tbuckley/cabot-search huggingface dataset:
Circadian Clock Gene <i>Bmal1</i> Inhibits Tumorigenesis and Increases Paclitaxel Sensitivity in Tongue Squamous Cell Carcinoma
Authors: Qingming Tang, Bo Cheng, Mengru Xie, Yatao Chen, Jiajia Zhao, Xin Zhou, Lili Chen
Journal: Cancer Research (2016)

Circadian clock genes regulate cancer development and chemotherapy susceptibility. Accordingly, chronotherapy based on circadian phenotypes might be applied to improve therapeutic efficacy. In this study, we investigated whether the circadian clock gene Bmal1 inhibited tumor development and increased paclitaxel sensitivity in tongue squamous cell carcinoma (TSCC). Bmal1 expression was downregulated and its rhythmic pattern of expression was affected in TSCC samples and cell lines. Ectopic Bmal1 inhibited cell proliferation, migration and invasion in vitro, and tumor growth in mouse xenograft models of TSCC. After exposure to paclitaxel, Bmal1-overexpressing cells displayed a relative increase in apoptosis and were more susceptible to paclitaxel treatment in vivo Mechanistic investigations suggested a regulatory connection between Bmal1, TERT, and the oncogenic transcriptional repressor EZH2 (enhancer of zeste homolog 2), the recruitment of which to the TERT promoter increased paclitaxel-induced apoptosis and cell growth inhibition. Clinically, paclitaxel efficacy correlated positively with Bmal1 expression levels in TSCC. Overall, our results identified Bmal1 as a novel tumor suppressor gene that elevates the sensitivity of cancer cells to paclitaxel, with potential implications as a chronotherapy timing biomarker in TSCC. Cancer Res; 77(2); 532-44. ©2016 AACR.
Circulating Versus Progenitor Endothelial Cells Levels Are Abnormal in Patients with Different Types of Von Willebrand Disease and Correlate with Markers of Angiogenesis
Authors: Giuseppe Gritti, Augusto B Federici, Agostino Cortelezzi, Luciano Baronciani, Silvia Lonati, Margherita Punzo, Ilaria Silvestris, Rosanna Garavaglia, Giorgio Lambertenghi, Pier M Mannucci
Journal: Blood (2008)
Rugby union needs a contact skill-training programme
Authors: Sharief Hendricks, Kevin Till, James Craig Brown, Ben Jones
Journal: British Journal of Sports Medicine (2016)

The ability to engage in rugby contact is a highly demanding sports skill. In an 80 min match, these contact skills occur at different frequencies, have distinct injury risk profiles and each has specific physical and technical requirements. Therefore, developing effective contact skills is essential for safe participation and optimal performance. Over the past decade, knowledge has been gained about the dynamic nature of contact, the physical match demands, fitness conditioning requirements, contact injury mechanisms, technical requirements and how to design training for open skills in order for it to effectively transfer to match play. Most of this work is intended to guide the design and development of contact training programmes. However, the translation of this research into practice has been slow. The Knowledge Transfer Scheme aims to bridge the gap between science and practice, by solving problems in practice using the available scientific evidence. Given the current available contact skill evidence, in combination with the literature on skill development and training prescription, it is reasonable to state that we can adequately prepare players of different ages and levels for rugby contact. This discussion piece proposes that rugby needs a contact skill-training programme that includes all contact forms—ruck, scrum, maul, line-out, tackling and ball carrying into contact. The programme should detail the frequency of contact, intensity, contact type, timing, conditions and number of sessions. The programme should be aimed at all ages and playing levels, from the developing school player to the elite player, and account for the player's …
Short –Term Intense Bcr-Abl Kinase Inhibition Is Adequate to Trigger Cell Death in CML Cell Lines but Not in CML-CD34+ Cells Unless They Are Growth Factor Deprived.
