of antibody became infected when held in room or cage contact with virus-inoculated mice, but at very low rates except in mothers of inoculated litters. These results were interpreted as indicating that artificial contamination of the environment is an important factor in determining the prevalence of infection in the colonies observed. There was no correlation between polyoma infection and spontaneous leukemia in AK. mice.
Abstract 10109: Left Atrial Wall Thickness Rather Than Epicardial Fat Related With the Complex Fractionated Atrial Electrogram
Authors: Junbeom Park, Chul Hwan Park, Jin Wi, Jae-Sun Uhm, Hye-Jeong Lee, Jong-Youn Kim, Hui-Nam Pak, Moonhyoung Lee, Young Jin Kim Kim, Boyoung Joung
Journal: Circulation (2013)

Background: The mechanism of complex fractionated atrial electrogram (CFAE) in patients with atrial fibrillation (AF) remains controversial. This study investigated the relationship between CFAE, t...
TT virus levels in the plasma of infected individuals with different hepatic and extrahepatic pathologies
Authors: Mauro Pistello, F. Maggi, C. Fornai, M. L. Vatteroni, Giulia Freer, A. Morrica, F. Casula, Santino Marchi, A. Ricchiuti, P. Ciccorossi, M. Bendinelli
Journal: Hepatology (2000)
Role and therapeutic potential of vascular stem/progenitor cells in pathological neovascularisation during chronic portal hypertension
Authors: Ester Garcia-Pras, Javier Gallego, Laura Coch, Marc Mejias, Gonzalo Fernandez-Miranda, Ricardo Pardal, Jaime Bosch, Raul Mendez, Mercedes Fernandez
Journal: Gut (2016)

Objective Pathological neovascularisation is intimately involved in portal hypertension (PH). Here, we determined the contribution of vascular stem/progenitor cells (VSPCs) to neovessel growth in PH and whether the RNA-binding protein cytoplasmic polyadenylation element binding protein-4 (CPEB4) was behind the mechanism controlling VSPC function. Design To identify and monitor VSPCs in PH rats (portal vein-ligated), we used a combinatorial approach, including sphere-forming assay, assessment of self-renewal, 5-bromo-2′-desoxyuridine label retention technique, in vitro and in vivo stem/progenitor cell (SPC) differentiation and vasculogenic capability, cell sorting, as well as immunohistochemistry, immunofluorescence and confocal microscopy expression analysis. We also determined the role of CPEB4 on VSPC proliferation using genetically engineered mouse models. Results We demonstrated the existence in the mesenteric vascular bed of VSPCs displaying capability to form cellular spheres in suspension culture, self-renewal ability, expression of molecules commonly found in SPCs, slow-cycling features, in addition to other cardinal properties exhibited by SPCs, like capacity to differentiate into endothelial cells and pericytes with remarkable vasculogenic activity. Such VSPCs showed, after PH induction, an early switch in proliferation, and differentiated in vivo into endothelial cells and pericytes, contributing, structurally and functionally, to abnormal neovessel formation. Quantification of VSPC-dependent neovessel formation in PH further illustrated the key role played by VSPCs. We also demonstrated that CPEB4 regulates the proliferation of the activated VSPC progeny upon PH induction. Conclusions These findings demonstrate that VSPC-derived neovessel growth (ie, vasculogenesis) and angiogenesis cooperatively stimulate mesenteric neovascularisation in PH and identify VSPC and CPEB4 as potential therapeutic targets.
Environment may play significant role in multiple sclerosis
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Environmental factors may play a far greater role in the onset of multiple sclerosis (MS) than previously thought, shows a study that compared rates of the condition in immigrants to east London with those of their ancestral groups.

