tbuckley/cabot-search huggingface dataset:
Association of Tobacco Control Policies With Youth Smoking Onset in Chile
Authors: G. Emmanuel Guindon, Guillermo R. Paraje, Frank J. Chaloupka
Journal: JAMA Pediatrics (2019)

Tobacco smoking is still responsible for more than 6 million preventable deaths annually, most of which occur in low- and middle-income countries. South American countries, Chile in particular, endure some of the highest cigarette smoking prevalence rates globally. Despite the lack of any meaningful increases in cigarette taxes (the most effective tobacco control measure) between 1999 and 2014, cigarette prices in Chile increased sharply almost entirely driven by British American Tobacco (BAT).To examine the associations between cigarette prices and nonprice tobacco control policies targeted at youth introduced in 2006 (Law 20105) and smoking onset among Chilean youths.This study used data from 8 waves of a large national school survey of urban communities in Chile conducted between October and December in 2001, 2003, 2015, 2007, 2009, 2011, 2013, and 2015 and discrete-time hazard models. Data analysis was performed from May 2017 to January 2019.Prices, advertising, and retail restrictions.Smoking onset (the transition between never smoking and smoking) in youth.In this study of 181 624 survey respondents in 8751 Chilean secondary schools, higher prices (own-price elasticity [percentage change in quantity demanded in response to a 1% change in price], -0.40; 95% CI, -0.45 to -0.36) and the tobacco control policies enacted in 2006 (hazard ratio, 0.83; 95% CI, 0.81-0.85) were associated with lower hazards of starting smoking. The study found that an increase in real prices of 58.6% and the introduction of Law 20105 were associated with similar lower hazards of starting smoking (hazard ratio, 0.83; 95% CI, 0.81-0.85); in comparison, between 1999 and 2017, inflation-adjusted cigarette prices increased by 206%.The findings suggest that higher prices initiated by BAT and the tobacco control policies enacted by the Ministry of Health in 2006 were associated with lower hazards of starting smoking in Chilean youth. Large cigarette tax increases may be a strategy that can be used to help reduce smoking among youths in Chile.
Concerning Greater Social Contexts in Bariatric Surgery Availability and Telomere Length Outcomes
Authors: Asghar Shah, Jaffer Shah
Journal: JAMA Surgery (2019)

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PB1926 THE RELATIONSHIP BETWEEN OXIDATIVE STRESS LEVELS, BCR-ABL1 TRANSCRIPT VALUES AND TREATMENT WITH TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA
Authors: E.G. Pascu, M.-A. Gaman, A.M. Gaman
Journal: HemaSphere (2019)

Background: Chronic myeloid leukaemia (CML) is a chronic myeloproliferative neoplasm associated with a BCR-ABL1 gene sequence. Some studies have shown that oxidative stress is involved in CML pathogenesis, genomic instability, disease progression and resistance to tyrosine-kinase inhibitors (TKI). Aims: To evaluate reactive oxygen species (ROS) levels and the total antioxidant capacity (TAC) in patients with CML at diagnosis and after treatment with TKI. Methods: ROS and TAC were evaluated in a group of CML patients, diagnosed according to the ELN/WHO criteria, and in a control group of healthy volunteers. Patients were divided by age, sex and treatment. ROS were measured using a CyFlow SPACE Sysmex flow-cytometer (reagents from Abcam). TAC was evaluated using a FLUOstar Omega microplate reader (reagents from Sigma-Aldrich). CML patients were initially prescribed cytoreductive treatment (hydroxyurea) and then first or second generation TKI. Informed consent was obtained from all recruited subjects and the study was approved by the Ethics Committee of the University of Medicine and Pharmacy of Craiova, Romania, approval no. 74/23.02.2017. Results: The study group involved 47 CML patients (mean age 59.89 ± 13.35 years, age range 22-87): 24 males (51.06%, mean age 59.00 ± 14.99 years, age range 22-87) and 23 females (48.94%, mean age 60.83 ± 11.32 years, age range 34-80). Oxidative stress levels were higher in patients with CML vs. controls (p = 0.006): the mean TAC value was lower and the mean ROS level was significantly higher in the CML group vs. controls (TAC: 0.28 mM vs. 0.35 mM; ROS: 10.42 FI vs. 10.07 FI, FI = fluorescence intensity). The mean TAC value was significantly lower for each treatment subgroup vs. controls, and in particular for imatinib and dasatinib subgroups, and the mean ROS value was significantly higher for each treatment subgroup vs. controls. Changes of redox status in CML patients during treatment were related to the BCR-ABL1 transcript value.Summary/Conclusion: In our study, CML patients had at diagnosis higher ROS levels and lower TAC values compared with healthy controls. We observed changes in the redox status of CML patients during treatment. Alterations in the redox status may contribute to genomic instability and disease progression and might also be involved in the development of treatment resistance.
PB1771 EFFECTS OF AJWA ON DISEASE COMPLICATIONS AND CARDIAC AMONG HEMATOLOGICAL MALIGNANCY AND AJWA NANOFORMULATIONS ON THE ANTI‐CANCER AND SAFETY
Authors: S. Al Jaouni, A. Hussein, D. Ezzat, M. Almuhayawi, R. Raddadi, S. Mousa
Journal: HemaSphere (2019)

