tbuckley/cabot-search huggingface dataset:
Safety and photochemotherapeutic application of poly(γ-glutamic acid)-based biopolymeric nanoparticle
Authors: Dongyoon Kim, Quoc-Viet Le, Young Bong Kim, Yu-Kyoung Oh
Journal: Acta Pharmaceutica Sinica B (2019)

The safety of nanomaterials, a crucial consideration for clinical translation, is enhanced by using building blocks that are biologically nontoxic. Here, we used poly(γ-glutamic acid) (γ-PGA) and dopamine as building blocks of polymeric nanomaterials for carrying hydrophobic anticancer drugs. The introduction of phenylalanine onto γ-PGA enabled the resulting amphiphilic derivative of γ-PGA acid to self-assemble in the presence of the anticancer drug paclitaxel (PTX) to form PTX-encapsulated micelles. The surfaces of PTX-loaded micelles were then coated with polymerized dopamine (PDA). The PDA-coated, amphiphilic γ-PGA-based micelles (AM) carrying PTX (PDA/AM/P) exerted near-infrared-responsive photothermal effects. Near-infrared irradiation of cancer cells treated with PDA/AM/P nanoparticles produced a greater anticancer effect than that observed in other treatment groups, indicating a synergistic effect. Intravenous administration of PDA/AM/P completely ablated tumors and prevented their recurrence. Notably, the in vivo safety profile of PDA/AM/P nanoparticles allowed PTX to be delivered at a 3.6-fold higher dose than was possible with PTX solubilized in surfactant, and circumvented the side effects of the surfactant. These results support the multifunctional potential of PDA/AM for the delivery of various hydrophobic drugs and imaging dyes for safe translation of nanomaterials into the clinic.
AB0747 Interstitial lung disease is independently associated with increased faecal calprotectin levels in systemic sclerosis
Authors: C. Caimmi, E. Bertoldo, A. Venturini, P. Caramaschi, L. Frulloni, R. Ciccocioppo, S. Brunelli, L. Idolazzi, D. Gatti, O. Viapiana, M. Rossini
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Interstitial lung disease (ILD) is one of the leading cause of death in systemic sclerosis (SSc). <h3>Objectives</h3> The aim of this paper was to evaluate the relationship between faecal calprotectin (FC) and ILD. <h3>Methods</h3> 129 outpatients with SSc were enrolled. Data about disease characteristics, in particular lung involvement, were collected and FC was measured. <h3>Results</h3> Eighty-seven patients (67.4%) had a limited subset with a mean disease duration of 13.3 (7.1) years. Anti-Scl70 antibodies were found in 35 (27.1%) patients. GI tract involvement was severe/end stage in 3 cases (2.4%). ILD affected 35 patients (27.1%). Median levels of FC were 80 ug/g (157 ug/g). FC was found to be higher in patients with a moderate/severe/end stage score for gastrointestinal tract (p=0.046) and on steroids (p=0.015). In addition, it positively correlated with age (p&lt;0.001). Other than well-known risk factors such as higher mRSS or diffuse subset, patients with ILD had higher values of FC (p&lt;0.001). In multivariate analysis correcting also for factors affecting FC levels (i.e. disease duration, mRSS, Valentini activity score, total Medsger severity score, proton pump inhibitor, anti-Scl-70 antibody, diverticulosis, limited cutaneous subset, faecal calprotectin levels, steroid treatment), diffuse disease subset (p=0.001), higher mRSS (0.04), longer disease duration (0.046), higher severity scores (0.026), higher FC levels (p=0.003) and steroid treatment (0.014) were associated with increased risk of ILD, while diverticulosis was protective. In addition, we ran a second multivariate analysis considering the 110 cases with FC level &lt;275 µg/g, in order to correct for a possible small intestine bacterial overgrowth. Increased FC levels (p=0.019), steroid treatment (p=0.03), higher severity scores (p=0.016) and diffuse disease subset (p=0.002) were confirmed to be associated with ILD. <h3>Conclusions</h3> in this paper we have found a possible link between gut inflammation and ILD. Many hypothesis may be done but it is intriguing that these data further support what previously found by other authors (Andreasson et al. 2016), that is a correlation between gut inflammation and dysbiosis and non-gastrointestinal disease manifestation. Our study may support the hypothesis of a role of gut dysbiosis in triggering a pathologic immune response leading to ILD. It may also be that increased FC simply reflects a more severe disease but this still doesn't explain why only ILD was found to be linked with FC. Is it because lung is a filter of molecule (i.e. antigens, cytokines, metabolites, etc.) produced in the gut? Further studies with longitudinal evaluation are warranted. <h3>Disclosure of Interest</h3> None declared