Authors: Devendra K. Hi Wase, Deborah L. White, Verity A. Saunders, Junia V. Melo, Sharad Kumar, Timothy P. Hughes
Journal: Blood (2008)
AB0760 Comparison of Life Quality, Pain Intensity and Fatigue with Patients Suferring from Rheumatoid Arthritis and Knee Osteoarthritis
Authors: M.S. Karadzic, J.V. Jovanovic
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> It is well known that chronical rheumatoid diseases have negative impact on life quality. Pain and joint swelling, limited motion, stiffness and deformity from one side, as well as fatigue, poor sleep quality and depression, on the other hand, significantly reduce life quality. <h3>Objectives</h3> Comparison of life quality, pain intensity and fatigue intensity of patients with rheumatoid arthritis (RA) and knee osteoarthritis (knee OA). <h3>Methods</h3> 150 patients have been examined: 75 patients with RA and 75 patients with knee OA. Groups were homogenous regarding gender and age. Life quality has been estimated by means of questionnaire- Short Form Medical Outcomes Instruments (SF 36) SF 36F-physical sphere and SF 36M-mental sphere. Pain and fatigue intensity was estimated by scale VAS. <h3>Results</h3> Average value of SF 36F with patients suferring from RA was 35.62±21.73 in regard to patients suffering from knee OA 61.72±18.85, p&lt;0001. Average value of SF 36M with patients suffering from RA was 44.79±24.18 compared to patients with knee OA having 68.12±20.77, p&lt;0001. Pain intensity with patients with RA was 47.79±24.66 compared to patients with knee OA ranging 46.08±18.82, p=0.622. Fatigue intensity with patients suffering from RA was 48.28±25.64 compared to patients with knee OA having 29.23±15.58, p&lt;0001. <h3>Conclusions</h3> Patients with RA have significantly less quality of life and greater fatigue intensity compared to patients with knee OA. Pain intensity was not statistically significantly different. Although patients with RA have poorer values of quality of life, taking into account a big number of patients with knee OA, a significant implication of this disease is recognized. Pain is significant predictor of poor quality of life. <h3>Disclosure of Interest</h3> None declared
Preconditioning Level of C-Reactive Protein and Disease Stage Are Key Prognostic Factors In Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Jiri Pavlu, Rajvi Shah, Holger W. Auner, Dragana Milojkovic, David Marin, Jeremy Sargent, Amin Rahemtulla, Donald H. MacDonald, Edward J. Kanfer, Katayoun Rezvani, Francesco Dazzi, John M. Goldman, Jane F. Apperley, Richard M. Szydlo
Journal: Blood (2010)
TP53 and IDH2 Somatic Mutations Are Associated with Poor Outcomes Following Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome
Authors: Mohamed A. Kharfan-Dabaja, Rami S. Komrokji, Qing Zhang, David Sallman, Asmita Mishra, Najla H. Al Ali, Taiga Nishihori, Teresa Field, Karma Z Salem, Janelle Perkins, Ling Zhang, Lynn C. Moscinski, Hugo F. Fernandez, Jeffrey E Lancet, Alan F. List, Claudio Anasetti, Eric Padron
Journal: Blood (2015)
Neutrophils Modulate Osteoblastic Niche for Hematopoietic Progenitors Via Prostaglandin E2 Production Triggered By Sympathetic Nervous System
Authors: Yuko Kawano, Chie Fukui, Kanako Wakahashi, Shinichi Ishii, Tomohide Suzuki, Mari Sato, Noboru Asada, Hiroki Kawano, Kentaro Minagawa, Akiko Sada, Satoshi Uematsu, Shizuo Akira, Toshimitsu Uede, Shuh Narumiya, Toshimitsu Matsui, Yoshio Katayama
Journal: Blood (2014)
Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial
