tbuckley/cabot-search huggingface dataset:
THU0594 Improved Psychological Well-Being and Physical Functioning in Rheumatoid Arthritis: A Cohort Study Covering Two Decades
Authors: C. L. Overman, M. S. Verhoef-Jurgens, P. M. Welsing, E. R. Bossema, J. W. Jacobs, J. W. Bijlsma, R. Geenen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Only a few decades ago, the common recommendation given to patients with rheumatoid arthritis (RA) was to rest. Nowadays, physical activity and other means to improve well-being and functioning are encouraged, and pharmacological treatment has improved tremendously. <h3>Objectives</h3> To examine if well-being and functioning in RA patients improved over the past two decades, and whether this is explained by a reduction of diseased activity. <h3>Methods</h3> From 1990 to 2011, consecutive annual cohorts of RA patients (N = 1151, age 17-86 years, 68% female, 62% rheumatoid factor positive) were monitored. Functional status, mood, and anxiety were assessed at diagnosis (baseline) and after 3 to 5 years of treatment (follow-up), and were subsequently predicted by year of assessment and disease activity (erythrocyte sedimentation rate, joint score) in hierarchical multiple regression analyses, controlled for age, gender, education level, marital status, and RF. Cohen’s <i>d</i> expressed effect size. <h3>Results</h3> At baseline, small improvements in depressed mood (<i>d =</i> -0.36, <i>p =</i>.01), anxiety (<i>d =</i> -0.46, <i>p =</i>.001), and functioning (<i>d =</i> 0.32, <i>p =</i>.02) were observed. At follow-up, level of depressed mood and (baseline-adjusted) levels of cheerful mood and anxiety showed small improvements over the two decades (0.24 ≤ <i>d</i> ≤ 0.43, <i>p</i> ≤.04). A medium (baseline-adjusted) improvement in follow-up physical functioning was observed (0.72 ≤ <i>d</i> ≤ 0.79, <i>p</i> &lt;.001). Taking decline in disease activity into account, trends in baseline functioning and follow-up well-being were no longer significant (<i>p</i> ≥.07) while upward trends in baseline well-being (<i>p</i> ≤.03) and follow-up functioning still were (<i>p</i> ≤.01; see Figure 1). Small effects on results were observed of variables that changed across the years such as an increase in education level and the number of males. <h3>Conclusions</h3> Over the past two decades, well-being and especially physical functioning have improved significantly. These trends are partly explained by a decline in disease activity. The results support the impression that improved pharmacological and educational interventions have contributed to an improved quality of life in RA. <h3>Disclosure of Interest</h3> None Declared
Venting the Spleen
Authors: Neal Varughese, Angie Duong, Sukru Emre, Mina Xu, Alfred Ian Lee
Journal: New England Journal of Medicine (2013)

A 19-year-old woman presented with a 4-day history of abdominal pain in the right upper quadrant and epigastrium, with occasional radiation to her back. She also noted profound fatigue and a 13.6-kg weight loss during the preceding months.
Disparities in Incidence of Diabetic End-Stage Renal Disease According to Race and Type of Diabetes
Authors: Catherine C. Cowie, Friedrich K. Port, Robert A. Wolfe, Peter J. Savage, Patricia P. Moll, Victor M. Hawthorne
Journal: New England Journal of Medicine (1989)

