tbuckley/cabot-search huggingface dataset:
PF328 PREDICTORS OF TREATMENT RESPONSE TO IMMUNOSUPPRESSANTS IN ACQUIRED HEMOPHILIA A
Authors: W.N. G. Lau, M.K. G. Leung, P.L. P. Yip, K.M. C. Cheung, S.M. J. Lau, K.K. H. Lee, W.M. V. Mak, S.K. S. Ho, C.H. K. Kwok
Journal: HemaSphere (2019)

Background: Acquired hemophilia A (AHA) is a rare bleeding disorder, caused by inhibitors against factor VIII, which may result in life‐threatening bleeding. Management of AHA is two pronged ‐ to arrest bleeding with hemostatic agent and to eradicate FVIII inhibitors by immunosuppressants. However, immunosuppressants are associated with frequent adverse events, with infection being the leading cause of morbidity and mortality. Identifying predictors of treatment response may help tailor treatment strategies and reduce treatment associated adverse events. Aims: The aims of the study were to evaluate the presenting features, treatment, and outcomes of patients with AHA in our local population, to identify the predictors of normalization of aPTT after immunosuppressive therapy and overall survival; and to investigate the patient characteristics that predict normalization of aPTT by steroid alone within 6 weeks. Methods: This was a retrospective multi‐center study which recruited 108 patients diagnosed with AHA between 1 st January 2002 and 31 st December 2016. AHA is defined by the presence of a neutralizing FVIII inhibitor ≥ 0.6 Bethesda units (BU)/ml and a FVIII activity &lt;50%. Patients with congenital hemophilia A with inhibitors were excluded. Prognostic factors for normalization of aPTT and overall survival were analyzed using Cox proportional hazards regression analysis. Results: Normalization of aPTT was an independent predictor of overall survival (OR 0.14, 95% CI 0.07–0.27, P &lt; 0.001). Patients with ECOG performance status ≤2 were more likely to attain normal aPTT (HR 2.09, 95% CI 1.28–3.42, P 0.003) while patients with underlying autoimmune diseases were less likely to achieve normal aPTT (HR 0.46, 95% CI 0.23–0.91, P 0.027). Female (OR 3.73, CI 1.15–12.2, P 0.028) and an inhibitor titer ≤20 BU/ml (OR 4.3, CI 1.36–13.63, P 0.013) predicted a higher chance of normalization of aPTT with steroid alone within 6 weeks. Summary/Conclusion: Identification of patients who are more likely to respond to steroid alone within 6 weeks may avoid unnecessary immunosuppressants and thus reduce treatment‐related adverse events. This finding may help individualize treatment strategies. Normalization of aPTT was an independent prognostic factor of survival. This finding echoed other studies and reiterated the importance of achieving remission. To date, the optimal immunosuppressive strategy remains elusive. Further high‐quality evidence is needed to guide the choice and intensity of treatment.