Authors: Gerd R Burmester, Yong Lin, Rahul Patel, Janet van Adelsberg, Erin K Mangan, Neil M H Graham, Hubert van Hoogstraten, Deborah Bauer, Juan Ignacio Vargas, Eun Bong Lee
Journal: Annals of the Rheumatic Diseases (2016)

To compare efficacy and safety of sarilumab monotherapy with adalimumab monotherapy in patients with active rheumatoid arthritis (RA) who should not continue treatment with methotrexate (MTX) due to intolerance or inadequate response.MONARCH was a randomised, active-controlled, double-blind, double-dummy, phase III superiority trial. Patients received sarilumab (200 mg every 2 weeks (q2w)) or adalimumab (40 mg q2w) monotherapy for 24 weeks. The primary end point was change from baseline in 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) at week 24.Sarilumab was superior to adalimumab in the primary end point of change from baseline in DAS28-ESR (-3.28 vs -2.20; p<0.0001). Sarilumab-treated patients achieved significantly higher American College of Rheumatology 20/50/70 response rates (sarilumab: 71.7%/45.7%/23.4%; adalimumab: 58.4%/29.7%/11.9%; all p≤0.0074) and had significantly greater improvement in Health Assessment Questionnaire-Disability Index (p=0.0037). Importantly, at week 24, more patients receiving sarilumab compared with adalimumab achieved Clinical Disease Activity Index remission (7.1% vs 2.7%; nominal p=0.0468) and low disease activity (41.8% vs 24.9%; nominal p=0.0005, supplemental analysis). Adverse events occurred in 63.6% (adalimumab) and 64.1% (sarilumab) of patients, the most common being neutropenia and injection site reactions (sarilumab) and headache and worsening RA (adalimumab). Incidences of infections (sarilumab: 28.8%; adalimumab: 27.7%) and serious infections (1.1%, both groups) were similar, despite neutropenia differences.Sarilumab monotherapy demonstrated superiority to adalimumab monotherapy by improving the signs and symptoms and physical functions in patients with RA who were unable to continue MTX treatment. The safety profiles of both therapies were consistent with anticipated class effects.NCT02332590.
Time Course Proteomic Profiling of Signal Transduction and Apoptosis Pathways in AML Survivor Cells Using Reverse Phase Protein Lysate Microarray (RPPA) Reveals Differential Effect of Time, Dose and Agent(s).
Authors: Steven M. Kornblau, YiHua Qiu, Raoul Tibes, Yiling Lu, Gordon B. Mills
Journal: Blood (2005)
Histone Deacetylase Inhibitors Induce FPGS mRNA Expression and Intracellular Accumulation of Long-Chain Methotrexate Polyglutamates in Childhood Acute Lymphoblastic Leukemia: Implications for Combination Therapy
Authors: Guy J Leclerc, Caihong Mou, Gilles M Leclerc, Abdul M Mian, Julio C Barredo
Journal: Blood (2008)
Liquoral liquid biopsy in neoplastic meningitis enables molecular diagnosis and mutation tracking: a proof of concept
Authors: Caterina Marchiò, Sara Mariani, Luca Bertero, Cristiana Di Bello, Paola Francia Di Celle, Mauro Papotti, Roberta Rudà, Riccardo Soffietti, Paola Cassoni
Journal: Neuro-Oncology (2016)
Pyopericardium secondary to achalasia-associated squamous cell carcinoma of the oesophagus
Authors: J. Mason, F. Dixon, H. Grimes, G. Jones
Journal: International Journal of Surgery (2016)

Patients with achalasia of the oesophagus are known to be at increased risk of oesophageal squamous cell carcinoma. To our knowledge, this is the first report of an achalasia-associated oesophageal squamous cell carcinoma presenting with acute sepsis secondary to pyopericardium.
