tbuckley/cabot-search huggingface dataset:
Gene Promoter Methylation in Plasma and Sputum Increases with Lung Cancer Risk
Authors: Steven A. Belinsky, Donna M. Klinge, Joseph D. Dekker, Mitzi W. Smith, Theresa J. Bocklage, Frank D. Gilliland, Richard E. Crowell, Daniel D. Karp, Christine A. Stidley, Maria A. Picchi
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Lung cancer is the leading cause of cancer mortality in the United States, due in part to the lack of a validated and effective screening approach for early detection. The prevalence for methylation of seven and three genes was examined in DNA from sputum and plasma, respectively, from women at different risk for lung cancer. Experimental Design: Lung cancer survivors (n = 56), clinically cancer-free smokers (n = 121), and never smokers (n = 74) comprised the study population. Plasma was collected from all three groups, whereas sputum was collected from lung cancer survivors and smokers. Results: Methylation was detected in plasma DNA from 10 of 74 women who never smoked. Prevalence for methylation of the p16 gene in plasma was highest in lung cancer survivors. Lung cancer survivors showed a significant increase in the odds of having at least one or more genes methylated in plasma (odds ratio, 3.6; 95% confidence interval, 1.9-9.1) than never smokers. The prevalence for methylation of the O6-methylguanine-DNA methyltransferase, ras effector homologue 1, death associated protein kinase, and PAX5α genes in sputum was significantly higher in lung cancer survivors compared with smokers. Lung cancer survivors had 6.2-fold greater odds (95% confidence interval, 2.1-18.5) for methylation of three or more genes in sputum compared with smokers. Methylation was more commonly detected in sputum than plasma for O6-methylguanine-DNA methyltransferase and ras effector homologue 1, but not p16, in lung cancer survivors. Conclusion: Concomitant methylation of multiple gene promoters in sputum is strongly associated with lung cancer risk.
Proteomic Portrait of Human Breast Cancer Progression Identifies Novel Prognostic Markers
Authors: Tamar Geiger, Stephen F. Madden, William M. Gallagher, Juergen Cox, Matthias Mann
Journal: Cancer Research (2012)

Breast cancer is the second leading cause of cancer death for women in the United States. Of the different subtypes, estrogen receptor-negative (ER(-)) tumors, which are ErbB2+ or triple-negative, carry a relatively poor prognosis. In this study, we used system-wide analysis of breast cancer proteomes to identify proteins that are associated with the progression of ER(-) tumors. Our two-step approach included an initial deep analysis of cultured cells that were obtained from tumors of defined breast cancer stages, followed by a validation set using human breast tumors. Using high-resolution mass spectrometry and quantification by Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC), we identified 8,750 proteins and quantified 7,800 of them. A stage-specific signature was extracted and validated by mass spectrometry and immunohistochemistry on tissue microarrays. Overall, the proteomics signature reflected both a global loss of tissue architecture and a number of metabolic changes in the transformed cells. Proteomic analysis also identified high levels of IDH2 and CRABP2 and low levels of SEC14L2 to be prognostic markers for overall breast cancer survival. Together, our findings suggest that global proteomic analysis provides information about the protein changes specific to ER(-) breast tumor progression as well as important prognostic information.
Suppression of in vitro Epstein-Barr virus infection. A new role for adult human T lymphocytes.
Authors: D A Thorley-Lawson, L Chess, J L Strominger
Journal: The Journal of Experimental Medicine (1977)

Studies have been performed on in vitro infection by Epstein-Barr virus (EBV) of subpopulations of human lymphocytes. B cells of adult peripheral or fetal cord blood transform with equal efficiency, whether assayed by DNA synthesis induction or by outgrowth of transformed lymphocytes. In contrast, unfractionated adult lymphocytes transform much less efficiently than those from fetal cord. Reconstitution experiments of different cell preparations indicated that this difference was due to a suppression of B-cell proliferation by adult Ig-negative lymphocytes which fetal Ig-negative lymphocytes were unable to perform. Separation of Ig-negative lymphocytes into various subpopulations revealed that the suppression was performed by T cells. Macrophages and null cells play little or no role in suppression. The relevance of this phenomenon to infection and recovery from EBV infection during and after infectious mononucleosis is discussed.
Active management of the third stage of labour
Authors: N. Aflaifel, A. D. Weeks
Journal: BMJ (2012)

