tbuckley/cabot-search huggingface dataset:
Aurora A and NF-κB Survival Pathway Drive Chemoresistance in Acute Myeloid Leukemia via the TRAF-Interacting Protein TIFA
Authors: Tong-You Wade Wei, Pei-Yu Wu, Ting-Jung Wu, Hsin-An Hou, Wen-Chien Chou, Chieh-Lin Jerry Teng, Chih-Ru Lin, Jo-Mei Maureen Chen, Ting-Yang Lin, Hsiang-Chun Su, Chia-Chi Flora Huang, Chang-Tze Ricky Yu, Shih-Lan Hsu, Hwei-Fang Tien, Ming-Daw Tsai
Journal: Cancer Research (2016)

Abstract Aurora A–dependent NF-κB signaling portends poor prognosis in acute myeloid leukemia (AML) and other cancers, but the functional basis underlying this association is unclear. Here, we report that Aurora A is essential for Thr9 phosphorylation of the TRAF-interacting protein TIFA, triggering activation of the NF-κB survival pathway in AML. TIFA protein was overexpressed concurrently with Aurora A and NF-κB signaling factors in patients with de novo AML relative to healthy individuals and also correlated with poor prognosis. Silencing TIFA in AML lines and primary patient cells decreased leukemic cell growth and chemoresistance via downregulation of prosurvival factors Bcl-2 and Bcl-XL that support NF-κB–dependent antiapoptotic events. Inhibiting TIFA perturbed leukemic cytokine secretion and reduced the IC50 of chemotherapeutic drug treatments in AML cells. Furthermore, in vivo delivery of TIFA-inhibitory fragments potentiated the clearance of myeloblasts in the bone marrow of xenograft-recipient mice via enhanced chemotoxicity. Collectively, our results showed that TIFA supports AML progression and that its targeting can enhance the efficacy of AML treatments. Cancer Res; 77(2); 494–508. ©2016 AACR.
Preclinical Testing Of a PI3K Inhibitor In T Lineage Leukemia: Target Validation and Notch1/Myc Down-Regulation In Drug Resistant Clones
Authors: Monique Dail, Jason Wong, Jessica Lawrence, Daniel O'Connor, Joy Nakitandwe, Shann-Ching Chen, Keiko Akagi, Leslie Lee, Jon C. Aster, Warren S. Pear, Deepak Sampath, James R. Downing, Kevin Shannon
Journal: Blood (2013)
OP0020 The Association of Gonadotropin-Releasing Hormone and Cytokines in Rheumatoid Arthritis: Table 1.
Authors: A. Kåss, I. Hollan, H.C. Gulseth, Ø. Førre
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Improvement of rheumatoid arthritis (RA) in pregnancy, and worsening postpartum is well known. This led to the finding that cortisone had anti-inflammatory effects. The hypothalamic proinflammatory hormone, gonadotropin-releasing hormone (GnRH), is the master regulator of the reproductive system, and also has a circadian rhythm. GnRH activity diminishes in pregnancy and increases postpartum. Prior to our AGRA (Antagonist to Gonadotropin Releasing Hormone in RA) trial, no research in RA had been performed on this principal hormone. GnRH can act like a cytokine in the periphery, being secreted by T cells (1). In the AGRA trial, GnRH antagonism showed anti-inflammatory effects including a significant reduction in TNF in RA patients. GnRH antagonists decrease inflammatory cytokine mRNA, and downregulate the NF-κB pathway. Conversely, GnRH agonists are associated with the onset and flares of autoimmune diseases. <h3>Objectives</h3> The purpose of this study was to investigate for the first time whether GnRH exists in the periphery in patients with an autoimmune disease. If GnRH exists in the periphery in patients with RA, is GnRH associated with cytokines? <h3>Methods</h3> Predefined endpoints from our proof-of-concept randomized, double-blind, Norwegian AGRA study (N=99, ITT population) with active RA have been reported earlier (ClinicalTrials.gov NCT00667758). Patients were randomized using computer-generated allocation (1:1) in dynamic blocks stratified for sex. Patients were assigned to cetrorelix, a GnRH antagonist (5mg days 1–2, 3mg days 3–5) or corresponding