tbuckley/cabot-search huggingface dataset:
FRI0722-HPR THE INVESTIGATION OF THE RELATIONSHIP BETWEEN PSYCHOSOCIAL AND FUNCTIONAL STATUS OF CHILDREN WITH JIA
Authors: Aybüke Seven, Aykut Özçadırcı, Fatma Birgül Kumbaroğlu, Gamze Arın, Nur Banu Karaca, Yasemin Özel Aslıyüce, Selcan Demir, Yelda Bilginer, Edibe Ünal, Seza Özen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> JIA is the most common rheumatic disease in children and may result in significant morbidity with joint deformity, growth disorder, and persistence of active arthritis to adulthood (1). According to the model of biopsychosocial pain, emotions affect the degree of functional impairment (2). <h3>Objectives</h3> The aim of this study is to investigate the relatıonshıp between the psychosocial and functional status of children with juvenile idiopathic arthritis (JIA). <h3>Methods</h3> 382 children with JIA were included in the study. Individuals were assessed with the Juvenile Arthritis Biopsychosocial Questionnaire (JAB-Q) (3) and Children Health Assessment Questionaire (CHAQ) was applied for functional status (4). <h3>Results</h3> The mean age of the subjects included in the study (n = 386) was 12.48 ± 3.81 years. The median value of the JAB-Q functional status was 2 (min: 0 max: 34), psychosocial status was 10 (min: 0 max: 38). And the median value of the CHAQ was 0,25 (min: 0 max: 3). Correlation coefficients and statistical significance were calculated by using Pearson's test. There was a low positive correlation between BETY-BQ functional status and BETY-BQ psychosocial status (r = 0.347, p &lt;0.001), a low positive correlation between CHAQ and BETY-BQ psychosocial status (r = 0.395, p &lt;0.001). There was a good positive correlation between BETY-BQ functional status and CHAQ (r = 0.678, p &lt;0.001) (Table 1). <h3>Conclusion</h3> The psychosocial status of children is not affected by functional status. Psychosocial status may be affected by different variables. It was concluded that children should be encouraged to participate in social activities independently their functional problems. Further studies are needed to examine the other variables' effects on psychosocial status in children with JIA. <h3>References</h3> [1] Kahn, P. Juvenile idiopathic arthritis: current and future therapies. Bulletin of the NYU hospital for joint diseases, 2009, 67(3), 291-291. [2] Gatchel R, Peng Y, Peters M, Fuchs P, Turk D. The biopsychosocial approach to chronic pain: Scientific advances and future directions, Psychological Bulletin, 2007, vol.1334 (pg.581-624) [3] Unal, Edibe, et al. "A new biopsychosocial and clinical questionnaire to assess juvenile idiopathic arthritis: JAB-Q."Rheumatology international2018: 1-8. [4] Singh G, Athreya BH, Fries JF, Goldsmith DP. Measurement of health status in children with juvenile rheumatoid arthritis. Arthritis Rheum1994;37:1761–9. <h3>Disclosure of Interests</h3> None declared
Effect Sizes of Somatic Mutations in Cancer
Authors: Vincent L Cannataro, Stephen G Gaffney, Jeffrey P Townsend
Journal: JNCI Journal of the National Cancer Institute (2018)

A major goal of cancer biology is determination of the relative importance of the genetic alterations that confer selective advantage to cancer cells. Tumor sequence surveys have frequently ranked the importance of substitutions to cancer growth by P value or a false-discovery conversion thereof. However, P values are thresholds for belief, not metrics of effect. Their frequent misuse as metrics of effect has often been vociferously decried, even in cases when the only attributable mistake was omission of effect sizes. Here, we propose an appropriate ranking-the cancer effect size, which is the selection intensity for somatic variants in cancer cell lineages. The selection intensity is a metric of the survival and reproductive advantage conferred by mutations in somatic tissue. Thus, they are of fundamental importance to oncology, and have immediate relevance to ongoing decision making in precision medicine tumor boards, to the selection and design of clinical trials, to the targeted development of pharmaceuticals, and to basic research prioritization. Within this commentary, we first discuss the scope of current methods that rank confidence in the overrepresentation of specific mutated genes in cancer genomes. Then we bring to bear recent advances that draw upon an understanding of the development of cancer as an evolutionary process to estimate the effect size of somatic variants leading to cancer. We demonstrate the estimation of the effect sizes of all recurrent single nucleotide variants in 22 cancer types, quantifying relative importance within and between driver genes.
