tbuckley/cabot-search huggingface dataset:
Abstract 4833: A genomic portrait of tumor progression using next-generation sequencing
Authors: Peter Johansson, Jun S. Wei, Qingrong Chen, Nikola Bowden, Tom C. Badgett, Young K. Song, Xinyu Wen, Catherine Holman, Susan Yeh, Javed Khan
Journal: Cancer Research (2011)

Abstract Genetic alterations are thought to enable cancers to proliferate and survive more effectively or to resist cytotoxic therapies. However, the molecular basis of tumorigenesis and progression is not fully understood. In order to understand the genetic aberrations underlying tumor progression in refractory neuroblastoma, we performed next-generation sequencing on the whole exomes of three sequential tumor samples taken from a high-risk stage 4 neuroblastoma patient at diagnosis, after cytotoxic therapies, and at death, paired with a germline DNA sample from the same patient. Each genomic DNA sample was first partitioned using SureSelect whole human exome kits targeting ∼38Mb of genomic regions, then subjected to sequencing. Each exome sequencing experiment yielded approximately 240 million mappable reads representing 12 billion base pairs. We used DiBayes to identify single nucleotide variants (SNVs). After filtering away the low-quality SNVs, we identified approximately 18,000 high-quality SNVs in each sample, of which ∼7500 are within the protein coding regions. Using the frequencies of the SNVs derived from the sequencing experiments, we discovered a shared LOH signature at the chromosome level among all three tumors indicating they originate from a common cancer progenitor. When we examined the germline DNA, we found about 97% of SNVs for each tumor sample were also found in the germline DNA, and each tumor had more than 300 unique somatic SNVs. These data showed that despite of the shared LOH pattern, tumor genomes are highly unstable at the single nucleotide level. Furthermore, we also found that the three tumor samples shared 64 SNVs which may be potential driver mutations. Twenty of those common 64 SNVs, located on 7 genes, are predicted to be damaging mutations by SIFT algorithm. These mutations are currently being validated using Sanger sequencing, and further RNA-seq in the same tumor samples to investigate for pathway disruption that may lead to chemo-refractory disease. 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 4833. doi:10.1158/1538-7445.AM2011-4833
The Effects of ACTH and of Cortisone on the Platelets in Idiopathic Thrombopenic Purpura
Authors: Bernard M. Jacobson, William D. Sohier
Journal: New England Journal of Medicine (1952)

THE following case reports illustrate the dramatic effects of ACTH and of cortisone on the platelets in 3 patients with idiopathic thrombopenic purpura.Case ReportsCase 1. C. I. (No. 13998), a 59-year-old woman, was first admitted to the Massachusetts General Hospital in March, 1945, with idiopathic thrombopenic purpura of several years' duration. Because of increasing purpura a splenectomy was performed, with marked improvement. In January, 1946, the patient underwent an uncomplicated cholecystectomy for cholelithiasis. She suffered no recurrent symptoms until the summer of 1950, when petechiae and later ecchymoses developed over her legs and trunk. For two months prior . . .
Differences in telomere length between sporadic and familial cutaneous melanoma
Authors: C. Menin, E. Bojnik, P. Del Bianco, L. Elefanti, K. Gianesin, S. Keppel, C. Stagni, S. Mocellin, A. Vecchiato, A. De Rossi
Journal: British Journal of Dermatology (2016)

