tbuckley/cabot-search huggingface dataset:
AB0331 DEPRESSION AND ANXIETY IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Wanruchada Katchamart, Pongthorn Narongroeknawin, Wanwisa Chanapai, Phakhamon Thaweeratthakul
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory joint disease leading to substantial morbidity and mortality and had a major economic and psychological impact on individuals with RA and their families. The prevalence of depressive disorder in RA was 17% and associated with poorer outcomes <h3>Objectives</h3> To evaluate prevalence of depression and anxiety and their related factors in patients with RA. <h3>Methods</h3> In this cross-sectional study, 464 patients with RA from two RA registries, the Siriraj Rheumatoid Arthritis (SiRA) registry and the Thai Army Rheumatoid Arthritis Cohort (TARAC) were enrolled. Demographic data and clinical variables, including disease activity, functional status, health-related quality of life, and cognitive function, were collected. Depression and anxiety were assessed using the Thai version of the Hospital Anxiety and Depression Scale (Thai HADS). <h3>Results</h3> Based on the Thai HADS cutoff value of more than 8 out of 21, 12.5% and 14.5% had some degrees of depression and anxiety, respectively. The proportion of depression and anxiety elevated with increasing disease activity or worsening functional status. However, in multivariate analyses, only global health [RR (95%CI) 0.98 (0.96 - 0.99), p 0.001] was negatively associated with depression, after adjusted for covariate. For anxiety, functional disability [RR (95%CI) 2.46 (1.33 - 4.54), p 0.004] and marital status [married: RR (95%CI) 2.43 (1.25 - 4.73), p 0.009] significantly increased the risk, while disease duration 10 years or more [RR (95%CI) 0.45 (0.25 - 0.80), p 0.007] and global health [RR (95%CI) 0.97 (0.95 - 0.98), p &lt; 0.001] decreased this risk. <h3>Conclusion</h3> Depression and anxiety are common in patients with RA. Patients' perception of their current health is significantly related to mood disorders. Therefore, mental health status, especially mood disturbances, should be addressed in routine practice to improve quality of life in RA. <h3>Disclosure of Interests</h3> None declared
AB1237 COST OF ILLNESS AND QUALITY OF LIFE IN ANKYLOSING SPONDYLITIS PATIENTS TREATED WITH ADALIMUMAB IN CHINA
Authors: Ya Xie, Liudan Tu, LV Qing, Yutong Jiang, Zetao Liao, Shuangyan Cao, Qiujing Wei, Jieruo Gu
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Ankylosing spondylitis (AS) is a chronic inflammatory disease which may lead to limited physical function, impaired quality of life and increased economic burden for society. There were many studies about the superior effects of biologic agents on symptom release, disease activity and functional remission in AS patients. However, studies on the economic burden and health-related quality of life of AS patients in China were spark. <h3>Objectives:</h3> To access the cost of illness, work limitation and quality of life in active ankylosing spondylitis (AS) patients using adalimumab in China. <h3>Methods:</h3> A prospective study was performed in 91 patients with active AS in China. Adult patients (aged ≥ 18 years) fulfilled the 1984 New York modified criteria of AS with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 and C reactive protein (CRP) 6 were enrolled from rheumatology center from Jan 2017 to Aug 2017. All participants received adalimumab (40mg per 2 weeks) therapy and completed questionnaires about disease characteristics, quality of life, direct and indirect costs. Only patients with pay-work completed the Work Limitation Questionnaire (WLQ) to accesses the impact of chronic health conditions on job performance and productivity. Quality of life was measured using the Ankylosing Spondylitis Quality of life (ASQoL) and EuroQol-5 Dimensions (EQ-5D). <h3>Results:</h3> A total of 91 patients with mean age of 30 years old (87.8% males) and mean disease duration of 10 years received adalimumab treatment for 24 weeks. 78.02% of patients have a paid job with average work productivity loss of 28% measured by WLQ. The annual estimated costs of each patient were $35238.8 while the direct cost accounted for 90.2% and the cost of medication accounted for 78.6%. There were significant differences in change of ASQoL (change, 3.89 [95%CI, 3.06 to 4.71]; <i>P</i>&lt;0.0001) and EQ-5D (change, -0.19 [95%CI, -0.24 to -0.31]; <i>P</i>&lt;0.0001) scores from baseline and 24 weeks, with more improvements after therapy compared with baseline. Cost of illness was estimated as $21927.38 per quality-adjusted life year and $15728.16 per BASDAI unit, respectively. <h3>Conclusion:</h3> The cost of AS patients treated with adalimumab therapy was high in China and symptoms and QoL improved significantly after therapy. <h3> Disclosure of Interests:</h3> None declared
THU0231 GELSOLIN A NEW BIOMARKER OF DISEASE ACTIVITY IN SLE PATIENTS ASSOCIATED WITH HDL-C
Authors: Sandra Parra, Mercedes de Las Heras, Pol Herrero, Nuria Amigó, Esperanza Garcés, Josepa Girona, Xavier Correig, Nuria Canela, Antoni Castro