Stratification for Age in Transfusion-Dependent Thalassemia
Authors: Alessia Pepe, Laura Pistoia, Mario Rocca, Giovanni Palazzi, Francesco Sorrentino, Aurelio Maggio, Antonella Quarta, Carlo Cosmi, Crocetta Argento, Sabrina Armari, Giuseppe Peritore, Matteo Oliva, Vincenzo Positano, Antonella Meloni
Journal: Blood (2018)
Progression-Free Survival Subset Analysis - Denosumab Vs Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Double-Dummy, Randomized Controlled Phase 3 Study
Authors: Evangelos Terpos, Wolfgang Willenbacher, Kazuyuki Shimizu, Ramon García-Sanz, Anthony Glennane, Xuesong Guan, Daniela Niepel, Noopur Raje
Journal: Blood (2018)
Preliminary Results from a Phase I Study of Isatuximab (ISA) in Combination with Bortezomib, Lenalidomide, Dexamethasone (VRd), and in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Non-Eligible for Transplant
Authors: Enrique M. Ocio, Paula Rodriguez Otero, Sara Bringhen, Stefania Oliva, Axel Nogai, Michel Attal, Philippe Moreau, Dheepak Kanagavel, Thomas F Fitzmaurice, Junlong Wu, Joaquin Martinez Lopez
Journal: Blood (2018)
<i>Diabetes Care</i> in 2019—Who, Why, What, and How?
Authors: Matthew C. Riddle
Journal: Diabetes Care (2019)

Once again it’s time for the editor’s annual message to the readers of Diabetes Care . Early last year we celebrated the 40th anniversary of the journal (1), and in midyear we discussed some of the big topics addressed by articles in 2018 (2). Shortly after that report, we were delighted to learn that the impact factor for Diabetes Care had risen from 11.9 in 2017 to 13.4 in 2018. For 2019, I want to offer a look inside the journal, a description of why and how the hardworking group behind the journal puts together its monthly issues. First, I want to thank everyone involved for their efforts to make the journal an important resource for the diabetes community. Next, just a few statistics. During 2018, we received approximately 2,700 initial submissions and 550 revised manuscripts with an overall acceptance rate of just below 13%. The acceptance rate for Original Articles continues to be near 10%. You may find it surprising that, over the course of the last two decades, >70% of yearly submissions have come from outside the U.S. The numbers of submissions are quite stable, but we believe their quality continues to rise.

It takes a lot of people to produce Diabetes Care . Contributors include authors, the editor in chief and 3 ad hoc editors in chief, 16 associate editors, 38 members of the editorial board, countless reviewers, the editorial staff, copyeditors, and production staff. Our families and friends sometimes ask why we spend so many hours at the keyboard. Why not work at other professional tasks, or take more time off? What most fail to realize is that the journal’s clock never stops. New and revised manuscripts, reviews, and communications about them never cease coming in, including evenings, weekends, and holidays. Sometimes hard decisions …
THU0173 Trends in hip fracture incidence in rheumatoid arthritis: a national observatinal cohort study
Authors: R. Mazzucchelli, E. Perez-Fernandez, N. Crespí, J. Quirós, C. Macía Villa, M. Espinosa, J.L. Morell Hita, M. Peña, V. Villaverde, C. Martinez-Prada, C. Morado Quiroga, C. Barbadillo, M. Fernández-Prada, H. Godoy, M. Galindo, A. García-Vadillo, O. Guzón Illescas, A. Herranz
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> During the last 20 years there have been significant changes in the treatment of patients with rheumatoid arthritis (RA) and in the prevention and treatment of osteoporosis. The potential impact of these strategies on important outcomes as the incidence of hip fracture in RA is unknown. <h3>Objectives</h3> To analyse the incidence and trend of hospital admissions for hip fracture in patients with RA, in Spain, during the period between 1999 and 2015. <h3>Methods</h3> This is a retrospective population based study. We analysed a national administrative database that includes a Minimum Basic Data Set (MBDS) of hospital admissions of patients with RA. Period: 1999 to 2015. The hip fracture cases were identified by the presence in primary and secondary diagnosis of ICD 9 codes. The population at risk was estimated through the population