tbuckley/cabot-search huggingface dataset:
AB1429-HPR Mediating role of coping styles in the relationship between anxiety and health behaviors in a group
Authors: E. Mojs, W. Samborski, M. Ziarko
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anxiety remains one of the consequences of chronic diseases such as rheumatoid arthritis. High anxiety levels not only decrease the patient’s QoL, but also trigger anti-health behaviours and may adversely influence the course of the disease. The connection between neuroticism and anxiety has been well-documented so far. Neuroticism remains a temperamental trait so it is hardly modifiable. Reduction of psychological costs connected with high neuroticism entails the need to learn factors, which may limit the impact of neuroticism on anxiety levels (factors moderating the relation between anxiety and neuroticism). <h3>Objectives</h3> The aim of the study was to determine moderator variables of the relation between anxiety and neuroticism. <h3>Methods</h3> The study involved 100 participants (78 women and 22 men), all of whom were RA patients. They were given a set of questionnaires to evaluate their anxiety levels, coping styles and personality dimensions. Pearson – r correlation analysis and moderator analysis of the relation between neuroticism and anxiety as a state mediated by coping styles were performed. The interaction testing was performed by way of the least-squares analysis and logistic regression. <h3>Results</h3> A directly proportional correlation was found between neuroticism and anxiety as a state (r =0.63; p&lt;0.01) (Table I). This correlation was not observed in highly neurotic subjects using avoidant coping style (R2 =0.19; F =7.00; p&lt;0.001) (Fig. 1) and in avoidant social coping style subjects (R2 =0.22; F =8.70; p&lt;0.001) (Fig. 2, Table II). The results show that strong neuroticism increases probability of the patient’s anxiety reaction to symptoms and risks which are consequences of the disease. <h3>Conclusions</h3> The observed correlation proves the hypothesis that temperament is a risk factor in behavioural disorders. They also suggest that neurotic RA patients should be persuaded to distance themselves from the illness and encouraged to activate their social life. <h3>Disclosure of Interest</h3> None Declared
OP0077 Erythromelalgia – Clinical Characteristics and Response to Therapy in 46 Patients from a Single Centre
Authors: L. Parker, C. Ponte, C. P. Denton, B. E. Schreiber
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Erythromelalgia is rare and its clinical characteristics and response to therapy are still poorly defined. <h3>Objectives</h3> To review our clinical experience of this rare condition and describe the clinical features and response to therapy. <h3>Methods</h3> We performed a search of electronic medical records for patients with a diagnosis of erythromelalgia. We then attempted to contact patients by telephone to complete a structured questionnaire. <h3>Results</h3> A total of 111 patients were identified, of whom 46 completed a telephone questionnaire. Mean age was 57 years and 41 of 46 were female. The mean time from symptom onset to diagnosis was 6 years, and the mean duration of symptoms was 16 years. 37 of 46 (80%) had Raynaud's phenomenon for an average of 22 years. 4 of the patients had systemic sclerosis, 26 were current or previous smokers, 3 had exposure to chronic vibration. 22 of the patients described their symptoms as continuous, 24 as intermittent. Overall the effect on quality of life was mild in 7, moderate in 14, severe in 16 and 6 patients reported they were intolerant to any physical activity. The symptoms affected the lower limbs in 45 (98%), upper limbs in 35 (76%), the face in 9 (20%) and the trunk in 5 (11%). The most common symptoms (n, out of 46) were of burning (44), heat (43), pain (40), redness (38), swelling (30) and numbness (25). Patients reported worsening with exercise (36), hot environments (39) and at night (35) and improvements with cooling (36) and elevation (24). Complications included infection in 3 and skin breakdown in 6 patients. Blood tests showed mean Hb 13.6, platelets 285, ESR 10. ANA was positive in 7 patients, ENA in 2 patients, ANCA and dsDNA in no patients and complements were low in 5 patients. Intravenous iloprost was attempted in 27 patients and the response was marked in 5, moderate in 8, mild in 4 and there was no response in 10 patients. A wide variety of medications were tried. We list here all patients tried in at least five patients and the subjective record of efficacy. <h3>Conclusions</h3> Erythromelalgia is a chronic debilitating condition which is usually present for years before diagnosis. Exercise, heat and night time are common triggers while cooling and elevation are often comforting. Current medical therapies are seldom effective and further research is sorely needed. <h3>Disclosure of Interest</h3> None Declared
Access to specialist palliative care is still inadequate, audit finds
Authors: Anne Gulland
Journal: BMJ (2016)

