tbuckley/cabot-search huggingface dataset:
Survival of MUTYH-Associated Polyposis Patients With Colorectal Cancer and Matched Control Colorectal Cancer Patients
Authors: M. Nielsen, L. N. van Steenbergen, N. Jones, S. Vogt, H. F. A. Vasen, H. Morreau, S. Aretz, J. R. Sampson, O. M. Dekkers, M. L. G. Janssen-Heijnen, F. J. Hes
Journal: JNCI Journal of the National Cancer Institute (2010)

MUTYH -associated polyposis is a recessively inherited disorder characterized by a lifetime risk of colorectal cancer that is up to 100%. Because specific histological and molecular genetic features of MUTYH -associated polyposis colorectal cancers might influence tumor behavior and patient survival, we compared survival between patients with MUTYH -associated polyposis colorectal cancer and matched control patients with colorectal cancer from the general population. In this retrospective multicenter cohort study from Europe, 147 patients with MUTYH -associated polyposis colorectal cancer were compared with 272 population-based control patients with colorectal cancer who were matched for country, age at diagnosis, year of diagnosis, stage, and subsite of colorectal cancer. Kaplan–Meier survival and Cox regression analyses were used to compare survival between patients with MUTYH -associated polyposis colorectal cancer and control patients with colorectal cancer. All statistical tests were two-sided. Five-year survival for patients with MUTYH -associated polyposis colorectal cancer was 78% (95% confidence interval [CI] = 70% to 84%) and for control patients was 63% (95% CI = 56% to 69%) (log-rank test, P = .002). After adjustment for differences in age, stage, sex, subsite, country, and year of diagnosis, survival remained better for MUTYH -associated polyposis colorectal cancer patients than for control patients (hazard ratio of death = 0.48, 95% CI = 0.32 to 0.72). In a European study cohort, we found statistically significantly better survival for patients with MUTYH -associated polyposis colorectal cancer than for matched control patients with colorectal cancer.
Quinine as a multidrug resistance inhibitor: a phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia
Authors: Eric Solary, Bernard Drenou, Lydia Campos, Patricia de Crémoux, Francine Mugneret, Philippe Moreau, Bruno Lioure, Annie Falkenrodt, Brigitte Witz, Marc Bernard, Mathilde Hunault-Berger, Martine Delain, José Fernandes, Christiane Mounier, François Guilhot, Francine Garnache, Christian Berthou, Fawzi Kara-Slimane, Jean-Luc Harousseau
Journal: Blood (2003)
Combination of the histone deacetylase inhibitor LBH589 and the hsp90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3
Authors: Prince George, Purva Bali, Srinivas Annavarapu, Anna Scuto, Warren Fiskus, Fei Guo, Celia Sigua, Gautam Sondarva, Lynn Moscinski, Peter Atadja, Kapil Bhalla
Journal: Blood (2004)
Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation
Authors: Mariana Toricelli, Fabiana HM Melo, Giovani B Peres, Débora CP Silva, Miriam G Jasiulionis
Journal: Molecular Cancer (2013)

Anoikis resistance is one of the abilities acquired along tumor progression. This characteristic is associated with metastasis development, since tumorigenic cells must survive independently of cell-matrix interactions in this process. In our laboratory, it was developed a murine melanocyte malignant transformation model associated with a sustained stressful condition. After subjecting melan-a melanocytes to 1, 2, 3 and 4 cycles of anchorage impediment, anoikis resistant cells were established and named 1C, 2C, 3C and 4C, respectively. These cells showed altered morphology and PMA independent cell growth, but were not tumorigenic, corresponding to pre-malignant cells. After limiting dilution of 4C pre-malignant cells, melanoma cell lines with different characteristics were obtained. Previous data from our group showed that increased Timp1 expression correlated with anoikis-resistant phenotype. Timp1 was shown to confer anchorage-independent growth capability to melan-a melanocytes and render melanoma cells more aggressive when injected into mice. However, the mechanisms involved in anoikis regulation by Timp1 in tumorigenic cells are not clear yet.The β1-integrin and Timp1 expression were evaluated by Western blotting and CD63 protein expression by flow cytometry using specific antibodies. To analyze the interaction among Timp1, CD63 and β1-integrin, immunoprecipitation assays were performed, anoikis resistance capability was evaluated in the presence or not of the PI3-K inhibitors, Wortmannin and LY294002. Relative expression of TIMP1 and CD63 in human metastatic melanoma cells was analyzed by real time PCR.Differential association among Timp1, CD63 and β1-integrins was observed in melan-a melanocytes, 4C pre-malignant melanocytes and 4C11- and 4C11+ melanoma cells. Timp1 present in conditioned medium of melanoma cells rendered melan-a melanocytes anoikis-resistant through PI3-K signaling pathway independently of Akt activation. In human melanoma cell lines, in which TIMP1 and beta-1 integrin were also found to be interacting, TIMP1 and CD63 levels together was shown to correlate significantly with colony formation capacity.Our results show that Timp1 is assembled in a supramolecular complex containing CD63 and β1-integrins along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway, independently of Akt phosphorylation. In addition, our data point TIMP1, mainly together with CD63, as a potential biomarker of melanoma.
Fibrin Sealing in Peptic Ulcer Bleeding: The Fate of the Clot
Authors: P Pescatore, C Verbeke, M Härle, B C Manegold
Journal: Endoscopy (1998)