Targeting Bruton's Tyrosine Kinase As a Novel Approach to Inhibit Osteoclast Function in Multiple Myeloma
Authors: Homare Eda, Loredana Santo, Diana D. Cirstea, Samantha Pozzi, Miriam Canavese, Tyler A. Scullen, Sonia Vallet, Erica Evans, Juswinder Singh, Noopur S. Raje
Journal: Blood (2011)
S63 Postoperative pulmonary complications and physiotherapy requirements after open thoracotomy versus vats lobectomy: a propensity score-matched analysis
Authors: P Agostini, ST Lugg, K Adams, N Vartsaba, M Kalkat, PB Rajesh, RS Steyn, B Naidu, A Rushton, E Bishay
Journal: Thorax (2016)

<h3>Introduction</h3> Video-assisted thoracoscopic surgical (VATS) lobectomy is increasingly used for curative intent lung cancer surgery compared to open thoracotomy due to its minimally invasive approach and associated benefits. However, the effect of the VATS approach on postoperative pulmonary complications (PPC), rehabilitation and physiotherapy requirements is unclear; our study aimed to use propensity score matching to investigate this. <h3>Methods</h3> Between January 2012 and January 2016 all consecutive patients undergoing lobectomy via thoracotomy or VATS were prospectively observed. Exclusion criteria included VATS converted to thoracotomy, re-do thoracotomy, sleeve/bi-lobectomy and tumour size &gt;7 cm diameter (T3/T4). All patients received physiotherapy assessment on postoperative day 1 (POD1), and subsequent treatment as deemed appropriate. PPC frequency was measured daily using the Melbourne Group Scale.<sup>1</sup> Postoperative length of stay (LOS), high dependency unit (HDU) LOS, intensive therapy unit (ITU) admission and in-hospital mortality were observed. Propensity score matching (PSM) was performed using previous identified PPC risk factors (age, ASA score, BMI, COPD, current smoking) and lung cancer staging. <h3>Results</h3> Over 4 years 736 patients underwent lobectomy with 524 remaining after exclusions; 252 (48%) thoracotomy and 272 (52%) VATS cases. PSM produced 215 matched pairs. VATS approach was associated with less PPC (7.4% Vs 18.6%; p &lt; 0.001), shorter median LOS (4 days vs 6; p &lt; 0.001), and a shorter median HDU LOS (1 day vs 2; p = 0.002) (Table 1). Patients undergoing VATS required less physiotherapy contacts (3 Vs 6; p &lt; 0.001) and reduced therapy time (80 min vs 140; p &lt; 0.001). More patients mobilised on POD1 (84% vs 81%; p = 0.018), and significantly less therapies to treat sputum retention and lung expansion were required (p &lt; 0.05). <h3>Conclusions</h3> This study demonstrates that patients undergoing VATS lobectomy developed less PPC and had improved associated outcomes compared to thoracotomy. Patients were more mobile earlier, required half the physiotherapy resources, having fewer pulmonary and mobility issues. <h3>Reference</h3> Agostini P, <i>et al</i>. Postoperative pulmonary complications following thoracic surgery: are there any modifiable risk factors? <i>Thorax</i> 2010;<b>65</b>(9):815–8.
Decision-Tree Algorithm Optimize Hematopoietic Progenitor Cell-Based Prediction in Peripheral Blood Stem Cell Mobilization
Authors: Chia-Yun Wu, Tzeon-Jye Chiou, Chun-Yu Liu, Feng-Chang Lin, Jeong-Shi Lin, Man-Hsin Hung, Liang-Tsai Hsiao, Jyh-Pyng Gau, Jin-Hwang Liu, Hsiu-Ju Yen, Giun-Yi Hung, Hui-Chi Hsu, Cheng-Hwai Tzeng, Muh-Hwa Yang, Po-Min Chen, Yuan-Bin Yu
Journal: Blood (2015)
AB0734 Quality of Life at Baseline in Early Psoriatic Arthritis Related To Initial Presentation of Mono-, Oligo-, and Polyarthritis and Tender Enthesis: Results from The Depar Study
Authors: K. Wervers, J.J. Luime, I. Tchetverikov, A.H. Gerards, M.R. Kok, C.W.Y. Appels, W.L. van der Graaff, J.H.L.M. van Groenendael, L.-A. Korswagen, J. Veris, J.M.W. Hazes, M. Vis
