tbuckley/cabot-search huggingface dataset:
FRI0473-HPR Does the overall validity of the childhood health assessment questionnaire (CHAQ) improve with the use of revised versions in children with juvenile idiopathic arthritis (JIA)?
Authors: M. Nørgaard, T. Herlin
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The Childhood Health Assessment Questionnaire (CHAQ) is widely used to measure functional impairment in children with juvenile idiopathic arthritis (JIA) (1). However, the original version (CHAQ30) has reduced overall validity in terms of an increasing ceiling effect and a decreasing discriminative ability due to considerable improvements in functional ability of JIA-children (2). <h3>Objectives</h3> The aim of this study was to evaluate and validate a revised version including eight physically demanding questions (CHAQ38) with a new categorical response model (CAT2) (3) and a simplified scoring of the original response model (CAT1) (4) in a Danish population of JIA-children and an age- and gender-matched group of healthy controls. <h3>Methods</h3> 68 patients and 118 controls aged 10-16 years filled in the CHAQ30 with eight new items (CHAQ38) and two response models (CAT1 and CAT2). Demographic data in both groups and disease-specific data among patients was obtained. Statistical analysis of the four revisions was done to evaluate score distribution and test the ability to distinguish between patients and controls and among patients, and avoid a ceiling effect. <h3>Results</h3> All versions had scores close to zero in both groups (median/mean values in patients: -0.0789-0.1053/-0.1602-0.1896. In controls: 0/0.0215-0.1024), indicating only mild disease in patients. Nevertheless, all versions equally distinguished between patients and controls (p&lt;0.001) and between patients with or without active disease (p≤0.008). In both groups all versions suffered from a ceiling effect (% at ceiling in patients: 16.2-33.8. In controls: 39.6-75.4) and deviated significantly from a normal distribution (Kolmogorov-Smirnov values in patients: 0.176-0.233. In controls: 0.299-0.384). However, both ceiling effect and score distribution was best improved with the CHAQ38 and to some extent the CAT2. <h3>Conclusions</h3> The overall validity was increased with the CHAQ38, though still not optimally with either of the two scoring models (CAT1/CAT2). This calls for more complex assessment tools in well-functioning JIA-patients in the future. <h3>Disclosure of Interest</h3> None Declared
Abstract 1732: Elevated expression of YKL-40, a cancer biomarker, is associated with tumor angiogenesis
Authors: Wei Yan, Jackie Qing Cao, Richard B. Arenas, Brook Bentley, Rong Shao
Journal: Cancer Research (2010)