The incidence of end-stage renal disease in patients with diabetes mellitus is reportedly higher among blacks than among whites. This finding may be explained by the greater prevalence of diabetes among blacks. The relation of the type of diabetes to the risk of diabetic end-stage renal disease is largely unstudied. We addressed these issues in a study of all the black and white diabetic patients with end-stage renal disease (470 blacks and 861 whites) reported to the Michigan Kidney Registry who began treatment during 1974 through 1983. We also reviewed the medical records of a subpopulation of such patients (284 blacks and 310 whites) who were less than 65 years of age at the start of treatment for end-stage renal disease to determine what type of diabetes they had. In this study, we made use of national data on the prevalence of diabetes. We found that the incidence of diabetic end-stage renal disease was 2.6-fold higher (P≤0.0001) among blacks after we adjusted for the higher prevalence of diabetes among blacks, with the excess risk occurring predominantly among blacks with non-insulin-dependent diabetes mellitus (NIDDM). Most black patients with diabetic end-stage renal disease had NIDDM (77 percent), whereas most white patients with diabetic end-stage renal disease had insulin-dependent diabetes mellitus (IDDM) (58 percent) (P≤0.0005 for the difference between the races). For both races combined, the risk of diabetic end-stage renal disease during the 10-year period we studied was markedly greater for patients with IDDM (5.8 percent) than for those with NIDDM (0.5 percent). Our results indicate an increased risk of diabetic end-stage renal disease among blacks as compared with whites, particularly blacks with NIDDM. Although the risk of diabetic end-stage renal disease is higher in patients with IDDM, the majority of patients with diabetic end-stage renal disease in the population we studied had NIDDM. (N Engl J Med 1989; 321:1074–9.)
PMO-240 Better disease specific patient knowledge is associated with greater anxiety in inflammatory bowel disease patients
Authors: C Selinger, J McLaughlin, J Eaden, R Leong, S Lal
Journal: Gut (2012)

<h3>Abstract</h3> <h3>Background</h3> N-acetyl aspartate (NAA) is a marker of neuronal integrity and metabolism. Deficiency in neuronal plasticity and hypometabolism are implicated in the pathophysiology of Major Depressive Disorder (MDD). To test if cerebral NAA concentrations decrease progressively over the MDD course, we conducted a meta-analysis of Proton Magnetic Resonance Spectroscopy (<sup>1</sup>H-MRS) studies comparing NAA concentrations in chronic MDD (cMDD) and first episode of depression (FED) to healthy controls. <h3>Methods</h3> We searched Scopus® and Web of Knowledge℠ using search terms related to depression and NAA. Hedges’ g was used as effect size measure, together with heterogeneity analyses, test of moderators and publication bias and quality assessment. The protocol is pre-registered in PROSPERO (CRD42020221050). Sixty-two studies were included and meta-analyzed using a random-effect model for each brain region. <h3>Results</h3> NAA concentrations were significantly reduced in cMDD compared to healthy controls within the frontal lobe (Hedges’ g =-0.330; p=0.018), the occipital lobe (Hedges’ g=-0.677; p=0.007), the thalamus (Hedges’ g=-0.673; p=0.016) and the frontal (Hedges’ g=-0.471; p=0.034) and periventricular white matter (Hedges’ g=-0.478; p=0.047). We highlighted a gap of knowledge regarding NAA levels in FED. Sensitivity analyses indicated that antidepressant treatment may reverse NAA alterations in the frontal lobe. None of the clinical or <sup>1</sup>H-MRS-related methodological moderators had a significant impact on the effect sizes. <h3>Conclusions</h3> Our findings are in line with the hypometabolism hypothesis of MDD. Future studies should assess NAA alterations in the early stages of the illness and their longitudinal progression, also considering the modifying effect of antidepressant treatment.
Abstract 13883: Cyclosporin-A Inhibits Nuclear Localization of theTranscription Factor Nrf2 in Human Coronary Artery Endothelial Cells
Authors: Arash Ghashghai, Mitesh Badiwala, Jack Wallen, Laura Tumiati, Jemy Joseph, Feng Xu, Vivek Rao
Journal: Circulation (2010)

Background: Cyclosporin-A (CsA) is known to cause endothelial dysfunction. However, the mechanisms behind CsA-induced damage have not been fully elucidated. We investigated the effect of CsA on the...
The Effects of a 5-Lipoxygenase Inhibitor on Asthma Induced by Cold, Dry Air
Authors: Elliot Israel, Robert Dermarkarian, Mitchell Rosenberg, Richard Sperling, Graham Taylor, Paul Rubin, Jeffrey M. Drazen
Journal: New England Journal of Medicine (1990)

The enzyme 5-lipoxygenase catalyzes the metabolism of arachidonic acid to form products that have been implicated in the airway obstruction of asthma. We hypothesized that if products of the 5-lipoxygenase pathway are important in mediating this obstruction, then prevention of their formation should decrease the severity of an induced asthmatic response.
Initial experience with endoscopic sleeve gastroplasty: technical success and reproducibility in the bariatric population
Authors: Reem Sharaiha, Prashant Kedia, Nikhil Kumta, Ersilia DeFilippis, Monica Gaidhane, Alpana Shukla, Louis Aronne, Michel Kahaleh
Journal: Endoscopy (2014)

