tbuckley/cabot-search huggingface dataset:
Abstract 1256: Profiling protein-coding RNA and thousands of large non-coding RNAs from nanogram amounts of total RNA using a single microarray design
Authors: Anne Bergstrom Lucas, Vinayak Kulkarni, Emily LeProust, Maithreyan Srinivasan, Stephanie Fulmer-Smentek
Journal: Cancer Research (2012)

Abstract Large intergenic non-coding RNAs (lincRNAs) are emerging as key regulators of diverse cellular processes, yet determining the function of individual lincRNAs remains challenging. Recently, more than 8,000 human lincRNAs were annotated and cataloged from more than 4 billion RNA-Seq reads across 24 tissues and cell types by scientists at the Broad Institute of MIT and Harvard. Data from this project indicates that lincRNA expression is highly tissue-specific as compared to protein coding gene expression. As researchers continue to investigate the function of lincRNAs, there is a need for tools that can rapidly and accurately measure the expression of the recently annotated lincRNAs along with mRNA expression. We have previously developed and recently updated the content of the human SurePrint G3 microarrays so that they are comprised of all known protein-coding mRNAs and lincRNAs, to enable systematic profiling and simultaneous detection of coding and non-coding gene expression from a single sample. To demonstrate the utility of the new microarray design we used low nanogram amounts RNA from matched tumor and adjacent normal tissues to produce cyanine-labeled cRNA. The labeled cRNA was applied to the microarrays to detect differences in coding and non-coding gene expression profiles. Using the GeneSpring GX software we are able to identify differentially expressed lincRNAs and protein-coding RNAs in the tumor and normal samples in less than two days. Comparisons of probe signals from technical replicate samples demonstrated high reproducibility with wide dynamic ranges and high sensitivity. Data from the microarrays correlates well with whole transcriptome sequencing of the same matched tumor/normal samples. Using this approach we show that lincRNA expression coincides with key genes known to regulate biological processes involved in cancer progression and this work demonstrates how profiling mRNA and lincRNA from matched tumor and adjacent normal samples can enable researchers to further define the role of lincRNAs in gene regulation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1256. doi:1538-7445.AM2012-1256
A mobility gradient in the organization of vertebrate movement: The perception of movement through symbolic language
Authors: Ilan Golani
Journal: Behavioral and Brain Sciences (1992)

Abstract Ordinary language can prevent us from seeing the organization of whole-animal movement. This may be why the search for behavioral homologies has not been as fruitful as the founders of ethology had hoped. The Eshkol-Wachman (EW) movement notational system can reveal shared movement patterns that are undetectable in the kinds of informal verbal descriptions of the same behaviors that are in current use. Rules of organization that are common to locomotor development, agonistic and exploratory behavior, scent marking, play, and dopaminergic drug-induced stereotypies in a variety of vertebrates suggest that behavior progresses along a “mobility gradient” from immobility to increasing complexity and unpredictability. A progression in the opposite direction, with decreasing spatial complexity and increased stereotypy, occurs under the influence of the nonselective dopaminergic drugs apomorphine and amphetamine and partly also the selective dopamine agonist quinpirole. The behaviors associated with the mobility gradient appear to be mediated by a family of basal ganglia-thalamocortical circuits and their descending output stations. Because the small number of rules underlying the mobility gradient account for a large variety of behaviors, they may be related to the specific functional demands on these neurological systems. The EW system and the mobility gradient model should prove useful to ethologists and neurobiologists.
Waterhouse–Friderichsen Syndrome
Authors: T Schoeller, E Schmutzhard
Journal: New England Journal of Medicine (2001)

Figure 1. Two hours after the onset of fever and malaise, a 15-year-old boy began to have tachycardia and tachypnea and became unconscious. He was taken to the intensive care unit, where he was found to be in septic shock (pulse, 180; blood pressure, 70/45 mm Hg; temperature, 40.2°C; and partial-thromboplastin time, 90 seconds). He had bullous lesions about the elbow and confluent petechial and purpuric lesions on his face, arms, and legs (Panel A). His hands and feet were cool and cyanotic. He had no signs of meningeal irritation. He was intubated, placed on cardiopulmonary support, and given large . . .