The injection of fibrin tissue glue is a promising endoscopic method for hemostasis of peptic ulcer bleeding. So far, no clinical study has focused on the ulcer healing process after endoscopic fibrin injection.A morphological study was performed on all resection specimens from patients operated on between 1 January 1994 and 31 December 1996 for gastroduodenal ulcer bleeding with prior endoscopic injection of fibrin glue. The fibrin clot was characterized histologically for its size, location and aspect.Of 227 patients endoscopically treated with a double-lumen needle, 20 underwent resection. The interval between fibrin injection and resection ranged from 6 hours to 9 days. In 15 patients the ulcer was identified in the resection specimen. No fibrin remnants were detectable in three, sparse fibrin deposits were seen in eight and large amounts of fibrin were noted in the submucosa or subserosa in four specimens. With increasing time, the clot was gradually organized by phagocytes and angio-fibroblasts and was finally replaced by endogenous granulation tissue. An exuberant or tissue-destructive reaction did not appear.In this study, endoscopic fibrin sealing of bleeding ulcers resulted in appearance of a bland fibroblast-rich granulation tissue. The depth of fibrin glue injection is difficult to standardize with the aid of double-lumen needles.
Lost Productive Time and Cost Due to Common Pain Conditions in the US Workforce
Authors: Walter F. Stewart
Journal: JAMA (2003)

Common pain conditions appear to have an adverse effect on work, but no comprehensive estimates exist on the amount of productive time lost in the US workforce due to pain.To measure lost productive time (absence and reduced performance due to common pain conditions) during a 2-week period.Cross-sectional study using survey data from the American Productivity Audit (a telephone survey that uses the Work and Health Interview) of working adults between August 1, 2001, and July 30, 2002.Random sample of 28 902 working adults in the United States.Lost productive time due to common pain conditions (arthritis, back, headache, and other musculoskeletal) expressed in hours per worker per week and calculated in US dollars.Thirteen percent of the total workforce experienced a loss in productive time during a 2-week period due to a common pain condition. Headache was the most common (5.4%) pain condition resulting in lost productive time. It was followed by back pain (3.2%), arthritis pain (2.0%), and other musculoskeletal pain (2.0%). Workers who experienced lost productive time from a pain condition lost a mean (SE) of 4.6 (0.09) h/wk. Workers who had a headache had a mean (SE) loss in productive time of 3.5 (0.1) h/wk. Workers who reported arthritis or back pain had mean (SE) lost productive times of 5.2 (0.25) h/wk. Other common pain conditions resulted in a mean (SE) loss in productive time of 5.5 (0.22) h/wk. Lost productive time from common pain conditions among active workers costs an estimated 61.2 billion dollars per year. The majority (76.6%) of the lost productive time was explained by reduced performance while at work and not work absence.Pain is an inordinately common and disabling condition in the US workforce. Most of the pain-related lost productive time occurs while employees are at work and is in the form of reduced performance.
Identification of HIV patients with active pulmonary tuberculosis using urine based polymerase chain reaction assay
Authors: A. Aceti, S. Zanetti, M. S Mura, L. A Sechi, F. Turrini, F. Saba, S. Babudieri, F. Mannu, G. Fadda
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Despite the increased dissemination of tuberculosis among HIV infected patients, the diagnosis is difficult to establish. Traditional microbiological methods lack satisfactory sensitivity. We have developed a highly sensitive and specific nested polymerase chain reaction (PCR) capable of detecting <i>Mycobacterium tuberculosis</i> DNA in urine specimens and have used this test to examine urine specimens from HIV patients with active pulmonary tuberculosis. <h3>METHODS</h3> Urine specimens from 13 HIV infected patients with microbiologically proven active pulmonary tuberculosis, 10 AIDS patients with non-tuberculous mycobacterial infection (documented by blood culture), 53 AIDS patients with no evidence of mycobacterial disease, and 80 healthy subjects (25 with positive skin test to purified protein derivative) were tested for<i>M tuberculosis</i> using PCR, acid fast staining (AFS), and culture. <h3>RESULTS</h3> Of the urine specimens from patients with active tuberculosis, all tested positive by PCR, two by culture, and none by AFS. No reactivity was observed in urine specimens from patients with non-tuberculous mycobacterial infection. Of the 53 AIDS patients without mycobacterial infection, one had a positive urine PCR. Normal subjects were all negative. <h3>CONCLUSIONS</h3> Urine based nested PCR for <i>M tuberculosis</i> may be a useful test for identifying HIV patients with pulmonary tuberculosis.
Feasibility of 1 hour infliximab infusions
Authors: R F van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2005)