volumes of placebo. Blood sampling was at the same time of day and frozen to -80. We investigated serum GnRH baseline pretreatment levels using newly available ELISA assays according to the manufacturer9s instructions, in duplicates, inter-assay CV&lt;10% (USCN Life Science Inc.). Four serum cytokines were measured with multiplex technology (Luminex Inc.). <h3>Results</h3> Mean peripheral GnRH level at baseline was 241 pg/mL (s.d. ±83 pg/mL). By day 5, TNF levels were significantly reduced by the GnRH antagonist vs. placebo (p=0.023). GnRH levels were not significantly changed by day 5. <h3>Conclusions</h3> Peripheral GnRH is presented for the first time in autoimmunity. Due to GnRH9s potential association with cytokines, the existence of peripheral GnRH may be due to GnRH production by T cells (1). These results could support preexisiting literature on GnRH and the immune system, that GnRH stimulates the secretion of cytokines peripherally, and help to explain clinical observations. These results warrant confirmation. <h3>References</h3> Chen et al. The neuropeptides GnRH –II and GnRH-I are produced by human T cells and trigger laminin receptor gene expression, adhesion, chemotaxis, and homing to specific organs. Nat Med 2002; 8: 1421–6. <h3>Disclosure of Interest</h3> None declared
Impairment of HuR-Mediated FOS mRNA Stabilization in Granulocytes From Myelodysplastic Syndrome Patients.
Authors: Xiaomin Feng, Yayoi Shikama, Tsutomu Shichishima, Hideyoshi Noji, Kazuhiko Ikeda, Ogawa Kazuei, Yasuchika Takeishi, Junko Kimura
Journal: Blood (2012)
The Earliest Thymic T Cell Progenitors Sustain B Cell and Myeloid Lineage Potentials
Authors: Sidinh Luc, Iain C Macaulay, Natalija Buza-Vidas, Tiphaine Bouriez-Jones, Michael Lutteropp, Petter Woll, Adam J. Mead, Hanane Boukarabila, Tiago C Luis, Takuo Mizukami, Sahoko Matsuoka, John Brown, Helen Ferry, Kristina Anderson, Sara Duarte, Deborah Atkinson, Shamit Soneji, Aniela Domanski, Alison Farley, Alejandra Sanjuan-Pla, Cintia Carella, Roger Patient, Marella de Bruijn, Tariq Enver, Claus Nerlov, Clare Blackburn, Isabelle Godin, Sten Eirik W Jacobsen
Journal: Blood (2011)
Rare cause of abdominal pain and fever in a pregnant woman
Authors: Sophie Hillaire, Jean-Emmanuel Kahn, Olivier Picone, Dominique Cazals-Hatem
Journal: Gut (2016)

<h3>Clinical presentation</h3> A pregnant woman (third trimester) presented with intense abdominal pain, nausea and myalgia. The patient was obese (body mass index 38) and was being treated for high blood pressure, hyperuricemia and hypothyroidism. She had chronic renal deficiency related to focal segmental glomerular sclerosis requiring dialysis. The physical examination at admission revealed a fever of 39°C and an acute abdomen with abdominal guarding in the right upper quadrant without hepatomegaly or splenomegaly. There were no clinical signs of pre-eclampsia. Fetal ultrasound and a Doppler of the umbilical vessels were normal. Laboratory tests showed normal liver and liver function (total protein 95%, alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin normal). The white cell count was 10×10<sup>9</sup>/l (90% neutrophils), with a normal platelet count. Blood, urine and vaginal cultures were negative. Abdominal ultrasound revealed isolated thickening of the gallbladder wall without cholelithiasis. Empirical antibiotic treatment was begun with intravenous amoxicillin. Six days later, the patient9s condition had worsened with increased abdominal pain, persistent fever and liver test abnormalities (AST–ALT 6N). However, bilirubin, hepatic synthesis tests, as well as leucocyte and platelet counts were still normal. A caesarean section followed by coelioscopy was decided. Coelioscopy revealed a liver with numerous necrotic spots (see figure 1). <h3>Question</h3> What is the diagnosis?