The prevalence of MS is far greater in white people than in other ethnic groups, but this study, published in the Multiple Sclerosis Journal ,1 showed that MS prevalence in minority ethnic groups in east London was far higher than in people in their ancestral countries, suggesting that …
Demonstration by Immunoelectrophoresis of Antigen in Human Myelogenous Leukemia&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Richard M. Hyde, Solomon Garb, A. James Bennett
Journal: JNCI Journal of the National Cancer Institute (1967)

Washed leukocytes from patients with acute and chronic myelogenous leukemia were injected into normal rabbits as well as rabbits given tolerance-inducing injections of normal human blood soon after birth. Other rabbits were immunized with normal human leukocytes. Serum harvested from the rabbits was doubly absorbed with pooled normal human leukocytes. The serum was tested by immunoelectrophoresis against pooled myelogenous leukemia leukocytes, leukemic leukocytes from individual patients, normal and leukemic bone marrow specimens, C-rcactivc protein, phytohemagglutinin, and heparin. The rabbit sera before absorption produced several sets of precipitin lines with leukemic or normal leukocytes. After absorption, however, sera from 42 of 105 rabbits still produced a precipitin line with pooled leukemic material, while none showed a reaction to the normal leukocyte preparation. None of the serum samples from 62 rabbits immunized with normal leukocytes and then absorbed in the same manner showed any precipitin lines when tested with leukemic material. The antigen was detected only in the leukocytic fraction of the blood and was present in both acute and chronic myelogenous leukemia leukocytes, but was not detected in the leukocytic fraction of blood from either patients with chronic lymphatic leukemia or normal individuals. The antigen appeared to be somewhat labile to storage at −20 C. Apparently the leukocytes in human myelogenous leukemia have an antigen which is absent or not ordinarily found in detectable quantities in normal or other leukemic materials tested.
Phase II study of weekly docetaxel in patients with recurrent or metastatic endometrial cancer, AGO Uterus-4
Authors: A. R. Günthert, S. Ackermann, L. Kiesel, E. Steiner, W. Schröder, O. Camara, P. Mallmann, G. Emons
Journal: Journal of Clinical Oncology (2005)

5083 Background: Patients with recurrent or metastatic endometrial cancer have a poor prognosis. It has been shown that taxanes are active in this situation. The Aim of this study was to evaluate the safety, toxicity and efficacy of docetaxel administered weekly as first line chemotherapy in patients with recurrent or metastatic endometrial cancer. Methods: Between December 2000 and March 2004 35 patients with recurrent or metastatic endometrial cancer without previous chemotherapy were enrolled to receive three 6-week cycles of docetaxel 35 mg/m2/week with 2-week breaks between the cycles. Eligible patients had histologically confirmed and bi-dimensional measurable manifestations of metastatic or recurrent endometrial cancer, which were not locally controllable by surgery or radiation. Therapy response was evaluated after every 6-week cycle. Toxicities were evaluated by the NCI common toxicity criteria. Results: 35 patients were evaluable for toxicity assessment, one patient presented with severe anaphylactic reaction during the second application of docetaxel and therapy was discontinued. Thus, 34 patients were assessable for response. Overall response rate was 20.6% (3 PR and 4 CR). Clinical benefit (SD + PR + CR) was 29.4% (4 SD). One year overall survival was 47% (16/34). Median TTP and OAS were 30.7 weeks and 51.8 weeks, respectively. No grade 3 or 4 hematological toxicities occurred. Grade 3 toxicities included 1 pt with mucositis, 3 pts with non specific pain, 3 pts with alopecia, 1 pt with onychodystrophy, and 1 case of severe epistaxis. Conclusion: Docetaxel weekly has a favourable toxicity profile, is well tolerated and, compared with other single agent therapies, shows encouraging activity in patients with advanced endometrial cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
NF-κB Activation Mediates Induction Of Anti-Inflammatory Adenosine A2A Receptors In iNKT Cells Of Sickle Cell Patients During Vaso-Occlusive Episodes and Upon Activation Of Cultured Human iNKT Cells
Authors: Joel Linden, Gene Lin, Jennifer C. Yu, Donna S. Neuberg, David G. Nathan, Joshua J. Field
Journal: Blood (2013)
The psoriasis-protective IL23R A/Glu381 allele promotes interleukin-23 unresponsiveness in human memory T helper (Th) 17 cells and impairs Th17 response in patients with psoriasis
Authors: Paola Di Meglio, Federica Villanova, Luca Napolitano, I. Tosi, M. Terranova Barberio, Rose Mak, S. Nutland, C Smith, Jonathan Barker, J. A. Todd, Frank Nestle
Journal: British Journal of Dermatology (2012)
The drug industry can help reduce cancer drug costs
Authors: Peter J Gilbar, Margot J Tannock
Journal: BMJ (2016)