census of the National Institute of Statistics, with an estimated prevalence of RA of 0.5%. The crude and adjusted rates of hip fracture were calculated. The trend was analysed using Generalised Linear Models (GLM) using the year variable as the analysis variable. <h3>Results</h3> Of a total of 338.343 admissions of patients with RA, 6.656 (2%) was due to hip fracture, 5.608 (84.2%) in women and 1.048 (15.7%) in men. The mean age was 77.54 (SD 9.6). Mean age increased linearly during the study period (from 75,3 years in 1999 to 79,9 in 2015). There was a total of 326 (4.9%) deaths during admission. The fracture age-adjusted rate during the study period was 243,66/100.000 RA-patients*year (245,24 in women and 198,05 in men). The fracture age-adjusted rate increased from 150.11/100.000*year in 1999, to 303.12 in 2015 (in both sex). In women from 134.71 in 1999 to 304.83 in 2015) and in men from 99.63 in 1999 to 268.5 in 2015). An annual increase in the fracture rate of 3.1% is estimated. <h3>Conclusions</h3> In Spain, during the period from 1999 to 2015, although the mean age has increased, the incidence of hip fracture has not been reduced. We estimate an annual increase of 3.1%. <h3>Disclosure of Interest</h3> None declared
Food‐related anaphylaxis fatalities: Analysis of the Allergy Vigilance Network<sup>®</sup> database
Authors: Guillaume Pouessel, Etienne Beaudouin, Luciana K. Tanno, Martine Drouet, Antoine Deschildre, Julien Labreuche, Jean‐Marie Renaudin
Journal: Allergy (2019)

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Pembrolizumab Enhances the Anti-Leukemia Activity of Antigen Specific Cytotoxic T Lymphocytes
Authors: Mao Zhang, Pariya Sukhumalchandra, Anne V. Philips, Na Qiao, Celine Kerros, Lisa St. John, Alexander A. Perakis, Karen Clise-Dwyer, Elizabeth Mittendorf, Naval G. Daver, Jeffrey J. Molldrem, Qing Ma, Gheath Alatrash
Journal: Blood (2018)
Tumor-infiltrating human CD4 <sup>+</sup> regulatory T cells display a distinct TCR repertoire and exhibit tumor and neoantigen reactivity
Authors: Mojgan Ahmadzadeh, Anna Pasetto, Li Jia, Drew C. Deniger, Sanja Stevanović, Paul F. Robbins, Steven A. Rosenberg
Journal: Science Immunology (2019)

Intratumoral T reg cells are tumor/neoantigen reactive.
Cannabinoid CB1 receptors in the amygdalar cholecystokinin glutamatergic afferents to nucleus accumbens modulate depressive-like behavior
Authors: Chen-Jie Shen, Di Zheng, Ke-Xin Li, Jian-Ming Yang, Hao-Qi Pan, Xiao-Dan Yu, Jia-Yu Fu, Yi Zhu, Qi-Xin Sun, Meng-Yu Tang, Ying Zhang, Peng Sun, Yi Xie, Shumin Duan, Hailan Hu, Xiao-Ming Li
Journal: Nature Medicine (2019)
AB0638 Clinical significance of esr in chinese patients with systemic lupus erythematosus
Authors: Y. Xu, X. Feng, L. Sun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> During the process of systemic lupus erythematosus (SLE), disease flare and infection are often accompanied by each other and always pose a major challenge to clinical treatments. Although erythrocyte sedimentation rate (ESR) has been tested in SLE patients for many years, there is still a lack of consensus on its value. <h3>Objectives</h3> To validate the value of ESR in Chinese SLE patients at the time of their first admission and to determine whether it is related to a poor outcome. <h3>Methods</h3> Clinical data of patients with ESR tested on their first admission were extracted from our SLE database; (Feng et al. PLoS ONE 2016;11(12): e0168619) and analysed for the relation with disease activity (SLEDAI), infection status, organ involvements and survival situation. To determine the risk of ESR for long-term mortality, cumulative survival was illustrated with the Kaplan-Meier plot and factors were compared using the Log-rank test. <h3>Results</h3> Totally 1225 patients were included in this study, of which 92.2% were female and the median age at admission was 34.3 years. The most often seen organ involvements were mucocutaneous (66.4%), musculoskeletal (55.0%), renal (51.7%) and hematologic (45.2%) respectively. ESR levels were correlated with SLEDAI scores (r=0.145, p=0.000), but not elevated in patients with infections. Patients with cardiopulmonary, renal or hematologic impairments had higher ESR levels (all p&lt;0.05). Subgroup analysis showed that serositis, renal insufficiency and anaemia might be responsible for the respective organ involvement. The ten year survival rates for patients with elevated ESR was 80.57%, lower that of 88.62% for patients with normal ESR (p&lt;0.01) (figure 1). <h3>Conclusions</h3> High ESR levels in SLE patients are associated with active disease and specific organ involvements, and may predict a poor prognosis. It should be checked routinely for the monitoring of SLE patients. <h3>Disclosure of Interest</h3> None declared
