tbuckley/cabot-search huggingface dataset:
Abstract LB-419: Multi-scalar approaches to interrogate the IκBα:NF-κB negative feedback loop: Quantitative dynamics in single cells, cell populations, and live animals <i>in vivo</i>
Authors: Britney Moss, Adnan Elhammali, Tiffanie Fowlkes, Shimon Gross, Anant Vinjamoori, Christopher H. Contag, David Piwnica-Worms
Journal: Cancer Research (2012)

Abstract Cells have evolved complex molecular networks to sense environmental signals, transmit this information through the cell, and elicit appropriate biological responses. In particular, negative feedback loops represent a widely-utilized network motif capable of eliciting transient responses. To truly understand the biological significance of negative feedback processes, it is critical to study them at multiple scales: in single cells, in cell populations, and in animals. The IκBα:NF-κB negative feedback loop, a pivotal regulatory node of innate immunity and inflammation active in both immune cells and non-immune tissues, represents a model system for the use of multi-scalar reporter systems. To this end, we have utilized the κB5→IκBα-FLuc bioluminescent reporter to study dynamics of this transcriptionally-coupled negative feedback loop in response to diverse modes of stimulation which may be particularly relevant during cellular responses to inflammatory cytokines, such as TNFα. The κB5→IκBα-FLuc reporter enabled rigorous evaluation of the stimulus-specific dynamics of βκγα degradation and the downstream consequences of NF-κΔ nuclear translocation (i.e., NF-κΔ transcriptional activity) in single cells, cell populations and live animals in vivo. In response to modulation of TNFα concentration and pulse duration, complex, differential patterns in βκγα degradation and re-synthesis were discovered in both cell populations and single cells. Furthermore, IκBα dynamics observed in live animals in vivo upon modulation of TNFα dose strongly resembled those observed in single cells and cell populations upon modulating TNFα pulse duration, suggesting that increased doses of circulating TNFα were perceived by hepatocytes in vivo as pulses of increasing duration. Thus, a single bioluminescent reporter strategy enabled correlative quantitation of dynamic NF-κα:βκβα negative feedback loop responses in live single cells, cell populations, and tissues in vivo with a variety of rapid, low-cost, high-throughput approaches. 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 LB-419. doi:1538-7445.AM2012-LB-419
Etude rétrospective sur la prise en charge de 41 cas d'angiodysplasies digestives dans le service d'hépatogastroentérologie du CHU de Limoges
Authors: M Vincent, A Giraud, D Sautereau, A Le Sidaner, A Bouygues
Journal: Endoscopy (2012)

Les angiodysplasies digestives sont des lésions vasculaires de la sous muqueuse. Ces lésions touchent majoritairement une population âgée et fragile. Leur présentation clinique majeure reste l'anémie obscure et les saignements digestifs itératifs, avec un risque non négligeable de récidive.Leur prise en charge thérapeutique repose sur le traitement endoscopique par coagulation au plasma argon.
Extreme Precipitation and Emergency Room Visits for Gastrointestinal Illness in Areas with and without Combined Sewer Systems: An Analysis of Massachusetts Data, 2003–2007
Authors: Jyotsna S. Jagai, Quanlin Li, Shiliang Wang, Kyle P. Messier, Timothy J. Wade, Elizabeth D. Hilborn
Journal: Environmental Health Perspectives (2015)