In conclusion, infliximab can be used safely in daily clinical practice, but both doctors and patients should be aware of the (infection) risks, especially in patients receiving a higher dose (.3 mg/kg) of infliximab, in order to anticipate and minimise these risks.
MYC-Induced Cancer Cell Energy Metabolism and Therapeutic Opportunities
Authors: Chi V. Dang, Anne Le, Ping Gao
Journal: Clinical Cancer Research (2009)

Although cancers have altered glucose metabolism, termed the Warburg effect, which describes the increased uptake and conversion of glucose to lactate by cancer cells under adequate oxygen tension, changes in the metabolism of glutamine and fatty acid have also been documented. The MYC oncogene, which contributes to the genesis of many human cancers, encodes a transcription factor c-Myc, which links altered cellular metabolism to tumorigenesis. c-Myc regulates genes involved in the biogenesis of ribosomes and mitochondria, and regulation of glucose and glutamine metabolism. With E2F1, c-Myc induces genes involved in nucleotide metabolism and DNA replication, and microRNAs that homeostatically attenuate E2F1 expression. With the hypoxia inducible transcription factor HIF-1, ectopic c-Myc cooperatively induces a transcriptional program for hypoxic adaptation. Myc regulates gene expression either directly, such as glycolytic genes including lactate dehydrogenase A (LDHA), or indirectly, such as repression of microRNAs miR-23a/b to increase glutaminase (GLS) protein expression and glutamine metabolism. Ectopic MYC expression in cancers, therefore, could concurrently drive aerobic glycolysis and/or oxidative phosphorylation to provide sufficient energy and anabolic substrates for cell growth and proliferation in the context of the tumor microenvironment. Collectively, these studies indicate that Myc-mediated altered cancer cell energy metabolism could be translated for the development of new anticancer therapies.
Response to Open Peer Commentaries on “Personhood and Neuroscience: Naturalizing or Nihilating?”: Getting Personal
Authors: Martha J Farah, Andrea S. Heberlein
Journal: The American Journal of Bioethics (2007)

Why do we have such strong intuitions that persons—as opposed to merely humans, thinking things, or sentient beings—exist? Why can't we identify the traits that determine personhood, or agree on wh...
Podocyte Depletion Causes Glomerulosclerosis
Authors: Bryan L. Wharram, Meera Goyal, Jocelyn E. Wiggins, Silja K. Sanden, Sabiha Hussain, Wanda E. Filipiak, Thomas L. Saunders, Robert C. Dysko, Kenji Kohno, Lawrence B. Holzman, Roger C. Wiggins
Journal: Journal of the American Society of Nephrology (2005)

