tbuckley/cabot-search huggingface dataset:
A novel PDE4 inhibitory agent with endothelial cell specific activity.
Authors: Jennifer E. Rosen, Walter Miller, Mei He, Sarah O’Connor, H. Richard Alexander, Faribourz Payvandi, David Stirling, Peter Schafer, Steven K. Libutti
Journal: Cancer Research (2004)

2372   Anti-angiogenic agents selective for tumor vasculature have shown promise as anti-cancer therapies in clinical trials. We evaluated the potential anti-angiogenic role of a novel class of orally available small molecules known as selective cytokine inhibitory drugs or SelCids. One member of this class of compounds, designated CC10004, was investigated for its effects on endothelial cells, new blood vessel formation and wound healing. Cell proliferation was determined for human umbilical vein endothelial cells (HUVEC), and two human colon cancer cell lines (HT29 or KM12) using a WST-1 cell proliferation assay. Effects on vessel growth were measured using the rat aortic ring assay and the chicken chorioallantoic membrane assay (CAM). Wound healing was assessed in C57/Bl 6 mice following daily topical administration of the compound or control carrier using tensile strength assessment (Instron Tensometer) and by calculating time to wound closure. CC10004 demonstrated selective inhibitory effects on human umbilical vein endothelial cells (HUVEC) but not on HT29 or KM12, two human colon cancer cell lines, at doses from 73 to 7300 nM compared to controls (HUVEC 73 nM 61.4% decrease p
Chemoimmunotherapy with a Modified Hyper-CVAD and Rituximab Regimen Improves Outcome for Patients with De Novo Philadelphia Negative Precursor B-Cell Acute Lymphoblastic Leukemia (ALL).
Authors: Deborah A. Thomas, Hagop M. Kantarjian, Stefan Faderl, William G. Wierda, Jorge Cortes, Jan A. Burger, Alessandra Ferrajoli, Zeev Estrov, Charles Koller, Marina Konopleva, Gautam Borthakur, Elias Jabbour, Farhad Ravandi, Tapan Kadia, Guillermo Garcia-Manero, Steven M. Kornblau, Michael Andreeff, Rebecca Garris, Michael J. Keating, Susan O'Brien
Journal: Blood (2009)
Immune-related response assessment during PD-1 inhibitor therapy in advanced non-small-cell lung cancer patients
Authors: Mizuki Nishino, Nikhil H. Ramaiya, Emily S. Chambers, Anika E. Adeni, Hiroto Hatabu, Pasi A. Jänne, F. Stephen Hodi, Mark M. Awad
Journal: Journal for ImmunoTherapy of Cancer (2016)

Tumor response characteristics using immune-related RECIST1.1 (irRECIST1.1) in advanced non-small-cell lung cancer (NSCLC) patients treated with nivolumab monotherapy in the clinical setting have not been previously described with a direct comparison with the assessments according to the conventional RECIST1.1.Fifty-six advanced NSCLC patients treated with nivolumab monotherapy after its Food and Drug Administration (FDA) approval were retrospectively studied. Tumor burden was quantified on serial CT scans during therapy using irRECIST1.1, which uses unidimensional measurements and includes new lesion measurements in total tumor burden. Response assessments by irRECIST1.1 were compared with assessments by RECIST1.1. Responses of individual lesions in different organs were also compared.Tumor burden change at best overall response ranged from -66.8 to +278.1% (median: +3.9%). Response rate was 14% (8/56; 8 partial responses, 0 complete responses) by irRECIST1.1 and by RECIST1.1. Time-to-progression (TTP) by irRECIST1.1 was longer than TTP by RECIST1.1 (median TTP: not reached vs. 1.9 months, respectively). No patients experienced pseudoprogression during the study. Among 128 target lesions, the lesion-based size change at best response differed significantly across different organs, with adrenal lesions and lymph nodes having greater size decrease, followed by lung, while liver and other miscellaneous lesions had lesser degree of size decrease (p = 0.002).Immune-related response evaluations using irRECIST1.1 in advanced NSCLC patients treated with nivolumab resulted in the identical response rate and longer TTP compared to RECIST1.1. No pseudoprogression cases were observed during the study. Adrenal lesions and lymph nodes were more responsive and liver lesions were less responsive to nivolumab.
Suppression of Cyclin D1 by on 01910.Na Is Associated with Decreased Survival of Trisomy 8 Myelodyplastic Bone Marrow Progenitors: A Potential Targetted Therapy.