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Little data is available on quality of life in newly diagnosed psoriatic arthritis (PsA) patients and its relation to the extent of the disease. <h3>Objectives</h3> To describe quality of life in newly diagnosed PsA related to the extent of the disease as defined by the number of swollen joints and the presence or absence of tender enthesis. <h3>Methods</h3> Baseline data of consecutively recruited incident PsA patients was used from the Dutch south west Psoriatic Arthritis Registry (DEPAR) study between August 2013 to November 2015. Health-related quality-of-life (HRQoL) was assessed by the 8 subscales of the Short-Form 36 (SF-36) questionnaire (0–100, higher score represents a better HRQL) and the PsA-specific quality-of-life (PsAQoL) questionnaire (0–20, lower score represents a better HRQL). Patients were classified in the three arthritis subtypes (i.e. mono-, oligo- or polyarthritis) based on evaluation of the rheumatologist. A tender enthesis was defined as having at least one tender enthesis using the Leeds Enthesitis Index (LEI) and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES). <h3>Results</h3> 209 patients with arthritis at time of inclusion completed the SF-36 questionnaire. Average age was 51.4 years (SD 13.7) and 55% were male. Of these patients 49 had monoarthritis, 92 oligoarthritis and 68 polyarthritis. At least one tender enthesis was present in 45%, 38% and 53% of the patients. Mean scores of the subdomains in the SF-36 were similar across the different arthritis-groups, with better scores for monoarthritis compared to oligo and polyarthritis. However, when separating the groups based on the presence of a tender enthesis HRQoL decreased substantially for all groups across all subdomains of the SF-36, with a mean difference of 15 points (Figure 1). Mean scores of all subdomains were significantly lower in the tender enthesis group (n=106) compared to the non-tender enthesis group (n=131). Comparable results were observed for the PsAQoL scores (mono: 7.09 (SD 6.24) vs. 2.15 (SD 2.85); oligo: 7.11 (5.21) vs 4.18 (5.65) and 8.52 (6.04) vs 2.16 (2.90) <h3>Conclusions</h3> Stratifying the HRQoL for the presence of tender enthesis, present in about half of newly diagnosed PsA patients, showed lower levels of health-related quality-of-life across both physical and mental scales, independent of arthritis classification, emphasizing the importance of the enthesis in PsA. <h3>Disclosure of Interest</h3> None declared
Use of Antibiotic Lock for Salvage of Tunneled Central Venous Catheters with Catheter Colonisation and Catheter Related Blood Stream Infection in a Tertiary Care Hematopoietic Stem Cell Transplantation Unit- a Strategy Revisited
Authors: Saurabh Zanwar, Anant Ganesh Gokarn, Santhosh Devdas, Sachin Khurana, Avinash Bonda, Ritesh Pruthy, Vivek Bhat, Sajid Qureshi, Tapan Saikia, Navin Khattry
Journal: Blood (2015)
A Fully Magnetically Levitated Circulatory Pump for Advanced Heart Failure
Authors: Mandeep R. Mehra, Yoshifumi Naka, Nir Uriel, Daniel J. Goldstein, Joseph C. Cleveland, Paolo C. Colombo, Mary N. Walsh, Carmelo A. Milano, Chetan B. Patel, Ulrich P. Jorde, Francis D. Pagani, Keith D. Aaronson, David A. Dean, Kelly McCants, Akinobu Itoh, Gregory A. Ewald, Douglas Horstmanshof, James W. Long, Christopher Salerno
Journal: New England Journal of Medicine (2016)

Continuous-flow left ventricular assist systems increase the rate of survival among patients with advanced heart failure but are associated with the development of pump thrombosis. We investigated the effects of a new magnetically levitated centrifugal continuous-flow pump that was engineered to avert thrombosis.
