tbuckley/cabot-search huggingface dataset:
The Anti-Tumor Effects of M1 Macrophage-Loaded Poly (ethylene glycol) and Gelatin-Based Hydrogels on Hepatocellular Carcinoma
Authors: Alberto Daniel Guerra, Oscar W.H. Yeung, Xiang Qi, W. John Kao, Kwan Man
Journal: Theranostics (2017)

Background and Aims: Recently we reported that direct injection of M1 macrophages significantly caused tumor regression in vivo. Despite the promising result, a major limitation in translating this approach is the induction of acute inflammatory response. To improve the strategy, a biocompatible scaffold for cell presentation and support is essential to control cell fate. Here, we aimed to elucidate the anti-tumor effects of a poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) cross-linked hydrogels capsulated with M1 macrophages in both in vitro and in vivo disease models. Methods: Hydrogels were made at 0.5% (w/v) Iragcure 2959 photoinitiator, 10% (w/v) PEGdA, and 10% (w/v) Gel-PEG-Cys. Monocytic THP-1 cells were loaded into hydrogels and differentiated into M1 macrophages with lipopolysaccharide (LPS) and interferon gamma (IFN-γ). The M1 hydrogels were then cocultivated with HCC cell-lines Hep3B and MHCC97L to investigate the anti-tumor capacities and the associated molecular profiles in vitro. A nude mice ectopic liver cancer model with dorsal window chamber (DWC) and a subcutaneous tumor model were both performed to validate the in vivo application of M1 hydrogels. Results: M1 hydrogels significantly decreased the viability of HCC cells (MHCC97L: -46%; Hep3B: -56.9%; P<0.05) compared to the control in vitro. In response to HCC cells, the hydrogel embedded M1 macrophages up-regulated nitrite and tumor necrosis factor alpha (TNF-α) activating caspase-3 induced apoptosis in the tumor cells. Increased tumor necrosis was observed in DWC filled with M1 hydrogels. In addition, mice treated with M1 hydrogels exhibited a significant 2.4-fold decrease in signal intensity of subcutaneous HCC tumor compared to control (P=0.036). Conclusion: M1 hydrogels induced apoptosis in HCC cells and tumor regression in vivo. Continuous development of the scaffold-based cancer immunotherapy may provide an alternative and innovative strategy against HCC.
OP0266 Presence of monosodium urate crystals by dual-energy computed tomography in gout patients treated with allopurinol
Authors: N Dalbeth, S Nicolaou, S Baumgartner, J Hu, M Fung, HK Choi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Chronic hyperuricemia predisposes to deposition of monosodium urate (MSU) crystals in musculoskeletal and other tissues, causing chronic inflammation, acute gout flares, joint damage, and disfiguring tophi. Dual-energy computed tomography (DECT) is a useful imaging tool to detect and quantify MSU crystal deposits. <h3>Objectives</h3> This study assessed the evidence of MSU crystal deposition using DECT scanning among gout patients treated with allopurinol and the potential determinants associated with the observed deposits. <h3>Methods</h3> The multicenter DECT study recruited patients with gout from the USA and New Zealand who were taking allopurinol at ≥300 mg daily for at least 3 months. MSU crystal deposition was measured using DECT in hands/wrists, knees, and feet/ankles bilaterally. The presence of MSU crystals as well as the total volume of crystals were assessed according to gout characteristics and serum uric acid (sUA) levels. <h3>Results</h3> Patients (N=153) were predominately male (92.2%), with mean (SD) age 58.5 (11.4) years, and gout duration 14.9 (10.3) years. sUA was ≥6.0 mg/dL in 49.0% of patients. 