tbuckley/cabot-search huggingface dataset:
The pH-Triggered Triblock Nanocarrier Enabled Highly Efficient siRNA Delivery for Cancer Therapy
Authors: Lili Du, Junhui Zhou, Lingwei Meng, Xiaoxia Wang, Changrong Wang, Yuanyu Huang, Shuquan Zheng, Liandong Deng, Huiqing Cao, Zicai Liang, Anjie Dong, Qiang Cheng
Journal: Theranostics (2017)

Small interfering RNA (siRNA) therapies have been hampered by lack of delivery systems in the past decades.Nowadays, a few promising vehicles for siRNA delivery have been developed and it is gradually revealed that enhancing siRNA release from endosomes into cytosol is a very important factor for successful delivery.Here, we designed a novel pH-sensitive nanomicelle, PEG-PTTMA-P(GMA-S-DMA) (PTMS), for siRNA delivery.Owing to rapid hydrolysis in acidic environment, PTMS NPs underwent hydrophobic-to-hydrophilic transition in endosomes that enabled combination of proton sponge effect and raised osmotic pressure in endosomes, resulting in vigorous release of siRNAs from endosomes into cytosol.In vitro results demonstrated that PTMS/siRNA complexes exhibited excellent gene silencing effects in several cell lines.Their gene silencing efficiency could reach ~91%, ~87% and ~90% at the N/P ratio of 50/1 in MDA-MB-231, A549 and Hela cells respectively, which were better than that obtained with Lipofectamine 2000.The highly efficient gene silencing was then proven from enhanced siRNA endosomal release, which is mainly attributed to pH-triggered degradation of polymer and acid-accelerated siRNA release.In vivo experiments indicated that NPs/siRNA formulation rapidly accumulated in tumor sites after i.v.injection.Tumor growth was effectively inhibited and ~45% gene knockdown efficacy was determined at the siRRM2 dose of 1mg/kg.Meanwhile, no significant toxicity was observed during the whole treatment.We also found that PTMS/siRNA formulations could lead to significant gene silencing effects in liver (~63%) and skin (~80%) when injected by i.v. and s.c., respectively.This research work gives a rational strategy to optimize siRNA delivery systems for tumor treatments.
“America’s Health First”: A Misnomer
Authors: Lawrence O. Gostin
Journal: JAMA (2017)

On July 7, Tom Price, MD, secretary of the Department of Health and Human Services (HHS), announced the appointment of Brenda Fitzgerald, MD, as the 17th director of the Centers for Disease Control and Prevention (CDC). To this position, Dr Fitzgerald brings her experience as Commissioner of the Georgia Department of Public Health, a role in which she championed infant health and survival, tobacco control, and obesity prevention. Other significant choices of individuals to head agencies that affect the public’s health include the recent nomination of Jerome Adams, MD, MPH, as surgeon general, and reappointment of Francis Collins, MD, PhD, as National Institutes of Health director. 
While such choices appear to bode well for public health, how well these agencies and others will be funded for programs affecting public health both inside and outside the United States matters enormously. What has the Trump administration signaled about its intentions in its proposed budget?