Changes in Obesity Among US Children Aged 2 Through 4 Years Enrolled in WIC During 2010-2016
Authors: Liping Pan, David S. Freedman, Sohyun Park, Deborah A. Galuska, Anna Potter, Heidi M. Blanck
Journal: JAMA (2019)

Prevalence of childhood obesity is high in the United States, especially among children from lower-income families. 1Among children aged 2 through 4 years enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), obesity prevalence increased between 2000 and 2010 but declined through 2014. 2 The decline was statistically significant among all racial/ethnic groups and in 34 of 56 state WIC agencies.The present study examines trends in overweight and obesity by age, sex, and race/ ethnicity using WIC data from 2010 to 2016. Methods |The WIC Participant and Program Characteristics survey includes all participants certified to receive WIC benefits.Data are extracted from state WIC agencies in April of even reporting years.WIC applicants must have nutritional risk and gross household income less than or equal to 185% of the US poverty level or participate in the Supplemental Nutrition Assistance Program, Medicaid, or Temporary Assistance for Needy Families.Children's weight and height were measured by trained WIC professionals during certification or recertification visits.Children aged 2 through 4 years from 50 states, the District of Columbia, and 5 US territories enrolled in WIC in 2010, 2012, 2014, and 2016 were included in this study.The Centers for Disease Control and Prevention (CDC) determined that this study was not subject to review because deidentified secondary data were used.
Antibiotic Resistance Evolution Is Contingent on the Quorum-Sensing Response in Pseudomonas aeruginosa
Authors: Sara Hernando-Amado, Fernando Sanz-García, José Luis Martínez
Journal: Molecular Biology and Evolution (2019)

Different works have explored independently the evolution toward antibiotic resistance and the role of eco-adaptive mutations in the adaptation to a new habitat (as the infected host) of bacterial pathogens. However, knowledge about the connection between both processes is still limited. We address this issue by comparing the evolutionary trajectories toward antibiotic resistance of a Pseudomonas aeruginosa lasR defective mutant and its parental wild-type strain, when growing in presence of two ribosome-targeting antibiotics. Quorum-sensing lasR defective mutants are selected in P. aeruginosa populations causing chronic infections. Further, we observed they are also selected in vitro as a first adaptation for growing in culture medium. By using experimental evolution and whole-genome sequencing, we found that the evolutionary trajectories of P. aeruginosa in presence of these antibiotics are different in lasR defective and in wild-type backgrounds, both at the phenotypic and the genotypic levels. Recreation of a set of mutants in both genomic backgrounds (either wild type or lasR defective) allowed us to determine the existence of negative epistatic interactions between lasR and antibiotic resistance determinants. These epistatic interactions could lead to mutual contingency in the evolution of antibiotic resistance when P. aeruginosa colonizes a new habitat in presence of antibiotics. If lasR mutants are selected first, this would constraint antibiotic resistance evolution. Conversely, when resistance mutations (at least those studied in the present work) are selected, lasR mutants may not be selected in presence of antibiotics. These results underlie the importance of contingency and epistatic interactions in modulating antibiotic resistance evolution.
PB2150 EFFICACY AND SAFETY OF THE ANTITUMOR RVP PROGRAM (LENALIDOMIDE, BORTEZOMIB, PREDNISONE) IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA
Authors: K. Belousov, T. Mitina, Y. Chuksina
Journal: HemaSphere (2019)

Background: antitumor programs using lenalidomide have shown high efficacy and safety in patients with refractory and recurrent MM. We wanted to evaluate this program as a treatment first line for MM, in order to find new treatment options. Aims: study of the efficacy and safety of the RVP program (lenalidomide, bortezomib, prednisone) as a first line therapy in patients with multiple myeloma (MM). Methods 40 patients with MM (15 women, 25 men), the median age is 61 years (30-76 years), all have stage 3 Salmon-Durie disease. Fourteen (35.0%) patients had plasmacytomas. In 8 (20%) patients, there was renal failure requiring renal replacement therapy. The average Karnovsky index was 50%. All patients received RVP (lenalidomide 25 mg 1-14 days, bortezomib 1.3 mg/m2 1,4,8,11 days, prednisolone 60 mg/m2 1-4 days, 56 days cycle). Evaluation of the effectiveness of therapy was carried out after 6 cycles of treatment. Results: median observation was 18 months, median overall survival was not achieved. Objective antitumor response reached 30 patients (75,0%), including complete remissions 6 (15,0%), very good partial remissions 9 (22,5%), partial remissions 15 (37.5%). In 2 patients out of 8 treated with renal replacement therapy, a renal response was obtained - independence from dialysis therapy. Cases of hematological and non-hematological toxicity 3-4st. in the study was not noted. Summary/Conclusion: The antitumor RVP program showed high efficacy and safety as a first-line therapy in a non-selective group of patients, including those with a complicated course of MM.