Copper Deficiency Remains An Underappreciated Cause of Ineffective Hematopoiesis
Authors: Amelia Langston, Jessica Neely, Leonard Heffner, D. Griffith, Martha Arellano, Gregory Esper, Morgan L. McLemore, Thomas Ziegler, Christine Kempton, Rajni Sinha, H. Jean Khoury, Elliott Winton
Journal: Blood (2008)
Library Preparation Is the Major Factor Affecting Differences in Results of Immunoglobulin Gene Rearrangements Detection on Two Major Next-Generation Sequencing Platforms
Authors: Michaela Kotrova, Henrik Knecht, Jack Bartram, Vojtech Bystry, Giovanni Cazzaniga, Grazia Fazio, Simone Ferrero, Elisa Genuardi, Ramon Garcia-Sanz, Andrea Grioni, Jeremy Hancock, Cristina Jiminez, Marco Ladetto, John Moppett, Simona Songia, Dietrich Herrmann, Christiane Pott, Anton W. Langerak, Nikos Darzentas, Jan Trka, Eva Fronkova, Monika Bruggemann
Journal: Blood (2015)
Update of An Open-Label Extension Study Evaluating the Long-Term Safety and Efficacy of Romiplostim in Thrombocytopenic Patients with Myelodysplastic Syndromes (MDS)
Authors: Pierre Fenaux, Hagop M. Kantarjian, Petra Muus, Roger M. Lyons, Richard A. Larson, Mikkael A. Sekeres, Pamela S. Becker, Catherine Jia, Allen S. Yang
Journal: Blood (2011)
AB0851 Improvement of Work Capacity Is Dependent of A Decrease in The Kinesiophobia
Authors: M. Norberg, L. Belgrand, M. Norberg, M. Norberg
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The avoidances of movement is a key structure in the chronic pain patient. In this situation the kinesiophobia has a great importance. It could be evaluated using different questionnaires (Tampa, TSK, but also the Fabq).According to Vlayen, the kinesiophobia is the most important prognostic factor when evaluating the return to work. <h3>Objectives</h3> In this situation, we wanted to evaluate the evolution of the kniesiophobia before and after a functional restoration program, and its relationship to the work capacity in a group of chronic lumbar back pain patients. <h3>Methods</h3> We included 702 patients who had followed an outpatient program of functional restoration during 3 weeks. The program was composed of physical exercices, occupational therapy and psychologcial follow. The patientes were followed on questionnaires (Tampa (3), Fabq, Pact (2) -subective work capacity-) their work capacity and their physical performances (using different tests as Shirado, Biering-Sörensen, Bruce, lumbar mobility) <h3>Results</h3> There were a clear relationship between a decrease in kinesiophobia and an increase of work capacity. In fact in patient were the Tampa score decreased with more than 10 points, there were a still staying increased work capaciry. On the other side, none of he physical characteristics were associated with an increase or decrease of work capacity. <h3>Conclusions</h3> We have confirmed the observation of Vlayen from 1996, saying that the kinesiophobia is an important prognostic factor for work capacity. This observation is important in functional restoration programs. <h3>References</h3> Waddell G et coll. Pain 1993;52:157–68 Matheson LN, Matheson M (1989) Spinal function sort: Performance Assessment and Capacity Testing PACT, Trabuco Canyon, California. Kori SH, Miller RP, Todd DD: Kinesiophobia: A new view of chronic pain behaviour. Pain Manage Jan/Feb:35–43, 1990 Kori SH, Miller RP, Todd DD: Kinesiophobia: A new viewof chronic pain behaviour. Pain Manage Jan/Feb:35–43, 1990 <h3>Disclosure of Interest</h3> None declared
Poorly differentiated pancreatic carcinoma with sarcomatoid differentiation: confocal endomicroscopy of an uncommon pancreatic cystic lesion
Authors: Feng Li, Samer El-dika, Rohan Modi, Wei Chen, Somashekar Krishna
Journal: Endoscopy (2016)

A 71-year-old man with a history of diabetes presented with unexplained weight loss. A cystic lesion was discovered incidentally in the tail of his pancreas during a computed tomography (CT) scan of the chest. A subsequent CT scan of the abdomen 5 months later revealed interval enlargement of the lesion to 6 × 5 cm, compared with 3.5 × 3 cm on the initial imaging. No pancreatic ductal dilatation was noted.