Authors: Elaine M. Sloand, Loretta Pfannes, Ramana Reddy, Premkumar Reddy, Jerome S. Groopman, Neal S. Young
Journal: Blood (2007)
AB0930 Quantitative Chest Ct in Ild-Ssc Patients with Divergent Risks of Mortality
Authors: A. Ariani, M. Silva, V. Seletti, E. Bravi, M. Saracco, S. Parisi, F. De Gennaro, F. Lumetti, L. Idolazzi, P. Caramaschi, C. Benini, F.C. Bodini, C.A. Scirè, V. Alfieri, E. Bonati, G. Lucchini, M. Aiello, D. Santilli, F. Mozzani, D. Imberti, E. Arrigoni, G. Delsante, E. Michieletti, R. Pellerito, E. Fusaro, A.A. Chetta, N. Sverzellati
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Quantitative analysis of chest CT (QCT) is increasingly applied to characterization of Interstitial Lung Disease (ILD) associated to Systemic Sclerosis (SSc). However, there is no prognostic evidence for QCT in predicting lung detrimental evolution or death. Many Authors proposed composite clinical indexes to predict 1-year mortality. Recently the ILD-GAP index and du Bois index were proven to stratify ILD-SSc patients in outcome-related subgroups. <h3>Objectives</h3> The main aim of this study was to compare QCT assessment of SSc-ILD and composite clinical indexes in the selection of patients with high risk of mortality. <h3>Methods</h3> Chest CT, anamnestic data and pulmonary function test of 146 patients with SSc were retrospectively collected and ILD-GAP and DuBois score were calculated. Each chest CT underwent a quantitative assessment. Correlation between clinical prediction models and QCT parameters was tested. p&lt;0,05 was considered statistically significant. <h3>Results</h3> All QCT parameters had a statistically different distribution in patients with diverging mortality risk according to both clinical prediction models. The cut-off of QCT parameters were calculated by ROC curve analysis, with statistically significant value as compared to clinical prediction models (AUC &gt;0.7, p&lt;0.0001). <h3>Conclusions</h3> QCT assessment of SSc-ILD can distinguish between different mortality risk categories, therefore it yields prognostic value. These findings, together with the operator-independence, strengthen the accuracy of QCT for assessment of SSc-ILD. <h3>Disclosure of Interest</h3> None declared
PTH-024 The Role of Preassessment in Bowel Preparation
Authors: I Stasinos, J Britto, S Gulati, G Chang-Faye, D Joshi, P Dubois, A Haji, B Hayee
Journal: Gut (2016)

<h3>Introduction</h3> Inadequate bowel preparation reduces the diagnostic accuracy of colonoscopy. This has a significant impact on patients’ safety and the endoscopy units waiting lists. 90% adequate bowel preparation is a quality and safety indicator for endoscopy according to the Joint Advisory Group (JAG). The aim of this study is to determine the effect of patient pre-assessment on the quality of bowel preparation. The role of the cleansing agent was also assessed. <h3>Methods</h3> This is a retrospective observational study on consecutive patients undergoing elective colonoscopy in our centre from October 2014 until September 2015. Adults undergoing routine diagnostic colonoscopy, bowel cancer screening colonoscopy and chromoendoscopy were included. Sodium picosulphate (PIC) was used as cleansing agent in the first two groups whereas pegylated ethylene glycol with senna (PEG) was used in the latter. According to duration pre-assessment was either limited (LIM, 15 mins) or prolonged (PRO, 45 mins). Quality of bowel preparation was rated as inadequate, adequate and excellent. <h3>Results</h3> 2900 procedures were evaluated. 60% of the patients were male and the mean age was 58.8 +/- 15.68 years. 1670 (57.58%) were pre-assessed, of which 1329 received LIM/PIC, 280 PRO/PIC and 65 LIM/PEG. 1230 (42, 42%) were not preassessed and had PIC (NO/PIC). Inadequate bowel preparation was reported in 13.31% (n = 386) of the whole cohort. The rate of inadequate bowel preparation in each group was: NO/PIC (17.8%), LIM/PIC (11.51%), LIM/PEG (10.77%), PRO/PIC (2.53%). Pre-assessment showed significant association with bowel preparation outcome (p &lt; 0.001), while the type of cleansing agent used had no impact on the quality of bowel preparation (p = 0.241). Further multiple regression analysis showed that patients who had no pre-assessment were more likely to present with inadequate bowel preparation (OR 15.46, CI [7.15–33.4]) compared to patients who underwent prolonged preassessment. Patients undergoing limited preassessment were more likely to present with inadequate bowel preparation (OR 8.16, CI [3.76–17.70]) compared to patients who underwent prolonged pre-assessment. <h3>Conclusion</h3> This study identifies a prognostic role of preassessment in bowel preparation for colonoscopy. The cleansing agent seems to have no effect but only a small number of patients receiving preparation with PEG were included in this study. Further analysis of more categorical independent variables is required to formulate a predictive model for inadequate bowel preparation. <h3>Reference</h3> 1 R. Valori. BSG Quality and Safety Indicators for Endoscopy, March 2007 Joint Advisory Group. <h3>Disclosure of Interest</h3> None Declared