Abstract 1130: mPGES-1 drives the oncogenic potential of EGFR signaling
Authors: Federica Finetti, Terzuoli Erika, Sandra Donnini, Antonio Giachetti, Marina Ziche
Journal: Cancer Research (2011)

Abstract Prostaglandins, mostly PGE-2, have assumed an important role in cancer biology. Regarding of PGE-2 production, recent investigations have focused on PGE-2 synthases (mPGEs-1, mPGEs-2 and cPGEs), specifically on mPGEs-1, the only inducible enzyme among those so far identified in cells. Whereas cPGEs and mPGEs-2 are constitutively expressed at relatively low levels, mPGEs-1 is highly inducible by pro-inflammatory stimuli. mPGEs-1 upregulation has been detected in many epithelial tumors, and its silencing has been reported to reduce preneoplastic lesions. Despite the evidence linking mPGEs-1 and tumorigenesis, most studies investigating the inducible nature of the enzyme in cultured cells have been performed using a variety of inflammatory stimuli, while little is known about the behavior of the enzyme in tumor cells challenged with oncogenic stimuli. In this work we investigated mPGES-1 regulation in cultured epithelial tumor cells exposed to epidermal growth factor (EGF), an oncogene product which, through its receptor, EGF-receptor, is responsible for tumorigenisis in a wide array of solid tumors. We used three cell lines, representative of colon (HT-29), epidermoid (A431) and lung (A549) tumors, examining the expression of mPGEs-1 protein following EGF-receptor activation by EGF. We found that cells responded to EGF-receptor stimulation with a transient surge of the transcription factor Egr-1, its translocation from cytosol to necleus, an increase of mPGEs-1 mRNA and protein, as well as, an enhanced PGE-2 formation. These changes were suppressed by silencing Egr-1 and by EGF-receptor blockade or by inhibitors of the EGF-receptor-dependent mediators, such as MAP-kinase, ERK1/2. Moreover, cell activation through EGF-receptor induced a tumorigenic phenotype, detectable by clonogenic assay, which regressed when mPGEs-1 was silenced. We also explored the effect of inhibiting the EGF-receptor in A431 xenografts on mPGEs-1 expression and tumor growth, finding a parallel decline of both. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1130. doi:10.1158/1538-7445.AM2011-1130
Abstract 1286: FANCA binds to nucleic acids and stimulates endonuclease activity of FEN1.
Authors: Liangyue Qian, Fenghua Yuan, Paola Rodriguez-Tello, Xinliang Zhao, Limin Song, Gennaro D'Urso, Chaitanya Jain, Yanbin Zhang
Journal: Cancer Research (2013)

Abstract Fanconi anemia is a rare autosomal recessive or X-linked genetic disease characterized by progressive bone marrow failure, various developmental anomalies, and cancer predisposition. Fanconi anemia complementation group A (FANCA) gene is one of the 15 disease-causing genes and has been found to be mutated in ∼60% of Fanconi anemia patients. Except for its constituent role in the ubiquitin ligase of the Fanconi anemia core complex, no other biochemical activity has been identified thus far. Using purified protein, we observed that human FANCA has intrinsic affinity to nucleic acids. FANCA binds to both single-stranded and double-stranded DNA; however, its affinity to single-stranded DNA is dramatically higher. FANCA also binds to RNA with an intriguingly higher affinity than its DNA counterpart. A patient-derived FANCA truncation mutant, Q772X, has diminished affinity to both DNA and RNA. On the contrary, the complementing C-terminal fragment of Q772X, C772-1455, retains the differentiated nucleic acids binding activity (RNA&amp;gt;ssDNA&amp;gt;dsDNA), indicating that the nucleic acids binding domain of FANCA is primarily located at its C-terminus. Using DNA and RNA ladders, we determined that the minimum numbers of nucleotides required for FANCA recognition are ∼30 for both DNA and RNA. By testing the affinity between FANCA and a variety of DNA structures, we found that a 5’ flap or tail on DNA facilitates its interaction with FANCA. In addition, we observed that FANCA greatly stimulates the endonuclease activity of flap endonuclease 1 (FEN1), which processes 5’ flap structures. Our study reported that purified human FANCA binds to nucleic acids with strong preference for single-stranded forms. Our finding suggests that FANCA FANCA may participate in maintenance of replication forks by regulating removal of Okazaki fragment during maturation of lagging strand replication. Citation Format: Liangyue Qian, Fenghua Yuan, Paola Rodriguez-Tello, Xinliang Zhao, Limin Song, Gennaro D'Urso, Chaitanya Jain, Yanbin Zhang. FANCA binds to nucleic acids and stimulates endonuclease activity of FEN1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1286. doi:10.1158/1538-7445.AM2013-1286
