tbuckley/cabot-search huggingface dataset:
UK sets target to halve exposure to toxic air in 10 years
Authors: Jacqui Wise
Journal: BMJ (2019)

The government’s new Clean Air Strategy aims to tackle air pollution from a wide range of sources and includes an ambitious new target to reduce fine particulate matter in line with World Health Organization guidelines.1

Ministers say the targets go far beyond existing European Union requirements and make the UK the first major economy to adopt air quality goals that are based on the WHO recommendations. The plan has been broadly welcomed, although environmental campaigners say it is severely lacking in detail.

The strategy says that fine particulate matter (PM2.5) will be reduced everywhere so that the number of people living in locations with concentrations above the WHO guideline of 10 μg/m3 will be halved by 2025, from 2016 numbers. The UK already meets the EU limit of 25 μg/m3 and is on track to meet the second stage limit of 20 μg/m3.

Without giving many details, the government said it will set a “new, ambitious, …
FRI0033 Trends in the incidence of orthopaedic surgeryin patients with rheumatoid arthritis in spain. a national observational cohort study
Authors: R. Mazzucchelli, J. Quirós, M. Peña, E. Perez-Fernandez, N. Crespí, C. Macía Villa, M. Espinosa, V. Villaverde, J.L. Morell Hita, C. Martinez-Prada, A. García-Vadillo, C. Morado Quiroga, M. Fernández-Prada, C. Barbadillo, H. Godoy, M. Galindo, O. Guzón Illescas, A. Herranz
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The need of orthopaedic surgery (OS) is a marker of disease severity in RA. During the last 20 years, the treatment in RA has changed, incorporating strategies based on "treat-to-target" and biological therapies. But, have these new strategies modified the incidence of OS in RA? <h3>Objectives</h3> To analyse the incidence and trend of hospital admissions for OS in patients with RA, in Spain, during the period between 1999 and 2015. <h3>Methods</h3> This is a national retrospective population based study. We analysed a national administrative database that includes a Minimum Basic Data Set (MBDS) of all hospital admissions of patients with RA. Period: 1999 to 2015. The OS were identified by the presence of ICD9 codes for arthrodesis, Total Hip Arthroplasty -THA-, Total Knee Arthroplasty -TKA-, Total Superior Limb Arthroplasty -TSLA. The population at risk was estimated through the population census of the National Institute of Statistics. The adjusted rates of hip fracture were calculated, by sex and age. The trend was analysed by Generalised Linear Models (GLM). <h3>Results</h3> Of a total of 338.343 hospital admissions, 21.088 (6,62%) were for OS. The main clinical-demographic characteristics are shown in the next table 1. The mean age of OS increased 6 years during the study period (p&lt;0,001). The OS age-adjusted rate during the study period was 752,9/10<sup>5</sup> inhab-year. The global fracture age-adjusted remained stable during de study period (IRR 1,002; IC95% 0,9–1,01). In RA patients&gt;60 the rate increase while in RA &lt;60 years the rate decrease (figure 1). <h3>Conclusions</h3> In Spain, during the period from 1999 to 2015, the global incidence rate of orthopaedic surgery in patients with RA has remained stable. In RA patients&gt;60 years the rate increase while in RA &lt;60 years the rate decrease. The mean age of OS increased 6 years. <h3>Disclosure of Interest</h3> None declared