Several pieces of evidence indicate that a complex relationship exists between constitutional telomere length (TL) and the risk of cutaneous melanoma. Although the general perception is that longer telomeres increase melanoma risk, some studies do not support this association. We hypothesize that discordant data are due to the characteristics of the studied populations.To evaluate the association of TL with familial and sporadic melanoma.TL was measured by multiplex quantitative polymerase chain reaction in leukocytes from 310 patients with melanoma according to familial/sporadic and single/multiple cancers and 216 age-matched controls.Patients with sporadic melanoma were found to have shorter telomeres compared with those with familial melanoma. In addition, shorter telomeres, while tending to reduce the risk of familial melanoma regardless of single or multiple tumours, nearly trebled the risk of single sporadic melanoma.This is the first time that TL has been correlated to opposite effects on melanoma risk according to the presence or absence of familial predisposition. Individual susceptibility to melanoma should be taken into account when assessing the role of TL as a risk factor.
The ACPA IgM fine specificity differs from the ACPA IgG antigen-recognition profile
Authors: A Willemze, P Suwannalai, L van Toorn, G Stoeken-Rijsbergen, E W N Levarht, J W Drijfhout, T W J Huizinga, R E M Toes, L A Trouw
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> The antigen-recognition pattern of immunoglobulin M (IgM) could, in case directed against protein-antigens, provide an indication of the antigenic moieties triggering new B cells. The half-life of IgM is short and memory B cells against T cell dependent protein antigens, typically produce IgG and not IgM antibodies. Here the authors analysed whether a difference exists between the fine specificity of IgM versus IgG anticitrullinated protein antibodies (ACPA). <h3>Materials and methods</h3> The authors determined the fine specificity of ACPA IgM and IgG in 138 ACPA positive rheumatoid arthritis (RA) patients. Fine specificity assays were performed by ELISA, using citrullinated peptides derived from, vimentin, fibrinogen-β, fibrinogen-α and α-enolase, as well as citrullinated protein antigens, fibrinogen and myelin basic protein. The arginine counterparts were used as control. <h3>Results</h3> Recognition of defined citrullinated antigens by IgM ACPA was confined to samples that also display recognition by IgG ACPA. However, the IgM ACPA response displayed a more restricted antigen recognition profile as compared to IgG ACPA (OR 0.26, p&lt;0.0001). <h3>Conclusion</h3> Our data show that the immune response against several defined citrullinated antigens varies as some are only recognised by IgG ACPA and others also by IgM ACPA. The recognition of some but not other citrullinated antigens by IgM ACPA suggest that not all citrullinated antigens activate new B cells despite concurrent recognition by IgG ACPA.
Paradoxical Vasoconstriction Induced by Acetylcholine in Atherosclerotic Coronary Arteries
Authors: Paul L. Ludmer, Andrew P. Selwyn, Thomas L. Shook, Richard R. Wayne, Gilbert H. Mudge, R. Wayne Alexander, Peter Ganz
Journal: New England Journal of Medicine (1986)

Acetylcholine is believed to dilate normal blood vessels by promoting the release of a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). By contrast, if the endothelium is removed experimentally, acetylcholine constricts blood vessels. We tested the hypothesis that muscarinic cholinergic vasodilation is impaired in coronary atherosclerosis. Graded concentrations of acetylcholine and, for comparison, the nonendothelial-dependent vasodilator nitroglycerin were infused into the left anterior descending artery of eight patients with advanced coronary stenoses (>50 percent narrowing), four subjects with angiographically normal coronary arteries, and six patients with mild coronary atherosclerosis (<20 percent narrowing). Vascular responses were evaluated by quantitative angiography. In several segments each of four normal coronary arteries, acetylcholine caused a dose-dependent dilation from a control diameter of 1.94±0.16 mm to 2.16±0.15 mm with the maximal acetylcholine dose (P<0.01). In contrast, all eight of the arteries with advanced stenoses showed dose-dependent constriction, from 1.05±0.05 to 0.32±0.16 mm at the highest concentration of acetylcholine (P<0.01), with temporary occlusion in five. Five of six vessels with minimal disease also constricted in response to acetylcholine. All vessels dilated in response to nitroglycerin, however. We conclude that paradoxical vasoconstriction induced by acetylcholine occurs early as well as late in the course of coronary atherosclerosis. Our preliminary findings suggest that the abnormal vascular response to acetylcholine may represent a defect in endothelial vasodilator function, and may be important in the pathogenesis of coronary vasospasm. (N Engl J Med 1986; 315:1046–51.)
SAT0429 Sexual life is more perturbed in men than women suffering from chronic low back pain. Rsults of a cross sectional study in a moroccan sample
Authors: H. Bahouq, H. Rkain, F. Allali, N. Hajjaj Hassouni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Chronic Low Back Pain (CLBP) is a major public health problem responsible of disability and use of health services. Sexual difficulties in CLBP patients seem to be wide-ranging and probably different between men and women. A few published studies have focused on analyzing the impact of CLBP on sexual life of patients with gender comparison. <h3>Objectives</h3> Thus, we aimed to compare the impact of CLBP on sexual life of Moroccan patients between men and women in our context of Arabic Muslim country and to identify factors that may contribute to alter sexual functioning in the 2 genders. <h3>Methods</h3> 50 women and 50 men (mean age 43.28±7.5 years) suffering from CLBP and sexually active were included. None of those patients was affected by any of other chronic diseases which could disturb sexual life. Men and women were adjusted for age, duration and functional impact of CLBP. CLBP characteristics and aspects of impact of CLBP on sexuality were assessed. Sexual quality of life was measured by the sexual quality of life questionnaire (SQOL-M for men, SQOL-F for women). A score of 100% means an excellent SQOL. <h3>Results</h3> Eighty one percent of our patients complained about sexual difficulties related to CLBP. Men estimated having a sexual life more disturbed than women (90 vs. 72%; p=0.022). They were less satisfied than women with their sexual life after the CLBP (2.90 vs. 3.76; p=0.04). Decrease of libido was more reported by women (20 vs. 4%; p=0.01). The SQOL was more decreased in men than women (38.95±17.2 vs. 50.35±15.7; p=0.001). In women, SQOL was significantly correlated with age (r= -0.276; p=0.05) and back pain (r= -0.271; p=0.05). In men, SQOL was correlated with age (r= -0.425; p=0.02), disease duration (r= -0.61; p&lt;0.001), back pain (r= -0.337; p=0.01) and functional impact of CLBP (r= -0.30; p=0.03). In multiple linear regressions, decreased SQOL was associated with an advanced age (p=0.02) and a chronic pain (p=0.002) in men but there was no significant contributors to a decreased SQOL in women. <h3>Conclusions</h3> Sexual life is significantly disturbed by CLBP. These disturbances appear more important in men than women. Older men suffering from a chronic back pain were more concerned by a deteriorated sexual quality of life. For this, sexual function should be taken into account in management of CLBP. Further studies on large samples are needed to confirm those results. <h3>Disclosure of Interest</h3> None Declared
Endoscopic ultrasound-guided thrombin injection in a large splenic artery aneurysm: first report in a patient with tropical chronic pancreatitis
Authors: Praveer Rai, Shantam Mohan, Malay Sharma
Journal: Endoscopy (2014)