81.7% of patients took allopurinol at a stable dose of 300 mg/day and the remainder at &gt;300 mg/day. 69.1% of patients had MSU crystal deposits with a total median crystal volume of 0.16 cm<sup>3</sup> (range, 0.01 to 19.53 cm<sup>3</sup>). Those with sUA ≥6.0 mg/dL and palpable tophi showed the highest prevalence of urate deposits (90%), and those with sUA &lt;6.0 mg/dL and no palpable tophi showed the lowest prevalence (47%). Those who reported a gout flare within the prior 3 months (versus none), were prescribed allopurinol doses &gt;300 mg (versus 300 mg), and had palpable tophi (versus none) had greater deposit volume. <h3>Conclusions</h3> Despite a stable dose of allopurinol for more than 3 months, and even with sUA at the target level, a substantial proportion of patients with gout continue to have evidence of MSU crystal deposition by DECT scan. Patients with palpable tophi, sUA levels ≥6.0 mg/dL, and gout flares within the prior 3 months have a greater volume of MSU crystal deposition. These patients may need continuation and/or intensification of their urate-lowering therapy regimen. <h3>Acknowledgements</h3> This study was sponsored by Ardea Biosciences/AstraZeneca. <h3>Disclosure of Interest</h3> N. Dalbeth Grant/research support from: AstraZeneca, Consultant for: AstraZeneca, Fonterra, Takeda, Pfizer, Cymabay, Crealta, Speakers bureau: Menarini, AstraZeneca, Takeda, S. Nicolaou Grant/research support from: Siemens Healthcare, S. Baumgartner Employee of: Ardea Biosciences, Inc, J. Hu Employee of: Ardea Biosciences, Inc, M. Fung Employee of: Ardea Biosciences, Inc, H. Choi: None declared
Tailored Approaches in Drug Development and Diagnostics: From Molecular Design to Biological Model Systems
Authors: Cecilia Sahlgren, Annika Meinander, Hongbo Zhang, Fang Cheng, Maren Preis, Chunlin Xu, Tiina A. Salminen, Diana Toivola, Daniel Abankwa, Ari Rosling, Didem Şen Karaman, Outi M. H. Salo‐Ahen, Ronald Österbacka, John E. Eriksson, Stefan Willför, Ion Petre, Jouko Peltonen, Reko Leino, Mark Johnson, Jessica Rosenholm, Niklas Sandler
Journal: Advanced Healthcare Materials (2017)

Abstract Approaches to increase the efficiency in developing drugs and diagnostics tools, including new drug delivery and diagnostic technologies, are needed for improved diagnosis and treatment of major diseases and health problems such as cancer, inflammatory diseases, chronic wounds, and antibiotic resistance. Development within several areas of research ranging from computational sciences, material sciences, bioengineering to biomedical sciences and bioimaging is needed to realize innovative drug development and diagnostic (DDD) approaches. Here, an overview of recent progresses within key areas that can provide customizable solutions to improve processes and the approaches taken within DDD is provided. Due to the broadness of the area, unfortunately all relevant aspects such as pharmacokinetics of bioactive molecules and delivery systems cannot be covered. Tailored approaches within (i) bioinformatics and computer‐aided drug design, (ii) nanotechnology, (iii) novel materials and technologies for drug delivery and diagnostic systems, and (iv) disease models to predict safety and efficacy of medicines under development are focused on. Current developments and challenges ahead are discussed. The broad scope reflects the multidisciplinary nature of the field of DDD and aims to highlight the convergence of biological, pharmaceutical, and medical disciplines needed to meet the societal challenges of the 21st century.