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Recent proteomics techniques have demonstrated that high-density lipoprotein (HDL) associated proteins are involved in functions related to systemic inflammatory and immune responses in several pathological conditions, including autoimmune diseases. HDL undergoes structural and functional modifications in systemic lupus erythematous (SLE) patients. <h3>Objectives:</h3> To identify potential biomarkers of disease activity analyzing the proteome of HDL particles from SLE patients in clinical remission and when they develop a flare compared to a healthy control group. <h3>Methods:</h3> Quantitative proteomic analyses of purified HDL were performed using Tandem Mass Tag (TMT) isobaric tag-labeling and nanoLC-Orbitrap (nLC-MS/MS) from 9 SLE patients in clinical remission when they developed a flare and from 9 healthy controls (9-9-9). We verified the identified proteins by Western blot and ELISA in a cohort of 104 SLE women patients, 46 healthy women and 14 SLE patients when developed a flare. <h3>Results:</h3> A total of 83 proteins associated with HDL were identified. We found 17 proteins with a significant fold-change (&gt;1.1) compared with their levels in control patients. In lupus patients experiencing a flare compared with those in remission, we identified 4 proteins with a significant fold-change (C4, Indian Hedgehog protein, S100A8 and gelsolin). Plasma Gelsolin (pGSN) levels were decreased in the 104 SLE patients (176.02(74.9) mcg/l) compared with the control group (217.13(86.7)mcg/l); p =0.005 and when they developed a clinical flare (104.84(41.7)mcg/l); p = 0002). pGSN levels were associated with HDL-c levels (<i>r</i> =0.316, p&lt; 0.001). Antimalarial treated patients showed significant higher levels of pGSN (214.56(88.94)mcg/l respect 170.35(66.36) mcg/l); p = 0.017. <h3>Conclusion:</h3> The proteome cargo from HDL differentiates SLE patients from healthy controls. HDL from SLE patients carries proteins that are involved in the activation of the immune system. Decreased pGSN are associated with clinical disease activity in SLE patients. Antimalarial treatment and HDL-c are associated with higher levels of pGSN in SLE patients. pGSN is a potential biomarker of disease activity in SLE patients. <h3>Disclosure of Interests:</h3> None declared
Peptidomimetic Blockade of MYB in Acute Myeloid Leukemia
Authors: Kavitha Ramaswamy, Lauren Forbes, Fiona C Brown, Richard Koche, Tatyana Gindin, Gerard Minuesa, Michael G. Kharas, Andrei Krivtsov, Scott A. Armstrong, Eric Still, Elisa de Stanchina, Randi Isenhart, Guangwu Guo, Birgit Knoechel, Alex Kentsis
Journal: Blood (2016)
A Multidisciplinary Toxicity Team for Cancer Immunotherapy–Related Adverse Events
Authors: Jarushka Naidoo, Jiajia Zhang, Evan J. Lipson, Patrick M. Forde, Karthik Suresh, Kendall F. Moseley, Seema Mehta, Shawn G. Kwatra, Alyssa M. Parian, Amy K. Kim, John C. Probasco, Rosanne Rouf, Jennifer E. Thorne, Satish Shanbhag, Joanne Riemer, Ami A. Shah, Drew M. Pardoll, Clifton O. Bingham, Julie R. Brahmer, Laura C. Cappelli
Journal: Journal of the National Comprehensive Cancer Network (2019)

Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events (irAEs). Methods to obtain real-time multidisciplinary input for irAEs that require subspecialist care are unknown. This study aimed to determine whether a virtual multidisciplinary immune-related toxicity (IR-tox) team of oncology and medicine subspecialists would be feasible to implement, be used by oncology providers, and identify patients for whom multidisciplinary input is sought.Patients treated with ICIs and referred to the IR-tox team in August 2017 through March 2018 were identified. Feasibility was defined as receipt of electronic referrals and provision of recommendations within 24 hours of referral. Use was defined as the proportion of referring providers who used the team's recommendations, which was determined through a postpilot survey. Demographics and tumor, treatment, and referral data were collected. Patient features and irAE associations were analyzed.The IR-tox team was found to be feasible and used: 117 referrals from 102 patients were received in 8 months, all providers received recommendations within 24 hours, 100% of surveyed providers used the recommendations, and 74% changed patient management based on IR-tox team recommendations. Referrals were for suspected irAEs (n=106; 91%) and suitability to treat with ICIs (n=11; 10%). In referred patients, median age was 64 years, 54% were men, 13% had prior autoimmunity, and 46% received ICI combinations versus monotherapy (54%). The most commonly referred toxicities were pneumonitis (23%), arthritis (16%), and dermatitis (15%); 15% of patients had multisystem toxicities. Multiple referrals were more common in those treated with combination ICIs (odds ratio [OR], 6.0; P=.035) or with multisystem toxicities (OR, 8.1; P=.005). The IR-tox team provided a new multidisciplinary forum to assist providers in diagnosing and managing complex irAEs. This model identifies educational and service needs, and patients with irAEs for whom multidisciplinary care is most sought.A virtual multidisciplinary toxicity team for irAEs was a feasible and used service, and facilitated toxicity identification and management.