Patients Receiving Palifermin in Conjunction with Melphalan 200 Required Fewer Platelet Transfusions: Analysis of a Retrospective Cohort Study.
Authors: Donald A. Hutcherson, Amelia Langston, Cheryl H. Lin, Christopher Flowers, Mary Jo Lechowicz, Ned Waller, Jolynn K. Sessions, Jonathan L. Kaufman, H. Jean Khoury, Sagar Lonial
Journal: Blood (2006)
Nilotinib Exposure-Response Analysis In Patients with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia (CML)
Authors: Francis J. Giles, Ophelia Yin, Yen Lin Chia, Philipp D. le Coutre, Richard C. Woodman, Oliver G. Ottmann, Michele Baccarani, Hagop M. Kantarjian
Journal: Blood (2010)
ACE-536, a Novel, GDF-Trap, Promotes Rapid Increase of Red Blood Cells In Vivo in An EPO-Independent Manner.
Authors: Dianne Mitchell, Samuel Cadena, Chris Rogers, June Liu, Kathleen Tomkinson, Joe Barberio, Asya Grinberg, Kathryn W. Underwood, R. Scott Pearsall, Ravindra Kumar
Journal: Blood (2009)
DDEL-03INTRAVENOUS NANOPARTICLE DELIVERY TO GLIOBLASTOMA
Authors: Jenny Holt, Regina Martuscello, Loic Deleyrolle, Ana Tari Ashizawa
Journal: Neuro-Oncology (2015)

A major obstacle in the treatment of glioblastoma (GBM) is the blood brain barrier (BBB), which restricts drug molecules in the bloodstream from reaching the tumor. The BBB may be disrupted at or near the GBM tumor core, but it is intact at the growing edge of the tumor, where invasive cells reside and can cause disease recurrence. To combat GBM more effectively, novel drug transport technology that crosses intact BBB is urgently needed. Brain microvascular endothelial cells (BMEC) found in the BBB are lined with low-density lipoprotein receptors (LDLr) and LDL-like receptor proteins (LRP), which are essential to the endocytosis/ transcytosis processes of BMEC. GBM cells are known to express higher levels of LDLr and LRP than normal brain cells. The objective of our research is to develop a novel lipid nanoparticle (NP) that targets LDLr and LRP to facilitate BMEC endocytosis/ transcytosis and GBM uptake. We focused on developing antisense oligonucleotides (oligos) as the drug cargo for our NP. Less than 20% of disease-associated genes are targetable by conventional drug molecules; however, we hypothesize that disease-associated genes, like EZH2 and ZEB1 transcriptional repressors, are amendable to antisense oligo inhibition. We engineered a novel NP which is composed of neutral lipids: phosphatidylcholine (PC), cholesterol (Chol) and a polymer called poloxamer (PXR). Toxicology studies indicated that NP composed of PC/Chol/PXR did not have adverse effects on mice. Flow cytometry and fluorescent microscopy revealed that PC/Chol/PXR NP was avidly taken up by BMEC, and that PC/Chol/PXR efficiently delivered antisense oligos to GBM cells. Additionally, intravenous injection of PC/Chol/PXR led to deposition of antisense oligos in intracranial GBM xenografts. Future studies will determine the efficacy of the innovative PC/Chol/PXR NP in suppressing target gene expression in intracranial GBM. (Supported by Florida Center for Brain Tumor Research and Accelerate Brain Cancer Cure).