Association between urinary dickkopf-3, acute kidney injury, and subsequent loss of kidney function in patients undergoing cardiac surgery: an observational cohort study
Authors: Stefan J Schunk, Alexander Zarbock, Melanie Meersch, Mira Küllmar, John A Kellum, David Schmit, Martina Wagner, Sarah Triem, Stefan Wagenpfeil, Hermann-Josef Gröne, Hans-Joachim Schäfers, Danilo Fliser, Thimoteus Speer, Stephen Zewinger
Journal: The Lancet (2019)
FRI0066 ASSESSMENT OF LUNG INVOLVEMENT IN RHEUMATOID ARTHRITIS IN A NORTH AFRICAN COUNTRY
Authors: Olfa Saidane, Leila Gafsi, Hana Sahli, Aicha Ben Tekaya, Rawdha Tekaya, Ines Mahmoud, Leila Abdelmoula
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a common inflammatory disease developing within joints but extra-articular organs such as the lung could be involved. <h3>Objectives:</h3> To determine the frequency and the characteristics of lung involvement in RA Tunisian patients. <h3>Methods:</h3> A retrospective study including patients with RA fulfilling ACR/EULAR 2010 criteria was conducted in a department of rheumatology in the north of Tunisia between 2014 and 2017. Pulmonary involvement was evaluated based on chest clinical symptoms, combined results from chest-X-ray, computed tomography of the chest and pulmonary functional tests. Patients with pulmonary involvement not directly related to RA were excluded from this study (emphysema, neoplasm, infection…) <h3>Results:</h3> Sixty five patients with RA were collected. The mean age was 56 years ± 12.8 years. The mean age of disease onset was 46.4 ± 13.8 years ranging from 17 to 75 years. The mean disease duration was a 9.6 ±10.1 year.A total of 13 patients (20%) were noted to have clinical chest symptoms. It was dyspnea (9 cases (13.8%)), chest pain (2 cases (3%)), dry cough (5 cases (7.7%)) and expectoration (3 cases (4.4%)). Eight patients (12.3%) had crackles in pulmonary auscultation. Mean time to pulmonary involvement onset was 2.5 years [1-4 years]. Chest-X-ray was available in all patients and showed abnormalities in 24 cases (37%). Chest computed tomography was practiced in 24 patients (36.9%). It revealed pulmonary abnormalities in 18 patients (75% of those scanned). Chest computed tomography revealed abnormalities in 3 patients (4.6%) who hadn't respiratory complaints. Pulmonary functional tests was performed in 26 patients (40%) and revealed abnormalities in 3 cases(obstructive signs in 2 cases and association of obstructive and restrictive signs in 1 case). The overall frequency of lung involvement based on different lung investigations was 27.6% (18 patients). Parenchyma was the most frequent site of pulmonary involvement: interstitial lung disease was found in 7 cases (38.8%); it was a usual interstitial pneumonia in 5 patients (27.7%) and nonspecific interstitial pneumonia in 2 cases (11.1%). Bronchiectasis was found in 5 cases (27.7%), rheumatoid nodule in 4 cases (22.2%) and pleural disease in 2 cases (11.1%). <h3>Conclusion:</h3> Lung involvement is frequent in RA Tunisian patients and the interstitial lung disease represented the most encountered pulmonary manifestation. <h3>References:</h3> [1] Megan S, Bridget FC, Lawrence AH, Ganesh R. Rheumatoid arthritis-associated lung disease. Eur Respir Rev. 2015;24:1-16. [2] Kawassaki AM, Pereira DAS, Kay FU, Laurindo IMM, Carvalho CRR, Kairalla RA. Pulmonary involvement in rheumatoid arthritis: evaluation by radiography and spirometry. J Bras Pneumol. 2015;41(4):331-42. <h3>Disclosure of Interests:</h3> None declared
C3- and CR3-dependent microglial clearance protects photoreceptors in retinitis pigmentosa
Authors: Sean M. Silverman, Wenxin Ma, Xu Wang, Lian Zhao, Wai T. Wong
Journal: The Journal of Experimental Medicine (2019)

Complement activation has been implicated as contributing to neurodegeneration in retinal and brain pathologies, but its role in retinitis pigmentosa (RP), an inherited and largely incurable photoreceptor degenerative disease, is unclear. We found that multiple complement components were markedly up-regulated in retinas with human RP and the rd10 mouse model, coinciding spatiotemporally with photoreceptor degeneration, with increased C3 expression and activation localizing to activated retinal microglia. Genetic ablation of C3 accelerated structural and functional photoreceptor degeneration and altered retinal inflammatory gene expression. These phenotypes were recapitulated by genetic deletion of CR3, a microglia-expressed receptor for the C3 activation product iC3b, implicating C3-CR3 signaling as a regulator of microglia-photoreceptor interactions. Deficiency of C3 or CR3 decreased microglial phagocytosis of apoptotic photoreceptors and increased microglial neurotoxicity to photoreceptors, demonstrating a novel adaptive role for complement-mediated microglial clearance of apoptotic photoreceptors in RP. These homeostatic neuroinflammatory mechanisms are relevant to the design and interpretation of immunomodulatory therapeutic approaches to retinal degenerative disease.