Combined sewer overflows (CSOs) occur in combined sewer systems when sewage and stormwater runoff are released into water bodies, potentially contaminating water sources. CSOs are often caused by heavy precipitation and are expected to increase with increasing extreme precipitation associated with climate change.The aim of this study was to assess whether the association between heavy rainfall and rate of emergency room (ER) visits for gastrointestinal (GI) illness differed in the presence of CSOs.For the study period 2003-2007, time series of daily rate of ER visits for GI illness and meteorological data were organized for three exposure regions: a) CSOs impacting drinking water sources, b) CSOs impacting recreational waters, c) no CSOs. A distributed lag Poisson regression assessed cumulative effects for an 8-day lag period following heavy (≥ 90th and ≥ 95th percentile) and extreme (≥ 99th percentile) precipitation events, controlling for temperature and long-term time trends.The association between extreme rainfall and rate of ER visits for GI illness differed among regions. Only the region with drinking water exposed to CSOs demonstrated a significant increased cumulative risk for rate (CRR) of ER visits for GI for all ages in the 8-day period following extreme rainfall: CRR: 1.13 (95% CI: 1.00, 1.28) compared with no rainfall.The rate of ER visits for GI illness was associated with extreme precipitation in the area with CSO discharges to a drinking water source. Our findings suggest an increased risk for GI illness among consumers whose drinking water source may be impacted by CSOs after extreme precipitation.Jagai JS, Li Q, Wang S, Messier KP, Wade TJ, Hilborn ED. 2015. Extreme precipitation and emergency room visits for gastrointestinal illness in areas with and without combined sewer systems: an analysis of Massachusetts data, 2003-2007. Environ Health Perspect 123:873-879; http://dx.doi.org/10.1289/ehp.1408971.
“Hyperfrontality” as Seen on FDG PET in Unmedicated Schizophrenia Patients With Positive Symptoms
Authors: Ajit S. Shinto, K.K. Kamaleshwaran, D. Srinivasan, S. Paranthaman, K. Selvaraj, M.B. Pranesh, G.N. Lakshminarayanan, B. Prakash
Journal: Clinical Nuclear Medicine (2014)

Decreased frontal activity has been reported widely in unmedicated schizophrenic patients with predominantly negative symptoms. Not many studies have assessed the frontal lobe status in unmedicated patients with positive symptoms.Fifty-one patients with schizophrenia (all unmedicated, 38 never medicated) and 12 healthy age-matched controls were evaluated with FDG PET CT. The patients met ICD-10 and DSM-IV criteria for schizophrenia, and all reported psychotic, "positive" symptoms when tested.Schizophrenic patients with positive symptoms had a hypermetabolic frontal metabolic pattern on quantification by region to occipital ratio comparison. Associated statistically significant differences were also found when comparing ratios of occipital to thalamic, striatal and temporal cortex in schizophrenic patients.The finding of a hyperfrontality in unmedicated and never medicated psychotic schizophrenic patients is observed when there is a predominance of positive symptoms. There could be a possible disruption of cortico-striato-thalamic feedback loops causing hyperfrontality as seen in experimentally induced models of psychosis .
Abstract A8: Role of the WWOX gene in non-small cell lung cancer
Authors: Nur Buyru, Onur Baykara, Ahmet Demirkaya, Kamil Kaynak, Alper Toker, Serhat Tanju
Journal: Cancer Research (2009)