SAT0429 Effect of Vitamin D Supplementation on Effusion-Synovitis in Knee Osteoarthritis: A Randomized Controlled Trial
Authors: X. Wang, F. Cicuttini, X. Jin, A.E. Wluka, W. Han, Z. Zhu, L. Blizzard, B. Eathakkattu Antony, T. Winzenberg, G. Jones, C. Ding
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Synovial inflammation is commonly observed in osteoarthritis (OA). Vitamin D has showed anti-inflammatory properties in joint disorders which have not been reported in OA. <h3>Objectives</h3> To examine the effect of vitamin D supplementation on synovial inflammation in patients with symptomatic knee osteoarthritis (OA) and low vitamin D levels over 24 months. <h3>Methods</h3> In a multi-center, randomized, placebo-controlled and double-blind trial, symptomatic knee OA patients with a low 25-(OH)D level (12.5–60 nmol/l) were recruited. 413 patients (age 63.2±7.0 years, 208 females) were allocated to either a 50,000IU monthly vitamin D<sub>3</sub> capsule (n=209) or placebo (n=204) for 24 months. In this post-hoc analysis, changes in knee effusion-synovitis volume and score (0–3) were assessed using MRI (fig 1). A least significant criterion (LSC) was used to define an increase of effusion-synovitis volume by correcting measurement errors. <h3>Results</h3> At baseline, total effusion-synovitis volume was 8.0 ml with a prevalence of 47.7% (score ≥2). Over 24 months, the total effusion-synovitis volume remained stable in vitamin D group (mean: 0.26 ml, 95% CI: -0.82, 1.34) but increased significantly in placebo group (mean: 2.20 ml, 95% CI: 1.01, 3.38) (difference between groups: -1.94 ml, 95% CI: -3.54, -0.33). This effect was evident in those with baseline effusion-synovitis (difference: -2.04 ml, 95%CI: -3.83, -0.25) and in suprapatellar pouch (difference: -2.49 ml, 95%CI: -4.74, -0.25). Increases in total (relative risk: 0.66, 95%CI: 0.49, 0.90) and suprapatellar (relative risk: 0.64, 95%CI: 0.44, 0.93) effusion-synovitis volume were less in vitamin D than placebo group. <h3>Conclusions</h3> Vitamin D supplementation over 24 months significantly reduced progression of effusion-synovitis in patients with knee OA and low 25-(OH)D level. <h3>Acknowledgement</h3> We specially thank the participants who made this study possible, and we gratefully acknowledge the role of Vitamin D Effect on Osteoarthritis Study staff and volunteers in collecting the data. We thank the research assistants Jodi Barling, Kay Nguo, Judy Hankin and Alice Noone who were involved in the coordination of this study. Special thank to Yuelong Cao who wrote the study protocol. We also thank Rob Warren measured knee cartilage volume. <h3>Disclosure of Interest</h3> None declared
RASSF1a Is Applicable as Universal Fetal Identifier in RQ-PCR-Based Non-Invasive Prenatal Genotyping Assays
Authors: Aicha Ait Soussan, Bernadette Bossers, Ahmed Tissoudali, Godelieve C Page-Christiaens, Masja de Haas, C. Ellen Van der Schoot
Journal: Blood (2008)
THU0319 Suboptimal Vitamin D Levels in Patients with Systemic Lupus Erythematosus
Authors: C. Ramos, J.L. Andreu, M. Bascuas, M. Cuadros, M. Espinosa, B.J. Flores, J. Campos, J. Sanz
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that mainly affects women of childbearing age. Recent studies suggest a high prevalence of vitamin D insufficiency and deficiency in patients with SLE. Inadequate levels of vitamin D could determinate not only skeletal problems but also a potentiation of autoimmune activity in SLE. <h3>Objectives</h3> The purpose of this study was to determine the prevalence of vitamin D insufficiency and deficiency in SLE patients attended in a tertiary care center. <h3>Methods</h3> Consecutive patients with SLE seen in the Lupus Clinic of a Rheumatology Service belonging to a high complexity center in the Spanish Public Health System were included. Patients had to fulfill the 1997 ACR criteria for the classification of SLE. Different epidemiological, clinical, laboratory and serological variables were recorded. Levels of vitamin D and PTH, as well as serum levels of calcium, phosphorus, and alkaline phosphatase were systematically determined in all patients serum. Serum vitamin D levels at 25 nmol/L and 