Association of Trauma and Posttraumatic Stress Disorder With Incident Systemic Lupus Erythematosus in a Longitudinal Cohort of Women
Authors: Andrea L. Roberts, Susan Malspeis, Laura D. Kubzansky, Candace H. Feldman, Shun‐Chiao Chang, Karestan C. Koenen, Karen H. Costenbader
Journal: Arthritis & Rheumatology (2017)

Objective To conduct the first longitudinal study examining whether trauma exposure and posttraumatic stress disorder ( PTSD ) are associated with increased risk of incident systemic lupus erythematosus ( SLE ) in a civilian cohort. Methods We examined the association of trauma exposure and PTSD symptoms with SLE incidence over 24 years of follow‐up in a US longitudinal cohort of women (n = 54,763). Incident SLE in women meeting ≥4 American College of Rheumatology criteria was ascertained by self‐report and confirmed by medical record review. PTSD and trauma exposure were assessed with the Short Screening Scale for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition PTSD and the Brief Trauma Questionnaire, respectively. Women were categorized as having no trauma, trauma and no PTSD symptoms, subclinical PTSD (1–3 symptoms), or probable PTSD (4–7 symptoms). We examined whether longitudinally assessed health risk factors (e.g., smoking, body mass index [ BMI ], oral contraceptive use) accounted for increased SLE risk among women with trauma exposure and PTSD versus those without. Results During follow‐up, 73 cases of SLE occurred. Compared to women with no trauma, probable PTSD was associated with increased SLE risk (for 4–7 symptoms, hazard ratio [ HR ] 2.94 [95% confidence interval {95% CI } 1.19–7.26], P &lt; 0.05). Subclinical PTSD was associated with increased SLE risk, although this did not reach statistical significance (for 1–3 symptoms, HR 1.83 [95% CI 0.74–4.56], P = 0.19). Smoking, BMI , and oral contraceptive use slightly attenuated the associations (e.g., for 4–7 symptoms, adjusted HR 2.62 [95% CI 1.09–6.48], P &lt; 0.05). Trauma exposure, regardless of PTSD symptoms, was strongly associated with incident SLE ( HR 2.83 [95% CI 1.29–6.21], P &lt; 0.01). Conclusion This study contributes to growing evidence that psychosocial trauma and associated stress responses may lead to autoimmune disease.
Imaging Tunneling Membrane Tubes Elucidates Cell Communication in Tumors
Authors: Emil Lou, Sepideh Gholami, Yevgeniy Romin, Venugopal Thayanithy, Sho Fujisawa, Snider Desir, Clifford J. Steer, Subbaya Subramanian, Yuman Fong, Katia Manova-Todorova, Malcolm A.S. Moore
Journal: Trends in cancer (2017)
SAT0157 Mycobacterium tuberculosis specific responses from CD8+ and CD4+ T cells in patients with latent and active form of tuberculosis
Authors: E Zanova, D Kozakova, M Polanova, I Solovic, I Rybar
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Testing the presence of latent or active tuberculosis using IGRA tests is necessary part of the diagnostic screening at risk individuals. QuantiFERON-TB Gold Plus (QFT-Plus) is a test for cell-mediated immune (CMI) responses to peptide antigens that simulate mycobacterial proteins. Peptide antigens in TB1 tube elicit CMI responses from CD4+ T-helper lymphocytes, in TB2 tube from CD8+ T-cytotoxic lymphocytes. Test is based on the ability of effector T lymphocytes to produce the cytokine interferon gamma (IFN-γ). <h3>Objectives</h3> To compare and evaluate levels of IFN-γ produced by CD4+ and CD8+ cells in TB1 and TB2 tubes. <h3>Methods</h3> It was studied 33 subjects with latent form of tuberculosis (LTBI) and 33 subjects with active TB. QFT-Plus was used to detect in vitro responses to peptide antigens associated with <i>Mycobacterium tuberculosis</i> infection (ELISA, QIAGEN). Results were obtained by calculation of INF-γ levels in Mitogen, TB antigen (TB1, TB2) and Negative control tubes using QFT analysis software. <h3>Results</h3> QFT-Plus positive results were observed in both groups of people. Increased levels of IFN-γ produced by CD4+ cells (TB1) has been detected in 21 subjects with LTBI (63,64%) and in all 33 subjects with active TB (100,0%). Increased levels of IFN-γ produced by CD8+ cells (TB2) has been detected in 27 people with LTBI (81,82%) and in all 33 people with active TB (100,0%). Joint increase levels of IFN-γ in the tubes TB1 and TB2 was observed in 16 individuals with LTBI (48,48%) and in all 33 individuals with active TB (100,0%). In the group of patients with a negative QFT-Plus it was not observed increased levels of IFN in tubes TB1 and TB2. <h3>Conclusions</h3> Our findings confirm specific CD4+ and CD8+ T cell response to mycobacterial protein antigens in individuals with LTBI and also in active TB subjects, in which INF-γ was frequently found. The immunological response represented by CD4+ and CD8+ T cells was not detected in subjects with QFT-Plus negative. <h3>Disclosure of Interest</h3> None declared
FDA Oversight of Postmarketing Studies
Authors: Mwango Kashoki, Cathryn Lee, Peter Stein
Journal: New England Journal of Medicine (2017)

The FDA aims to ensure the timely dissemination of information from postmarketing studies of drugs. The authors argue that an analysis of the effect of the FDA Amendments Act would evaluate the timeliness of FDAAA postmarketing requirements separately from that of other types of requirements.