Just 11% of trusts offer face to face access to specialist palliative care 24 hours a day and seven days a week, an audit of care at the end of life by the Royal College of Physicians has found.1

In its first major audit of the care of dying patients since the axing of the Liverpool Care Pathway in 2014,2 the college found that just 16 of the 137 trusts that submitted data offered 24/7 access to a palliative care specialist. Some 53 of the trusts (37%) offered access from 9 am to 5 pm seven days a week, but while most trusts offered around the clock telephone support from specialist nurses, 26 trusts (19%) had no specialist medical out of …
Abstract 2786: Identification and preclinical characterization of EMD 1204831 – A selective c-Met kinase inhibitor in clinical phase 1
Authors: Friedhelm Bladt, Andree Blaukat, Dieter Dorsch, Claus Fittschen, Manja Friese-Hamim, Ulrich Graedler, Christine Knuehl, Michael Meyring, Oliver Schadt, Frank Stieber
Journal: Cancer Research (2011)

Abstract The involvement of the mesenchymal endothelial transition factor (c-Met) in the primary event of oncogenic transformation and the secondary ability to mediate metastatic spread has been convincingly demonstrated in preclinical and early clinical settings. The clinical benefits of c-Met kinase inhibitors with various modes of actions and selectivity profiles are currently under investigation hoping that inhibitors of c-Met might emerge as valuable cancer therapeutics in the future. During an HTS run 3-(diethylamino)propyl N-[3-[[5-(3,4-dimethoxyphenyl)-2-oxo-6H-1,3,4-thiadiazin-3-yl]methyl]phenyl]carbamate was identified as an attractive lead structure with an interesting overall profile (clogD (7.4): 2.5, S (pH 7.4): &amp;gt;100 µg/ml, IC50 (cMet enzyme): 30 nM, IC50 (cMet A549): 800 nM) providing a valid starting point. The co-crystal structure of 1 revealed the binding mode and the essential structural features. The initial HTS hit was bound in a DFG-in conformation interacting with the main chain nitrogen atom of Met1160 within the hinge region and with the main chain nitrogen of Asp1222. After subsequent optimization of potency, efficacy, PK properties and the safety profile of thiadiazinone 1, EMD1204831 was identified as development compound. EMD1204831 is currently being investigated in a phase 1 clinical trial. The pyridazinone EMD1204831 inhibits enzymatic and cellular c-Met kinase activity with IC50 values of 12 nM and 15 nM, respectively. EMD1204831 displayed an exquisite selectivity when tested in vitro against a panel of more than 400 potential off-targets, including kinases, GPCRs, ion channels, transporters and various enzymes. EMD 1204831 demonstrated excellent anti-tumor activity in vivo in a variety of xenograft models, including U87-MG glioblastoma cells (autocrine HGF expression), TPR-Met-transformed mouse fibroblasts (oncogenic Met fusion protein) or Hs746T gastric cancer cells (c-Met gene amplification and HGF-independent activation). Depending on the particular model, complete regressions were observed with doses as low as 6 mg/kg/d administered per os. PK/PD analysis revealed efficient, dose- and time-dependent inhibition of c-Met phosphorylation, reduction of IL-8 and cyclin D1 expression as well as an induction of the cell cycle inhibitor p27. The overall profile of EMD1204831 including first time structural disclosure, some structure activity relationships, in vitro potency, selectivity profile and in-vivo data will be presented. 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 2786. doi:10.1158/1538-7445.AM2011-2786
A Novel Methylation Signature that Reflects Intratumoral Lymphocyte Infiltration in Breast Cancer and Predicts for Response to Anthracycline Treatment
Authors: J. Jeschke, M. Defrance, C. Desmedt, M. Bizet, S. Dedeurwaerder, E. Calonne, C. Sotiriou, F. Fuks
Journal: Annals of Oncology (2014)
A novel method to obtain biopsy samples from proximal biliary strictures
Authors: Fatih Tekin, Ilker Turan, Galip Ersoz, Oktay Tekesin, Omer Ozutemiz
Journal: Endoscopy (2014)