AB0514 The effect of hydroxychloroquine on reducing proteinuria in stable sle patients
Authors: H. Takahashi, Y. Nasa, E. Takamasu, S. Sugii, N. Yokogawa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> It is thought that hydroxychloroquine (HCQ) reduces proteinuria by preventing endothelial dysfunction in mouse models, but the effects in systemic lupus erythematosus (SLE) patients are not known. <h3>Objectives</h3> To investigate the effects of HCQ on proteinuria in stable SLE patients. <h3>Methods</h3> This was a single-centre, retrospective cohort study. We included stable SLE patients who met the updated or revised American College of Rheumatology 1997 criteria for SLE or the 2012 Systemic Lupus International Collaborating Clinics criteria, and had no active organ dysfunction that needed an increase in immunosuppressive therapy. The subjects (HCQ group) were SLE patients with proteinuria &gt;0.2 g/gCr who started HCQ between 11/1/2015 and 8/1/2017. The controls (non-HCQ group) were SLE patients with proteinuria &gt;0.2 g/ gCr seen between 5/1/2016 and 10/31/2016. The reduction in proteinuria over 6 months in the HCQ and non-HCQ groups was compared. The following patients were excluded from the analysis: those who had proteinuria of other aetiologies (diabetic nephropathy, etc.), those who increased the prednisolone (PSL) dose or started immunosuppressive agents, angiotensin converting enzyme inhibitors, or angiotensin II receptor blockers beginning 1 month before the observation period started until its end. Improvement was defined as a reduction in proteinuria ≥0.1 g/gCr. The statistical analysis was performed with the <i>t-</i>test and chi-square test. <h3>Results</h3> There were no significant differences in disease duration, sex, Systemic Lupus Erythematosus Disease Activity Index, or the use of immunosuppressants at baseline between the HCQ (n=16) and non-HCQ (n=14) groups. The respective mean PSL dose at baseline was 5.9±2.8 and 3.3±3.8 mg in the HCQ and non-HCQ groups (p=0.042). Patients in the HCQ group were younger (mean 47±12 <i>vs</i>. 63±14 years, p=0.005). The kidney pathology of the HCQ group was 6.25, 25, 6.25, 6.25, and 6.25% class I to V, respectively, compared with 7.14% class IV, 14.2% class V, and 14.2% class IV+V in the non-HCQ group. The other patients were diagnosed with lupus nephritis clinically. Proteinuria was significantly lower in the HCQ group than in the non-HCQ group (–0.170±0.343 g/gCr <i>vs</i>. +0.129 ±0.401 g/gCr, p=0.036). The mean proteinuria at baseline and 6 months later was 0.501±0.276 and 0.331±0.274 g/gCr, respectively, in the HCQ group, and 0.587±0.409 and 0.717±0.720 g/gCr in the non-HCQ group. The proportion of patients who improved in the HCQ and non-HCQ groups was 68.7% (11/16) and 28.5% (4/14), respectively (p=0.028). <h3>Conclusions</h3> HCQ may reduce proteinuria in SLE patients. This suggests that HCQ administration protects the kidneys of SLE patients. <h3>Disclosure of Interest</h3> None declared
Abstract 17773: Baseline Cardiovascular Disease, Risk Factors, and Subsequent Changes Among Newly Diagnosed Prostate Cancer Patients
Authors: Jai Singh, Nirmanmoh Bhatia, Eric Farber-Eger, Quinn Wells, Javid Moslehi
Journal: Circulation (2016)