Novel endoscopic techniques have been developed as effective treatments for obesity. Recently, reduction of gastric volume via endoscopic placement of full-thickness sutures, termed endoscopic sleeve gastroplasty (ESG), has been described. Our aim was to evaluate the safety, technical feasibility, and clinical outcomes for ESG.Between August 2013 and May 2014, ESG was performed on 10 patients using an endoscopic suturing device. Their weight loss, waist circumference, and clinical outcomes were assessed.Mean patient age was 43.7 years and mean body mass index (BMI) was 45.2 kg/m(2). There were no significant adverse events noted. After 1 month, 3 months, and 6 months, excess weight loss of 18 %, 26 %, and 30 %, and mean weight loss of 11.5 kg, 19.4 kg, and 33.0 kg, respectively, were observed. The differences observed in mean BMI and waist circumference were 4.9 kg/m(2) (P = 0.0004) and 21.7 cm (P = 0.003), respectively.ESG is effective in achieving weight loss with minimal adverse events. This approach may provide a cost-effective outpatient procedure to add to the steadily growing armamentarium available for treatment of this significant epidemic.
Abstract 2282: Inhibition of vasculogenesis, but not angiogenesis, reduces tumor recurrence following irradiation
Authors: Martin Brown, Mitomu Kioi, G-one Ahn
Journal: Cancer Research (2010)

Abstract Tumor blood vessels can derive from two sources: by angiogenesis, or the sprouting of endothelial cells from nearby blood vessels, and by vasculogenesis, which is produced by circulating cells. We have proposed that the radiation doses given in radiotherapy, will severely restrict local angiogenesis and thereby force tumor regrowth to rely on vasculogenesis. This involves the recruitment of proangiogenic circulating cells many of which are derived from the bone marrow. To investigate this hypothesis, we used the subcutaneously implanted FaDu human head and neck tumor and an orthotopic brain tumor using human U251 GBM cells. We found that local tumor irradiation induced the influx of bone marrow derived cells (BMDCs) in a dose-dependent manner into both tumor models with most of this increase reflecting influx of CD11b+ myelomonocytes. We postulated that this influx of BMDCs was stimulated by increased tumor hypoxia and HIF-1 levels caused by radiation damage to the tumor vasculature. To determine HIF-1 activity in real-time in our brain implanted U251 GBM, we stably expressed the HIF-1 reporter construct 5HRE-luc in U251 cells and showed that HIF-1 activity increased rapidly starting at about two weeks following 15 Gy, in parallel to the increase in tumor hypoxia that we observed at this time. To test our hypothesis that the increased HIF-1 levels were responsible for the increased influx of CD11b+ cells into the tumors, we used the HIF-1 inhibitor NSC-134754. When this was given daily for 2 weeks, starting immediately following irradiation, the increased tumor levels of CD11b+ monocytes observed after 15 Gy was abrogated. This treatment also prevented the regrowth of the irradiated tumors following irradiation. As a further test of our hypothesis we determined the effect of inhibiting the interaction of SDF-1 with its receptor CXCR4 using the clinically approved drug AMD3100, which we infused starting immediately following irradiation. This had no effect on the growth of unirradiated tumors in the brain but completely inhibited the recurrence of the irradiated tumors following either a single dose of 15 Gy or the more clinically relevant scheme of 5 daily doses of 2 Gy. Inhibition of angiogenesis with DC101 increased tumor growth delay but did not prevent tumor recurrences. We also showed that the recurrence of FaDu tumors locally irradiated with 20 Gy was prevented using a monoclonal neutralizing antibody against CD11b+ monocytes. This treatment did not increase the radiosensitivity of normal skin thereby providing a therapeutic gain. 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 2282.
Abstract 3086: Gain of chromosome 13 is a cause of CDK8 overexpression associated with colorectal adenoma to carcinoma progression
Authors: Beatriz Carvalho, Cindy Postma, Sandra Mongera, Pien van Diemen, Bauke Ylstra, Gerrit A. Meijer
Journal: Cancer Research (2010)