75 nmol/L were the cut-off values for vitamin D deficiency and vitamin D insufficiency, respectively. The local ethical committee authorized the study. Descriptive statistics was used to present the results; chi-square test, Student t test, and Mann-Whitney U test were used to establish statistical significance. A p&lt;0.05 was considered significant. Statistical analyses were performed by using Stata v12.0. <h3>Results</h3> One hundred and twenty patients were included, with a mean age of 51 years. Eighty-nine percent were women and 89% were caucasian. The average time of disease evolution was 13 years. Seventy-six percent of patients were taking hydroxychloroquine, 42% were taking glucocorticoids, and 37% of them were taking calcium plus vitamin D supplements. Nine percent of patients had vitamin D deficiency and 56% had vitamin D insufficiency. Elevated levels of PTH were detected in 18% of patients with vitamin D insufficiency and in 45% of patients with vitamin D deficiency. There were no statistically significant differences between them and patients with optimal levels of vitamin D. Likewise, no statistically significant association was observed between suboptimal vitamin D levels and skin involvement, photosensitivity, use of photoprotection, use of glucocorticoids, use of antimalarial or use of anticonvulsants. <h3>Conclusions</h3> Despite taking vitamin D and calcium supplements, vitamin D deficiency and insufficiency are common among SLE patients. Therefore, it might be advisable to monitor serum vitamin D levels in order to adjust the dose of vitamin D prescribed. <h3>Disclosure of Interest</h3> None declared
SAT0091 Major Clinical Characteristics of Chinese Rheumatoid Arthritis (RA) Patients with Smart System of Disease Management (SSDM) under Treat-To-Target (T2T) Recommendations
Authors: X. Liu, F. Xiao, J. Yang, R. Mu, H. Wang, H. Wei, X. Xin, Y. Zhu, Y. Zhang, Y. Jia, L. Zhang, Y. Liu, M. Wang, X. Li
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Treat-to-target (T2T) is a widely accepted management strategy for rheumatoid arthritis (RA) to achieve defined outcomes (remission or low disease activity). Moreover, mobile applications of patient-centered care created by multidisciplinary teams have been used for disease management in rheumatology. Smart System of Disease Management (SSDM) is a series of applications system for chronic diseases management. <h3>Objectives</h3> To describe major clinical characteristics of Chinese RA patients using SSDM under T2T recommendation in real world. <h3>Methods</h3> The SSDM includes doctors9 application system and patients9 application system. The patient application system includes self-assessment (DAS28, HAQ), medication management, adverse events management and laboratory records. After data entry, patients can synchronize data to the authorized doctor. The data were collected online from 173 rheumatology centers that cover 27 provinces in China. All patients fulfilling the 1987 ACR (formerly the American Rheumatism Association) criteria for RA were recruited. The median of each variable was analyzed using t-test assuming normality for DAS28 distribution and the level disease activity was analyzed using Pearson9s statistics. <h3>Results</h3> Since December 14th, 2014 to January 25th, 2016, 2,585 patients, 1,854 (71.7%) women and 731 (28.3%) men, participated in this study. Average age was 49.4 ±12.86 (15–90) years with mean disease duration of 8.9 years. The mean DAS28 scores was 4.03±1.54 (0.62–8.84) and the mean HAQ scores was 2.80±4.33 (0–24). At the Baseline, 19.5% of patients got remission, 12.9% low disease activity (LDA), 43.5% moderate disease activity (MDA) and 24.1% high disease activity (HDA). Clinical remission rate was negatively correlated with HAQ scores. For the entire cohort, the most commonly used treatment were conventional DMARDs (92.7%) include leflunomide (65.52%), hdroxychloroquine (48.52%), methotrexate (39.00%) and sulfasalazine (5.77%). <h3>Conclusions</h3> SSDM has provided demographic and clinical data of Chinese RA patients in real world practice. Clinical data and biologic samples would be valuable resources for future national and international studies. <h3>Disclosure of Interest</h3> None declared
AB0250 Assessment of Balance and Its Relation with Clinical Parameters in Rheumatoid Arthritis Patients
Authors: C. Sanal Top, T. Duruoz, H. Gunduz