Identification of OATP1B3 as a high-affinity hepatocellular transporter of paclitaxel
Authors: Nicola F. Smith, Milin R. Acharya, William D. Figg, Alex Sparreboom
Journal: Cancer Research (2005)

4112  It is now recognized that knowledge of the interplay between transporters and drug metabolizing enzymes in the intestine, liver and kidney is critical for a better understanding of drug disposition. The organic anion transporting polypeptides (OATPs) mediate the cellular uptake of a large number of structurally diverse endogenous compounds and xenobiotics. Expression of two members of this family, namely OATP1B1 (OATP-C, OATP2, LST-1) and OATP1B3 (OATP8, LST-2), is restricted to the liver. These transporters are localized on the basolateral membrane of hepatocytes and are likely to influence the hepatic metabolism of substrates. In addition, OATP inhibition may be the basis of drug-drug interactions. Paclitaxel is a tubulin-binding agent, which is widely used for the treatment of breast and ovarian cancers. This agent undergoes extensive hepatic metabolism by cytochrome P450 2C8 and 3A4, and pharmacokinetic drug-drug interactions have been reported. The aim of this work was to determine whether paclitaxel is a substrate for OATP1B1 and/or OATP1B3 using Xenopus laevis oocytes injected with OATP cRNA. Whilst accumulation of [3H]paclitaxel by oocytes expressing OATP1B1 was not significantly different from that by water-injected controls, paclitaxel uptake by OATP1B3 expressing oocytes was 3.25-fold higher (P
PF215 THE ROLE OF GROWTH FACTOR INDEPENDENCE 1 (GFI1) IN GENOME STABILITY, DNA REPAIR AND LEUKEMIA GENOMIC EVOLUTION
Authors: D. Frank, Y. Al‐Matary, C. Khandanpour
Journal: HemaSphere (2019)

Background: Growth factor independence 1 (GFI1) is a transcriptional repressor, which regulates the proliferation and differentiation of hematopoietic stem cells. We have previously shown that lower expression of GFI1 promotes the development of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients and murine models of leukemiua. Additionally, a germline single nucleotide polymorphism variant of GFI1, called GFI1–36N (Ser36 replaced by Asn36) contributes to the development of MDS and AML. Both lower expression of GFI1 and presence of GFI1–36N leads to expression of a number key AML associated oncogenes and signaling cascades promoting AML development, as low level of GFI1 or GFI1–36N are not able to repress these patways. Aorund 30% of all AML patients have either low expression levels of GFI1 or are carrier of GFI1–36N. This patient cohort has a particular poor prognosis. However, we also have preliminary data that GFI1 might be involved in DNA repair. Aims: We analyzed whether GFI1 plays a role in DNA repair. Methods: We analyzed genome wide mutational analysis from AML patient cohorts and gene wide expression data. Results: We reanalyzed available genomic data of MDS/AML patients with expression of GFI1–36N or low expression of GFI1. These patients showed significantly more cytogenetic aberrations than patients with normal level of GFI1–36S. We have established two different mouse strains, which express either low level of GFI1 or express GFI1–36N. In murine models of human AML, low level of GFI1 or expression of GFI1–36N led to a significantly higher rate of genomic alterations such as mutations, deletions and insertions than GFI1 wildtype (wt) expressing murine leukemic cells. These findings indicate that low expression of GFI1 or expression of GFI1–36N is associated with genomic instability. To understand the molecular pathways GFI1 is involved with regad to DNA repair, we irradiated GFI1 wt, GFI1 low expressing and GFI1–36N expressing thymocytes. Using comet and γH2AX assay we showed that presence of Gfi1–36N or reduced level of GFI1 is associated with diminished DNA repair. Furthermore we found that presence of GFI136N or reduced level of GFI1 is associated with low level of MGMT. Other groups have shown that patients with low expression of MGMT respond well to treatment with Temozolomide (alkylating agent). Due to this fact we treated leukemic cells differently expressing GFI1 with Temozolomide. We found that the leukemic cells with low level of GFI1 or GFI1–36N are highly susceptible to Temozolomide compared to the leukemic control cells. Summary/Conclusion: In summary, low expression of GFI1 or expression of GFI1–36N leads to a clonal genetic evolution by impeding DNA repair. Therefore GFI1 could be a new target in leukemia therapy by using Temozolomide for these patients.