Background: Phoenix dactylifera, (Ajwa) has been known for a long time for its nutritive and medicinal properties. Aims: To evaluate the benefit of Ajwa in minimizing disease complications and cardiac on Pediatric Hematological malignancy at King Abdulaziz University Hospital, Jeddah, Saudi Arabia and to preclinically evaluate Nanoformulated Ajwa Bioactive compounds (N‐Ajwa) on Anti‐cancer efficacy and prevention of cardiac toxicity‐mediated by Doxorubicin (DOX). Methods: Our investigation include clinical and preclinical studies. The clinical study is a controlled trial of pediatric cancer patients between 2008 and 2018. A total of 200 patients were screened. Out of the 200 patients, 56 patients were included, 10 patients were AML (17.8%). Out of those 56, 26 (46.43%) agreed to take Ajwa and 30 served as control (53.57%). Both groups were assessed based on the following parameters: infection rates, frequency of hospital admissions for fever neutropenia, safety and mortality rate. The preclinical study examined the impact of N‐Ajwa on the anti‐cancer efficacy and cardiac safety of DOX in human breast cancer in female nude mice model. Results: Out of the 56 patients included, twenty six patients opted to be on Ajwa and the rest served as control. The supplementation of Ajwa significantly reduced hospital admissions and infections ( P = 0.009 and P &lt; 0.001 respectively). Ajwa group had a better survival rate in comparison to those in the non‐Ajwa group (stratified log‐rank P = 0.005), where the main cause of death of patients on the non‐Ajwa group was disease progression associated with infections (77%), cardiac problems were documented in 3 AML patients(30%). Those who were compliant on Ajwa showed recovery of cardiac problems. Ajwa showed some sort of cardiac protection in cardiac patients. N‐Ajwa bioactive ingredients protected against cardiac toxicity without any impact on anti‐cancer effects of DOX. Summary/Conclusion: This controlled study showed the regular intake of Ajwa is safe and significantly decreases disease complications including cardiac and infection and improved survival. Additionally, Ajwa have an effective role in cardiac protection against Doxorubicin.
Abstract 12590: Usefulness of Trough Level of Activated Partial Thromboplastin Time to Predict Bleeding Events in Clinical Use of Dabigatran for Patients With Atrial Fibrillation
Authors: Hiroshi Tasaka, Kazushige Kadota, Satoki Fujii, Kazuaki Mitsudo
Journal: Circulation (2013)

Background: Usefulness of activated partial thromboplastin time (APTT) to predict bleeding events in clinical use of dabigatran was reported in previous study. However, it is unknown whether the pe...
The Intestine Harbors Functionally Distinct Homeostatic Tissue-Resident and Inflammatory Th17 Cells
Authors: Sara Omenetti, Claudio Bussi, Amina Metidji, Andrea Iseppon, Sunjae Lee, Mauro Tolaini, Ying Li, Gavin Kelly, Probir Chakravarty, Saeed Shoaie, Maximiliano G. Gutierrez, Brigitta Stockinger
Journal: Immunity (2019)