AB0866 Evaluation of the achievement of a therapeutic target of&lt;6 mg/dl in algerian patients treated for gout
Authors: B Bengana, S Slimani, K Testas, F Rahal, M Makhloufi, A Ladjouze, S Lefkir-Tafiani
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Gout is one of the most prevalent rheumatic conditions in the developing world, due of the aging of the population and the modifications in the life style. The 2014 EULAR recommendations for the management of gout have defined the therapeutic target of 60 mg/L for gouty patients (recommendation 8). The aim of the study was to assess the adherence of Algerian patients with gout to these recommendations. <h3>Methods</h3> We have retrospectively analyzed patients files aged 18 and more, followed in a rheumatology setting for gout, in 4 centers in Algeria. Demographic, clinical and lab data were collected. We have excluded files with missing data. Were noted the used therapeutics and serum uric acid in every patient through time. Tolerance was noted. <h3>Results</h3> We have analyzed 145 complete files: 98 men (68%), with a mean age of 65.4±11.4 years. All patients except two had rheumatic manifestations, 20 patients had renal insufficiency and 15 had tophi. Main comorbidities were hypertension (40 patients) and diabetes (25 patients). The mean serum uric acid level was 96±14 mg/L. Concerning symptomatic drugs, 81 patients have taken colchicine and 15 NSAIDs, the remaining patients have taken other drugs or combination therapy. All patients but one have received serum uric acid lowering therapy (allopurinol in majority of cases), with a median dosage of 200 mg/day, and only 5 patients taking more than 300mg/day. The mean serum uric acid level at 6 months was 58±14 mg/L, with 58% of patients achieving a level of &lt;60 mg/L. <h3>Conclusions</h3> In rheumatology settings in Algeria, more than 93% of gouty patients received allopurinol, with an excellent tolerance. However, it seems that dosage is insufficient, with only 58% of patients achieving the EULAR recommendation 8. More efforts have to be provided to optimize this therapy. <h3>Disclosure of Interest</h3> None declared
AB0718 Prevalence of risk factors for fractures in axial spondyloarthritis: a systematic review
Authors: J García Ramírez, R Curbelo, JC Nieto, S Castañeda, L Carmona
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Spinal fractures occur more than expected in axial spondyloarthritis (Ax-Sp). However, it is not totally clear whether fracture risk depends solely on biomechanical problems of the spondyloarthritic spine or whether the prevalence of risk factors for fracture is larger than expected in these patients. <h3>Objectives</h3> To describe the prevalence of risk factors for osteoporotic fractures (both axial and peripheral) in Ax-Sp. <h3>Methods</h3> A systematic literature search was conducted. Medline, Embase and Cochrane Library databases were searched with a sensitive strategy including type of study and synonyms of Ax-Sp. All contemporary cross sectional studies or baseline results from representative cohorts of Ax-Sp published between January 2006 and 2016 were selected for detailed review. Only studies that fulfilled a minimum quality for survey data were included. Data on bone mineral density, prevalence of osteoporosis, and risk factor for fractures in Ax-Sp patients were collected. <h3>Results</h3> After screening 3597 titles and abstracts, only 43 studies (34 cross-sectional, 3 prospective and 6 retrospective) were reviewed in detail. Of these, 20 studies compared Ax-Sp patients with a control