<i>FADS1</i>and the Timing of Human Adaptation to Agriculture
Authors: Sara Mathieson, Iain Mathieson
Journal: Molecular Biology and Evolution (2018)

Variation at the FADS1/FADS2 gene cluster is functionally associated with differences in lipid metabolism and is often hypothesized to reflect adaptation to an agricultural diet. Here, we test the evidence for this relationship using both modern and ancient DNA data. We show that almost all the inhabitants of Europe carried the ancestral allele until the derived allele was introduced ∼8,500 years ago by Early Neolithic farming populations. However, we also show that it was not under strong selection in these populations. We find that this allele, and other proposed agricultural adaptations at LCT/MCM6 and SLC22A4, were not strongly selected until much later, perhaps as late as the Bronze Age. Similarly, increased copy number variation at the salivary amylase gene AMY1 is not linked to the development of agriculture although, in this case, the putative adaptation precedes the agricultural transition. Our analysis shows that selection at the FADS locus was not tightly linked to the initial introduction of agriculture and the Neolithic transition. Further, it suggests that the strongest signals of recent human adaptation in Europe did not coincide with the Neolithic transition but with more recent changes in environment, diet, or efficiency of selection due to increases in effective population size.
Loss of CREST leads to neuroinflammatory responses and ALS-like motor defects in mice
Authors: Cheng Cheng, Kan Yang, Xinwei Wu, Yuefang Zhang, Shifang Shan, Aaron Gitler, Anirvan Ghosh, Zilong Qiu
Journal: Translational Neurodegeneration (2019)

Amyotrophic lateral sclerosis (ALS) is a late onset neurodegenerative disease with fast progression. ALS has heavy genetic components in which a series of genetic mutations have been identified. In 2013, Mutations of the CREST gene (also known as SS18L1), which functions as a calcium-regulated transcriptional activator, were found in sporadic ALS patients. However, the pathogenic causality and mechanisms of ALS-associated mutations of CREST remain to be determined. In this study, we constructed CREST knockout and Q394X knock-in mice with CRISPR/Cas9 system. Using biochemical and imaging tools, we illustrated core pathological phenotypes in CREST mutant mice and claimed the possible pathogenic mechanisms. Furthermore, we also observed locomotion defects in CREST mutant mice with behavioural tests. We demonstrate that ALS-related CREST-Q388X mutation exhibits loss-of-function effects. Importantly, the microglial activation was prevalent in CREST haploinsufficiency mice and Q394X mice mimicking the human CREST Q388X mutation. Furthermore, we showed that both CREST haploinsufficiency and Q394X mice displayed deficits in motor coordination. Finally, we identified the critical role of CREST-BRG1 complex in repressing the expression of immune-related cytokines including Ccl2 and Cxcl10 in neurons, via histone deacetylation, providing the molecular mechanisms underlying inflammatory responses within mice lack of CREST. Our findings indicate that elevated inflammatory responses in a subset of ALS may be caused by neuron-derived factors, suggesting potential therapeutic methods through inflammation pathways.