Highlights•Tissue-resident, SFB-elicited Th17 cells are non-inflammatory•Citrobacter-elicited Th17 cells show high plasticity towards inflammatory cytokines•SFB Th17 cells are metabolically similar to resting memory cells•Citrobacter Th17 cells are highly glycolytic effector cellsSummaryT helper 17 (Th17) cells are pathogenic in many inflammatory diseases, but also support the integrity of the intestinal barrier in a non-inflammatory manner. It is unclear what distinguishes inflammatory Th17 cells elicited by pathogens and tissue-resident homeostatic Th17 cells elicited by commensals. Here, we compared the characteristics of Th17 cells differentiating in response to commensal bacteria (SFB) to those differentiating in response to a pathogen (Citrobacter rodentium). Homeostatic Th17 cells exhibited little plasticity towards expression of inflammatory cytokines, were characterized by a metabolism typical of quiescent or memory T cells, and did not participate in inflammatory processes. In contrast, infection-induced Th17 cells showed extensive plasticity towards pro-inflammatory cytokines, disseminated widely into the periphery, and engaged aerobic glycolysis in addition to oxidative phosphorylation typical for inflammatory effector cells. These findings will help ensure that future therapies directed against inflammatory Th17 cells do not inadvertently damage the resident gut population.Graphical abstract
Genomic landscape of oxidative DNA damage and repair reveals regioselective protection from mutagenesis
Authors: Anna R. Poetsch, Simon J. Boulton, Nicholas M. Luscombe
Journal: Genome biology (2018)

DNA is subject to constant chemical modification and damage, which eventually results in variable mutation rates throughout the genome. Although detailed molecular mechanisms of DNA damage and repair are well understood, damage impact and execution of repair across a genome remain poorly defined.To bridge the gap between our understanding of DNA repair and mutation distributions, we developed a novel method, AP-seq, capable of mapping apurinic sites and 8-oxo-7,8-dihydroguanine bases at approximately 250-bp resolution on a genome-wide scale. We directly demonstrate that the accumulation rate of apurinic sites varies widely across the genome, with hot spots acquiring many times more damage than cold spots. Unlike single nucleotide variants (SNVs) in cancers, damage burden correlates with marks for open chromatin notably H3K9ac and H3K4me2. Apurinic sites and oxidative damage are also highly enriched in transposable elements and other repetitive sequences. In contrast, we observe a reduction at chromatin loop anchors with increased damage load towards inactive compartments. Less damage is found at promoters, exons, and termination sites, but not introns, in a seemingly transcription-independent but GC content-dependent manner. Leveraging cancer genomic data, we also find locally reduced SNV rates in promoters, coding sequence, and other functional elements.Our study reveals that oxidative DNA damage accumulation and repair differ strongly across the genome, but culminate in a previously unappreciated mechanism that safeguards the regulatory and coding regions of genes from mutations.
SP0189 UPDATE ON EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF SLE
Authors: Antonis Fanouriakis
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Recent advances in treatment strategies and goals of treatment in systemic lupus erythematosus (SLE) called for an update of the EULAR recommendations for the disease, capitalizing on the strengths of and experience from similar previous projects. <h3>Objectives:</h3> To update the EULAR recommendations for the management of SLE <h3>Methods:</h3> Systematic literature review (01/2007-12/2017) followed by modified Delphi method to form questions, elicit expert opinions and reach consensus. <h3>Results:</h3> Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all lupus patients, at a dose not exceeding 5mg/kg real body weight. During chronic maintenance treatment, glucocorticoids should be minimized to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of glucocorticoids. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. SLE patients should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile, and preventative strategies be tailored accordingly. <h3>Conclusion:</h3> The recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion. <h3>Disclosure of Interests:</h3> Antonis Fanouriakis Paid instructor for: Amgen, GSK, Speakers bureau: Abbvie, Enorasis, Genesis Pharma
Abstract 18879: Low Income is Associated With Higher Risk of Cardiovascular Events and Mortality in Community Dwelling, Medicare Eligible, College Educated Older Adults With Background Professional Occupation
Authors: Amiya A Ahmed, Charity J Morgan, Gregg C Fonarow, Kanan Patel, Vera Bittner, Prakash Deedwania, Wilbert Aronow, Gerasimos Filippatos, Stefan Anker, Sumanth Prabhu, Richard M Allman, Ali Ahmed
Journal: Circulation (2013)