Abstract Growing evidence from clinical investigations has shown that increased serum levels of YKL-40 are correlated with short survival and metastasis in a broad type of human cancers. These data suggest that YKL-40 in the blood may present a powerful tool for cancer diagnosis and prognosis. However, pathological activity of YKL-40 in cancer development is poorly understood. Here, we explored a functional role for YKL-40 in vasculature development of human cancer. In a survey of twenty cases of breast ductal carcinoma in situ (DCIS) and thirty-eight cases of infiltrating ductal carcinoma (IDC), we found that expression levels of YKL-40 in specimens from DCIS were barely detectable, but different levels of YKL-40 were present in IDC. Nine out of thirty-eight IDC cases showed high levels of YKL-40 and nine cases displayed medium levels of YKL-40, whereas the rest twenty cases were low or negative. Interestingly, in an analysis of vasculature formation in these IDC samples, we found that different blood vessel densities significantly correlated with different degrees of YKL-40 expression. To test this possible angiogenic activity of YKL-40 in tumor development, we utilized angiogenic xenograft models by subcutaneous injection of SCID/Beige mice with a brain tumor line U87 cells which express strong endogenous YKL-40 and U87 cells with siRNA knockdown of YKL-40. siRNA knockdown of YKL-40 notably suppressed tumor angiogenesis and tumor development relative to high levels of YKL-40 expressed in control U87 cells. Further, to dissect cellular and molecular mechanisms underlying YKL-40-induced tumor angiogenesis, we treated human microvascular endothelial cells with YKL-40 and found that YKL-40 was capable of binding to heparan sulfate on ectodomain of membrane receptor syndecan-1 (S1). The activated S1 prompted its interaction with adjacent receptor integrin αvβ3, leading to activation of intracellular cascades including phosphorylation of focal adhesion kinase and MAP kinase. A series of individual signaling inhibitors blocked YKL-40-induced angiogenesis in vitro. Collectively, these data strongly suggest that YKL-40 expressed in cancer activates vascular endothelial cell angiogenesis to promote tumor development. These findings may hold promise for developing novel therapeutic agents targeting YKL-40, a cancer biomarker that is overexpressed in a wide range of human cancers. 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 1732.
THU0273 Mycophenolate Mofetil in SLE and Systemic Vasculitis: Treatment Outcome in a Large Referred Center
Authors: C. Lourdudoss, S. Jamil, R. van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) and systemic vasculitis are autoimmune diseases. SLE is of an unknown cause that occurs primarily in women and can involve many organs. Systemic vasculitis is characterized by inflammatory destruction of the blood vessels and tissue necrosis, there are several types of vasculitis classified by size of the affected blood vessels. Mycophenolate mofetil (MMF) is an immunosuppressive drug that is commonly used within the transplantation area, but also for autoimmune systemic diseases such as SLE and systemic vasculitis. <h3>Objectives</h3> The aim of this study was to investigate the outcome of MMF in patients with SLE and systemic vasculitis. <h3>Methods</h3> This study included patients with SLE or systemic vasculitis with ongoing or previous MMF treatment at Karolinska University Hospital, Stockholm, Sweden. Data on specific information regarding disease and treatment was obtained through medical record review. <h3>Results</h3> Out of a total of 648 patients with SLE and 455 with systemic vasculitis; 135 patients (21%) with SLE and 43 patients (9%) with vasculitis had ongoing or previous MMF treatment. The most common organ manifestation at baseline was renal involvement (50%) among SLE patients. Median MMF dose was 2g/day and glucocorticoids (GC) doses were significantly reduced during MMF treatment from 21.7 mg/day to 8.3 mg/day after 12 months. By physician assessment, 79% of the patients were good or moderate responders to MMF treatment after 12 months. The most common adverse events leading to discontinuation were side effects in the gastrointestinal tract (40%) and general side effects (30%). A "survival-on-drug" Kaplan-Meier curve showed that 40% of the patients remained on long-term MMF treatment. <h3>Conclusions</h3> MMF was used in 16% of all patients with SLE and systemic vasculitis. The treatment appeared to be effective with a reasonable survival-on-drug as well as a GC sparing effect for many patients with SLE or systemic vasculitis. <h3>Disclosure of Interest</h3> C. Lourdudoss: None Declared, S. Jamil: None Declared, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, MSD, Pfizer, Roche, UCB, Consultant for: AbbVie, BMS, GSK, MSD, Pfizer, Roche, UCB
Encephalitis claims 13 more lives as Indian government launches vaccine against one cause of the outbreak
Authors: M. Kay
Journal: BMJ (2013)

Thirteen children have died over the past few days in a fresh outbreak of encephalitis in Uttar Pradesh, India, raising the death toll to 343, the Press Trust of India has reported.1

Five Indian states—Assam, Bihar, Tamil Nadu, Uttar Pradesh, and West Bengal—are worst affected by encephalitis …
Delayed peritonitis after endoscopic ultrasound-guided fine-needle aspiration of a metastatic celiac lymph node
Authors: T. Cârţână, A. Săftoiu, C. Popescu, D. Gheonea, T. Ciurea, I. Georgescu
Journal: Endoscopy (2011)

A 48-year-old man presented with dysphagia, lower retrosternal pain following food ingestion, and significant weight loss. Clinical examination found epigastric pain during palpation, while laboratory workup revealed only an elevated erythrocyte sedimentation rate.
Abstract 5528: Toxicology and drug delivery by Cucurbit[n]urils and derivatives
Authors: Gaya Hettiarachchi, Duc Nguyen, Jing Wu, Derick Lucas, Da Ma, Lyle Isaacs, Volker Briken
Journal: Cancer Research (2010)