Effect of the FDA Regulatory Approach on the 0/1-h Algorithm for Rapid Diagnosis of MI
Authors: Raphael Twerenbold, Patrick Badertscher, Jasper Boeddinghaus, Thomas Nestelberger, Karin Wildi, Maria Rubini Gimenez, Òscar Miró, F. Javier Martín-Sánchez, Tobias Reichlin, Christian Mueller
Journal: Journal of the American College of Cardiology (2017)
SP0034 Share recommendations on systemic vasculitides
Authors: MW Beresford
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Primary systemic vasculitides (PSV) are very rare in children and consequently, little evidence exists. Evidence-based guidelines are lacking; this is an important and unmet need. The European initiative SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) aims to optimize care for children with rheumatic diseases. <h3>Objectives</h3> To provide recommendations for diagnosis and treatment for children with rare forms of PSV. <h3>Methods</h3> Recommendations were developed by a consensus process in accordance with the European League Against rheumatism standard operating procedures. An extensive systematic literature was performed and evidence-based or evidence-informed recommendations were extrapolated from the included papers. These were evaluated by a panel of 16 experts via an online survey and subsequently in two consensus meetings, using nominal group technique. Recommendations were accepted when ≥80% of experts agreed. <h3>Results</h3> A total of 78 recommendations were accepted in the two consensus meetings. Recommendations pertained to general cross-cutting recommendations for diagnosis and treatment of PSV, as well as disease-specific statements for childhood-onset Polyarteritis Nodosa, Granulomatosis with Polyangiitis, Microscopic Polyangiitis, Eosinophilic Granulomatosis with Polyangiitis, and Takayasu Arteritis. <h3>Conclusions</h3> European-wide recommendations for the diagnosis and treatment of rare forms of paediatric PSV have been formulated through an evidence-based consensus process. The SHARE project aims to provide international recommendations and significantly improve the standard of care for children with rheumatic diseases. <h3>Disclosure of Interest</h3> None declared
FRI0009 Accelerated development of aging-associated and instability-induced osteoarthritis in 12/15-lipoxygenase deficient mice
Authors: L Habouri, F El Mansouri, Y Ouhaddi, J-P Pelletier, J Martel-Pelletier, M Benderdour, H Fahmi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> 12/15-Lipoxygenase (12/15-LOX) catalyzes the generation of various anti-inflammatory lipid mediators, and has been implicated in several inflammatory and degenerative diseases. However, there is currently no evidence that 12/15-LOX has a role in osteoarthritis (OA). <h3>Objectives</h3> The aim of this study was to investigate the role of 12/15-LOX in the pathogenesis of OA <h3>Methods</h3> The development of aging-associated and destabilization of the medial meniscus (DMM)-induced OA were compared in 12/15-LOX-deficient (12/15-LOX<i>-/-</i>) and wild-type (WT) mice. The extent of cartilage damage was evaluated by histology. The expression of OA markers was evaluated by immunohistochemistry and RT-PCR. Cartilage explants were stimulated with IL-1α in the absence or presence of the 12/15-LOX metabolites, 15-HETE, 13-HODE or LXA4, and the levels of MMP-13, NO and PGE<sub>2</sub> were determined. The effect of LXA4 on the progression of OA was evaluated in WT mice. <h3>Results</h3> The expression of 12/15-LOX in cartilage increased during the progression of DMM-induced OA and with aging in WT mice. Cartilage degeneration was more severe in 12/15-LOX-/- mice compared to WT mice in both models of OA, and this was associated with increased expression of MMP-13, ADAMTS5, iNOS, and mPGES-1. Treatment of cartilage explants with 12/15-LOX metabolites, suppressed IL-1α-induced production of MMP-13, NO and PGE<sub>2</sub>, with LXA4 being the most potent. Intra-peritoneal injection of LXA4 reduced the severity of DMM-induced cartilage degradation. <h3>Conclusions</h3> These data demonstrate an important role of 12/15-LOX in OA and suggest that activation of this pathway may provide a novel strategy for prevention and treatment of OA. <h3>Acknowledgements</h3> This work was supported by the Canadian Institutes of Health Research (CIHR) Grant MOP-130293, the Arthritis Society, and the Fonds de la Recherche du Centre de Recherche du Centre Hospitalier de l9Université de Montréal (CRCHUM). <h3>Disclosure of Interest</h3> None declared