Purpose: Community-dwelling older adults with low income have been shown to be at a higher risk for incident heart failure (HF) and other cardiovascular (CV) events (Circulation 2011; 124: A12064 ). In the current analysis, we further studied the impact of income in community-dwelling, Medicare-eligible, college-educated older adults with professional occupation. Methods: Of the 5795 community-dwelling Medicare-eligible adults ≥65 years old, in the Cardiovascular Health Study (1989-1999), 1404 had college or higher education and a background professional occupation. Of these, 465 (33%) had low income, defined as annual household income &lt;$25,000 (2002 median income for Medicare beneficiaries, $20,400). Results: Patients had a mean (±SD) age of 73 (±5) years; 40% were women; and 13% African American. Unadjusted and age-sex-race-adjusted associations of low-income with outcomes during 13 years of follow-up are displayed in the Table . Conclusions: Nearly one-third of community-dwelling, Medicare-eligible, college-educated older adults with background professional occupation had low income, which was associated with higher risk of incident CV events and deaths. Future studies need to explore underlying mechanisms of these disparities despite Medicare coverage and if this disparity will be attenuated in the future under the new US health care reform law that makes provisions for free preventive care for Medicare beneficiaries.
FRI0061 THE CONTRIBUTION OF TENOSYNOVITIS OF SMALL JOINTS TO THE SYMPTOM MORNING STIFFNESS IN PATIENTS PRESENTING WITH UNDIFFERENTIATED AND RHEUMATOID ARTHRITIS
Authors: Aleid Boer, Debbie Boeters, Ellis Niemantsverdriet
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Morning stiffness (MS) is characteristic of Rheumatoid Arthritis (RA) that is associated with functional disability. Despite the known parallel in the circadian rhythm of MS and that of several hormones and pro-inflammatory cytokines in the systemic circulation, it is insufficiently known to what extent local inflammatory processes contribute to this symptom. The correlation between MS and the number of swollen joints is relatively weak but may be underestimated by insufficient sensitivity in measuring local inflammation. MRI is more sensitive in detecting local inflammation. Furthermore, MRI-detected tenosynovitis of small joints is increasingly recognized as early feature of RA which is also associated with functional impairments. Recently it was proposed that this may contribute to MS. <h3>Objectives</h3> We assessed the relationship between MS and MRI-detected inflammation and tenosynovitis in particular. <h3>Methods</h3> 286 consecutive patients newly presenting with undifferentiated and rheumatoid arthritis underwent contrast-enhanced 1.5T-MRI of (2-5)MCP-, (1-5)MTP-, and wrist-joints. Scans were scored for tenosynovitis according to Haavardsholm and for synovitis, osteitis conform the RAMRIS-method. MS was dichotomized as&gt;60 minutes. Associations between MS and tenosynovitis/synovitis were tested with logistic regression and the presence of a biologic interaction was assessed categorically (solitary or simultaneous presence of synovitis/tenosynovitis). <h3>Results</h3> MS was present in 40% of patients. Tenosynovitis was more often present in patients with MS than without MS (80% versus 65%), OR 2.11 (95%CI 1.21;3.69). Also synovitis was more often present in patients with MS (58% versus 44%), OR 1.83 (1.12;2.96). In categorized analyses the largest association was found for concurrent synovitis and tenosynovitis OR 2.43 (1.30;4.54); whereas single presence of synovitis was not associated (OR 0.85 (0.21;3.47)). The variance explained in all analyses on morning stiffness was small, ranging 3-6%. <h3>Conclusion</h3> Tenosynovitis, and simultaneous presence of tenosynovitis and synovitis in particular, was associated with MS. However, effect sizes suggested that the contribution of local inflammation to this symptom is rather limited. <h3>Acknowledgement</h3> E.C. Newsum and W.P. Nieuwenhuis are acknowledged for scoring MRI-scans. <h3>Disclosure of Interests</h3> Aleid Boer: None declared, Debbie Boeters: None declared, Ellis Niemantsverdriet: None declared, Annette van der Helm - van Mil Grant/research support from: The research leading to these results has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Starting grant, agreement No 714312) and from the Dutch Arthritis Foundation. The funding source had no role in the design and conduct of the study.
Abstract 24015: Genome-Wide Association Study of Vasodilator Response in Pulmonary Arterial Hypertension
Authors: Jason H Karnes, Ken Batai, Amit Arora, Justin Kaye, Heidi Steiner, Vineet Nair, Joe GN Garcia, Jason Yuan, Mike Pauciulo, William Nichols, Ankit Desai
Journal: Circulation (2017)