Bach and colleagues’ article is particularly relevant because cancer drug expenditure is of major concern.1 Increasing the range of vial strengths is one way to contain spending. Unfortunately vial sharing is not always feasible. In Australia, many cancer centres outsource cancer drug manufacturing to accredited commercial suppliers, who, for high …
<i>p53</i>mRNA and p53 Protein Structures Have Evolved Independently to Interact with MDM2
Authors: Konstantinos Karakostis, Anand Ponnuswamy, Leïla T. S. Fusée, Xavier Bailly, Laurent Laguerre, Erin Worall, Borek Vojtesek, Karin Nylander, Robin Fåhraeus
Journal: Molecular Biology and Evolution (2016)

The p53 tumor suppressor and its key regulator MDM2 play essential roles in development, ageing, cancer, and cellular stress responses in mammals. Following DNA damage, MDM2 interacts with p53 mRNA in an ATM kinase-dependent fashion and stimulates p53 synthesis, whereas under normal conditions, MDM2 targets the p53 protein for degradation. The peptide- and RNA motifs that interact with MDM2 are encoded by the same conserved BOX-I sequence, but how these interactions have evolved is unknown. Here, we show that a temperature-sensitive structure in the invertebrate Ciona intestinalis (Ci) p53 mRNA controls its interaction with MDM2. We also show that a nonconserved flanking region of Ci-BOX-I domain prevents the p53-MDM2 protein–protein interaction. These results indicate that the temperature-regulated p53 mRNA–MDM2 interaction evolved to become kinase regulated in the mammalian DNA damage response. The data also suggest that the negative regulation of p53 by MDM2 via protein–protein interaction evolved in vertebrates following changes in the BOX-I flanking sequence.
Myeloid Derived Suppressor Cell Expansion Correlates With Increased regulatory T Cells In Myelodysplastic Syndrome
Authors: Astrid Olsnes Kittang, Shahram Kordasti, Kristoffer Evebø Sand, Pilar Perezabellan, Thomas Seidl, Kristin Paulsen Rye, Karen Marie Hagen, Geir Hallan, Austin G Kulasekararaj, Øystein Bruserud, Ghulam J. Mufti
Journal: Blood (2013)
ΔNp63α Silences a miRNA Program to Aberrantly Initiate a Wound-Healing Program That Promotes TGFβ-Induced Metastasis
Authors: Lidia Rodriguez Calleja, Camille Jacques, François Lamoureux, Marc Baud'huin, Marta Tellez Gabriel, Thibaut Quillard, Debashish Sahay, Pierre Perrot, Jerome Amiaud, Celine Charrier, Regis Brion, Fernando Lecanda, Franck Verrecchia, Dominique Heymann, Leif W. Ellisen, Benjamin Ory
Journal: Cancer Research (2016)

Primary cancer cell dissemination is a key event during the metastatic cascade, but context-specific determinants of this process remain largely undefined. Multiple reports have suggested that the p53 (TP53) family member p63 (TP63) plays an antimetastatic role through its minor epithelial isoform containing the N-terminal transactivation domain (TAp63). However, the role and contribution of the major p63 isoform lacking this domain, ΔNp63α, remain largely undefined. Here, we report a distinct and TAp63-independent mechanism by which ΔNp63α-expressing cells within a TGFβ-rich microenvironment become positively selected for metastatic dissemination. Orthotopic transplantation of ΔNp63α-expressing human osteosarcoma cells into athymic mice resulted in larger and more frequent lung metastases than transplantation of control cells. Mechanistic investigations revealed that ΔNp63α repressed miR-527 and miR-665, leading to the upregulation of two TGFβ effectors, SMAD4 and TβRII (TGFBR2). Furthermore, we provide evidence that this mechanism reflects a fundamental role for ΔNp63α in the normal wound-healing response. We show that ΔNp63α-mediated repression of miR-527/665 controls a TGFβ-dependent signaling node that switches off antimigratory miR-198 by suppressing the expression of the regulatory factor, KSRP (KHSRP). Collectively, these findings reveal that a novel miRNA network involved in the regulation of physiologic wound-healing responses is hijacked and suppressed by tumor cells to promote metastatic dissemination. Cancer Res; 76(11); 3236-51. ©2016 AACR.