Abstract Drug candidates are continuously being discovered using high-through put screens of small compound chemical libraries, however, many of these drugs are not pursued into development because of low bioavailability. Therefore, drug delivery systems that improve bioavailability are of great importance. Cucurbit[n]urils (CB[n]) are a new class of molecular container compounds that are beginning to show great promise as a novel drug delivery system. Here we analyzed the toxicology of two unmodified cucurbit[n]urils, (CB[5] and CB[7]), and three CB[n] derivatives (Pentamer, Me-Hexamer and Ph-Hexamer). All five containers showed high cell tolerance at concentrations of up to 1mM in HEK293, HepG2 and RAW264.7 cell lines using assays for metabolic activity and cytotoxicity. We also studied uptake, and bioactivity using CB[7], the most soluble of the containers presented above. Bioactivity assays conducted with RAW264.7 cells infected with M. Smegmatis showed no inhibition of the activity of the antituberculosis drug ethambutol (EMB) by CB[7] after 3 days of incubation. This study provides a proof of principle towards the use of these containers as a novel drug delivery system. 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 5528.
Biodegradable rapamycin-eluting nano-fiber membrane-covered metal stent placement to reduce fibroblast proliferation in experimental stricture in a canine model
Authors: Y. Zhu, W. Cui, Y. Cheng, J. Chang, N. Chen, L. Yan, M. Li
Journal: Endoscopy (2013)

<b>Background and study aims:</b> The aim of the current study was to assess whether placement of the biodegradable rapamycin-eluting nano-fiber membrane-covered metal stent is followed by less fibroblast proliferation and tissue hyperplasia compared with bare stents in experimental stricture in a dog model. <b>Methods: </b>A total of 80 dog models of stricture were randomly divided into a control group (n = 20, no stent insertion), a bare stent group (BSG, n = 20, 1-week retention), and two drug-eluting stent sub-groups (DESG-1w, n = 20, 1-week retention; DESG-4w, n = 20, 4-week retention). Lower esophageal sphincter (LES) pressure, 5-minute barium height (5-mBH), and cardia diameter were assessed before, immediately after the procedure, and regularly thereafter for 6 months. Five dogs in each group were euthanized for histological examination at each follow-up assessment. <b>Results: </b>Stent insertion was well tolerated, with similar migration rates (0 % in BSG vs. 7.5 % in DESGs; <i>P</i> = 0.5441). At 6 months, LES pressure and 5-mBH improved in DESG-1w (26.70 ± 5.02 mmHg and 6.50 ± 2.98 cm) and DESG-4w (20.16 ± 5.50 mmHg and 1.54 ± 0.98 cm) compared with BSG (39.94 ± 5.22 mmHg and 11.1 ± 5.46 cm) (<i>P</i> < 0.05), with DESG-4w being more stable than DESG-1w (<i>P</i> < 0.05). The cardia maintained greater patency in the DESGs (7.10 ± 3.09 mm in DESG-1w; 9.16 ± 3.77 mm in DESG-4w) than in the BSG (1.86 ± 2.45 mm; <i>P</i> < 0.05). Reduced peak inflammatory reactions and scarring occurred in DESGs compared with the BSG (<i>P</i> < 0.05), with a better outcome in DESG-4w than in DESG-1w (<i>P</i> < 0.05). <b>Conclusions:</b> In this experimental stricture model, rapamycin-eluting stents were more effective than bare stents for the reduction of fibroblast proliferation and tissue hyperplasia after stent placement. Furthermore, 4-week retention of the drug-eluting stent led to a better outcome than 1-week retention.
Abstract LB-93: The epigenetic basis of the tumorigenic action of retinoic acid
Authors: Stefano Rossetti, MingQiang Ren, Giulia Somenzi, Luigina Tagliavacca, Nicoletta Sacchi
Journal: Cancer Research (2010)