Oxytocin is all you need

The original description of active management of the third stage of labour had three components—delivery of a prophylactic uterotonic drug, early cord clamping and cutting, and controlled cord traction.1 When randomised trials in the 1980s found that this package reduced the risk of severe postpartum haemorrhage by 70%,2 active management was adopted widely. It was thought to be especially important in low resource settings, where more than 20 000 deaths occur each year as a result of haemorrhage.3 In these settings, active management of the third stage has almost become a mantra for the safe motherhood movement.

But in the half century since active management was described, we have never known which component is the most important. Guidelines from around the world have varied widely in their selection of oxytocic agent, early cord clamping, cord traction, uterine massage, and cord drainage.4 Controlled cord traction became popular only when it was incorporated into the active management package in 1962, and, although there were no major randomised trials of cord traction, it was thought to decrease the incidence of postpartum haemorrhage and retained placenta.5

The required evidence on cord traction appeared in March this year.6 Gulmezoglu and colleagues from the World Health Organization’s maternal health research network conducted a large multicentre controlled trial to examine the effect of active management of the third stage of labour with and without …
Circulating Monocyte-Platelet Aggregates Are a More Sensitive Marker of In Vivo Platelet Activation Than Platelet Surface P-Selectin
Authors: Alan D. Michelson, Marc R. Barnard, Lori A. Krueger, C. Robert Valeri, Mark I. Furman
Journal: Circulation (2001)

Background Platelet surface P-selectin is considered the “gold standard” marker of platelet activation. Degranulated, P-selectin–positive platelets, however, aggregate with leukocytes in vitro and rapidly lose surface P-selectin in vivo. Methods and Results Flow cytometric tracking of autologous, biotinylated platelets in baboons enabled us to directly demonstrate for the first time in vivo that (1) infused degranulated platelets very rapidly form circulating aggregates with monocytes and neutrophils, and (2) 30 minutes after infusion of the degranulated platelets, the percentage of circulating monocytes aggregated with infused platelets persist at high levels, whereas the percentage of circulating neutrophils aggregated with infused platelets and the platelet surface P-selectin of nonaggregated infused platelets return to baseline. We therefore performed 2 clinical studies in patients with acute coronary syndromes. First, after percutaneous coronary intervention (n=10), there was an increased number of circulating monocyte-platelet (and to a lesser extent, neutrophil-platelet) aggregates but not P-selectin–positive platelets. Second, of 93 patients presenting to an Emergency Department with chest pain, patients with acute myocardial infarction (AMI) (n=9) had more circulating monocyte-platelet aggregates (34.2±10.3% [mean±SEM]) than patients with no AMI (n=84, 19.3±1.4%, P &lt;0.05) and normal control subjects (n=10, 11.5±0.8%, P &lt;0.001). Circulating P-selectin–positive platelets, however, were not increased in chest pain patients with or without AMI. Conclusions As demonstrated by 3 independent means (in vivo tracking of activated platelets in baboons, human coronary intervention, and human AMI), circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin.
Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts
Authors: Weronica E Ek, Anna Reznichenko, Stephan Ripke, Beate Niesler, Marco Zucchelli, Natalia V Rivera, Peter T Schmidt, Nancy L Pedersen, Patrik Magnusson, Nicholas J Talley, Elizabeth G Holliday, Lesley Houghton, Maria Gazouli, George Karamanolis, Gudrun Rappold, Barbara Burwinkel, Harald Surowy, Joseph Rafter, Ghazaleh Assadi, Ling Li, Evangelia Papadaki, Dario Gambaccini, Santino Marchi, Rocchina Colucci, Corrado Blandizzi, Raffaella Barbaro, Pontus Karling, Susanna Walter, Bodil Ohlsson, Hans Tornblom, Francesca Bresso, Anna Andreasson, Aldona Dlugosz, Magnus Simren, Lars Agreus, Greger Lindberg, Guy Boeckxstaens, Massimo Bellini, Vincenzo Stanghellini, Giovanni Barbara, Mark J Daly, Michael Camilleri, Mira M Wouters, Mauro D'Amato
Journal: Gut (2014)