Abstract Lung cancer is the most common cause of cancer-related deaths worldwide and like many other cancers is affected by different genetic, epigenetic and environmental factors. The WWOX gene is a tumor supressor gene located on 16q23.3–24.1. It has been shown that it loses its function due to differences in genetic and epigenetic mechanisms. In this study we investigated whether the presence of WWOX gene mutations in lung cancer. The entire coding exons and flanking intronic sequences of the gene were analysed by PCR amplification from the genomic DNA and direct sequencing in 50 patients with non-small cell lung cancer (NSCLC). WWOX gene mutations were detected in five out of 50 primary tumors (10%). One of these mutations was an insertion in exon 4 at the third nucleotide of codon 120. This mutation was observed in 2 patients and leads to a frameshift creating a stop codon at codon 133. The second mutation was an insertion at position 2583 which also causes a shift in the reading frame. Finally, heterozygous C→G transitions on position 2807 at the first nucleotide of codon 282 (exon 8) were identified in 2 patients. This mutation affecting codon 282 leads to the substitution of alanine instead of proline. We also observed a previously defined G to A polymorphism at the nucleotide 2196 in homozygous and heterozygous form in 20 and 5 patients, respectively. Additionally we detected 12 different intronic substitutions. In addition to inactivating mutations target genes may also be silenced epigenetically. Therefore, besides mutation screening we also analyzed the methylation profile of the promoter region of the WWOX gene in tumor tissue and adjacent non-cancerous tissue samples by bisulphite modification and methylation-specific PCR. Promoter methylation was detected in 76% of the tumor tissue samples. While 20% of the samples displayed partial methylation 56% were completely methylated. In the adjacent normal tissue samples partial and complete methylation frequencies were 6% and 58%, respectively. Methylation frequency was significantly higher in the tumor tissue samples than in normal tissue samples (p=0.014). The high frequency of mutations and epigenetic modifications suggest that the WWOX gene may play a significant role in the etiology of NSCLC. Citation Information: Cancer Res 2009;69(23 Suppl):A8.
FRI0415 Patients' Illness Perceptions Are Associated with Physical Health-Related Quality of Life Independent of Psychological Distress and Disease Severity in Primary Sjogren's Syndrome, Systemic Lupus Erythematosus and Rheumatoid Arthritis
Authors: K. Kotsis, T. Hyphantis, N. Tsifetaki, P.V. Voulgari, A.A. Drosos
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Illness perceptions and psychological distress are important in determining outcomes in rheumatic diseases. <h3>Objectives</h3> We aimed to assess illness perceptions and psychological distress and their associations with Physical health-related quality of life (HRQoL) in primary Sjogren9s Syndrome (pSS), Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA). <h3>Methods</h3> In 57 pSS, 75 SLE and 199 RA patients we administered the Patient Health Questionnaire (PHQ-9), the Symptom Distress Check-List (SCL-90-R) and the Brief-Illness Perception Questionnaire (B-IPQ) to assess psychological variables and the World Health Organization Quality of Life Instrument, Short-Form (WHOQOL-BREF) to assess HRQoL. Hierarchical regression models were used adjusting for demographic and clinical variables. <h3>Results</h3> The prevalence of clinically significant depressive symptoms (PHQ-9≥10) was 24.6% in pSS, 29.3% in SLE and 25.1% in RA. Patients with pSS showed little understanding of their disease (<i>comprehensibility</i>) and attributed more symptoms to their illness (<i>identity</i>) compared to SLE and RA. Depressive symptoms and concerns about the <i>consequences</i> of the disease were associated with Physical HRQoL independently of pain, disease duration and disease severity in all three diseases. In pSS, however, the patients9 worries about the <i>consequences</i> of their illness totally mediated the relationship of pain with Physical HRQoL. Moreover, SLE patients9 concerns about numerous bodily symptoms attributed to the illness (<i>illness identity</i>) were also important independent correlates of Physical HRQoL. <h3>Conclusions</h3> These findings indicate that patients9 illness perceptions are important correlates of HRQoL in these disease groups and encourage the design of psychotherapeutic trials targeting disease-related cognitions in an attempt to improve patients9 HRQoL. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3177
Abstract 4132: Rapid microfluidic-based isolation of tumor cells from pleural effusions for cytodiagnostics.
Authors: James Che, Albert Mach, Derek Go, Ish Talati, Yong Ying, Jianyu Rao, Dino Di Carlo, Rajan Kulkarni
Journal: Cancer Research (2013)