Brush cytology and forceps biopsy are the most commonly used techniques to allow a diagnosis to be reached in patients found with suspected proximal biliary malignancies during endoscopic retrograde cholangiography. However, the sensitivity of brush cytology for diagnosis of malignant biliary strictures ranges only from 30 % to 60 % [1], while in the case of the biopsy forceps it may in some cases be impossible to advance the forceps to the level of the stricture. Recently, we had experience of three cases of proximal biliary stricture in which cholangiocarcinoma was strongly suspected. In all three it proved possible to obtain sufficient biopsy samples for a diagnosis using a novel method.
Abstract 2218: Whole exome DNA sequencing in human cancers of the digestive system
Authors: David A. Wheeler, Marie-Claude Gingras, Ronald Cotton, Jacques Guiteau, Sally Hodges, Min Wang, Yuan-Qing Wu, Irene Newsham, Lynne V. Nazareth, William E. Fisher, John A. Goss, Francis C. Brunicardi, Donna M. Muzny, Richard A. Gibbs
Journal: Cancer Research (2010)

Abstract The onset and progression of cancer is driven by extensive rearrangement and mutation of the genome. The ever-expanding sequencing capacity ushered in by the second generation of DNA sequencers has enabled complete base-level description of the cancer genome and is therefore deepening our understanding of the etiology of the disease. We have combined a variety of approaches centered on next generation sequencing technologies aimed at comprehensive characterization of the cancer genome to define the key molecular lesions that drive tumor initiation and progression. These include targeted exonic sequencing to define coding sequence mutation, whole genome shotgun sequencing to define structural rearrangements, and cDNA sequencing to define alteration in expression levels, aberrant splicing and fusion transcripts. We have applied these approaches to pancreatic adenocarcinoma, hepatocellualr carcinoma and colorectal carcinoma. Results of genome sequencing have yielded an unprecedented picture of the rearrangements and mutations from analysis of read sequence and read coverage across the chromosomes. Evident in both the cancers is a dramatic reduction in SNP variation in the tumor genome compared to the germline from the same individual owing to extensive loss of heterozygosity. Superimposed on this are a few thousand mutations, some of which drive the tumor phenotype. The corresponding set of analog data generated by SNP-array microarray platforms provide validation of the central results from sequencing which leads to a new appreciation of the relationship between genetic change and the malignant phenotype. 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 2218.
417O Phase 3, randomized trial (CheckMate 057) of nivolumab vs docetaxel in advanced non-squamous (non-SQ) non-small cell lung cancer (NSCLC): subgroup analyses and patient reported outcomes (PROs)
Authors: L. Horn, J. Brahmer, M. Reck, H. Borghaei, D.R. Spigel, M. Steins, N.E. Ready, L.Q. Chow, E.E. Vokes, E. Felip, E. Holgado, F. Barlesi, M. Kohlhäufl, M.A. Burgio, J. Fayette, S.N. Gettinger, C.T. Harbison, A. Li, F.G. Finckenstein, L. Paz-Ares
Journal: Annals of Oncology (2015)
Prophylactic Administration of Respiratory Syncytial Virus Immune Globulin to High-Risk Infants and Young Children
Authors: Jessie R. Groothuis, Eric Simoes, Myron J. Levin, Caroline B. Hall, Christine E. Long, William J. Rodriguez, Julita Arrobio, H. Cody Meissner, David R. Fulton, Robert C. Welliver, Debra A. Tristram, George R. Siber, Gregory A. Prince, Mark Van Raden, Val G. Hemming
Journal: New England Journal of Medicine (1993)

Infants with cardiac disease or prematurity are at risk for severe illness caused by respiratory syncytial virus. Immune globulin with a high titer of antibodies against respiratory syncytial virus may offer infants and young children at risk protection from this serious, common respiratory illness.
S109 Contribution of aberrant monocyte-natural killer T (NKT) cell axis to immune-pathology in sarcoidosis
Authors: A. P. Crawshaw, W. L. Kok, L. Denney, L.-P. Ho
Journal: Thorax (2011)