Background: Currently there are 3 million prostate cancer (PCa) survivors in the US with roughly 500,000 receiving androgen-deprivation therapy (ADT), a mainstay of treatment. As cancer survival co...
Abstract P281: Longitudinal Associations of Diet, Screen Time, and Physical Activity Behaviors With Cardiometabolic Risk Factors Among Chinese Children and Their Parents
Authors: Fei Dong, Annie Green Howard, Amy Herring, Linda Adair, Amanda Thompson, Barry Popkin, Allison Aiello, Bing Zhang, Penny Gordon-Larsen
Journal: Circulation (2017)

Background: Understanding intergenerational differences in associations of urbanization-related lifestyle behaviors with cardiometabolic disease (CMD) risk factors in children and their parents is important in rapidly urbanizing China. Objective: We tested the intergenerational differences in longitudinal associations of away-from-home eating, snacking, screen time, and leisure-time sports with high waist-to-height ratio (WHtR), elevated blood pressure (BP), elevated hemoglobin A1c (HbA1c), and elevated C-reactive protein (CRP) among Chinese children and their parents. Method: We studied 5,180 children (aged 7-17y) and their parents participated in China Health and Nutrition Survey (1991-2009) with measured WHtR, BP, HbA1c, and CRP. We used three-day 24-hour dietary recall to derive away-from-home eating (non-consumer, &lt;1meal/day, and ≥1meals/day) and consumption of fruit/vegetable snacks (any/none) and other snacks (any/none). We used a seven-day physical activity recall to collect screen time (≤1hr/day, 1-2hrs/day, and &gt;2hrs/day) and leisure-time sports (any/none). Random-effects logistic regression was used to examine the associations of lagged behaviors with CMD risk factors. Results: We detected intergenerational differences in associations between lagged behaviors and risk factors ( P interaction &lt;0.1). Generation-specific models showed that lagged away-from-home eating ≥1 (versus no) meals/day was negatively associated with parents’ high WHtR (OR=0.68, 95% CI=0.53, 0.89) but positively associated with children’s high WHtR (OR=1.46, 95% CI=1.01, 2.12) at follow-up. Lagged fruit/vegetable snack consumption was negatively related to parents’ high WHtR, parents’ elevated BP, and children’s high WHtR at follow-up. Lagged screen time was positively associated with parents’ high WHtR and children’s high WHtR, elevated BP, and high CRP at follow-up. The behavior-risk factor associations did not differ across years. Conclusion: CMD risk factors were negatively associated with fruit/vegetable snack consumption and positively associated with screen time in both generations. Away-from-home eating was associated with higher WHtR in children but lower WHtR in parents. Generation-specific intervention strategies may be needed for behavioral changes to reduce CMD risk.
N6-Methyladenosine Modification Regulates Cell Metabolism in Acute Myeloid Leukemia
Authors: Hengyou Weng, Huilin Huang, Huizhe Wu, Mingli Sun, Savanna Stanford, Sean Robinson, zhen-Hua Chen, Xi Qin, Xiaolan Deng, Xi Jiang, Ying Qing, Chao Shen, Rui Su, Minjie Wei, Jianjun Chen
Journal: Blood (2018)
Hydroxyurea — An Essential Medicine for Sickle Cell Disease in Africa
Authors: Lucio Luzzatto, Julie Makani
Journal: New England Journal of Medicine (2019)

Higher levels of fetal hemoglobin (HbF) ameliorate the clinical course of sickle cell disease. Hydroxyurea, an inhibitor of the enzyme ribonucleoside diphosphate reductase, increases HbF synthesis by erythroid cells (Figure 1). More than 20 years ago, a major clinical trial of hydroxyurea in the management of sickle cell disease proved successful.1 Subsequent studies, including eight randomized, controlled trials, that have involved adults, children, and specific clinical situations all showed benefit from hydroxyurea,2 with particular effects on pain reduction, prolonged survival, improvement in quality of life, and recently, prevention of end-organ damage. Hydroxyurea is now recognized in national and international guidelines . . .
Targeted Allele Suppression Prevents Progressive Hearing Loss in the Mature Murine Model of Human TMC1 Deafness
Authors: Hidekane Yoshimura, Seiji B. Shibata, Paul T. Ranum, Hideaki Moteki, Richard J.H. Smith
Journal: Molecular Therapy (2019)

Hearing loss is the most common human sensory deficit. Its correction has been the goal of several gene-therapy based studies exploring a variety of interventions. Although these studies report varying degrees of success, all treatments have targeted developing inner ears in neonatal mice, a time point in the structural maturation of the cochlea prior to 26 weeks gestational age in humans. It is unclear whether cochlear gene therapy can salvage hearing in the mature organ of Corti. Herein, we report the first study to test gene therapy in an adult murine model of human deafness. Using a single intracochlear injection of an artificial microRNA carried in an AAV vector, we show that RNAi-mediated gene silencing can slow progression of hearing loss, improve inner hair cell survival, and prevent stereocilia bundle degeneration in the mature Beethoven mouse, a model of human TMC1 deafness. The ability to study gene therapy in mature murine ears constitutes a significant step toward its translation to human subjects.
Abstract 16329: A Prostacyclin Analogue-Incorporated Nanoparticles Attenuates Ischemia Reperfusion Injury in Rat Heart
Authors: Shin Yajima, Shigeru Miyagawa, Satsuki Fukushima, Yoshiki Sakai, Kayako Isohashi, Hiroko Iseoka, Motoko Shiozaki, Akima Harada, Genki Horitsugi, Jun Hatazawa, Yoshiki Sawa
Journal: Circulation (2017)