817 RANDOMISED CONTROLLED TRIAL OF 24 AND 48 WEEKS OF PEGYLATED INTERFERON alfa 2a PLUS RIBAVIRIN IN PATIENTS WITH GENOTYPE 3 HCV AND CIRRHOSIS
Authors: G. Foster, D. Shoeb, A. Weatherall, S. Moreea, J. Vilar, D. Freshwater, S. Ryder, G. Alexander, D. Forton, P. Mills
Journal: Journal of Hepatology (2013)
An Unusual Perfusion Pattern of Hepatic Metastases
Authors: JAMES D. VANHOOSE, EDWARD B. MOODY, LUIS ARRAZOLA
Journal: Clinical Nuclear Medicine (1997)

A 47-year-old woman with hepatic metastases from colon adenocarcinoma underwent hepatic arterial perfusion scintigraphy (HAPS) to confirm catheter placement before initiation of intra-arterial chemotherapy. After Tc-99m macroaggregated albumin (MAA) infusion, two discrete foci of activity were seen within the right upper quadrant, but the liver parenchyma was not delineated. A Tc-99m albumin colloid scan localized the foci within the right lobe of the liver and defined the liver parenchyma not seen on the MAA study. The foci of MAA deposition correlated with CT evidence of hepatic metastases. The unusual pattern of activity seen on HAPS reflects altered hepatic arterial hemodynamics secondary to lesion hypervascularity and surgically altered hepatic arterial supply.
Abstract 5288A: Multivalent fluorescent probes for in vivo tumor targeting
Authors: Ning Zhang, Jae-Beom Kim, Ed Lim, Dan Ansaldi, Angel Ang, Raj Singh
Journal: Cancer Research (2011)

Abstract Conventional fluorescence probes are monovalent molecules that interact with cellular or extra-cellular target molecules through affinity binding. To improve the binding affinity and sensitivity of detection of the fluorescence probe, we describe a novel strategy for the synthesis designed to contain multiple targeting moieties and a near infrared fluorescent dye Iflour750 for optimal in vivo detection. In this study, we applied several multivalent probes to in vivo tumor targeting and monitored the targeting process using fluorescence imaging. Deoxyglucose based fluorescence probes have been applied to tumor labeling as the high metabolic rate of the tumor cells causes preferential labeling of the tumor mass. With a multivalent 2-deoxy-D- glucose Iflour750 (2-DG-IF750) probe, we demonstrated sensitive in vivo targeting as compared to a control mono-valent 2DG probe in several tumor models, including PC3M-luc2 prostate tumor cells, MDA-MB-231-luc2 mammary fat tumor cells as well as LL/2-luc and H460-luc2 lung cancer cells. Distinct tumor signal was visualized within a few hours after intravenous delivery and reached the peak of signal/background ratio between 6-24 hours. With a multivalent cyclooxygenase (COX) binding fluorescence probe Indomethacin-IF750, we observed an interesting targeting of COX2 negative colon tumor cells HCT116-luc2, but not the COX2 positive HT29-luc2, hypothetically due to selective binding to COX1. We also tested a multivalent RGD probe for targeting integrin avb3, the expression of which is associated with tumor angiogenesis and metastasis. With our iFlur750-(RGD)4 probe, we demonstrated in vivo targeting of U87-MG-luc2, HCT116-luc2 and HT29-luc2 tumor cells. Finally, we demonstrated that optical imaging was conveniently applied to evaluating the PK/PD profile of the probes. Our multivalent probes showed a fast clearance with a half life of less than 1 hour, which is a desirable feature for achieving maximal tumor/background contrast. In summary, we have developed a new class of multi-valent fluorescence probes with improved specificity and sensitivity of tumor targeting as compared to mono-valent analogs. Utility of this class of multivalent probes is likely to pass beyond pre-clinical models, as imaging guided tumor surgery is on the verge of clinical applications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5288A. doi:10.1158/1538-7445.AM2011-5288A
Abstract 5341: Clinical relevance of metastasis-related miRNAs in early breast cancer.