FRI0659 REMISSION PERSISTENCE IN RHEUMATOID ARTHRITIS, PSORIATIC ARTHRITIS AND AXIAL SPONDYLOARTHRITIS UNDER BIOLOGIC TREATMENT
Authors: Pedro Ávila-Ribeiro, Joao Eurico Fonseca, Elsa Vieira-Sousa
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) under biologic treatment are increasingly achieving prolonged remission and tapering treatment is becoming standard practice. However, the optimal timing to start tapering remains unclear and predictors of loss of remission (LOR) are missing. Guidelines disagree on whether to wait for 6 or 12 months of sustained remission before tapering. <h3>Objectives</h3> To determine whether longer sustained remission (6 versus 12 months) influences subsequent LOR rates and to identify predictors of LOR. <h3>Methods</h3> We used the Rheumatic Diseases Portuguese Register (Reuma.pt), to identify RA, PsA and axSpA patients on stable biologic treatment in a single center and retrospectively analyze those who achieved sustained remission for at least 6 and 12 months. Survival analysis was used to characterize stability of remission and identify predictors of LOR. The Cox proportional hazards regression was stratified by diagnosis and adjusted for age, gender, smoking, baseline disease activity, type of biologic, previous switches and starting year of biologic treatment. <h3>Results</h3> 195 patients (100 RA, 51 PsA and 44 AxSpA) of 1078 patients (785 RA, 116 PsA, 177 axSpA) registered in Reuma.pt at a single center and treated with biologics between 1999 and 2018, had at least one remission period with a minimal duration of 6 months. This corresponded to 310 individual remission periods longer than 6 months, 232 of which (74.8%) were longer than 12 months. Median remission time (since the start of remission period) was 78.6 weeks overall vs. 99.0 weeks for patients with a minimum 12 months remission (difference in median survival: 20.4 weeks). PsA patients showed significantly longer remission periods (p&lt;0.0001), followed by axSpA and RA. We identified active smoking (HR 1.96, p=0.008 for the total population; HR 1.53, p=0.20; HR 7.42, p=0.01, HR 0.74, p=0.79 for RA, PsA and axSpA, respectively), and infliximab use (HR 2.23, p=0.005 for the total population; HR 4.07, p&lt;0.001, HR 3.20, p=0.36, HR 0.62, p=0.62 for RA, PsA and axSpA, respectively; subcutaneous TNF inhibitors (TNFi) used as index category) to be significantly associated with LOR. A sensitivity analysis excluding infliximab patients further suggested female gender (HR 3.21, p=0.005) and duration of disease until first biologic (HR 1.05, p=0.031) as important co-variates. <h3>Conclusion</h3> 6 vs. 12 months of sustained remission did not influence the subsequent rate of LOR. Smoking, the type of TNFi, female gender and duration of disease until biologic treatment were identified as predictors of LOR. <h3>Disclosure of Interests</h3> Pedro Ávila-Ribeiro: None declared, Joao Eurico Fonseca: None declared, Elsa Vieira-Sousa Grant/research support from: MSD, Novartis
SP0059 HELPING PEOPLE MAINTAIN PHYSICAL ACTIVITY
Authors: Keegan Knittle
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Regular physical activity (PA) has clear benefits for individuals with rheumatic diseases, but PA levels among these individuals consistently fall below recommended levels. While interventions to increase PA are often successful in the short term, these effects are not generally maintained over time. Therefore, to be able to optimally support PA maintenance, rheumatology health professionals should be familiar with the relevant theory and evidence base for behavioral maintenance. <h3>Objectives:</h3> This talk will outline several psychological theories of behavioral maintenance, and present evidence on the interventions and behavior change techniques most strongly associated with physical activity maintenance. <h3>Methods:</h3> A review of the most recent and relevant health psychology and behavioral science literature surrounding issues of physical activity maintenance, particularly among individuals with rheumatic conditions. <h3>Results:</h3> Theories of behavioral maintenance focus on social and environmental influences, motives, resources, self-regulation, and habits. Several studies will be presented to highlight the influence of these theoretical domains in PA maintenance among individuals with rheumatic disease. Physical activity interventions which specifically target these theoretical domains have the greatest likelihood to produce PA maintenance, and several case studies from successful interventions will be presented. <h3>Conclusions:</h3> While helping patients to maintain PA is always a challenge, especially in the face of degenerative or progressive arthropathies, behavioral science can offer health professionals in rheumatology some theory and evidence-based methods to support PA maintenance in practice. <h3>Disclosure of Interests:</h3> None declared