FRI0650 Non omeract -expert rheumatologists sonographers and inter-ultrasound machine reliability of the omeract ultrasound scoring in rheumatoid arthritis in a clinical-based setting: a belgian study
Authors: J-P Hauzeur, M-J Kaiser, J Bentin, J-P Brasseur, B André, P Carron, E Deflandre, C Naveau, C Ribbens, C Rinkin, R Wittoek, M-A D'Agostino, V De Maertelaer
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The OMERACT Ultrasound scoring system (USSS) of joint in RA has been shown to be reliable and sensitive to change when used in clinical trial setting. However it is unclear whether this reliability is also achieved in clinical daily practice among Rheumatologists performing US in a non-research setting and using different machines. <h3>Objectives</h3> To assess agreement between non-research sonographers in scoring synovitis using the OMERACT USSS and using the scoring of an OMERACT expert as gold standard. To assess the reliability of the USSS by using different US machines. <h3>Methods</h3> First an OMERACT US expert presented the scoring method and supervised a training session. The wrist, MCP 2 and 3 joints of the left hand (dorsal aspect) of 3 RA patients were then successively evaluated by 9 Rheumatologists with 3 different US machines: Hitachi Arietta = H, GE Logic E9 = G, Esaote MyLab 7= E. The USSS included B-mode acquisition of synovial hypertrophy (SH), joint effusion (JE) and bone erosion (BE), and Power-Doppler (PD) activity. JE, SH and BE were scored binary; SH and PD were score semi quantitatively (0 to 3), by both the 9 participating Rheumatologists and the OMERACT US expert. The agreement between each participant with the scoring of the OMERACT US expert was quantified by proportions. The inter-US machine reproducibility was assessed by kappa statistics for discrete variables and weighted kappa9s for ordinate. <h3>Results</h3> The 3 joints of 3 patients each were evaluated on the 4 US items (SH, JF, BE, PD) on a different US machine. So 27 values were obtained for each joint within each item. The percentages of exact agreement (PEA) between these 27 values and the scores of the OMERACT US expert were calculated and ranged between 33% (9/27) for SH-MCP3, 37% for JF-MCP2 and PD-Wrist, 41% for SH-wrist, 48% BE-MCP3, 52% PD-MCP3, 56% PD-MCP3, 59 JF-wrist and BE-MCP2, 63% JF-MCP3, 67% SH-MCP2 and 78% (21/27) for BE-wrist. For the inter-US machines reproducibility, kappa between the 3 machines was calculated on 9 data (3 patients x 3 joints). The reliability was low for detecting JE ≤0.211. Acceptable reliability among machines was found for SH, BE and PD (table 1). <h3>Conclusions</h3> Non OMERACT-expert Rheumatologists can apply the USSS, and this score works well across different machines. The difference among machines and sonographers is mostly captured by the low reliability of JE. The OMERACT USSS could be used by sonographers in their everyday clinical practice to evaluate the activity of RA patients. Further studies in clinical-based settings will allow to define more precisely the applicability of this scoring system. <h3>Disclosure of Interest</h3> None declared
THU0108 Subclinical central nervous system damage in patients with rheumatoid arthritis: disease activity and cytokines
Authors: I Tekeoğlu, S Sağ, A Kamanlı, MS Sağ, K Nas
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> We aimed in this study to investigate blood-brain barrier (BBB) dysfunction in RA patients who had no neurological symptoms, and were receiving synthetic DMARD treatment. <h3>Objectives</h3> We investigated correlations between cranial MRI images and brain specific proteins (S100 Beta, GFAP), cytokines (IL-1 beta, IL-17) in plasma which had important roles in disease activity. <h3>Methods</h3> In our study, 57 patients (46 females and 11 males) were included included in RA group, and 34 patients (24 females and 10 males) in the control group. All of RA patients were receiving synthetic DMARD treatment. Demographic characteristics of all patients were recorded. Disease activity was evaluated by using DAS-28. Mini-mental test (MMT) was used for evaluation of cognitive functions, and Fazekas scale was used to evaluate cranial MR lesions. S100 beta, GFAP, claudin, IL-17, and IL-1 beta levels were measured in peripheral blood of both groups. <h3>Results</h3> Demographic characteristics were similar between the groups, and there was no statistically significant difference in gender, age, and body mass index (BMI) between