<h3>Objective</h3> IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. <h3>Design</h3> We conducted a GWA study (GWAS) of IBS in a general population sample of 11 326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. <h3>Results</h3> One locus at 7p22.1, which includes the genes <i>KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein),</i> showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10<sup>−6</sup> in a meta-analysis of all datasets. Several SNPs in this region are associated with <i>cis</i> effects on <i>KDELR2</i> expression, and a trend for increased mucosal <i>KDLER2</i> mRNA expression was observed in IBS cases compared with controls. <h3>Conclusions</h3> Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.
CAPSULATION OF PNEUMOCOCCUS WITH SOLUBLE CELL WALL-LIKE POLYSACCHARIDE
Authors: Gerald Schiffman, Donald L. Bornstein, Robert Austrian
Journal: The Journal of Experimental Medicine (1971)

Methods are described for the separation of the C or cell wall polysaccharide from the C(s) or soluble C-like capsular polysaccharide of C(s) pneumococcal strains. Immunologic analysis has shown that both the C and C(s) polysaccharides of a variety of pneumococcal strains are heterogeneous and that the dissimilarities appear to reside in the mucopeptide portion of the molecule or in the region of its attachment to the teichoic acid moiety of the molecule rather than in the teichoic acid fraction. Differences of the type described have been observed in the C polysaccharides of wild-type capsulated strains of several types, in those of independently isolated noncapsulated variants derived from a single strain of a given capsular type, and in the C and C(s) polysaccharides of spontaneous mutant or transformed strains of pneumococci producing capsules of C(s) polysaccharide.
LPA Receptor Heterodimerizes with CD97 to Amplify LPA-Initiated RHO-Dependent Signaling and Invasion in Prostate Cancer Cells
Authors: Yvona Ward, Ross Lake, Juan Juan Yin, Christopher D. Heger, Mark Raffeld, Paul K. Goldsmith, Maria Merino, Kathleen Kelly
Journal: Cancer Research (2011)

Abstract CD97, an adhesion-linked G-protein–coupled receptor (GPCR), is induced in multiple epithelial cancer lineages. We address here the signaling properties and the functional significance of CD97 expression in prostate cancer. Our findings show that CD97 signals through Gα12/13 to increase RHO-GTP levels. CD97 functioned to mediate invasion in prostate cancer cells, at least in part, by associating with lysophosphatidic acid receptor 1 (LPAR1), leading to enhanced LPA-dependent RHO and extracellular signal–regulated kinase activation. Consistent with its role in invasion, depletion of CD97 in PC3 cells resulted in decreased bone metastasis without affecting subcutaneous tumor growth. Furthermore, CD97 heterodimerized and functionally synergized with LPAR1, a GPCR implicated in cancer progression. We also found that CD97 and LPAR expression were significantly correlated in clinical prostate cancer specimens. Taken together, these findings support the investigation of CD97 as a potential therapeutic cancer target. Cancer Res; 71(23); 7301–11. ©2011 AACR.
Large ongoing measles outbreak in a religious community in the Netherlands since May 2013
Authors: M J Knol, A T Urbanus, E M Swart, L Mollema, W L Ruijs, R S van Binnendijk, M J te Wierik, H E de Melker, A Timen, S J Hahné
Journal: Eurosurveillance (2013)