Visceral pseudoaneurysm is an uncommon but serious complication of acute or chronic pancreatitis. It affects the splenic artery in 40 % of cases [1]. Traditional treatment includes surgical excision or ligation and endovascular techniques [2] [3]. This article describes the first reported case of a large splenic artery pseudoaneurysm that was managed by endoscopic ultrasound (EUS)-guided thrombin injection in a patient with tropical chronic pancreatitis.
AB0852 Early improvement in enthesis by us predict later favorable response in TNF inhibotors with SPA
Authors: K. Kume, K. Amano, S. Yamada, N. Kuwaba
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Lower limbs enthesis by ultrasound (US) detects inflammatory activity in patients with spondyloarthritis (SpA) and is a diagnostic tool of early SpA. <h3>Objectives</h3> The present objective was to follow SpA patients starting anti-TNF inhibitors with US and clinical assessments to explore whether any variable could predict a major decrease in disease activity after 12 weeks. <h3>Methods</h3> This study is prospective and blinded study. Patients with SpA starting anti-TNF inhibitors were consecutively included and examined at baseline and, after 1 and 12 weeks with standardized bilateral ultrasound of six entheses (Madrid sonography enthesitis index (MASEI)). In addition, the patients were assessed clinically with ASDAS, assessor global VAS (study nurse), ESR and CRP. Patients with ASDAS clinical important improvement at the 12 weeks examination was defined as responders. The results of US score (MASEI), clinical and laboratory assessments at baseline and after 1 week were explored by Mann-Whitney tests to examine for associations with the responders. <h3>Results</h3> A total of 21 patients were included (mean (SD) age 62.3 (21.2) years, disease duration12.2 (6) years, and 35% women, with 76% using infliximab and 24% adalimumab).A total of 67% of the patients were defined as ASDAS responders, and they had significantly lower US score (MASEI) (p=0.03), assessor global VAS (study nurse) (p=0.02), and CRP (p=0.02)at the 12 weeks examination. Baseline US score (MASEI), ASDAS, assessor global VAS, ESR or CRP did not separate between responders and non-responders. At 1 week examination the only variable differing between responders and non-responders was the US score (MASEI), with a significant reduction in US score (MASEI) in the responders versus non-responders 12.6 (5.4) versus 2.3(3.3) (p=0.03). <h3>Conclusions</h3> US enthesis images at 1 week after TNF inhibitors are useful to identify responders early. <h3>References</h3> Alcalde M, Acebes JC, Cruz M, et al. A sonographic enthesitic index of lower limbs is a valuable tool in the assessment of ankylosing spondylitis. Ann Rheum Dis 2007; 66:1015-19. Machado P, Landewé R, Lie E, Kvien TK et al. Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and improvement scores. Ann Rheum Dis. 2011; 70:47-53 <h3>Disclosure of Interest</h3> None Declared
Mucosectomies endoscopiques duodénales: une expérience monocentrique
Authors: S Leblanc, J Barbieri, R Coriat, M Gaudric, S Chaussade, F Prat
Journal: Endoscopy (2009)