FRI0248 Validity of random urinary uric acid-to-creatinine ratio for estimating 24-hour urine uric acid excretion in patients with gout
Authors: S. Choi, S.-J. Moon, E.-J. Kang, K.-H. Lee
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Gout is one of a heterogeneous group of diseases related to hyperuricemia. The measurement of 24 hour urinary uric acid excretion is frequently used to evaluate disease status and select drugs that lower uric acid level. However, 24 hour urine collection is inconvenient and frequently unreliable, due to errors in collection. Therefore, a simpler alternative to the 24 hour urine collection is needed. <h3>Objectives</h3> We investigated the utility of the random urine uric acid-to-creatinine (UA/CR) ratio in predicting 24 hour urine uric acid excretion in patients with gout. <h3>Methods</h3> Ninety patients with gout without any use of uric acid lowering agents were enrolled in this study. The mean age was 50.0±16.7 years old and the male patient was 90.0% (81/90) of all participants. For the evaluation of uric acid excretion and renal function, patients were collected 24 hour urine. Random urine uric acid and creatinine specimens were gained on the same day of 24 hour urine collection. Chronic kidney disease was defined as a creatinine clearance (CCr) level of less than 60 ml/min/1.73m<sup>2</sup> measured in 24 hour urine collection sample. Excretion of more than 600 mg of uric acid in the 24 hour urine sample was defined as uric acid over-excretion. <h3>Results</h3> Mean serum uric acid level was 7.73±1.89 mg/dl, and the mean 24 hour uric acid excretion was 666.5±236.2 mg. The random urinary UA/CR ratio showed positive correlation with 24 hour urine uric acid excretion (<i>γ</i>=0.398, p<i>&lt;</i>0.001). Correlation between these two variables was also found in the patients with chronic kidney disease (<i>γ</i>=0.762, p=0.028 In the linear regression analysis, absolute 24 hour urine uric acid excretion was estimated to be 581 x (random urinary UA/Cr)+432 (p<i>&lt;</i>0.001, adjusted R<sup>2</sup>=0.398). The best cut-off value for the random urinary UA/Cr ratio to distinguish between uric acid over-excretion and normal uric acid excretion was 0.342, with a sensitivity of 74.1%, specificity of 66.7%. The areas under the curves (AUCs) of the random urine UA/CR ratio was 0.763 [95% confidence interval (CI), 0.665–0.861, p<i>&lt;</i>0.001]. <h3>Conclusions</h3> The random urine UA/CR ratio correlated with 24 hour urine uric acid excretions in patients with gout. The best cut-off random urine UA/CR ratio value to discriminate uric acid over-excretion was 0.342, with a sensitivity of 74.1% and a specificity of 66.7%. The random urine UA/CR ratio would be a useful predictor to detect patients with urinary uric acid underexcretion, who could then be treated with uricosuric drugs. <h3>Disclosure of Interest</h3> None declared
THU0064 Antibodies against carbamylated proteins from patients with rheumatoid arthritisactivate endothelial cells
Authors: A. Pecani, T. Colasanti, F.R. Spinelli, C. Barbati, F. Conti, G. Valesini, C. Alessandri
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Inflammation contributes to the excess of cardiovascular morbidity in rheumatoid arthritis (RA), by promoting endothelial activation; this brings toward the production of adhesion molecules and the activation of signalling mediators. Antibodies against carbamylated proteins (anti-CarP) detected in RA patients correlate with subclinical atherosclerosis. <h3>Objectives</h3> Aims of the present study were: 1) to determine the effect of anti-CarP antibodies purified from the sera of RA patients, on the production of VCAM1 and ICAM1 as well as the activation of IRAK1 and NF-kB by human endothelial cell line EAhy926. 