PWE-015 Inflammatory Bowel Disease in The Elderly: Characteristics and Risk Factors for Disease
Authors: J Clough, M Mendall, D Braim, A Hong
Journal: Gut (2016)

<h3>Introduction</h3> The number of patients presenting with IBD at older ages is increasing and the proportion of patients over the age of 60 is increasing as the IBD epidemic matures. There are only a few case series in literature concerning IBD presenting at older age ages. It is unknown whether the risk factors for disease differ compared to younger age groups. <h3>Methods</h3> A database was established at CUH in 2002 and currently has 1326 subjects registered. Information was obtained pertaining to the subjects’ age at diagnosis, exposure to established risk factors (smoking history and appendectomy), and disease profile. Their requirement for progression therapy was assessed, in terms of the need for immunosuppression, biological agents, and surgery. Patients who had required surgery for peri-anal disease only were not counted as having required surgery. <h3>Results</h3> The characteristics of the subjects are shown in the table. A higher proportion of patients diagnosed over the age of 60 had UC compared to other age groups. In all in December 2015 303/1326 were aged over 60 giving a prevalence of 22.9% of all subjects with IBD versus an incidence in the over 60 age group of 11.5%. Male predominance is present at older ages of diagnosis of CD as opposed to female preponderance at younger ages. The female predominance in UC did not change across the age groups. Smoking although more common in older CD did not reach significance unlike at younger ages. Likewise appendectomy was not a risk factor in the over 60 s for CD unlike at younger ages. Older subjects were less likely to have had surgery or be on immunomodulators or biologics. For CD colonic disease was common in older subjects. <h3>Conclusion</h3> CD diagnosed in later years is phenotypically different in terms of the associated risk factors and disease trajectory. It appears to run a more indolent course, with fewer patients requiring immunosuppressive or biologic therapy, and fewer surgical procedures. This raises the question as to whether old age CD disease is a different disease to that observed in younger subjects. The behaviour of UC does not demonstrate such marked differences with age of diagnosis. <h3>Disclosure of Interest</h3> None Declared
NHS spent 8% more on medicines last year
Authors: Ingrid Torjesen
Journal: BMJ (2016)

The amount of money the NHS spent on medicines in England increased by 8% last year and the largest rise was in spending by hospitals, a report by NHS Digital shows.1

Overall spending on medicines in 2015-16 was £16.8bn (€19.7bn; $20.9bn), up from £15.5bn in 2014-15. Spending by hospitals on medicines rose most rapidly, by 13.6%, and accounted for 45.2% (£7.6bn) of the total cost spent on medicines in 2015-16, up from 43.0% …
Hypermethylation of CXCR4 Promoter, and Its Reactivation by Hypomethylating Agent, in CD34+ Cells from Primary Myelofibrosis Patients
Authors: Paola Guglielmelli, Costanza Bogani, Vanessa Ponziani, Giada Poli, Vittorio Rosti, Cristophe Desterke, Alberto Bosi, Marie Caroline Le Bousse-Kerdiles, Giovanni Barosi, Alessandro M. Vannucchi
Journal: Blood (2007)
Prospective Evaluation of Graft-Versus-Host Disease-Specific Proteomics Pattern in Patients after Allogeneic Stem Cell Transplantation.
Authors: Eva M. Weissinger, Meike Hillmann, Hans-Jochem Kolb, Axel R. Zander, Ernst Holler, Harald Mischak, Arnold Ganser, Bernd Hertenstein
Journal: Blood (2005)
In a Prospective Inceptional Cohort Study of Children with Thrombosis, a Persistently Positive Dilute Russell Viper Venom Time Is Associated with Thrombus Progression or Recurrence and Multiple Antiphospholipid Antibodies
Authors: Hannah A Hathaway, Emily L. Joachim, Linda Jacobson, Chris G. Bombardier, Neil A Goldenberg, William E. Hathaway, Marilyn J. Manco-Johnson
Journal: Blood (2008)
Incidence and Risk Factors for Central Nervous System Relapse in Adult Patients with Acute Myeloid Leukemia: A Single Center Experience.