PWE-031 How Long is The Pre-Clinical Phase of Crohn’s Disease: Clues from Adult Height Measurements
Authors: J Clough, M Mendall, D Braim, A Hong
Journal: Gut (2016)

<h3>Introduction</h3> Inflammatory bowel disease (Crohns disease more than ulcerative colitis) is known to affect growth and final adult height when diagnosed before the end of puberty. Onset after the growth period has stopped would not be expected to have an effect on peak adult height unless there were pre-clinical changes in host physiology pre-dating the onset of disease. This question has never been addressed. Adult height progressively increased during the last century. A clue therefore to the duration of pre-clinical changes in IBD could be obtained by studying at what age peak adult height is reached and by how much this differs from the end of the growth period (approximately 18 yrs of age for women and 22 for men). <h3>Methods</h3> An IBD database was established at Croydon University Hospital in 2002. 717 subjects had adult height recorded. Adult height was modelled against age at diagnosis, and age at diagnosed squared to ascertain the inflexion point of the age at diagnosis vs. adult height. Significance tests were performed using ANOVA. The distance of this inflexion point from the end of puberty would give a guide to the latency period of IBD. Men and women, UC and CD were analysed separately and analyses were adjusted for age of the subject by December 2015. <h3>Results</h3> Regression plots of age at diagnosis squared modelled against adult height were curvilinear for patients with CD, with an inflexion point at 34 years of age for females and 28 years of age for males, indicating that patients diagnosed below these ages did not reach peak expected adult height. The same effect was not seen for patients with UC in whom there was a constant trend towards shorter adult height throughout the range from younger to older. <h3>Conclusion</h3> As predicted, patients diagnosed with CD during the pubertal period failed to reach expected peak adult height. However reduced peak adult height was also seen in patients diagnosed in young adulthood (up to 34 years in females; 28 years in males). This suggests that CD has a latent period lasting up to 20 years prior to the manifestation of symptoms, during which changes in host physiology could be acting to reduce growth in childhood. UC did not exert the same effect on peak adult height. <h3>Disclosure of Interest</h3> None Declared
THU0461 Rebound-Associated Vertebral Fractures after Denosumab Discontinuation: A Series of 8 Women with 35 Spontaneous Vertebral Fractures
Authors: B. Aubry Rozier, D. Stoll, E. Gonzalez Rodriguez, D. Hans, O. Lamy
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Osteoporosis (OP) treatments are given for a limited period of time because of a risk/benefice balance. Reversibility of OP treatment is observed by the measurements of bone markers turnover (BMTs) and bone mineral density (BMD). The effect on vertebral fracture (VFx) is difficult to evaluate. The OP treatment discontinuation is associated with an increase of BMTs and a more or less rapid decrease of BMD. Denosumab (Dmab) discontinuation is associated with a severe rebound effect on BTMs and BMD for near 24 months. A recent publication suggests an increase of VFx [1]. <h3>Methods</h3> We report the cases of 8 postmenopausal women. They received Dmab 60mg every 6 months for 2 to 8 doses. The 8 women were on calcium and vitamin D. A wide biological assessment excluded a secondary cause of OP. VFx were documented by MRI. <h3>Results</h3> Five OP women without any prior fragility fracture were treated every 6 months with 4 to 6 Dmab doses. Dmab was stopped because there was no more OP on BMD (3 women 55, 56 and 59 y old), the aromatase inhibitors were stopped (77y old) and according to the wish of the patient (77y old). 9 to 16 months after Dmab discontinuation, they presented respectively 5 (D11, D12, L2-L4), 7 (D9, D12-L5), 2 (D11 and D12), 3 (D12-L2) and 9 (D5-D9 and D11-L2) symptomatic spontaneous (SS) VFx. A 65 y old woman with osteoporosis and 3 prevalent VFx was treated every 6 months with 8 Dmab doses. Ten months after Dmab discontinuation she presented 2 SSVFx (D12, L3). These 62 y old woman (osteopenia, treated with <i>aromatase</i> inhibitors) received 2 Dmab doses every 6 months. The subsequent Dmab dose was forgotten. Twelve months after the last Dmab dose she presented a D10 SSFx. A 71 y old woman (one prevalent VFx and one hip fracture) received 2 Dmab doses with a delay of 11 months because of a lack of compliance. Eleven months after the last Dmab dose she presented 5 SSVFx (D12, L2-L5). <h3>Conclusions</h3> These 8 cases show a severe increased risk of vertebral fractures in the 9 to 16 months after the last injection of Dmab. The occurrence of these fractures can be explained by the severe rebound effect observed after denosumab discontinuation. It is urgent to: 1) inform the health authorities and patients of this risk; 2) determine treatment regimens before or at the time of denosumab discontinuation. <h3>References</h3> Aubry-Rozier B, Gonzalez-Rodriguez E, Stoll D, Lamy O. Severe vertebral fractures after denosumab discontinuation: 3 cases reports. Osteoporos Int. 2015 Oct 28. <h3>Disclosure of Interest</h3> None declared