patient and control groups (p&gt;0.05). S100 beta, and GFAP levels were significantly higher in RA group (p&lt;0.05). No difference was determined in hyperintense lesions diagnosed in cranial MR between patient and control groups (p&gt;0.05). There were positive correlations between IL-17 S100 beta and GFAP, and IL-1 beta and S100 beta. <h3>Conclusions</h3> In our study, we have shown that blood-brain barrier may be damaged subclinically in RA patients, brain specific proteins related to BBB dysfunction may be increased in the peripheral blood, and BBB dysfunction may be related to cytokines which play an important role in disease pathogenesis. In conclusion, cytokines which circulate in the peripheral blood in RA may cause subclinical BBB damage. Further large scale studies with long-term follow-up are required which will support this hypothesis. <h3>Disclosure of Interest</h3> None declared
AB0474 Thyroid dysfunction in systemic lupus erythematosus: its impact as a cardiovascular risk factor
Authors: A Mabrook, MI Abd elkareem, MM Rayan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease caused by immune system–mediated tissue damage Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with rheumatologic autoimmune diseases, such as SLE <h3>Objectives</h3> The aim of the study Was to assess thyroid function and anti-thyroid antibodies in SLE patients and evaulate the effects of the thyroid dysfunction on the clinical parameters, disease activity and assess its impact as a cardiovascular risk factor. <h3>Methods</h3> A total number of Fifty SLE female patients were selected, Triglycerides (TG), total cholesterol (TC), LDL and high density lipoprotein (HDL).Thyroid Stimulating Hormone (TSH),serum freeT3 (FT3), freeT4 (FT4).Serum thyroid peroxidase antibodies (TPOab) and serum thyroglobulin antibodies (TGab) erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IMT (intima-media thickness) of the carotid arteries and Echocardiography was done for all patients <h3>Results</h3> There is a statistically significant correlation between SLE and thyroid disorder p. value&lt;0.05.clinical hypothyroidism was the most common abnormality presented followed by subclinical hypothyrodism.There is a statistically significant correlation between IMT and thyroid disorder p. value&lt;0.05.There is a statistically significant correlation between cardiac valves disorder and thyroid disorderT, we found a statistically significant correlation between pericardial effusion and thyroid disorder p. value&lt;0.05. <h3>Conclusions</h3> we conclude that thyroid disorder is more common in lupus patients especially those in exacerbation and +ve for antithyroid Ab and Those with thyroid dysfunction had increased cardiovascular risk. These patients should be investigated for Lipid profile echocardiography and neck US for detection of early atherosclerosis and other CVD Those with thyroid dysfunction had increased cardiovascular risk. <h3>References</h3> Nakisa R, Mesbah Sh, Eskandar K-S, and Nazarinia M.A,(2015). The Prevalence of Thyroid Dysfunction in Patients With Systemic Lupus Erythematosus. Iran Red Crescent Med J. 2015 December; 17(12): e17298. Tektonidou MG, Anapliotou M, Vlachoyiannopoulos P, Moutsopoulos HM. (2004) Presence of systemic autoimmune disorders in patients with autoimmune thyroid diseases. Ann Rheum Dis. 2004;63(9):1159–61. doi: 10.1136/ard.2004.022624. <h3>Disclosure of Interest</h3> None declared
Aryl Hydrocarbon Receptor Controls Monocyte Differentiation into Dendritic Cells versus Macrophages
Authors: Christel Goudot, Alice Coillard, Alexandra-Chloé Villani, Paul Gueguen, Adeline Cros, Siranush Sarkizova, Tsing-Lee Tang-Huau, Mylène Bohec, Sylvain Baulande, Nir Hacohen, Sebastian Amigorena, Elodie Segura
Journal: Immunity (2017)
AB0126 Autophagy and systemic lupus erythematosus: clinical significance of ATG14+, FOXP3+, and CD25+ expression on T regulatory cells and nk cells
Authors: A Rodríguez, EJ Zurita, AR Durán, R Bustamante, A Sánchez, MΆ Saavedra, C Arroyo, G Medina, LJ Jara