Authors: Athina N. Markou, George M. Yousef, Yu Liang, E Stathopoulos, Vassilios Georgoulias, Evi S. Lianidou
Journal: Cancer Research (2013)

Abstract Introduction It was recently demonstrated that miRNAs control breast cancer metastasis by influencing multiple metastatic steps. In this study we firstly evaluated the clinical relevance of specific miRNAs -recently shown to correlate with metastasis in breast cancer by exploring their expression profile in FFPEs samples of early breast cancer patients in respect to the clinical outcome of the patients. Finally, we investigated the correlations between the expression of these selected miRNAs and other parameters such as ER and PR expression. Materials and Methods One hundred and twelve (112) FFPE blocks were obtained from breast tumors of early breast cancer patients (follow-up period of 11 years) and 13 mammoplasty specimens from healthy tissues which were used as controls. The median overall survival (OS) and disease free interval (DFI) were 84 and 68 months respectively. We have chosen to quantify the expression of six metastasis related miRNAs, namely: miR-10b, miR-2,1 miR-205, miR-210, miR-335 and let-7a by RT-qPCR in the LightCycler (Roche). HER2, ER and PR expression of the primary tumors was detected by immunohistochemistry with the monoclonal antibody CB11 and with monoclonal antibodies to ER and PR, respectively, using the OPTIMAX automated system. For all miRNAs relative expression was determined using the ΔCq approach and expression values were normalized to miR-191 which has been shown to be a suitable reference miRNA. Results Kaplan-Meier survival curves demonstrated that patients with high miR-21 expression (n=56) had a significant shorter DFI than those with low miR-21 expression (P=0.043). Moreover, patients with low expression of miR-205 (n=57) had both shorter DFI and OS time than those with high expression levels (P=0.040 and P=0.047 respectively). However, the expression levels of the other four miRNAs were not related with the DFI and OS. We also found that in the ER-negative subgroup (n=46), disease relapse was more common in patients where miR-10b was over-expressed (P=0.019), while in the PR-negative subgroup (n=47), disease relapse was more common in patients with miR-21 overexpression (P&amp;lt;0.001) or miR-10b overexpression (P =0.016). Finally, in the group of PR-negative patients we noticed that patients who overexpressed miR-21 had shorter OS (P=0.021). Conclusions Quantification of metastasis related miRNAs expression in primary tumors can give important prognostic information in patients with early breast cancer. Citation Format: Athina N. Markou, George M. Yousef, Yu Liang, E Stathopoulos, Vassilios Georgoulias, Evi S. Lianidou. Clinical relevance of metastasis-related miRNAs in early breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5341. doi:10.1158/1538-7445.AM2013-5341
Effect of Stimulation of Human Macrophages on Intracellular Survival of<i>Mycobacterium bovis</i>Bacillus Calmette–Guerin
Authors: MARCEL BONAY, FRANCINE BOUCHONNET, VLADIMIR PELICIC, BEATRICE LAGIER, MARTINE GRANDSAIGNE, DENISE LECOSSIER, ALAIN GRODET, MARTIN VOKURKA, BRIGITTE GICQUEL, ALLAN J. HANCE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The mechanisms through which immune and inflammatory responses stimulate the expression of antimycobacterial activity by human macrophages remain poorly defined. To study this question, we developed a method permitting the rapid quantification of viable mycobacteria, based on the detection of luciferase activity expressed by a Mycobacterium bovis Bacillus Calmette–Guerin (BCG) reporter strain, and used this approach to evaluate mycobacterial survival in human monocyte-derived macrophages following stimulation with cytokines and through crosslinking of costimulatory molecules expressed on the cell surface. Modest proliferation, followed by persistence of mycobacteria, was observed in unpretreated macrophages as assessed both by measurement of luciferase activity and by the evaluation of colony forming units. Of the 19 cytokines tested, only granulocyte–macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) were found to improve the mycobactericidal activity of monocyte-derived macrophages. In both cases, this effect was observed only when macrophages were pretreated with the cytokines prior to infection. In contrast, pretreatment of human macrophages with interferon- γ , either alone or in combination with other mediators (including tumor necrosis factor- α and 1,25[OH]2-vitamin D3), did not improve mycobacterial killing. The stimulation of macrophages through several different costimulatory molecules known to participate in macrophage–lymphocyte interactions (CD4, CD40, CD45, CD86, CD95 [Fas/Apo-1]) also failed to improve mycobactericidal activity. This study shows that GM-CSF and IL-3, cytokines whose receptors are known to share a common subunit and to use common second messengers, may contribute to the stimulation of mycobactericidal activity in humans. The ability to rapidly screen the effects of different macrophage stimuli on mycobacterial survival through the detection of luciferase activity should help define additional signals required for optimal antimycobacterial responses.