Abstract Preformed vitamin A, or Retinol, is found in animal foods, such as liver and whole milk, and in some fortified food products. Carotenoids, such as beta-carotene from fruit and vegetables, are also efficiently converted into Retinol. Retinol, once converted into its bioactive form, retinoic acid (RA), plays a major role in cell division, cell death, and cell differentiation. We found that RA can exert a double-edged action: it can either inhibit, or promote, tumorigenesis according to the functional status of one of its receptors, the RA receptor alpha (RARA). Further, we found that RA, through RARA, controls a network of tumor suppressor genes governing cell death, cell proliferation, cell differentiation, migration, and invasion. Finally, we observed that concomitant with epigenetic silencing of the tumor suppressor gene network, due to loss/functional inhibition of RARA, RA exerts a clear tumor-promoting action, raising the question as to whether dietary sources of RA, or RA precursors, can also promote tumorigenesis in cells with an impaired RARA. Using an isogenic breast cancer cell model (T47D), comprising two clonal cell lines, one with a functional RARA-regulated gene network (T47DLXC5) and one without functional RARA (T47DDNC8) (Ren et al., MCB, 2006), we generated subcutaneous xenograft tumors in athymic female nude mice. A 6-week diet with either RA (5 or 10 mg/kg) or Retinol (50 mg/kg) induced an opposite effect on xenograft tumor growth. T47DDNC8 xenograft tumors were stimulated to grow and metastasize to distant sites by RA/Retinol, while T47DLXC5 xenograft tumors were growth-inhibited by RA/Retinol, and did not invade. In breast cancer RARA function is often impaired due to a variety of upstream causes, including faulty RA transport by CRABP2 onto RARA and/or loss of Estrogen Receptor alpha (ERA), a pivotal RARA transcriptional regulator. Early detection of epigenetic silencing of tumor suppressor genes of the RARA network can be used to prevent tumorigenic effects of dietary sources of RA on breast tumorigenesis. This work was funded by R01 CA127614 (NS), PRIN 2007 (LT, SR). 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 LB-93.
Abstract 2461: Gene deletion of mPGES-1 results in a significant reduction in tumor stage and burden in the BBN mouse model of bladder cancer
Authors: Masako Nakanishi, Shilpa Choudhary, Poornima Hegde, Carol Pilbeam, Daniel Rosenberg, John A. Taylor
Journal: Cancer Research (2010)

Abstract Introduction and Objective: Prostaglandins (PG) play a critical role in the development of solid tumors. Inhibition of cyclooxygenase-2 (COX-2), the committed step in PG synthesis, has been shown to impact tumor development in the BBN mouse model of bladder cancer. However, clinical translation has been impeded by the well documented cardiovascular problems with COX-2 inhibitors. Inhibition of other synthases downstream of COX-2 in the PG cascade may prove useful for chemoprevention or chemotherapy. In the following study, we evaluated the impact of gene deletion of membrane-associated prostaglandin synthase-1 (mPGES-1), the terminal synthase in the generation of PGE2, in the BBN mouse model. Methods: Two month old male C57Bl/6 mice with global homozygous deletion for Ptges (mPGES-1 KO) and wild-type (WT) were treated with and without BBN in drinking water (n=5/grp) for 23 weeks. Bladders were harvested, weighed, fixed, step sectioned and evaluated by H&amp;E for pathologic stage and grade and percent involvement of tissue by tumor. Urine was collected prior to sacrifice and evaluated for PGE-2 metabolites (PGEM) by ELISA. Results: All animals had high-grade cancer at the time of euthanasia. WT bladders were significantly heavier than KO bladders (mean 0.18 vs 0.04 g respectively; p=0.03). Four of 5 WT mice had pT3 and one pT2 disease. Three of 5 KO mice had pT1 and 2 had pT2 disease. % tissue involvement was significantly less in the KO animals as well (54 vs 87%, p=0.03). Pearson's correlation for bladder weight and percent tumor involvement was 0.73 (p=0.02). Pathologic stage was dependant on genotype by Wilcoxon Rank Sum Test (p=0.02). Urine metabolites were reduced 50% in the KO compared to WT animals (mean 18.9 vs 45.2 pg/ml respectively; p&amp;lt;0.01). Conclusions: Genetic deletion of mPGES-1 resulted in significant decreases in PGE-2 as evidenced by lower urinary PGEM and in pathologic stage and % tissue involvement by tumor. Increased bladder weights in the WT mice compared to KO mice were directly related to the increased tumor burden. These results suggest that inhibitors of mPGES-1 may prove to be an alternative to COX inhibition and possibly prove useful in the management of high-grade bladder cancer. 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 2461.
Evidence that increased alcohol consumption following portacaval anastomosis results from alterations of the endogenous brain opiate system
Authors: J DEWAELE
Journal: Hepatology (1995)