Glomerular injury and proteinuria in diabetes (types 1 and 2) and IgA nephropathy is related to the degree of podocyte depletion in humans. For determining the causal relationship between podocyte depletion and glomerulosclerosis, a transgenic rat strain in which the human diphtheria toxin receptor is specifically expressed in podocytes was developed. The rodent homologue does not act as a diphtheria toxin (DT) receptor, thereby making rodents resistant to DT. Injection of DT into transgenic rats but not wild-type rats resulted in dose-dependent podocyte depletion from glomeruli. Three stages of glomerular injury caused by podocyte depletion were identified: Stage 1, 0 to 20% depletion showed mesangial expansion, transient proteinuria and normal renal function; stage 2, 21 to 40% depletion showed mesangial expansion, capsular adhesions (synechiae), focal segmental glomerulosclerosis, mild persistent proteinuria, and normal renal function; and stage 3, >40% podocyte depletion showed segmental to global glomerulosclerosis with sustained high-grade proteinuria and reduced renal function. These pathophysiologic consequences of podocyte depletion parallel similar degrees of podocyte depletion, glomerulosclerosis, and proteinuria seen in diabetic glomerulosclerosis. This model system provides strong support for the concept that podocyte depletion could be a major mechanism driving glomerulosclerosis and progressive loss of renal function in human glomerular diseases.
International Union of Pharmacology. XXXIII. Mammalian gamma -Aminobutyric AcidB Receptors: Structure and Function
Authors: N. G. Bowery
Journal: Pharmacological Reviews (2002)

The γ-aminobutyric acid<sub>B</sub>(GABA<sub>B</sub>) receptor was first demonstrated on presynaptic terminals where it serves as an autoreceptor and also as a heteroreceptor to influence transmitter release by suppressing neuronal Ca<sup>2+</sup> conductance. Subsequent studies showed the presence of the receptor on postsynaptic neurones where activation produces an increase in membrane K<sup>+</sup> conductance and associated neuronal hyperpolarization. (−)-Baclofen is a highly selective agonist for GABA<sub>B</sub> receptors, whereas the established GABA<sub>A</sub>receptor antagonists, bicuculline and picrotoxin, do not block GABA<sub>B</sub> receptors. The receptor is G<sub>i</sub>/G<sub>o</sub> protein-coupled with mixed effects on adenylate cyclase activity. The receptor comprises a heterodimer with similar subunits currently designated 1 and 2. These subunits are coupled via coiled-coil domains at their C termini. The evidence for splice variants is critically reviewed. Thus far, no unique pharmacological or functional properties have been assigned to either subunit or the variants. The emergence of high-affinity antagonists for GABA<sub>B</sub> receptors has enabled a synaptic role to be established. However, the antagonists have generally failed to establish the existence of pharmacologically distinct receptor types within the GABA<sub>B</sub> receptor class. The advent of GABA<sub>B1</sub> knockout mice has also failed to provide support for multiple receptor types.
PWE-239 The accuracy of pre bone mineral density frax scores in predicting need for treatment in patients with inflammatory bowel disease at risk of osteoporosis
Authors: R O Butcher, T Law, J K Limdi
Journal: Gut (2012)

<h3>Introduction</h3> Patients with Inflammatory Bowel disease (IBD) are at increased risk of Osteoporosis. Dual-Emission x-ray absorptiometry (DEXA) scans are frequently used to assess for osteoporosis and guide the need for preventative therapy. The WHO fracture risk assessment web tool can be used with or without bone mineral density (BMD) to calculate a FRAX score (10-year probability of major osteoporotic fracture and hip fracture). Patients are assigned, based on their pre-BMD FRAX outcome into low, intermediate (requiring BMD measurement) and high (requiring preventative therapy) risk groups in accordance with guidelines from the National Osteoporosis Guidelines Group (NOGG). Our study aimed to assess the accuracy of Pre-BMD FRAX scores in predicting need for preventative therapy in an IBD cohort. <h3>Methods</h3> We conducted a retrospective review of 95 patients who had undergone an index DEXA scan while attending IBD clinics at our hospital between 2007 and 2011. Clinical data including demographics, disease characteristics and therapy were obtained from case note and electronic patient record review. Pre and post-BMD FRAX assessment scores were calculated retrospectively. All IBD patients were considered to have secondary osteoporosis as a risk factor for FRAX calculation. Fifteen patients were excluded as they had previously received bisphosphonates. Pre-BMD FRAX risk status was compared with Post-BMD FRAX outcome to identify patients requiring and not requiring therapy. <h3>Results</h3> 80 patients (female 56) with a median age of 53.8 and mean disease duration of 14.1 years were analysed. 52 (65%) patients had Crohn9s disease, 27 (34%) patients ulcerative colitis and one patient had IBD-type unclassified (IBDU). Pre-BMD FRAX risk status (low and intermediate/high risk) had a sensitivity of 100% (95% CI 87.9 to 100), in correctly identifying 28 out of 28 patients as needing treatment. Specificity was low at 31% (95% CI 19.9 to 44.3) identifying only 16 out of 52 patients as not needing treatment. The positive predictive value was low (44%; 95% CI 32.3 to 55.9) with 28 out of 64 patients correctly identified as needing treatment but the negative predictive value was high (100%; 95% CI 80.6 to 100) as all 16 patients were correctly identified as not needing treatment. Specificity and PPV results were influenced by the intermediate risk Pre-BMD FRAX sub-group of which 33 (73%) required lifestyle advice and 12 (27%) required preventative therapy following post-BMD FRAX assessment. <h3>Conclusion</h3> In IBD patients, pre-BMD FRAX risk status is sensitive at predicting need for osteoporosis treatment and can help guide clinical decision making potentially avoiding DEXA scanning in IBD sub-groups. <h3>Competing interests</h3> None declared.
Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial
Authors: Kazutoshi Fukase, Mototsugu Kato, Shogo Kikuchi, Kazuhiko Inoue, Naomi Uemura, Shiro Okamoto, Shuichi Terao, Kenji Amagai, Shunji Hayashi, Masahiro Asaka
Journal: The Lancet (2008)
Antiviral Resistance and the Control of Pandemic Influenza
Authors: Marc Lipsitch, Ted Cohen, Megan Murray, Bruce R Levin
Journal: PLoS Medicine (2007)