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Rheumatoid Arthritis (RA) one of the deformitive disease for feet. Patients generally need the special care, shoes and assistive devices because of their feet deformities. <h3>Objectives</h3> To evaluate the static and dynamic balances of the RA patients and to assess its relationship with clinical, functional and radiological parameters. <h3>Methods</h3> Patients diagnosed with RA according to ACR 2010 criteria were recruited into the study. A<i>ge and gender matched</i> healthy subjects were into the control group. The demographic (age, sex) and clinical properties (BMI, DAS28 etc) of patients were recorded. The state of balance of the patients was evaluated by means of “Berg Balance Scale” (BBS) and also 3 static and 4 dynamic balance tests with 25 parameters were assessed via the “<i>Neurocom Balance Master</i>” device. Radiographic assessments of feet were done to consider the deformities. “Foot and Ankle Outcome Score” (FAOS) was applied for foot function assessment. The level of fatigue (MAF: Multidimensional Assessment of Fatigue), depression (Beck Depression Inventory) and sleep disorders (Pitsbourg Sleep Quality Index) of all patients were evaluated and corelated with balance parameters. <h3>Results</h3> This study included 165 cases that consist of 81 RA group (66 female, 15 male) and 84 healthy control group (70 female, 14 male). The mean age of patients and controls were 48.90±10.36 and 45.89±12.07 years, respectively. Age, sex and BMI data of both groups were similar (p&gt;0.05). There was a significant difference between the static and dynamic balance test results of the patient and the control groups (p&lt;0.05). It was deduced that 66.7% of patients have depression, 64.2% sleep disorders and 93.8% fatigue according to surveys; however there was no correlation between these symptoms and presence of balance disorders. Although 92.4% of patients were established with foot deformities, these deformities were not correlated with FAOS and balance disorders. The presence of the swollen joint was determined as the most relevant factor about the balance disorders of RA patients. <h3>Conclusions</h3> Although RA patients have balance disturbances when we compared them with healthy controls, this disturbances has not significant relation with clinical, functional and radiological parameters. Balance problems are an important finding independently from other parameters during the course of the disease <h3>Disclosure of Interest</h3> None declared
Hemoglobin S-nitrosylation plays an essential role in cardioprotection
Authors: Rongli Zhang, Douglas T. Hess, James D. Reynolds, Jonathan S. Stamler
Journal: Journal of Clinical Investigation (2016)

Homeostatic control of tissue oxygenation is achieved largely through changes in blood flow that are regulated by the classic physiological response of hypoxic vasodilation. The role of nitric oxide (NO) in the control of blood flow is a central tenet of cardiovascular biology. However, extensive evidence now indicates that hypoxic vasodilation entails S-nitrosothiol-based (SNO-based) vasoactivity (rather than NO per se) and that this activity is conveyed substantially by the βCys93 residue in hemoglobin. Thus, tissue oxygenation in the respiratory cycle is dependent on S-nitrosohemoglobin. This perspective predicts that red blood cells (RBCs) may play an important but previously undescribed role in cardioprotection. Here, we have found that cardiac injury and mortality in models of myocardial infarction and heart failure were greatly enhanced in mice lacking βCys93 S-nitrosylation. In addition, βCys93 mutant mice exhibited adaptive collateralization of cardiac vasculature that mitigated ischemic injury and predicted outcomes after myocardial infarction. Enhanced myopathic injury and mortality across different etiologies in the absence of βCys93 confirm the central cardiovascular role of RBC-derived SNO-based vasoactivity and point to a potential locus of therapeutic intervention. Our findings also suggest the possibility that RBCs may play a previously unappreciated role in heart disease.
Serum Free Light Chain Ratio (FLCR) at Diagnosis Constitute a Powerful Prognostic Factor of Survival in Multiple Myeloma (MM).
Authors: Marie-Christine Kyrtsonis, Theodoros P. Vassilakopoulos, Nicoletta Kafasi, Sotirios Sachanas, Tatiana Tzenou, Argiroula Papadogiannis, Zacharoula Galanis, Christina Kalpadakis, Maria Dimou, Elias Kyriakou, Maria K. Angelopoulou, Maria N. Dimopoulou, Marina P. Siakantaris, Styliani I. Kokoris, Evangelia M. Dimitriadou, Panayiotis Panayiotidis, Gerassimos A. Pangalis
Journal: Blood (2006)
Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation
Authors: Thomas J Hoffmann, Georg B Ehret, Priyanka Nandakumar, Dilrini Ranatunga, Catherine Schaefer, Pui-Yan Kwok, Carlos Iribarren, Aravinda Chakravarti, Neil Risch
Journal: Nature Genetics (2016)