group, either healthy individuals (17 studies) or subjects with other diseases (6 studies). Reported prevalence of osteoporosis varied from 2% to 39.6%. Alcohol intake (58–61%), use of corticosteroids (11.7–67%), and 25-OH vitamin D deficit (26–76%) were unexpectedly high in Ax-Sp patients. All other factors were within expected frequencies for a not too old population. <h3>Conclusions</h3> Our systematic review found that alcohol intake, steroid use and 25-OH-vitamin D deficit should be taken into account when assessing comorbidity in Ax-Sp in order to avoid excess fractures. <h3>Acknowledgements</h3> this project was funded by Merck Sharp &amp; Dohme of Spain. <h3>Disclosure of Interest</h3> None declared
SAT0567 Impact of chikungunya fever on functional status and quality of life – a prospective cohort study of brazilian patients
Authors: LF da Rocha, MRDA Freitas, AGL de Mattos, HD de Lima, RM Correia, FGT Vieira, ALBP Duarte, CDL Marques, WLM de Oliveira, PRS de Melo, A Ranzolin
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> An epidemic of Chikungunya Fever (CF) spread throughout South America in 2014. The acute manifestation of CF typically consists of febrile arthritis. The burden of the chronic articular manifestations remains a public health issue affecting activities of daily life. There is a very important impact on quality of life in patients affected by CF, even at chronic phase. The long-term functional status may also be affected by CF. <h3>Objectives</h3> To evaluate longitudinally the disability, Health Related Quality of Life (HRQOL) and functional status of patients with CF and analyze the clinical and epidemiological factors associated with different outcomes. <h3>Methods</h3> Patients with clinical and demographic diagnosis of CF and persistent articular symptoms were evaluated in a cohort study between May 2016 and December 2016. HRQOL was rated by Short-Form 12 (SF-12) and the functional status was checked through Health Assessment Questionnaire (HAQ) and the Global Functional Status (GFS). Data were divided per weeks after disease onset and were analysed (Spearmans9s correlation coefficient and Mann-Whitney test). <h3>Results</h3> Sixty-five patients (58 females), mean age of 51.3 (±13.3) were assessed. As expected, a significant correlation between pain related scores and Physical Health Composite Scale Score (PCS), HAQ and GFS was found (p&lt;0.05)). Edema and morning stiffness correlated with PCS, HAQ and GFS status from 4 to 20 weeks after disease onset (p&lt;0.05). There was improvement in scores of all instruments used from 4–8 weeks of disease to 12–16 weeks of disease (table 1). The worst indices of PCS, Mental Health Composite Scale Score (MCS) and GFS were scored in the first month, mean scores of 30.07±5.77, 38.13±8.54 and 3.15±1.07 respectively. Higher HAQ values were demonstrated between 4 and 8 weeks after disease onset (mean score 1.87±0.82). <h3>Conclusions</h3> We demonstrated the impact of CF on HRQOL and Functional Status of patients. The SF-12 Health Survey, HAQ and GFS are influenced mostly by patients pain and worsening of this status are more prominent in the first 8 weeks of disease. Further clinical studies of the impact of CF on quality of life and functional studies are needed <h3>References</h3> Soumahoro MK, Gérardin P, Boëlle PY et al. Impact of Chikungunya virus infection on health status and quality of life: a retrospective cohort study. PLoS One. 2009 Nov 11;4(11):e7800. Rahim AA, Thekkekara RJ, Bina T et al. Disability with Persistent Pain Following an Epidemic of Chikungunya in Rural South India. J Rheumatol. 2016 Feb;43(2):440–4. Couturier E, Guillemin F, Mura M et al. Impaired quality of life after chikungunya virus infection: a 2-year follow-up study. Rheumatology (Oxford). 2012 Jul;51(7):1315–22. <h3>Disclosure of Interest</h3> None declared