Introduction: We developed a liposome-based biocompatible nanoparticle for drug-delivery-system for myocardial ischemia reperfusion (I/R) injury, in which the nanoparticle was selectively accumulat...
Proteogenomic Characterization of Human Early-Onset Gastric Cancer
Authors: Dong-Gi Mun, Jinhyuk Bhin, Sangok Kim, Hyunwoo Kim, Jae Hun Jung, Yeonjoo Jung, Ye Eun Jang, Jong Moon Park, Hokeun Kim, Yeonhwa Jung, Hangyeore Lee, Jingi Bae, Seunghoon Back, Su-Jin Kim, Jieun Kim, Heejin Park, Honglan Li, Kyu-Baek Hwang, Young Soo Park, Jeong Hwan Yook, Byung Sik Kim, Sun Young Kwon, Seung Wan Ryu, Do Youn Park, Tae Yong Jeon, Dae Hwan Kim, Jae-Hyuck Lee, Sang-Uk Han, Kyu Sang Song, Dongmin Park, Jun Won Park, Henry Rodriguez, Jaesang Kim, Hookeun Lee, Kwang Pyo Kim, Eun Gyeong Yang, Hark Kyun Kim, Eunok Paek, Sanghyuk Lee, Sang-Won Lee, Daehee Hwang
Journal: Cancer Cell (2019)
AB0155 1,25 dihydroxyvitamin d supplementation reduces hind paw edema in pristane-induced lupus model
Authors: E.C. Freitas, T.H. da Rosa, J.M.S. Silva, R.C. Espirito Santo, O.A. Monticielo
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a multifactorial, autoimmune inflammatory disease with pleomorphic clinical manifestations involving different organs and tissues. Vitamin D (VITD) deficiency is highly prevalent and evidence is mounting that it contributes to the morbidity and mortality in SLE. VITD is an essential steroid hormone with well-established effects on mineral metabolism, skeletal health, and more recently established profound effects on immune system health. <h3>Objectives</h3> To evaluate the development of SLE after VITD supplementation in pristane-induced lupus model. <h3>Methods</h3> Female BALB/c mice divided into 3 groups: healthy animals (CO), SLE animals (PIL) and SLE animals + vitamin D supplementation (PIL+VITD). PIL+VITD group received a subcutaneous injection of Calcijex® [2 ug/kg] in PBS-Tween 20 buffer every second day during 180 days. Animals were monitored every 2 months for body weight, free exploratory locomotion, grip strength, endurance exercise performance and edema size. Interleukin 2 (IL-2), IL-4, IL-6, IFN-γ and TNF-α were measured by Luminex technology. The histological and immunofluorescence parameters (IgG, IgM and C3) of the kidney and the joints are under analysis. Data was analyzed with ANOVA Two-Way followed by Bonferroni and independent sample t-test. p&lt;0.05 was considered significant. All data are represented as Mean±SEM. <h3>Results</h3> When compared with CO group (5.12±1.23 g), both PIL (7.53±1.09 g) and PIL+VIT D (8.08±2.28 g) groups exhibited a greater body weight gain by day 180 of the experiment (p&lt;0.05). There was no statistically significant difference in free exploratory locomotion and grip strength between the groups, but both the PIL (29.39±6.75 min) and the PIL+VITD (25.75±12.48 min) groups showed increased fatigue compared to the CO group (42.08±3.47 min). Still, VITD supplementation reduced mean paw swelling to compared PIL group (0.207±0.29 vs 0.24±0.051, p&lt;0.05) <h3>Conclusions</h3> The supplementation of VITD improves the clinical severity of PIL-manifestations, such as the reduction of hind paw edema. Further analysis of the histology of the joints and the kidney will complement the evaluation of the vitamin D modulating effects on the immune system. <h3>Disclosure of Interest</h3> None declared
AB0207 Calprotectin (S100A8/9) plasma levels decrease after abatacept therapy and correlate with disease activity in patients with rheumatoid arthritis
Authors: B. Šumová, H. Hulejová, K. Jarošová, M. Olejárová, Š. Forejtová, H. Ciferská, H. Mann, L. Šedová, J. Vencovský, K. Pavelka, L. Šenolt