Introduction: Pulmonary arterial hypertension (PAH) is a rare and fatal disease associated with variable therapeutic response, suggesting a genetic contribution. Vasodilator-responsive PAH accounts for a minority of PAH cases and is associated with dramatically improved survival over vasodilator-nonresponsive PAH. The objective of our study was to identify genetic influences on vasodilator drug response in PAH. Methods: Two cohorts of patients with Group I PAH confirmed by right heart catheterization were derived from the PAH Biobank (NHLBI R24HL105333), representing over 40 US institutions. Differences between hemodynamics at rest (baseline mean pulmonary arterial pressure, mPAP) and after vasodilator (nitric oxide, prostacyclin) administration were determined to define acute vasodilator drug response (with unchanged cardiac index) as a continuous measure. All cases were genotyped using HumanOmni5 with single nucleotide polymorphism (SNP) call rate &gt;99%, minor allele frequency (MAF)&gt;3%, and Hardy-Weinberg p-value&gt;0.01. Analysis was restricted to cases with European ancestry. We performed linear regressions in an additive model for acute vasodilator drug response with adjustment for baseline mPAP, age, gender, and first 3 principal components. A Bonferroni-corrected alpha=5x10 -8 was used in the discovery cohort and alpha=0.05 was used in the replication cohort. Results: The discovery cohort included 434 PAH cases and the replication cohort included 49 less severe PAH cases. QQ-plots showed no evidence of genomic inflation (lambda=1.00). Association of the intronic SNP rs8057488 (MAF 0.05) in the sorting nexin 29 gene ( SNX29 ) with acute vasodilator drug response reached genome-wide significance in the discovery cohort (beta= -7.03 mmHg, p=3.39x10 -8 ). A significant association between rs8057488 and acute vasodilator drug response was also observed in the replication cohort (beta = -6.48 mmHg, p=0.03). Conclusion: These findings implicate a novel association between SNX29 variation and differential responses to vasodilator treatment in Group I PAH. While requiring further replication in a larger independent cohort, these observations advance our understanding of the molecular underpinnings in PAH.
SP0081 STRUCTURAL DAMAGE PROGRESSION IN PSA
Authors: Philip Helliwell
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Psoriatic arthritis is a multifaceted disease in which the arthritis tends to be less frequent than in rheumatoid arthritis. This provides a challenge to measure radiographic progression using the simple and time-honoured fashion of assessing the hands and feet. Further, radiographic progression is slower in PsA and changes over a short time period, such as the placebo controlled phase of a trial, are minimal. Newer imaging, such as ultrasound and MRI may be more sensitive and responsive but data on these techniques are limited. These challenges, and how to overcome them, will be discussed. <h3>Disclosure of Interests:</h3> Philip Helliwell Grant/research support from: Paid to charity: from AbbVie, Janssen and Novartis, Consultant for: Paid to charity: from AbbVie, Amgen, Pfizer, and UCB and Celgene. Paid to self: from Celgene and Galapagos
Abstract 18470: Effect of High-dose Strong Statin on Preventing Periprocedural Ischemic Complications With Carotid Artery Stenting
Authors: Norihiko Shinozaki, Yuji Ikari
Journal: Circulation (2017)

Introduction: Statin therapy has shown to induce carotid atherosclerotic plaque regression and reduce the incidence of the periprocedural ischemic complications with carotid artery stenting (CAS). ...