Abstract Pleural effusions accumulate in patients with cancer or other illnesses and are often drained to provide symptomatic relief. Cells within this fluid are concentrated and analyzed to determine the cause of effusion. In patients with cancer, tumor cells may be present in the effusions and provide a source of cells for further diagnostics and mutational analysis. However, blood cell components and other non-cellular materials can create a significant background and can obscure the search for tumor cells. Furthermore, blood cell impurities can adversely impact the search for genomic or proteomic changes in the tumor cells by creating a large wild type background. A purity of at least 20% of target cells is necessary to ensure that background signal is suppressed. We have developed a microfluidic based “Centrifuge Chip” for the rapid isolation and purification of cancer cells. The Centrifuge Chip utilizes microvortices to trap cells based on size without the need for affinity-based capture. Isolated cells can subsequently be released on-demand and are viable to grow or can be analyzed for molecular changes. We utilized this chip for the isolation of tumor cells and mesothelial cells at high purity from pleural effusions and similar complex fluids such as blood. We then stained the cells with CK/DAPI for tumor cells and CD45 for white blood cells. Samples with high numbers of CK positive cells were deemed suspicious for malignancy; all our results were cross-checked to the standard Cytospin results. We routinely achieved improved purities in all samples, with greater than 70-fold increase in purity for samples positive for malignancy, and are developing a quantitative PCR (QPCR) based system to confirm the presence of activating EGFR or KRAS mutations in lung cancer cells isolated from patients with malignant pleural effusions secondary to lung cancer. The Centrifuge Chip can achieve rapid isolation of tumor cells from complex biofluids and allows for easier access to such cells for molecular analysis that will provide clinicians with critical information required for targeted cancer therapies. Citation Format: James Che, Albert Mach, Derek Go, Ish Talati, Yong Ying, Jianyu Rao, Dino Di Carlo, Rajan Kulkarni. Rapid microfluidic-based isolation of tumor cells from pleural effusions for cytodiagnostics. [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 4132. doi:10.1158/1538-7445.AM2013-4132
Rash Associated with Secondary Syphilis
Authors: Talel Badri, Salima Ben Jennet
Journal: New England Journal of Medicine (2011)

A previously healthy 25-year-old man presented with a 2-week history of multiple nonpruritic, well-circumscribed, scale-covered, erythematous plaques on his palms and soles (Panels A and B, respectively). He was otherwise asymptomatic, and a physical examination was unremarkable. He specifically reported not having a history of genital ulceration but did report having unprotected sexual intercourse with multiple female partners. A Venereal Disease Research Laboratory test was positive at a titer of 1:64, and a microhemagglutination assay for antibodies against Treponema pallidum (MHA-TP) was reactive, confirming a diagnosis of secondary syphilis. Tests for chlamydia, gonorrhea, and human immunodeficiency virus were all negative. . . .
NLRP3 and ASC suppress lupus-like autoimmunity by driving the immunosuppressive effects of TGF-β receptor signalling
Authors: Maciej Lech, Georg Lorenz, Onkar P Kulkarni, Marian O O Grosser, Nora Stigrot, Murthy N Darisipudi, Roman Günthner, Maximilian W M Wintergerst, David Anz, Heni Eka Susanti, Hans-Joachim Anders
Journal: Annals of the Rheumatic Diseases (2014)

Objectives The NLRP3/ASC inflammasome drives host defence and autoinflammatory disorders by activating caspase-1 to trigger the secretion of mature interleukin (IL)-1β/IL-18, but its potential role in autoimmunity is speculative. Methods We generated and phenotyped Nlrp3 -deficient, Asc -deficient, Il-1r -deficient and Il-18 -deficient C57BL/6-lpr/lpr mice, the latter being a mild model of spontaneous lupus-like autoimmunity. Results While lack of IL-1R or IL-18 did not affect the C57BL/6-lpr/lpr phenotype, lack of NLRP3 or ASC triggered massive lymphoproliferation, lung T cell infiltrates and severe proliferative lupus nephritis within 6 months, which were all absent in age-matched C57BL/6-lpr/lpr controls. Lack of NLRP3 or ASC increased dendritic cell and macrophage activation, the expression of numerous proinflammatory mediators, lymphocyte necrosis and the expansion of most T cell and B cell subsets. In contrast, plasma cells and autoantibody production were hardly affected. This unexpected immunosuppressive effect of NLRP3 and ASC may relate to their known role in SMAD2/3 phosphorylation during tumour growth factor (TGF)-β receptor signalling, for example, Nlrp3 -deficiency and Asc -deficiency significantly suppressed the expression of numerous TGF-β target genes in C57BL/6-lpr/lpr mice and partially recapitulated the known autoimmune phenotype of Tgf-β1 -deficient mice. Conclusions These data identify a novel non-canonical immunoregulatory function of NLRP3 and ASC in autoimmunity.
HIV and drugs: a common, common-sense agenda for 2016
Authors: Kent Buse, Eliot Albers, Shiba Phurailatpam
Journal: The Lancet Global Health (2016)