Binary file ES_Abstracts_Final_ECDC.txt matches
Retraction: Overexpression of Proteins HMGA1 Induces Cell Cycle Deregulation and Apoptosis in Normal Rat Thyroid Cells
Authors: Monica Fedele, Giovanna Maria Pierantoni, Maria Teresa Berlingieri, Sabrina Battista, Gustavo Baldassarre, Nikhil Munshi, Monica Dentice, Dimitris Thanos, Massimo Santoro, Giuseppe Viglietto, Alfredo Fusco
Journal: Cancer Research (2018)

The high mobility group (HMG) proteins (HMGA1a, HMGA1b, and HMGA2) bind to DNA and interact with various transcriptional factors. Therefore, they play an important role in chromatin organization. HMGA protein expression is low in normal adult tissues, but abundant during embryonic development and in several experimental and human tumors. Blockage of HMGA expression inhibits the transformation of rat thyroid PC Cl 3 cells treated with oncogene-carrying retroviruses, thus implicating HMGA in rat thyroid transformation. To better understand the role of HMGA and to establish whether its up-regulated expression is sufficient to induce the transformed phenotype, we generated PC Cl 3 cells that overexpress the protein. We demonstrate that HMGA1b protein overexpression does not transform normal rat thyroid PC Cl 3 cells, but it deregulates their cell cycle: cells enter S-phase earlier and the G(2)-M transition is delayed. HMGA1-overexpressing cells undergo apoptosis through a pathway involving caspase-3 activation, probably consequent to the conflict between mitogenic pressure and the inability to proceed through the cell cycle. Using various HMGA1b gene mutations, we found that the third AT-hook domain and the acetylation site K60 are the protein regions required for induction of apoptosis in PC Cl 3 cells. In conclusion, although HMGA1 protein overexpression is associated with the malignant phenotype of rat and human thyroid cells, it does not transform normal thyroid cells in culture but leads them to programmed cell death.
Perspectives of Patients on the Utility of Electronic Patient-Reported Outcomes on Cancer Care
Authors: Hsien Seow, Susan King, Esther Green, José Pereira, Carol Sawka
Journal: Journal of Clinical Oncology (2011)

TO THE EDITOR: We read with great interest the pair of original articles by Cleeland et al and Berry et al that focused on innovative strategies to engage clinicians in the integration of electronic patientreported outcomes into a clinical workflow. These articles demonstrated that flagging symptom and quality-of-life issues by using automated reporting systems can help to engage physicians to control symptoms and increase discussion of these issues at patient visits. However, there is a dearth of evidence from the perspective of the patient that electronic symptom assessment improves patient care. In Ontario, Canada, cancer centers have used an electronic version of the Edmonton Symptom Assessment System (ESAS) to measure symptom burden since 2007. In the winter of 2010, Cancer Care Ontario conducted a week-long, paper-based, patient survey in all 14 regional cancer centers that was given to all patients who had completed the ESAS at least once. A total of 2,921 patients completed the survey, and 87% of respondents strongly agreed or somewhat agreed that the “ESAS was important to complete because it helped the health care team to know what symptoms [they] were having and how severe they were.” In addition, 79% of respondents strongly agreed or somewhat agreed that “my health care team takes my ESAS symptom scores into account when they are deciding how to treat me,” whereas 6% of respondents somewhat disagreed or strongly disagreed with that statement. Last, 79% of respondents rated that their “pain and other symptoms have been controlled to a comfortable level” always or most of the time compared with 8% of respondents who rated this as rarely or never occurring. These results indicated that patients, themselves, feel that standardized symptom assessments, which were completed mostly electronically, positively influenced the care they received. Finally, Cleeland et al and Berry et al highlighted the potential value of automated symptom alerts to care improvement, but many clinicians struggle with what care plans to implement after symptom issues have been identified. To address that issue, Cancer Care Ontario has developed evidenced-based guides and algorithms on how to manage, in accordance with the best evidence, when certain ESAS symptoms reach a particular threshold. The guides are also available as a mobile application (iPhone [Apple, Cupertino, CA] and Windows Phone 7 [Microsoft, Redmond, WA]). They can be downloaded for free at: http://www.cancercare.on.ca/toolbox/symptools/.
Epoxyeicosatrienoic acids are involved in the C70 fullerene derivative–induced control of allergic asthma
Authors: Sarah K. Norton, Dayanjan S. Wijesinghe, Anthony Dellinger, Jamie Sturgill, Zhiguo Zhou, Suzanne Barbour, Charles Chalfant, Daniel H. Conrad, Christopher L. Kepley
Journal: Journal of Allergy and Clinical Immunology (2012)
Successful treatment of invasive pulmonary aspergillosis in chronic granulomatous disease with orally administered itraconazole suspension.
Authors: D A Spencer, P John, S R Ferryman, P H Weller, P Darbyshire
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