The aim of this study was to determine whether an artificial magnetic field with an amplitude and frequency equivalent to those of geomagnetic pulsations during geomagnetic storms could affect physiology and psychology. Three healthy volunteers wore an ambulatory BP monitor and an ECG recorder around the clock for 12 consecutive weekends in Winnipeg, Manitoba, Canada. In a room shielded against ELF and VLF waves, they were exposed for 8 hours per week to either a 50 nT 0.0016 Hz or a sham magnetic field at one of six circadian stages. Real exposure randomly alternated with sham exposure. They provided saliva and recorded mood and reaction time every 4 hours while awake. Systolic (S) and diastolic (D) blood pressure (BP), and heart rate (HR) were recorded every 30 minutes. Spectral analysis of HR variability (HRV) was performed using the maximum entropy method and a complex demodulation method. For these variables, daily means were compared between real and sham exposure, using paired t-tests. Their circadian MESOR, amplitude, and acrophase were analyzed and summarized using single cosinor and population-mean cosinor. Circadian rhythms were demonstrated for HR, SBP, DBP for sham exposure, salivary flow rate, positive affect, vigor, and subjective alertness (p<0.001, ∼0.02). One participant showed higher HR, lower LF, HF, and VLF powers, and a steeper power-law slope (p<0.005, ∼0.0001) in an early night exposure to the real magnetic field, but not in other circadian stages. There was no significant difference between circadian responses to real and sham exposure in any variable at any circadian stage.
P46 The prediction of liver related outcomes using histological tools as an endpoint for studies evaluating anti-fibrotic therapies
Authors: G. E. Dolman, G. Li, G. Burgess, T. Gray, A. M. Zaitoun, W. Irving, I. N. Guha
Journal: Gut (2011)

<h3>Introduction</h3> Liver related outcomes (LRO) represent a meaningful end-point for future anti-fibrotic therapies. Staging of liver fibrosis on histology is a surrogate for these outcomes but may not be an ideal tool. <h3>Aim</h3> Our initial aim was to determine liver related outcomes and survival from the individual stages of significant fibrosis. Our second aim was to assess the value of morphometric collagen quantification within cirrhosis to predict clinical outcomes. <h3>Method</h3> The study cohort was selected from a single centre within the Trent HCV study, a prospective cohort which began in 1991 to address the natural history of chronic hepatitis C. Inclusion criteria for this study were the presence of significant fibrosis (at least Ishak Stage (IS) three on biopsy) and at least 3-year follow-up post biopsy. LRO was defined as decompensation (variceal bleeding, ascites, encephalopathy), HCC, liver transplant and liver-related death. Automated morphometry was performed to measure the Collagen Area Fraction (CAF). Survival at 3, 5 and 7 years respectively was evaluated. <h3>Results</h3> The study cohort comprised 155 patients (70% male; mean age 49 years). The median follow-up time was 78 months. A LRO occurred in 48 patients (31.0%, estimated annual incidence 5.2%). HCC developed in 16 patients (10.6%, estimated annual incidence 1.6%) liver-related death occurred in 34 patients (21.9%, estimated annual incidence 3.3%); clinical decompensation developed in 20 patients (13.3%, estimated annual incidence 2.1%). See Abstract P46 table 1. CAF was measured in a subgroup of 89 patients. The median CAF was calculated for each Ishak stage and increased progressively towards the more advanced stages. (IS 3: median CAF 3.7%, IQR 1.5–5.1; IS 4: median CAF 5.2%, IQR 2.8–7.4; IS 5: median CAF 6.8%, IQR 3.4–9.5; IS 6: median CAF 9.9%, IQR 6.2–15.7). Within Ishak stage 6 the median CAF scores predicting LRO were higher (13.89, 12.48 and 12.69%) compared to median CAF scores in patients with no outcomes (8.59, 8.32 and 8.10%) at years 3, 5 and 7 respectively. <h3>Conclusion</h3> Clinical outcomes represent realistic and meaningful end-points for future trials evaluating anti-fibrotic agents once advanced fibrosis has developed. Further development and validation of morphometry within advanced fibrosis could enable better identification of patients at risk of more rapid progression of liver disease than Ishak stage alone.
TCT-396 Head-to-Head Comparison of Automated versus Manual Detection for Lumen Contour and Stent Struts in Optical Coherence Tomography Analysis
Authors: Kyuhachi Otagiri, Hideki Kitahara, Tomonori Yaguchi, Shigemitsu Tanaka, Kozo Okada, Yuhei Kobayashi, Takashi Miura, Soichiro Ebisawa, Yusuke Miyashita, Paul Yock, Peter J. Fitzgerald, Uichi Ikeda, Yasuhiro Honda
Journal: Journal of the American College of Cardiology (2014)