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Calprotectin (S100A8/9) is a damage-associated molecular pattern molecule that is involved in the early phase of tissue injury. It is found mainly in circulating neutrophils, monocytes and macrophages of rheumatoid arthritis (RA) synovial tissue where it acts as a chemoattractant and induces production of proinflammatory cytokines. Several studies have reported its association with clinical disease activity and radiographic damage in patients with RA. <h3>Objectives</h3> The aim of our study was to analyse the plasma levels of calprotectin in patients with established RA after the abatacept treatment compared with healthy individuals, and to examine their potential association with disease activity and treatment response. <h3>Methods</h3> The plasma levels of calprotectin were determined by ELISA (BÜHLMANN Laboratories AG) in 40 patients with established RA before and 3 months after initiation of abatacept treatment, and in 30 age–/sex-matched healthy subjects. Disease activity was evaluated by 28-joint Disease Activity Score (DAS28). The CRP levels and erythrocyte sedimentation rate (ESR) were determined by routine laboratory techniques. Data are presented as median ±IQR. <h3>Results</h3> Calprotectin levels at baseline were significantly higher in patients with established RA than in healthy individuals (1925 [741; 4093] vs. 506 [302; 754] p&lt;0.0001; ng/ml). After 3 months of therapy, the levels significantly decreased (from 1925 [741; 4093] to 1569 [695; 3115] p=0.045; ng/ml). Calprotectin baseline levels significantly correlated with CRP, ESR and DAS28 at baseline (r=0.57, p=0.0003; r=0.56, p=0.0003; r=0.40, p=0.014, respectively), with change in DAS28 over 3 months (r=–0.54, p=0.001) and with change in CRP over 3, 6, 12 months (r=–0.56, p=0.0006; r=–0.61, p=0. 001; r=–0.71, p=0.0001, respectively). Calprotectin levels at month 3 significantly correlated with ESR at month 3 (r=0.43, p=0.013), CRP levels at month 3 and 6 (r=0.39, p=0.27 and r=0.43, p=0.024, respectively) and with change in CRP over 12 months (r=-0. 45, p=0.023). Change in calprotectin levels over 3 months correlated with the change in DAS28 over 3 months (r=0.39, p=0.028) and with change in CRP over 3, 6 and 12 months (r=0.48, p=0.004; r=0.38, p=0.028; r=0.60, p=0.0009, respectively). <h3>Conclusions</h3> We demonstrate here decrease in plasma levels of calprotectin after 3 months of abatacept therapy in patients with established RA, its association with disease activity and disease activity improvement over time. <h3>Acknowledgements</h3> Supported by the project of MHCR for conceptual development of research organisation 00023728, research project SVV 260 373. <h3>Disclosure of Interest</h3> None declared
SP0074 Are all opioids the same?
Authors: C. Stein
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects such as respiratory depression, sedation, addiction, nausea and constipation. Novel strategies to avoid adverse effects include the design of "biassed agonists" and of environment-sensitive ligands. Exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, due to its low pKa, selectively activates peripheral mu-opioid receptors in injured/inflamed tissue, i.e. at the source of pain generation. Unlike conventional opioids, this agonist showed pH-sensitive binding, G-protein subunit dissociation, and cAMP inhibition <i>in vitro.</i> It produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation or addiction potential. <h3>Disclosure of Interest</h3> None declared
Long-Term Carfilzomib for High-Risk Patients with Newly Diagnosed Multiple Myeloma: A Pooled Analysis of Two Phase 1/2 Studies
Authors: Roberto Mina, Alessandra Larocca, Maria Teresa Petrucci, Gianluca Gaidano, Stelvio Ballanti, Pellegrino Musto, Massimo Offidani, Paola Omedé, Giulia Benevolo, Alessandra Malfitano, Piero Galieni, Michele Cavo, Tommaso Caravita di Toritto, Vittorio Del Fabro, Vittorio Montefusco, Antonio Palumbo, Mario Boccadoro, Sara Bringhen
Journal: Blood (2018)
Capture Rate of the Adaptive Next Generation Sequencing VDJ Assay in Multiple Myeloma
Authors: Malin Hultcrantz, Even H Rustad, Venkata Yellapantula, Theresia Akhlaghi, Allison Jacob, Akshar Patel, Neha Korde, Sham Mailankody, Nikoletta Lendvai, Alexander M. Lesokhin, Hani Hassoun, Eric L. Smith, Oscar B Lahoud, Heather J. Landau, Gunjan L. Shah, Michael Scordo, David J. Chung, Sergio Giralt, Elli Papaemmanuil, Ola Landgren
Journal: Blood (2018)
Allergen challenge increases capsaicin-evoked cough responses in patients with allergic asthma
Authors: Imran Satia, Richard Watson, Tara Scime, Rachel J. Dockry, Shilpi Sen, James W. Ford, Patrick D. Mitchell, Stephen J. Fowler, Gail M. Gauvreau, Paul M. O'Byrne, Jaclyn A. Smith
Journal: Journal of Allergy and Clinical Immunology (2019)