A7.8 Autonomic dysfunction in the preclinical phase of rheumatoid arthritis
Authors: FA Koopman, MW Tang, J Vermeij, MJ de Hair, IY Choi, MJ Vervoordeldonk, DM Gerlag, JM Karemaker, PP Tak
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Rheumatoid arthritis (RA) is accompanied by changes in the autonomic nervous system, mainly lower activity of the parasympathetic nervous system. Autonomic changes can be detected by changes in heart rate variability (HRV). RA development starts years before the first presentation of arthritis; we hypothesised that autonomic changes may be present in individuals at risk of development of arthritis. <h3>Material and methods</h3> 10-minutes recordings of continuous blood pressure and heart rate were made in supine (resting) and upright (active) position in healthy subjects (HS, n = 20), individuals at risk of RA development (individuals at risk, n = 50) and RA patients (RA, n = 20). In addition, sympathetic proteins, (nor)epinephrine and the parasympathetic nicotinic acetylcholine receptor type 7 (α7nAChR) on monocytes were measured in venous peripheral blood samples. Resting heart rate (RHR) was also evaluated by a single, non-continuous measurement in an independent cohort of autoantibody positive individuals at risk of developing RA (n = 45). <h3>Results/Discussion</h3> Individuals at risk had a significantly higher RHR (68 beats per minute (bpm)) compared to HS (60 bpm, p = 0.006) and similar to RA patients (68 bpm, p = 0.38), indicating lower parasympathetic activity compared to HS. Other parasympathetic HRV parameters were lower compared to HS and norepinephrine levels were higher in individuals at risk compared to HS and RA. Dichotomizing RHR in &lt; and ≥70 bpm in the group of individuals at risk, we could demonstrate that the majority of HRV parameters were significantly lower in individuals with RHR ≥ than &lt;70 bpm. The parasympathetic receptor α7nAChR on peripheral CD14<sup>+</sup> monocytes was lower in individuals at risk with RHR ≥ 70 bpm than &lt;70 bpm. In the independent cohort RHR was higher at baseline in individuals who developed arthritis (n = 14) vs. those who did not (n = 31; 73.8 vs. 65.8 bpm, p = 0.018) after follow, and this was associated with RA development in the future (hazard ratio 1.098: 95% CI 1.012–1.191, p = 0.025). <h3>Conclusions</h3> Individuals at risk of RA development have lower parasympathetic activity compared to HS, and resemble RA patients. Increased RHR in individuals at risk is associated with RA development and a RHR ≥70 bpm measured by short-term HRV registration is accompanied by detrimental changes in all HRV parameters. These data support the notion that decreased vagus nerve tone may contribute to RA development.
SP0095 Coping as Integral to Understanding and Assessing Health and Well-Being in Rheumatoid Arthritis. Pragmatist, Fighter or Minimiser? Possible Trajectories of Newly Diagnosed Patients
Authors: J.A. Taylor
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Individuals vary significantly in how they adjust to their arthritis and this is not always explained by the level of disease activity but by their ability to cope. Coping was originally conceptualised as a defence mechanism with its origins in psychoanalytic theory. Coping has been classified in terms of the focus of the strategies, for example: emotions-focused and problem-focused coping, or in terms of the expected outcome, for example active or passive coping. The term coping is often used interchangeably in the literature with "self-management", but patients have been shown to be able to distinguish between the terms (Nicklin <i>et al,</i> 2010). Little is known about the journeys patients take from pre diagnosis towards adjustment and possible acceptance in the first 12 months, yet treatment often includes standardised care protocols and self management programmes. This talk will focus on the findings from a PhD study that looks at how patients cope and manage within the first year, from pre-diagnosis through the first 12 months. It will describe different potential journey that patients may take on their road to adjustment and acceptance. Coping and self management are both key strategies within managing long term conditions, these results will show how patients take different trajectories needing differing support and self management techniques, and that one programme does not fit all. <h3>Disclosure of Interest</h3> None Declared