Elevated endothelial Sox2 causes lumen disruption and cerebral arteriovenous malformations
Authors: Jiayi Yao, Xiuju Wu, Daoqin Zhang, Lumin Wang, Li Zhang, Eric X. Reynolds, Carlos Hernandez, Kristina I. Boström, Yucheng Yao
Journal: Journal of Clinical Investigation (2019)

Lumen integrity in vascularization requires fully differentiated endothelial cells (ECs). Here, we report that endothelial-mesenchymal transitions (EndMTs) emerged in ECs of cerebral arteriovenous malformation (AVMs) and caused disruption of the lumen or lumen disorder. We show that excessive Sry-box 2 (Sox2) signaling was responsible for the EndMTs in cerebral AVMs. EC-specific suppression of Sox2 normalized endothelial differentiation and lumen formation and improved the cerebral AVMs. Epigenetic studies showed that induction of Sox2 altered the cerebral-endothelial transcriptional landscape and identified jumonji domain–containing protein 5 (JMJD5) as a direct target of Sox2. Sox2 interacted with JMJD5 to induce EndMTs in cerebral ECs. Furthermore, we utilized a high-throughput system to identify the β-adrenergic antagonist pronethalol as an inhibitor of Sox2 expression. Treatment with pronethalol stabilized endothelial differentiation and lumen formation, which limited the cerebral AVMs.
Abstract 3330: Genetic Deletion of CXCR4 in Cardiomyocytes Leads to Heart Failure
Authors: Min Cheng, Kentaro Jujo, Junlan Zhou, Qiutang Zeng, Raj Kishore, Douglas W Losordo, Gangjian Qin
Journal: Circulation (2009)

Objective: The CXC chemokine receptor 4 (CXCR4) is essential for hematopoiesis and vasculogenesis and is currently being validated as a therapeutic target for the recruitment of bone marrow progeni...
Dilated Pupil in a Patient With Hyperhidrosis
Authors: Robert Micieli, Jonathan A. Micieli
Journal: JAMA (2019)

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Abstract 9029: Fate Mapping of Monocytes Shows Rapid Turnover Kinetics in Acute Myocardial Infarction
Authors: Florian Leuschner, Takuya Ueno, Rostic Gorbatov, John M Higgins, Mikael J Pittet, Filip K Swirski, Ralph Weissleder, Matthias Nahrendorf
Journal: Circulation (2011)

While previous studies have addressed monocyte behavior in circulation, less is known about the kinetics of these cells once they enter inflamed tissue. It is commonly believed that monocytes are recruited shortly after ischemic injury, and remain in the infarct until inflammation resolves, although this assumption has not been tested experimentally. We therefore studied the turnover of monocytes in infarcted myocardium of mice after coronary ligation (MI). Methods and Results: Bromodeoxyuridine (BrdU) was injected 24 and 12 hrs prior to analysis into mice with MI for pulse-chase experiments. Cell cycle analysis showed no proliferation of monocytes in the infarct tissue. Flow cytometry of cells retrieved 3 days after MI revealed that 43 ± 4 % of monocytes in the infarct had incorprated BrdU into their DNA, and hence were produced and recruited after the first BrdU pulse (i.e. within the last 24 hrs). Monocyte subset analysis revealed faster kinetics for inflammatory Ly-6C-high monocytes when compared to the non-inflammatory Ly-6C-low monocyte subset. To evaluate these rapid cell fluxes with a second, independent method, we transplanted infarcted hearts between isogenic mice with diverging CD45 leukocyte surface markers on day 3 after MI. Transplantations of non-infarcted hearts served as controls. Flow cytometric analysis showed that 6 hrs after transplantation 20 ± 1 % of the monocytes in the infarct were newly recruited from the transplant recipient mouse. This number increased to 40 ± 3 % at 12 hrs, and after 24 hrs the majority (60 ± 0.5%) of monocytes in the infarct derived from the recipient. These data were fitted using a mathematical model of monocyte dynamics (least-squares fit R2 &gt; 99%; N (t) = e-(t/20) ), which reported an average monocyte residence time of 20 hours. Conclusion: We observed surprisingly fast monocyte turn-over in acute infarcts with an average tissue residence time of 20 hours.