OP0080 Risk of autism spectrum disorder in children born to mothers with systemic lupus erythematosus and rheumatoid arthritis in taiwan
Authors: P-H Tsai, C-F Kuo, L-H Huang, S-F Luo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> There is emerging evidence suggesting that offspring born to patients with rheumatic diseases has higher risk of neuropsychiatric diseases. Previous data from Quebec showed children born to women with SLE have an increased risk of autism spectrum disorder (ASD) but data regarding risk of ASD in offspring of mothers with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) mothers have not been reported in other population. <h3>Objectives</h3> We aimed to examine whether offspring of mothers with SLE and RA in Taiwan has a higher risk of developing ASD using data from a linkage between National Health Insurance (NHI) database and National Birth Registry in Taiwan. <h3>Methods</h3> We established a birth cohort of all live-births between 2001 and 2012 in Taiwan established using the National Health Insurance database and the National Birth Registry. Children born to mothers with SLE or RA were identified and matched up to 8 controls by maternal age, 1-minute Apgar score, 5-minute Apgar score, mode of delivery, sex of child, gestational age, birth weight, socioeconomic status (place of residence, income level, occupation). A marginal Cox proportional hazard models were used to estimate the relative risk (RR; 95% confidence interval [CI]) for ASD in newborns with affected mothers. <h3>Results</h3> Of 1,893,244 newborns, 0.08% (n=1,594) were born to mothers with SLE (mean age 30.43±4.37 years old) and 0.04% (n=673) were born to mothers with RA (31.97±4.51 years old). Overall, 5 of 673 (0.74%) RA offspring developed ASD, 7 of 1594 (0.44%) SLE offspring developed ASD and 10,631 of 1,893,244 (0.56%) all infants developed ASD. The incidence of ASD was 140.39 (95% CI, 45.58–327.62) per 100,000 person-years for RA group, 76.19 (95% CI, 30.63–156.97) per 100,000 person-years for SLE group, 89.85 (95% CI, 88.15–91.57) per 100,000 person-years for non-RA group and 89.87 (95% CI, 88.17–91.60) per 100,000 person-years for non-SLE group. The children born to RA and SLE mothers did not have higher risk of ASD with a HR (95% CI) of 1.42 (0.60–3.40) and 0.76 (0.36–1.59) for ASD, respectively. <h3>Conclusions</h3> Children born to women with SLE and RA do not have higher risk of developing ASD. <h3>References</h3> Lahita, R.G., Systemic lupus erythematosus: learning disability in the male offspring of female patients and relationship to laterality. Psychoneuroendocrinology, 1988. 13(5): p. 385–96. Vinet, E., et al., Increased Risk of Autism Spectrum Disorders in Children Born to Women With Systemic Lupus Erythematosus: Results From a Large Population-Based Cohort. Arthritis Rheumatol, 2015. 67(12): p. 3201–8. <h3>Disclosure of Interest</h3> None declared
Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalized lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma
Authors: Chao Liang, Fangfei Li, Luyao Wang, Zong-Kang Zhang, Chao Wang, Bing He, Jie Li, Zhihao Chen, Atik Badshah Shaikh, Jin Liu, Xiaohao Wu, Songlin Peng, Lei Dang, Baosheng Guo, Xiaojuan He, D.W.T. Au, Cheng Lu, Hailong Zhu, Bao-Ting Zhang, Aiping Lu, Ge Zhang
Journal: Biomaterials (2017)