2016 is set to be a historic year for people living with and affected by HIV and people who use drugs. The UN General Assembly Special Session (UNGASS) on drugs (April 19–21, 2016; New York, NY, USA), provides a rare occasion to review critically the global drug-control system and to advance alternatives that are balanced, evidence-informed, fair, public health-oriented, and rooted in human rights. The UN Secretary-General Ban Ki-moon urged that the Special Session "considers all options".1 The UN High-Level Meeting on AIDS (June 8–10, 2016; New York, NY, USA) offers an opportunity to commit to concrete steps to fast-track the response to ending the AIDS epidemic, including progressive approaches to drugs policy.
Abstract P5-03-08: A fluorescence STAT3 reporter preferentially expressed in human breast cancer tumor-initiating cells
Authors: W Wei, D Tweardy, M Zhang, K Roarty, J Rosen, M Lewis
Journal: Cancer Research (2012)

Abstract Cancer initiating/stem cells are thought to be responsible for treatment-resistance, disease-recurrence and metastasis. Current breast cancer stem cell markers lack direct correlation with stem cell function, which makes the targeted therapeutic design difficult. The STAT3 pathway is a critical regulator of the function of normal stem cells and evidence is accumulating for its important role in breast cancer stem cells, as well as associated “niche” cells. However, due to lack of method for pathway-activity-based live cell separation, whether STAT3 functions in the cancer stem cells themselves or in surrounding niche cells, or both remains unknown. To answer this question, we have constructed lentiviral fluorescent reporters, which enables FACS-sorting of cells differ in STAT3 activity as well as in vivo/in situ localization of STAT3 responsive cells. Our study for the first time separated the STAT3 positive and STAT3 negative cells from the same breast tumor in live, and for the first time provided functional evidences that the STAT3 positive cells are enriched for breast cancer stem cells compared to STAT3 negative cells, as tumor cells positive for reporter activity perform better in both mammosphere formation and dilution transplantation assays compared to the negatives. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-03-08.
Abstract 2190: Yeast-based pharmacogenomics approaches to identify Cisplatin responsive genes
Authors: Elisa Ferrari, Chiara Lucca, Gianluca Spitaleri, Filippo de Braud, Marco Foiani
Journal: Cancer Research (2010)

Abstract Platinum-based drugs are largely used in cancer treatment. Using genome-wide approaches we aimed at identifying cisplatin primary and secondary targets and at characterizing cisplatin responsive genes. The yeast Saccharomyces cerevisiae is widely used to study a variety of eukaryotic cellular processes including those that are relevant for human health. Yeast can be used for genetic, genomic and mechanistic studies as well as for pharmacogenomic approaches. Using yeast-based pharmacogenomic screens we identified novel genes relevant for the cisplatin response. In particular, we have identified genes involved in DNA repair pathways such as Nucleotide Excision Repair, Homologous Recombination and Post Replicative Repair, as well other genes. We also used mechanistic approaches to further characterize those factors that have obvious human ortologues and whose functions are still elusive. Altogether our approaches allowed us to unmask novel factors that contribute to cell viability and genome integrity in response to cisplatin treatment. Complementary studies on the human ortologues are ongoing. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2190.