2) To evaluate endothelial cell apoptosis induced by anti-CarP. <h3>Methods</h3> An indirect ELISA was used to detect the presence of anti-CarP in the sera of RA patients. To purify anti-CarP, carbamylated-FCS used as an antigen was spotted onto a nitrocellulose filter and incubated with patient's sera that recorded the highest titer. Antibodies were eluted with glycine 100 mM, pH 2.5 and neutralised with Tris-HCl 1M, pH 8. Antibodies concentration was measured by using a colorimetric Bradford assay. The immortalised hybridoma cell line EAhy926 was cultured in Dulbecco's Modified Medium containing 10% fetal bovine serum, 1 mM l-glutamine, 100 U/ml penicillin and 10 ml HAT. After cell stimulation with purified anti-CarP at different time points (30 min-48 h) and different concentrations (5–20–50 µg/ml), supernatants were gathered to investigate the production of VCAM-1, ICAM-1 using commercial ELISA kits while activation of IRAK1 and NF-kB was detected by Western Blot analysis using cell lysates. Apoptosis was measured using FITC-conjugated annexin V (AV) and a propidium iodide (PI) apoptosis detection kit at different times (30 min-48 h). <h3>Results</h3> After EAhy926 stimulation with anti-CarP we observed: 1) induction of VCAM-1 but not ICAM production in cell supernatants; 2) activation of IRAK1 and NFkB transcription factor in cell lysates and 3) induction of endotelial cell apoptosis. <h3>Conclusions</h3> These data suggest a potential involvement of anti-CarP antibodies in endothelial cell activation allowing to further speculate on its possible effect in excess cardiovascular risk in RA patients. <h3>References</h3> [1] Pecani A, et al. Arthritis Res Ther2016; [2] Spinelli FR, Pecani A, et al., BMC Musculosceletal Disord2017; [3] Gonzales-Gay MA, et al. Clin and Exp Rheumatol2006; [4] Jing Shi, et al. Autoimmun Rev2014. <h3>Acknowledgements</h3> .<sup>EULAR Scientific Bursaries, Programme of 2017</sup> <h3>Disclosure of Interest</h3> None declared
Long-term Visual Outcomes and Causes of Vision Loss in Chronic Central Serous Chorioretinopathy
Authors: Sarah Mrejen, Chandrakumar Balaratnasingam, Talia R. Kaden, Alexander Bottini, Kunal Dansingani, Kavita V. Bhavsar, Nicolas A. Yannuzzi, Samir Patel, Kevin C. Chen, Suqin Yu, Guillaume Stoffels, Richard F. Spaide, K. Bailey Freund, Lawrence A. Yannuzzi
Journal: Ophthalmology (2019)
Dexamethasone palmitate nanoparticles: An efficient treatment for rheumatoid arthritis
Authors: Mathilde Lorscheider, Nicolas Tsapis, Mujeeb ur-Rehman, Françoise Gaudin, Ivana Stolfa, Sonia Abreu, Simona Mura, Pierre Chaminade, Marion Espeli, Elias Fattal
Journal: Journal of Controlled Release (2019)
Longitudinal, Seasonal, and Occupational Trends of Multiple Pesticides in House Dust
Authors: Breana Bennett, Tomomi Workman, Marissa N. Smith, William C. Griffith, Beti Thompson, Elaine M. Faustman
Journal: Environmental Health Perspectives (2019)

Background: Children are especially vulnerable to pesticide exposure and can suffer lasting health effects. Because children of farmworkers are exposed to a variety of pesticides throughout development, it is important to explore temporal patterns of coexposures. Objectives: The objectives of this study were to characterize the pesticide co-exposures, determine how they change over time, and assess differences between farmworker and nonfarmworker households. Methods: Dust collected from 40 farmworker and 35 nonfarmworker households in the Yakima Valley of the State of Washington in 2005 and then again in 2011 was analyzed for 99 pesticides. Eighty-seven pesticides representing over 28 classes were detected. Pesticides were grouped into classes using U.S. EPA pesticide chemical classifications, and trends in concentrations were analyzed at the class level. Results: Levels of organophosphates, pyridazinones, and phenols significantly decreased between 2005 and 2011 in both farmworker and nonfarmworker households. Levels of anilides, 2,6-dinitroanilines, chlorophenols, triclosan, and guanidines significantly increased in both farmworker and nonfarmworker households in 2011 vs. 2005. Among farmworkers alone, there were significantly lower levels of N-methyl carbamates and neonicotinoids in 2011. Conclusions: We observed significant reductions in the concentrations of many pesticides over time in both farmworker and nonfarmworker households. Although nonfarmworker households generally had lower concentrations of pesticides, it is important to note that in comparison with NHANES participants, nonfarmworkers and their families still had significantly higher concentrations of urinary pesticide metabolites. This finding highlights the importance of detailed longitudinal exposure monitoring to capture changes in agricultural and residential pesticide use over time. This foundation provides an avenue to track longitudinal pesticide exposures in an intervention or regulatory context. https://doi.org/10.1289/EHP3644