Abstract Introduction: Colorectal adenomas are common precursors of colorectal cancer (CRC). About only 5% of adenomas progress to cancer and this progression is mostly associated with overall onset/increase of chromosomal instability. Gain of 13q is often implicated in this progression of adenoma to carcinoma (1). Until recently however no genes were identified to be the drivers of this amplicon. Recently, Firestein and collaborators (2) showed that cyclin 8 (CDK8), at 13q12.13, functions as an oncogene in CRC. The aim of this study was to evaluate CDK8 gene dosage effects in colorectal adenoma to carcinoma progression. Material and methods: Sixty seven colorectal tumours (34 adenomas and 28 carcinomas) were analysed by array CGH (5k BAC platform, including contig coverage of 13q) and by expression microarray (30k Compugen library). Integration of DNA copy number dosage and gene expression was performed using the Ace-it tool (3). Results: In the tumours analysed we observed 13q copy number gain in 9% and 46% of adenomas and carcinomas, respectively. Integrating copy number and mRNA expression with the differential upregulation of genes between carcinomas and adenomas, provided us with a list of 43 genes. Within this list, CDK8 ranked 7th in significancy (p=0.003). Conclusions: Copy number gain of 13q has a gene dosage effect on CDK8 mRNA expression, indicating a role of this gene in colorectal adenoma to carcinoma progression. (1) Hermsen M, Postma C, Baak J, Weiss M, Rapallo A, Sciutto A, Roemen G, Arends JW, Williams R, Giaretti W, De Goeij A, Meijer G. Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability. Gastroenterology 2002 Oct;123(4):1109-19. (2) Firestein R, Bass AJ, Kim SY, Dunn IF, Silver SJ, Guney I, Freed E, Ligon AH, Vena N, Ogino S, Chheda MG, Tamayo P, Finn S, Shrestha Y, Boehm JS, Jain S, Bojarski E, Mermel C, Barretina J, Chan JA, Baselga J, Tabernero J, Root DE, Fuchs CS, Loda M, Shivdasani RA, Meyerson M, Hahn WC. CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity. Nature 2008 Sep 25;455(7212):547-51. (3) van Wieringen WN, Belien JA, Vosse SJ, Achame EM, Ylstra B. ACE-it: a tool for genome-wide integration of gene dosage and RNA expression data. Bioinformatics. 2006 Aug 1;22(15):1919-20. 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 3086.
Abstract 4283: Cross-species hybridization of microarrays for studying tumor transcriptome of brain metastasis
Authors: Eun Sung Park, Sun-Jin Kim, Seung Wook Kim, Se-Lyun Yoon, Sun-Hee Leem, Sang-Bae Kim, Soo Mi Kim, Yun-Yong Park, Jae-Ho Cheong, Hyun Goo Woo, Gordon B. Mills, Isaiah J. Fidler, Ju-Seog Lee
Journal: Cancer Research (2012)

Abstract Although the importance of the cellular microenvironment (soil) during invasion and metastasis of cancer cells (seed) has been well-recognized, technical challenges have limited the ability to assess the influence of the microenvironment on cancer cells at the molecular level. Here, we show that an experimental strategy, competitive cross-species hybridization of microarray experiments, can characterize the influence of different microenvironments on cancer cells by independently extracting gene expression data of cancer and host cells when human cancer cells were xenografted into different organ sites of immunocompromised mice. Surprisingly, the analysis of gene expression data showed that the brain microenvironment induces complete reprogramming of metastasized cancer cells, resulting in a gain of neuronal cell characteristics and mimicking neurogenesis during development. We also show that epigenetic changes coincide with transcriptional reprogramming in cancer cells. These observations provide proof of principle for competitive cross-species hybridization of microarray experiments to characterize the effect of the microenvironment on tumor cell behavior 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 4283. doi:1538-7445.AM2012-4283
Presacral Neurectomy for Dysmenorrhea
Authors: Francis M. Ingersoll, Joe V. Meigs
Journal: New England Journal of Medicine (1948)