<h3>Introduction</h3> Sarcoidosis is a multisystem disorder characterisedby an overactive CD4 (T-helper 1) cell response to an undefined antigen, macrophage activation and granuloma formation. It has also been shown that monocytes (precursors to macrophages) are increased in sarcoidosis. We have shown that NKT cells, a specialised subset of immuneregulatory T cells, are deficient in sarcoidosis, and that in NKT knock-out mice, monocytes accumulate at sites of inflammation in both models of influenza A infection and multiple sclerosis. Here, we hypothesise that NKT cells control monocyte function and that NKT cell deficiency in sarcoidosis results in abnormal monocyte activity. <h3>Methods</h3> Twenty-five steroid-naïve non-smoking patients with histological confirmation of sarcoidosis were recruited from the Sarcoidosis-ILD service. Circulating monocyte numbers and phenotype were first characterised using multi-colour flow cytometry. We then isolated monocytes from blood using magnetic microbeads, examined cytokine production after LPS stimulation with intracellular cytokine FACS staining and ELISA; and using monocyte-NKT cell co-culture assays, questioned whether NKT cells affected these monocytic functions. <h3>Results</h3> We found an increase in circulating CD14CD16 inflammatory monocytes in patients with sarcoidosis, and identified a population of interleukin 10 producing monocytes in patients and controls after LPS stimulation. Monocytes from sarcoidosis patients have reduced capacity to produce IL-10 after LPS stimulation compared to control (6.37% vs 11.71% of total monocytes, p&lt;0.001, Abstract S109 figure 1A); but addition of NKT cells improved this capacity (6.37% to 9.13%, p&lt;0.001, Abstract S109 figure 1B). We then questioned the role of IL10-producing monocytes and show (with mixed lymphocyte reaction and CFSE assays) that these cells suppress T cell proliferation (p&lt;0.001, Abstract S109 figure 1C). <h3>Conclusions</h3> Our data show that sarcoidosis patients have increased inflammatory monocytes but a reduced IL-10-producing, T cell suppressing subset. NKTcells were able to interact with monocytes in vitro and increased IL-10 production by monocytes. These previously unrecognised findings, both in monocyte-NKT cross talk and in sarcoidosis immunobiology, suggest that one consequence of NKT deficiency in sarcoidosis is abnormal monocyte function with resultant loss in control of T cell proliferation. This reveals a potential new pathway of pathogenesis in sarcoidosis.
1217 EXPERIENCE OF HCV RESISTANCE AFTER 1.5 YEARS CLINICAL PRACTICE; DETECTION OF RESISTANCE MUTATIONS AFTER LONG PERIOD OF UNDETECTABILITY
Authors: M.-H. Teillon-Béranger, M.-A. Trabaud, C. Ramière, M. Maynard-Muet, P. Chevallier-Queyron, P. André, C. Scholtes
Journal: Journal of Hepatology (2013)
721 SOLUBLE LIGANDS FOR ACTIVATING NATURAL KILLER RECEPTOR (NKG2D) AS SCREENING TOOL TO PREDICT SEVERITY OF ALLOGRAFT FIBROSIS AFTER LIVER TRANSPLANTATION
Authors: S. Iacob, V.R. Cicinnati, M. Lindemann, F.M. Heinemann, V. Rebmann, I. Kabar, H.J. Schmidt, A. Radtke, S. Beckebaum
Journal: Journal of Hepatology (2013)
Abstract 5131: Identification of the genes that chemosensitize hepatocellular carcinoma cells to interferon-α and 5-fluorouracil therapy
Authors: Goshi Shiota, Tomohiko Sakabe, Hiroaki Nagano, Hiroyuki Tsuchiya
Journal: Cancer Research (2012)

Abstract The increasing numbers of patients with hepatocellular carcinoma (HCC), which is characterized by an extremely poor prognosis, are causing serious problems worldwide. To improve their prognosis, the development of a more effective therapy is required. Combination therapy with interferon-α (IFN-α) and 5-fluorouracil (5-FU) was reported to provide benefits to patients with advanced HCC, although its efficacy is still unsatisfactory. In this study, taking advantage of functional screening, three chemosensitizing genes for this therapy against HCC cells were identified. Identification of chemosensitizing genes was performed using ribozyme-based functional screening. We constructed a plasmid DNA library expressing random ribozyme genes with ∼6.0 × 106 target recognition sequences. We performed a positive-selection strategy based on the ability of 5-FU to eliminate cells expressing a ribozyme that targets chemosensitivity-unrelated genes. The ribozyme library was transfected into HepG2 cells, which were subsequently treated with the IC50 dose of 5-FU. This cycle was repeated 10 times to fully concentrate the ribozymes targeting those genes involved in the sensitivity of 5-FU. Consequently, 100 target ribozyme recognition sequences that were recovered before screening and after 10 cycles of screening were subjected to a BLAST search to retrieve genes with homologous sequences. This analysis indicated 3 genes (PRKAG2, TGFBR2, and EXT1) as candidate genes. The chemosensitizing effects of these genes on IFN-α/5-FU as well as 5-FU treatment were confirmed by adenovirus-mediated gene transfer. In addition, the mechanisms of effects of these genes on enhancing effects on combination therapy with IFN-α/5-FU were also evaluated. Furthermore, to evaluate the relationship between their expression levels in tumor tissues and the clinical outcome of IFN-α/5-FU combination therapy in advanced HCC patients, mRNA expression was measured using real-time reverse transcription-polymerase chain reaction. As a result, PRKAG2, TGFBR2, and EXT1 were identified as novel chemosensitizing genes for the combination therapy against HCC. TGFBR2 and EXT1 induced transforming growth factor-β signal activation and endoplasmic reticulum stress, respectively. Moreover, PRKAG2 and TGFBR2 were suggested to be promising predictive markers for the clinical outcome of this therapy. In conclusion, the identified genes are promising candidates as targets to enhance the therapeutic effect of IFN-α/5-FU combination therapy in advanced HCC and could be used as predictive markers for response to this therapy. 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 5131. doi:1538-7445.AM2012-5131
Abstract 1020: Combined effects of BCL-2 pathway gene variants on the risk of endometrial cancer: results from Shanghai Endometrial Cancer Study
Authors: Tsogzolmaa Dorjgochoo, Jirong Long, Yong-Bing Xiang, Qiuyn Cai, Hui Cai, Jiarong Cheng, Wei Zheng, Xiao-ou Shu
Journal: Cancer Research (2010)