SP0135 HOW TO DIFFERENTIATE MINIMAL DISEASE ACTIVITY IN RA + DEMO
Authors: Ilfita Sahbudin
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Ultrasound (US) is increasingly utilised as a point-of-care tool to diagnose early inflammatory joint disease, monitor treatment response and detect subclinical inflammation. This is feasible as US can detect joint, and tendon, inflammation before it becomes clinically apparent. Despite the increasing use of US in Rheumatology, the key research question yet to be addressed is defining 'the normal reference value at the joint level." Improvement in US technology over the last decade results in acquisition of higher resolution images. US can now detect subtle abnormality in joints of healthy individuals who are asymptomatic. Consequently, the imaging boundary between US changes of normal joints (i.e <i>physiological changes</i>), and those of early arthritis joints (i.e. <i>early pathological changes</i>) has become unclear. In addition, a proportion of US-defined pathology observed in normal joints may be attributed to age-related changes. Defining the concept of US-detected 'minimal disease" is crucial to enable investigators identify a threshold (or cut-off) to <i>differentiate normal physiological from minimal pathological changes</i> at the joint level. This threshold, subsequently, will be used to evaluate the best sensitivity to detect changes in therapeutic response and assess remission, as well as facilitate diagnosis of early disease. In order to address this important research question, the OMERACT US SIG has formed the US Minimal Disease Taskforce at the OMERACT 2016 meeting. This collaboration between 24 OMERACT ultrasound centres in 11 countries has successfully recruited more than 600 subjects into the Minimal Disease Study. US data of healthy individuals encompassing synovial hypertrophy, synovial effusion, and Doppler enhancement will be presented. <h3>Disclosure of Interests:</h3> None declared
PS1031 DECITABINE VERSUS INTENSIVE CHEMOTHERAPY IN ELDERLY UNTREATED ACUTE MYELOID LEUKEMIA
Authors: A. De La Fuente, M. Tormo, P. Beneit, C. Gil, T. Bernal Castillo, J. Serrano Lopez, K. Javier Gonzalez, A. Sampol Mayol, J. Davila Valls, C. Martinez Chamorro, S. Suarez Ordoñez, C. Benavente, J. Bergua, S. Jimenez Bravo de Laguna, A. Espadana, P. Martinez Sanchez, M.L. Amigo, M.J. Sayas LLoris, P. Herrera Puente, B. Boluda, R. Fernandez, S. Brunet, I. Oiartzabal, A. Muñoz Gama, M. Arnan Sangerman, D. Martinez‐Cuadron, S. Vives Polo, R. Coll Jorda, R. Garcia Boyero, A. Figuera, A. Diaz Lopez, B. Gonzalez Gonzalez, P. Montesinos
Journal: HemaSphere (2019)

Background: The combination cytarabine + anthracycline (IC) remains the standard of care for 60 year and above AML patients (Lowenberg et al. N Engl J Med 2009). Decitabine (Dec) has been EMA approved for first line AML patients not fit for intensive chemotherapy ( Kantarjian et al JCO 2012) . IC vs Dec have been not previously compared. Aims: The aim of this study is to analyze effectiveness and tolerability of IC vs Dec as first lines in 60 and above AML patients and to identify risk factors. Methods: We carried out the analysis on previously untreated AML ≥60yrs old patients included in PETHEMA AML epidemiological registry ( NCT02607059) and in the MDA‐AML‐2017–05 ( AEMPS code). Selection criteria for the study were as follows: Age &gt;60, diagnosis of AML under WHO criteria, treated with IC or Dec during the period 01/01/2012 to 31/12/2016. Response was assessed using the ELN‐2010 criteria, toxicity by the CTCAE v4.0 scale, OS by Kaplan‐Meier, as well as mortality within the first 8 weeks (M8wks). Results: A total of 756 of previously untreated AML patients were analyzed (625 treated with IC and 131 with Dec), baseline characteristics are summarized in table 1. A higher incidence of risk factors was observed in the Dec cohort. Safety: A total of 1051 IC and 716 Dec cycles were analyzed, mean 2.4 and 6.1, febrile neutropenia 74% and 47%, M8wks was 22.5% and 25.5% (p = 0.15) and composite complete response (CCR) 64% and 18% ( p &lt; .001). for IC and Dec respectively. In this study serum creatinine&gt;1.3 mg/dL (p = 0.02, p &lt; 0.01), ECOG≥2 ( p &lt; 0.01) and adverse cytogenetic ( p &lt; 0.01) were adverse prognostic factors for OS in both cohorts, and WBC pre‐Dec &gt;10.000/μL ( p &lt; 0.01) in Dec and Secondary AML (p = 0.02) in IC cohort. IC resulted superior for OS (11 vs 8 months p = 0.04) but this was not significant in 70 and above (7 vs 8 months p = 0.94) or after matching by mentioned risk factors. Summary/Conclusion: IC and Dec are not used for the same patients due to physicians judgement. Even the outcome seams superior with IC we observe similar OS after matching by risk factors age, creatinine, ECOG, or cytogenetic. The ongoing EORTC phase III randomized trial (INDACTION) will compare a Dec‐based vs IC front‐line approach for older patients with AML. image