Introduction: La résection par mucosectomie endoscopique (EMR) est une alternative à la chirurgie pour l'exérèse des lésions pré-cancéreuses ou des carcinomes superficiels du tube digestif. L'EMR est une technique reconnue pour les lésions néoplasiques de l'oesophage, de l'estomac et du côlon. Il existe moins de données sur la mucosectomie duodénale. Nous reportons l'expérience de patients traités par mucosectomie duodénale dans un centre de référence endoscopique. Les adénomes de la papille et les ampullectomies endoscopiques étaient exclus de l'étude. Le but de l'étude était de déterminer l'efficacité, la morbidité et la mortalité de l'EMR duodénale.
EFFECTS OF A NOVEL IMPLANTABLE COUNTERPULSATION ASSIST DEVICE ON LEFT VENTRICULAR MECHANOENERGETICS: COMPARISON WITH THE INTRA-AORTIC BALLOON PUMP IN A PORCINE MODEL OF ACUTE HEART FAILURE
Authors: Christos Kontogiannis, Yiannis Nanas, Smaragdi Sarchosi, Christos Kapelios, Sotiris Marinakis, Dionysios Aravantinos, Ioannis Tachliabouris, Christos Charitos, Despina Perrea, John Nanas, Konstantinos Malliaras
Journal: Journal of the American College of Cardiology (2016)
Food firms' pledge on saturated fat is "thinnest of thin interventions"
Authors: M. Limb
Journal: BMJ (2013)

Experts have challenged the UK government’s claims that new pledges by food producers and retailers to reduce saturated fats in many products would substantially improve people’s health.

Tim Lang, a food policy professor at City University London, said that the undertakings to cut saturated fat were a small step forward but the “thinnest of thin interventions,” given the scale of the public health challenge.

He told the BMJ , “If something’s really important, like tackling obesity, it is folly to rely on weak, self selected agreements. We need a commitment to toughen up regulation.”

The government announced on Saturday 26 October that “almost half” the food manufacturing and retail industry had signed up to its responsibility deal, the “saturated fat reduction pledge.”1 It said that their combined commitments would “remove more than one and a half Olympic size swimming pools of saturated fat from the nation’s diet.”

Nestle has said that it would remove 3800 tonnes of saturated fat from over a billion Kit Kat bars each year by “reformulating the recipe.”

Tesco …
Abstract 2400: Tumor suppressor EAF2 cooperates with p53 in control of prostate tumorigenesis and vascularity
Authors: Laura E. Pascal, Junkui Ai, Lara E. Graham, Jianhua Xu, Lora Rigatti, Jan Pilch, Wang Zhou
Journal: Cancer Research (2011)

Abstract Introduction: Inactivation of EAF2 has been shown previously to lead to tumorigenesis in multiple organs; however the mechanism of EAF2 tumor suppression remains unclear. Demonstrating functional interactions between p53 and EAF2 would link the newly discovered tumor suppressor EAF2 to the well-established p53 pathway, providing new insights into the mechanisms of p53 and EAF2 action. We previously have shown that EAF2 can co-localize and co-immunoprecipitate with p53 in transfected cells. In a TSP-1 promoter-driven luciferase reporter assay, p53 transfection suppressed the TSP-1 promoter activity and EAF2 co-transfection blocked the p53 suppression of TSP-1 promoter. However, EAF2 transfection alone had little or no effect on the TSP-1 promoter. In a murine model, EAF2 knockout caused TSP-1 down-regulation, supporting an in vivo role for EAF2 in regulation of TSP-1 expression. Methods: Mouse knockout, transient transfection, co-localization, co-immunoprecipitation, and luciferase-based promoter assay were employed in this study. Results: Ongoing animal studies show that loss of EAF2 and p53 displayed much more dramatic phenotypes than loss of EAF2 or p53 individually and resulted in more severe splenic extramedullary hematopoiesis, and further increased vessel density in the prostate and liver. Furthermore, double knockout of EAF2 and p53, but not knockout of EAF2 or p53 alone, resulted in prostate tumorigenesis. Conclusion: The above observations together suggest that EAF2 and p53 cooperate in prostate tumorigenesis and increased vascularity. 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 2400. doi:10.1158/1538-7445.AM2011-2400
VARIATIONS IN USE OF REMOTE MONITORING OF IMPLANTABLE DEFIBRILLATORS RELATIVE TO THE INTRODUCTION OF BILLING CODES SPECIFIC TO REMOTE MONITORING
Authors: Faseeha Altaf, Joseph Akar, Judith Lichtman, Haikun Bao, Paul Jones, Paul Varosy, Frederick Masoudi, Kenneth Stein, Leslie Saxon, Jeptha Curtis
Journal: Journal of the American College of Cardiology (2015)
1268 DIFFERENTIAL EXPRESSION OF HEPATIC FAS AND ITS LIGAND FASLG EXPRESSION IN NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
Authors: J.M. Estep, Z. Goodman, A. Zirzow, A. Afendy, H. Elariny, A. Baranova, Z.M. Younossi
Journal: Journal of Hepatology (2012)
ASSESSMENT OF SERIAL HEART RATE AND BETA BLOCKER USE IN A CONTEMPORARY CHRONIC SYSTOLIC HEART FAILURE PATIENTS: RESULTS FROM THE PROBNP OUTPATIENT TAILORED CHRONIC HEART FAILURE (PROTECT) STUDY
Authors: Hanna Kim Gaggin, Dustin Rabideau, Nasrien Ibrahim, Parul Gandhi, James Januzzi
Journal: Journal of the American College of Cardiology (2016)
Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) of the right adrenal gland
Authors: R. Sharma, S. Ou, A. Ullah, V. Kaul
Journal: Endoscopy (2012)