A 3-yr-old boy with known chronic granulomatous disease presented with a left-sided chest wall mass. Extensive intrathoracic and extrathoracic aspergillosis was confirmed by CT scan-guided percutaneous biopsy. Initially, he was treated intravenously with liposomal amphotericin and subcutaneous gamma-interferon, but his clinical condition deteriorated over 7 wk of treatment. The amphotericin was therefore discontinued, and itraconazole in an oral suspension was begun. There was progressive clinical improvement after 3 months of this regime, and marked radiologic clearing was apparent after 8 months of treatment. A multicenter trial of this mode of therapy in patients with invasive aspergillosis is indicated.
TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function
Authors: Fernando Gómez-Herreros, Janneke H M Schuurs-Hoeijmakers, Mark McCormack, Marie T Greally, Stuart Rulten, Rocío Romero-Granados, Timothy J Counihan, Elijah Chaila, Judith Conroy, Sean Ennis, Norman Delanty, Felipe Cortés-Ledesma, Arjan P M de Brouwer, Gianpiero L Cavalleri, Sherif F El-Khamisy, Bert B A de Vries, Keith W Caldecott
Journal: Nature Genetics (2014)
Minister admits NHS commissioning is weak but claims it is improving
Authors: A. O'Dowd
Journal: BMJ (2010)

The skills of some primary care trusts at commissioning services in the NHS are weak but are improving and have to develop because there is no alternative, MPs have been told.

The health minister Mike O’Brien, giving evidence on 4 February to the parliamentary health select committee, admitted that commissioning by primary care trusts was generally weak, which had led the government to launch its “world class commissioning” drive to improve standards.

MPs on the committee asked the minister as part of their inquiry into commissioning why performance in this area was still weak after several years.

Mr O’Brien said: “We’d be the first to say that world class commissioning …
Nanoparticle-Mediated Systemic Delivery of siRNA for Treatment of Cancers and Viral Infections
Authors: Mohamed Shehata Draz, Binbin Amanda Fang, Pengfei Zhang, Zhi Hu, Shenda Gu, Kevin C. Weng, Joe W. Gray, Fanqing Frank Chen
Journal: Theranostics (2014)

RNA interference (RNAi) is an endogenous post-transcriptional gene regulatory mechanism, where non-coding, double-stranded RNA molecules interfere with the expression of certain genes in order to silence it. Since its discovery, this phenomenon has evolved as powerful technology to diagnose and treat diseases at cellular and molecular levels. With a lot of attention, short interfering RNA (siRNA) therapeutics has brought a great hope for treatment of various undruggable diseases, including genetic diseases, cancer, and resistant viral infections. However, the challenge of their systemic delivery and on how they are integrated to exhibit the desired properties and functions remains a key bottleneck for realizing its full potential. Nanoparticles are currently well known to exhibit a number of unique properties that could be strategically tailored into new advanced siRNA delivery systems. This review summarizes the various nanoparticulate systems developed so far in the literature for systemic delivery of siRNA, which include silica and silicon-based nanoparticles, metal and metal oxides nanoparticles, carbon nanotubes, graphene, dendrimers, polymers, cyclodextrins, lipids, hydrogels, and semiconductor nanocrystals. Challenges and barriers to the delivery of siRNA and the role of different nanoparticles to surmount these challenges are also included in the review.