Background The response to the next influenza pandemic will likely include extensive use of antiviral drugs (mainly oseltamivir), combined with other transmission-reducing measures. Animal and in vitro studies suggest that some strains of influenza may become resistant to oseltamivir while maintaining infectiousness (fitness). Use of antiviral agents on the scale anticipated for the control of pandemic influenza will create an unprecedented selective pressure for the emergence and spread of these strains. Nonetheless, antiviral resistance has received little attention when evaluating these plans. Methods and Findings We designed and analyzed a deterministic compartmental model of the transmission of oseltamivir-sensitive and -resistant influenza infections during a pandemic. The model predicts that even if antiviral treatment or prophylaxis leads to the emergence of a transmissible resistant strain in as few as 1 in 50,000 treated persons and 1 in 500,000 prophylaxed persons, widespread use of antivirals may strongly promote the spread of resistant strains at the population level, leading to a prevalence of tens of percent by the end of a pandemic. On the other hand, even in circumstances in which a resistant strain spreads widely, the use of antivirals may significantly delay and/or reduce the total size of the pandemic. If resistant strains carry some fitness cost, then, despite widespread emergence of resistance, antivirals could slow pandemic spread by months or more, and buy time for vaccine development; this delay would be prolonged by nondrug control measures (e.g., social distancing) that reduce transmission, or use of a stockpiled suboptimal vaccine. Surprisingly, the model suggests that such nondrug control measures would increase the proportion of the epidemic caused by resistant strains. Conclusions The benefits of antiviral drug use to control an influenza pandemic may be reduced, although not completely offset, by drug resistance in the virus. Therefore, the risk of resistance should be considered in pandemic planning and monitored closely during a pandemic.
P1062 3-YEAR TREATMENT WITH TENOFOVIR IN REAL-LIFE IS EFFECTIVE AND WELL TOLERATED IN CHB PATIENTS, INCLUDING THE ELDERLY AND PATIENTS WITH COMORBIDITIES
Authors: X. Causse, G.-P. Pageaux, F. Zoulim, D. Larrey, D. Ouzan, R. Truchi, A. Pauwels, D. Guyader, V. De Ledinghen, V. Tilliet, J.-F. Cadranel, C. Stern, O. Libert, P. Marcellin
Journal: Journal of Hepatology (2014)
RedeR: R/Bioconductor package for representing modular structures, nested networks and multiple levels of hierarchical associations.
Authors: Mauro AA Castro, Xin Wang, Michael NC Fletcher, Kerstin B Meyer, Florian Markowetz
Journal: Genome biology (2012)

Abstract Visualization and analysis of molecular networks are both central to systems biology. However, there still exists a large technological gap between them, especially when assessing multiple network levels or hierarchies. Here we present RedeR, an R/Bioconductor package combined with a Java core engine for representing modular networks. The functionality of RedeR is demonstrated in two different scenarios: hierarchical and modular organization in gene co-expression networks and nested structures in time-course gene expression subnetworks. Our results demonstrate RedeR as a new framework to deal with the multiple network levels that are inherent to complex biological systems. RedeR is available from http://bioconductor.org/packages/release/bioc/html/RedeR.html .