Authors: Pau Montesinos, Guillermo Martin, Mari-luz Perez-sirvent, Jaime Sanz, Ignacio Lorenzo, Isidro Jarque, Susana Cantero, Federico Moscardo, Margarita Blanes, Noemi Puig, Jesus Martinez, Lorenzo Algarra, Guillermo Sanz, Miguel Sanz
Journal: Blood (2006)
SP0046 Sleep as A Modulator and Adjuvant in Immunity
Authors: T. Lange
Journal: Annals of the Rheumatic Diseases (2016)

Sleep and immunity are linked by bidirectional interactions. On the one hand, immune activation induces fatigue, sleepiness and non-rapid eye movement (NREM) sleep, whereas REM sleep is suppressed. On the other hand, sleep, in particular NREM sleep, regulates immune functions in an overall immunosupportive manner. Thus, NREM sleep drives the release of pro-inflammatory hormones such as growth hormone, prolactin and aldosterone at a time when anti-inflammatory hormones such as cortisol and catecholamines reach lowest levels. In healthy subjects this unique endocrine pattern during NREM sleep seems to facilitate T cell homing to lymph nodes, pro-inflammatory cytokine production by stimulated monocytes and dendritic cell precursors and vaccine-driven T and B cell responses. However, in addition to this adjuvant-like action, sleep also exerts anti-inflammatory, regulatory functions. Thus, sleep presumably counteracts sterile, low-grade systemic inflammation, shifts anti-inflammatory cytokine production of stimulated monocytes to the daytime period and supports regulatory T cell functions. In autoimmune diseases these fine-tuned interactions between sleep and immunity are distorted. Potential causes, consequences and therapeutic implications of this dysregulation will be outlined exemplarily for patients with rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. <h3>Disclosure of Interest</h3> None declared
AB0772 Prevelance of Osteoporosis in Adult Homocystinuria Patients
Authors: A. Mohamed Sathathulla, T. O'Neill, R. Sharma
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Homocystinuria is an inborn error of metabolism associated with elevated plasma and urine homocysteine levels. Osteoporosis is a recognised feature of the disease and is thought to be related to defective collagen cross-linkage. Limited data exists, however, concerning levels of bone health in unselected patients with homocystinuria. <h3>Objectives</h3> The aim of this analysis was to determine the prevalence of osteoporosis in a cohort of adult homocystinuria patients. <h3>Methods</h3> 46 adult homocystinuria patients, mean age 36.9 years, (Standard deviation [SD]=12.9) attending a specialist metabolic medicine clinic at Salford Royal Hospital NHS Trust (Salford, United Kingdom) were identified and retrospective analysis of their medical records performed. Information obtained included data on previous medications, and bone mineral density (BMD) scans which had been performed using Dual energy x-ray absorptiometry (DEXA). Also, when available information about plasma homocysteine levels was obtained. <h3>Results</h3> 78% of patients (n=36) had had at least one DEXA scan. The mean lumbar spine BMD Z-score was -0.51 (SD=1.20) and for the total hip site, mean Z-score was -0.36 (SD=1.40). Mean level of plasma homocysteine was 96.6 μmol/Litre (normal range: &lt;16μmol/Litre), (SD=69.7). Using the International Society of Clinical Densitometry (ISCD) criteria (Z-score &lt; -2.0), five (10.9%) patients had evidence of osteoporosis; while using the World Health Organisation (WHO) criteria (T-score &lt; -2.5), only three (6.5%) patients had evidence of osteoporosis. There was no association between either total hip or lumbar spine BMD Z-score and levels of plasma homocysteine. <h3>Conclusions</h3> In this cohort of patients with homocystinuria attending hospital clinics, the prevalence of osteoporosis was relatively low. <h3>References</h3> Ortop Traumatol Rehabil. 2007 Jul-Aug; 9(4): 337–56. J Clin Densitom. 2014; 17: 219–224. <h3>Acknowledgement</h3> Ms.Azita Rajai, Statistician, Manchester Biomedical Centre, Central Manchester NHS Foundation Trust, Manchester, United Kingdom <h3>Disclosure of Interest</h3> None declared
Sofosbuvir and Velpatasvir Combination Improves Patient-reported Outcomes for Patients With HCV Infection, Without or With Compensated or Decompensated Cirrhosis
Authors: Zobair M. Younossi, Maria Stepanova, Jordan Feld, Stefan Zeuzem, Mark Sulkowski, Graham R. Foster, Alessandra Mangia, Michael Charlton, Jacqueline G. O’Leary, Michael P. Curry, Fatema Nader, Linda Henry, Sharon Hunt
Journal: Clinical Gastroenterology and Hepatology (2016)