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Autophagy is a highly conserved protein degradation pathway, essential for removing protein aggregates and misfolded proteins in healthy cells. Autophagy and autophagy-molecules expression have been implicated in autoimmune diseases. Systemic Lupus Erythematosus (SLE) is a prototype of autoimmune disease whose main characteristic is the loss of immune tolerance. Recent evidences suggest that autophagy, and autophagy-related proteins participate in SLE immune regulation. However, little is known about the SLE clinical significance of autophagy-related proteins, T regulatory, and NK cells. <h3>Objectives</h3> To evaluate the expression of ATG14<sup>+</sup> (autophagy-related key regulator protein), FOXP3<sup>+</sup>, CD25<sup>+</sup>T regulators, CD56<sup>+</sup>NK cells in active and inactive SLE patients. <h3>Methods</h3> The expression of ATG14<sup>+</sup>, FOXP3<sup>+</sup>, CD25<sup>+</sup>, and CD56<sup>+</sup> were measured by flow cytometry, and expressed in percentages in T and NK cells of SLE patients (1997, ACR criteria), and healthy controls. Active SLE was considered by SLEDAI (≥4). The organs affected and treatments were evaluated. <h3>Results</h3> A total of 40 SLE patients and 20 healthy controls were included. The mean expression of autophagy in 20 active SLE patients was 11.19% in comparison with inactive SLE patients, 7.13%, (p=0.04), and in healthy donors, 7.445% (p=0.0281). The FOXP3<sup>+</sup> expression in NK cells in active SLE was lower in comparison with inactive patients (0.98% vs 3.82% respectively). In healthy donors was 2.89%. <h3>Conclusions</h3> We found that in active patients autophagy is higher than in inactive patients. In inactive patients FOXP3 expression in NK cells is normal. These results can be due to the effect of the different treatments given according to clinical manifestations. Autophagy-related key regulator protein may be a new target of SLE treatment <h3>References</h3> Lech M, Anders HJ. The pathogenesis of lupus nephritis. J Am Soc Nephrol. 2013, 24, 1357–1366. Chikte S, et. al. use of LysoTracker dyes: A flow cytometric study of autophagy. Cytometry. 2014, 85(2), 169–78. <h3>Disclosure of Interest</h3> None declared
THU0248 The association between systemic lupus erythematosus to bipolar disorder – a real-life study
Authors: S Tiosano, O Gendelman, D Comaneshter, H Amital, A Cohen, D Amital
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) is a chronic, autoimmune disease that has a wide variety of physical manifestations, including neuropsychiatric features. Bipolar Disorder (BD) is a chronic, phasic affective disorder that may present as depression or as mania. Neuropsychiatric symptoms in SLE develop in 20%&gt;70% of SLE patients during the course of the disease and in half of these patients they precede the diagnosis of SLE<sup>1–4</sup>. In half of the patients, neuropsychiatric manifestations occur prior to the diagnosis of SLE<sup>5</sup>. <h3>Objectives</h3> The objective of this study was to investigate the association between SLE and Bipolar Disorder (BD) using big data analysis methods. <h3>Methods</h3> Patients with SLE were compared with age- and sex-matched controls regarding the proportion of BD in a cross-sectional study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis, adjusting for confounders. The study was performed utilizing the chronic disease registry of Clalit Health Services medical database. <h3>Results</h3> The study included 5,018 SLE patients and 25,090 matched controls. BD was found in a higher proportion among SLE patients compared to controls (0.62% vs. 0.26%, respectively, p&lt;0.001). BD patients had a greater proportion of smokers compared to non-BD patients (62.5% vs 23.5%, respectively, p&lt;0.001). In a multivariate analysis, smoking and SLE were both found to be significantly associated with BD. <h3>Conclusions</h3> SLE was found to be independently associated with BD. These findings may imply that an autoimmune process affecting the central nervous system among lupus patients facilitates the expression of concomitant BD. <h3>References</h3> Kivity S, Shoenfeld Y. Association between autoantibodies and neuropsychiatric manifestations of autoimmune disease: comment on the article by Lauvsnes et al. Arthritis Rheumatol 2015; 67(6):1683. Meszaros ZS, Perl A, Faraone SV. Psychiatric symptoms in systemic lupus erythematosus: a systematic review. J Clin Psychiatry 2012; 73(7):993–1001. Unterman A, Nolte JE, Boaz M, Abady M, Shoenfeld Y, Zandman-Goddard G. Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum 2011; 41(1):1–11. Zandman-Goddard G, Chapman J, Shoenfeld Y. Autoantibodies involved in neuropsychiatric SLE and antiphospholipid syndrome. Semin Arthritis Rheum 2007; 36(5):297–315. Kivity S, Agmon-Levin N, Zandman-Goddard G, Chapman J, Shoenfeld Y. Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Med 2015; 13:43. <h3>Disclosure of Interest</h3> None declared