There are few reported series of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of the right adrenal gland, probably because sampling of this gland at EUS is technically more difficult, given its retrocaval location and long endoscope position [1] [2] [3] [4]. Here, we describe two successful cases of EUS-FNA of the right adrenal gland without any immediate or delayed complications. Prior to EUS-FNA, pheochromocytoma was ruled out in both cases.
S101 Heterozygous loss of BMPR-II predisposes to inflammatory cytokine secretion and pulmonary vascular smooth muscle proliferation
Authors: E. Soon, A. Crosby, M. Southwood, J. Pepke-Zaba, P. Upton, N. W. Morrell
Journal: Thorax (2011)

<h3>Introduction</h3> Elevated levels of inflammatory cytokines are associated with idiopathic and heritable pulmonary hypertension (PAH) and predict mortality, but their role in the pathobiology of PAH and the underlying mechanisms remain unclear. We investigated whether loss of bone morphogenetic protein receptor type II (BMPR-II), the underlying cause of heritable PAH, predisposes to increased inflammatory cytokine expression and pulmonary vascular remodelling. <h3>Methods</h3> Regulation of cytokine expression by lipopolysaccharide (LPS) was studied in two in vitro models: (1) mouse pulmonary artery smooth muscle cells (PASMCs) heterozygous for a null allele in <i>bmpr2</i> (<i>BMPR2</i>±), and (2) human PASMCs with a mutation in <i>BMPR2</i> (<i>BMPR2mut</i>) and their wild-type counterparts. Cytokine production, regulation and effects on the pulmonary vascular system were examined in an in vivo model using the <i>bmpr2</i>± mouse. <h3>Results</h3> Both mouse and human in vitro models showed that loss of <i>BMPR2</i> function leads to increased mRNA expression and secretion of interleukin 6 and IL-8 both at baseline and after stimulation with LPS. This was associated with loss of expression of antioxidant enzymes such as superoxide dismutase 1 (SOD1) and SOD3, which is demonstrable in both mouse <i>bmpr2</i>± and human <i>BMPR2mut</i> cells. Treatment with the superoxide dismutase-mimetic, Tempol, partially reversed the exaggerated cytokine response to LPS but did not affect the underlying baseline increase. We demonstrated increased phospho-Stat3 signalling and pro-proliferative and pro-survival effects of IL-6 in <i>BMPR2mut</i> PASMCs which is not seen in the wild-type. This was confirmed in the in vivo model, as <i>bmpr2</i>± mice demonstrated increased IL-6 and IL-8 expression in sera, lung and liver tissue 3 and 24 h after exposure to 10 μg of LPS. A similar pattern of antioxidant enzyme reduction was also seen in lung tissue from these LPS-treated <i>bmpr2</i>± mice. <h3>Conclusions</h3> Loss of BMPR-II predisposes to both an abnormal increase in IL-6 and IL-8 after stimulation with LPS and a dysfunctional response to these cytokines in PASMCs and mice. The mechanism for this involves loss of antioxidant function. This abnormal response may underlie the additional lung-specific trigger that promotes the development of PAH in patients with BMPR-II mutations, and may represent a target for future therapeutic interventions.