Abstract The BCL-2 pathway genes may play important roles in regulation of apoptosis. It has been suggested that overexpression of the antiapoptotic Bcl2 gene variants associated with the risk of endometrial cancer. Proapoptotic BAX, BAK, BAD are believed to diffuse in cell carcinogenesis. We hypothesized that single-nucleic polymorphisms (SNPs) in the Bcl-2 pathway genes including Bcl2, BAX, BAD and BAK1 may be associated with endometrial cancer risk. Included in this study were 1,028 endometrial cancer cases and 1,003 controls from the Shanghai Endometrial Cancer Study. A total of 77 tagging SNPs were genotyped for these genes using the Affymetrix MegAllele Targeted Genotyping system. A logistic regression was used to estimate the association between SNPs and the cancer risk. Genetic risk score (GRS) was calculated using a simple count method that included the SNPs that showed significant associations and are not in LD with each other (r2 &amp;lt;0.8). Significant associations with cancer risk were found for SNP rs477895 in the BAD gene and 7 SNPs in the Bcl2 gene, including rs7243091, rs7230177, rs7231901, rs17759659, rs4941195, rs2279115 and rs1944423. Women carrying the minor homozygous and heterozygous genotypes of SNPs including rs7243091, rs17759659, rs4941195, rs2279115 and rs1944423 have an increased risk of endometrial cancer (age adjusted odds ratio [OR] range, 1.2-2.1; P trend &amp;lt;0.05 for all), compared with women carrying the major homozygous genotypes. For SNPs rs7230177 and rs7231901, a decreased risk was observed among individuals carrying minor homozygous genotype and heterozygous compared with the major genotype (P trend &amp;lt;0.01). Haplotype analyses of the Bcl2 gene showed two haplotypes, GTCGCTG and ACAAATG were associated with a significant increase in risk of endometrial cancer (P value &amp;lt;0.05). The risk of endometrial cancer tended to increase with higher GRS (based on 5 SNPs of the Bcl2) (multivariate OR=1.96, 95% CI: 1.44-2.65 for ≥5 vs. ≤1 GRS, P trend &amp;lt;0.01). This increased risk was stronger among postmenopausal or obese (BMI ≥27.5) women than among premenopausal or non-obese women (P trend &amp;lt;0.05 for both). These findings suggest that BCL-2 pathway genes, particularly Bcl2 genetic variations are significantly associated with an increased risk of endometrial cancer among Chinese women. A GRS which combines information from several variants of Bcl2 gene might have a potential to identify the women at a high risk of endometrial 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 1020.
Papilledema Associated with Intracranial Hypertension
Authors: W J Power, E Harris
Journal: New England Journal of Medicine (2001)

Figure 1. A 21-year-old woman presented with a two-month history of gradual loss of vision in both eyes and increasing headaches. A ventriculoperitoneal shunt had been inserted when she was one year old. Funduscopic examination demonstrated marked papilledema, with retinal hemorrhages, retinal edema, and the deposition of exudate in a star formation in the macula of both eyes (Panels A and B). Visual acuity was 20/400 in the right eye and was limited to counting fingers from a distance of 0.6 m (2 ft) in the left eye. Investigation revealed that the shunt was blocked. Repair of the shunt resulted . . .