AB1391-HPR PASSIVE COPING STRATEGIES BUT NOT PHYSICAL FUNCTION ARE ASSOCIATED WITH WORSE MENTAL HEALTH, IN WOMEN WITH CHRONIC WIDESPREAD PAIN– A MIXED METHOD STUDY
Authors: Katarina Aili, Stefan Bergman, Ann Bremander, Emma Haglund, Ingrid Larsson
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Chronic widespread pain (CWP) is a common condition (approximately 10% prevalence), that affects women twice as often as men. There is a lack of knowledge in how different coping strategies relates to health status during CWP development in a general population. <h3>Objectives</h3> To explore different ways of coping with CWP and to relate the different coping strategies to health-related factors, before and after developing CWP. <h3>Methods</h3> A sequential explorative mixed methods study including 19 women 45-67 of age, who had reported CWP in a survey 2016, but not in 1995. Individual interviews were analysed with a phenomenographic approach, and resulted in four categories of coping strategies. These categories were further explored with regard to four dimensions of health status (physical function, bodily pain, vitality and mental health) as measured by SF-36 (0-100, a lower score indicates more disability) and sleep problems measured both in 1995, and 2016. <h3>Results</h3> The qualitative analysis revealed four categories representing different coping strategies, where each woman was labelled by the most dominant category; the mastering woman, the persistent woman, the compliant woman and the conquered woman. The first two categories emerged as being active coping strategies, and the latter two as passive. Women with passive strategies reported significantly lower vitality (median 57.5 vs 75, p=0.007) and worse mental health (median 54 vs 93, p=0.021) in 1995, before they had developed CWP compared with those with active coping strategies. No differences were seen between the groups on physical function, bodily pain or sleep. In 2016, there were still a difference between the passive and active group regarding mental health (median 56 vs 80, p=0.022), but not for vitality (median 35 vs 40, p=0.707). No differences were seen between the groups on physical function or bodily pain. All eight women with passive strategies reported problems with sleep in 2016, as compared to 6 of the 11 women with active strategies (p=0.045). <h3>Conclusion</h3> Women that reported CWP in 2016, but not in 1995, described both active and passive coping strategies. The qualitative findings were associated with differences in vitality and mental health already in 1995, before they had developed CWP. Further, those with passive coping strategies reported worse health with regard to mental health and sleep problems in 2016. Interestingly, the groups did not differ in bodily pain or physical function neither in 1995 nor in 2016, which implicates the importance for the clinician to take the typical coping strategy into consideration, when meeting these patients in clinical settings. <h3>Disclosure of Interests</h3> None declared
Abstract P390: A Significant Inverse Association of Serum Docosahexaenoic Acid with Coronary Artery Calcification among Men in the General Population in Japan: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA)
Authors: Akira Sekikawa, Katsuyuki Miura, Akira Fujiyoshi, Sayaka Kadowaki, Aya Kadota, Emma Barinas-Mitchell, Rhoberrt W Evans, Takayoshi Ohkubo, Naoyuki Takashima, Sayuki Torii, Tomonori Okamura, Yasuyuki Nakamura, Takashi Yamamoto, Minoru Horie, Kiyoshi Murata, Hirotsugu Ueshima
Journal: Circulation (2013)

Background Dietary intake of marine n-3 fatty acids in Japanese in Japan is about 10 times as high as that in the US, e.g. 1.0 g/day vs. 0.1 g/day, respectively. Evidence from a large clinical tria...
Assessing taxonomic metagenome profilers with OPAL
Authors: Fernando Meyer, Andreas Bremges, Peter Belmann, Stefan Janssen, Alice C. McHardy, David Koslicki
Journal: Genome biology (2019)

The explosive growth in taxonomic metagenome profiling methods over the past years has created a need for systematic comparisons using relevant performance criteria. The Open-community Profiling Assessment tooL (OPAL) implements commonly used performance metrics, including those of the first challenge of the initiative for the Critical Assessment of Metagenome Interpretation (CAMI), together with convenient visualizations. In addition, we perform in-depth performance comparisons with seven profilers on datasets of CAMI and the Human Microbiome Project. OPAL is freely available at https://github.com/CAMI-challenge/OPAL .