THIS paper deals with a series of presacral neurectomies performed for relief of dysmenorrhea. A total of 111 operations have been done at the Massachusetts General Hospital and the Palmer Memorial Hospital from 1930-1946. In most cases the neurectomy was combined with dilatation and curettage, a suspension and any other necessary pelvic surgery that the gynecologic situation demanded. These 111 cases can be divided into a group with essential dysmenorrhea and a group with acquired dysmenorrhea. The patients in the former group had severe crampy pain starting shortly after the menarche, with painful menstruation that severely upset their social and . . .
Abstract 1142: Development and validation of a multiplexed PCR-coupled liquid bead array for gene expression in circulating tumor cells
Authors: Athina N. Markou, Areti D. Strati, Nikolaos Malamos, Vasileios Georgoulias, Evi S. Lianidou
Journal: Cancer Research (2010)

Abstract INTRODUCTION: The aim of our study was to develop and validate a multiplexed PCR-coupled liquid bead array to detect the expression of multiple genes in Circulating Tumor Cells (CTCs), and application of this assay in peripheral blood samples of breast cancer patients. PATIENTS AND METHODS: We designed a novel multiplexed PCR-coupled liquid bead array that consist of the following steps: a) in silico designed gene-specific primers and capture probes for CK-19, HER-2, Mammaglobin (hMAM), MAGE-A3, TWIST-1 and PBGD (as a control gene), b) RNA isolation from immunomagnetically enriched CTCs, c) multiplex PCR, d) sequence hybridization array, e) detection in the Luminex platform. We performed extensive optimization experiments using the SKBR3 and MDA-MB-231 cell lines as positive controls, to maximize analytical sensitivity and specificity and we further validated the performance of this array in respect to cross reactivity and intra and inter-precision. Finally, we applied the developed methodology in peripheral blood samples of 37 patients with operable breast cancer, 25 patients with verified metastasis and 17 healthy individuals. RESULTS: The analytical performance of the developed array was evaluated in tumor cell lines in respect to analytical sensitivity and specificity. Cross reaction studies were performed for each gene target in the presence of all other targets. The assay is highly specific for each gene in complex multiplexed formats, since the discriminatory power of fluorescent bead sets is unique to specifically detect by sequence hybridization the presence of individual gene specific PCR products. The developed liquid bead-based array is highly sensitive, since it can detect the expression of each individual gene at one SKBR3 cell level. The validation of the array included within day and between-days precision studies. None of the genes tested was detected in the CTC fraction of healthy donors while in patients with verified metastasis, CK-19 was detected in 45%, HER-2 in 20%, MAGE-A3 in 30%, hMAM in 15% and TWIST-1 in 20%. In operable breast cancer patients, CK-19 was detected in 13.5%, HER-2 in 5%, TWIST-1 in 16.2%, MAGE-A3 in 37.8% while hMAM was not detected in any sample. CONCLUSIONS: Our results show that individual gene expression can be readily measured in CTCs using a bead-based platform. This may form an efficient basis for a multiplex approach to measure multiple genes (up to 100) in the same sample, thus saving sample volume and reducing the total cost and time of analysis. This is the first time that the Luminex technology is used for gene expression studies in CTCs. 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 1142.
The emergence of a C/EBPα mutation in the clonal evolution of MDS towards secondary AML
Authors: A Kaeferstein, U Krug, J Tiesmeier, M Aivado, M Faulhaber, M Stadler, J Krauter, U Germing, W K Hofmann, H P Koeffler, A Ganser, W Verbeek
Journal: Leukemia (2003)
Brief Communication: Tumor Suppression by Mycobacterium bovis (Strain BCG) Enhanced by Vitamin A
Authors: Monte S. Meltzer, Benjamin E. Cohen
Journal: JNCI Journal of the National Cancer Institute (1974)

Tumor suppression mediated by Mycobacterium bovis (strain BCG) was enhanced in vitamin A-treated mice. A significant decrease in tumor incidence was observed with a transplantable, syngeneic, 3-methylcholanthrene-induced sarcoma when tumor cells were mixed with 6×104 colony-forming units of BCG and injected intradermally into vitamin A-treated animals. This level of tumor suppression required 100-fold higher concentrations of BCG in untreated animals. Vitamin A treatment without BCG had no effect on tumor incidence or growth.