FRI0037 DIAGNOSTIC PERFORMANCE OF CURRENT CVR SCORES FOR THE DIAGNOSIS OF CAROTID PLAQUE IN MEXICAN-MESTIZO RA SUBJECTS
Authors: Dionicio Ángel Galarza-Delgado, Iris Jazmin Colunga-Pedraza, José Ramón Azpiri-López, Karla Paola Cuéllar-Calderón, Ileana Cecilia Reynosa-Silva, Marielva Castro-González, Carolina Marlene Martínez-Flores, José Dionisio Castillo-Ortiz, Alberto Cárdenas
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is an inflammatory disease with an increased mortality compared to the general population. The measurement of carotid intima media thickness (CIMT) is used as an independent marker of subclinical atherosclerosis. <h3>Objectives:</h3> To determine the prevalence of carotid plaque (CP) in a cohort of Mexican RA subjects and diagnostic performance of cardiovascular risk (CVR) calculators for the prediction of augmented CIMT and CP. <h3>Methods:</h3> A cross-sectional study of subjects aged from 40-75 years that fulfilled the 2010 ACR/EULAR RA criteria. Exclusion criteria: previous CV disease and overlap syndromes. CVR was calculated by 6 scales: ACC/AHA 2013, Framingham-lipids (FRS-lipids), Framingham-Body Mass Index (FRS-BMI), Reynolds Risk Score (RRS), QRISK2 and SCORE. Carotid ultrasound (US) was performed by a board-certified radiologist and reviewed by other two. We defined an augmented CIMT as ≥0.9 mm and CP as CIMT ≥1.2 mm. We categorized subjects in 3 groups: 1) normal carotid US, 2) augmented CIMT, and 3) CP. We used Kruskal-Wallis test to compare the groups. <h3>Results:</h3> 130 patients were included, 124 (95.4%) were females with median age of 57 years old and disease duration of 9.7 years. Almost 50% of the subjects with CP were in the low-risk strata of every CVR calculator. The presence of CP was higher in subjects categorized as moderate/high risk using ACC/AHA 2013 CVR score (p=0.013), moderate/high risk strata of QRISK2 (p=0.004), and high-risk strata of ACC/AHA 2013 CVR score (p=0.02). Of these 3, the highest sensitivity was obtained by the moderate risk stratum of QRISK2 with 51%; the highest specificity was obtained by the high-risk stratum of the ACC/AHA 2013 CVR score with 84%. <h3>Conclusion:</h3> Increased CIMT or CP might be unidentified if the risk is exclusively determined by CVR calculators. Patients with a CIMT ≥0.9 mm had an average score that placed them in the low risk strata, leading to an underestimation of their real CVR. Calculators can be helpful to estimate the CVR, however, they don't seem to be an adequate screening tool for an increased CIMT or CP. Meanwhile, to assess CVR precisely, a carotid US should be performed in all RA patients. <h3>References:</h3> [1] Peters M, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. ARD 2010. [2] Meune C, et al. Cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatology 2009. <h3>Disclosure of Interests:</h3> None declared
bin3C: exploiting Hi-C sequencing data to accurately resolve metagenome-assembled genomes
Authors: Matthew Z. DeMaere, Aaron E. Darling
Journal: Genome biology (2019)

Most microbes cannot be easily cultured, and metagenomics provides a means to study them. Current techniques aim to resolve individual genomes from metagenomes, so-called metagenome-assembled genomes (MAGs). Leading approaches depend upon time series or transect studies, the efficacy of which is a function of community complexity, target abundance, and sequencing depth. We describe an unsupervised method that exploits the hierarchical nature of Hi-C interaction rates to resolve MAGs using a single time point. We validate the method and directly compare against a recently announced proprietary service, ProxiMeta. bin3C is an open-source pipeline and makes use of the Infomap clustering algorithm ( https://github.com/cerebis/bin3C ).
OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin
Authors: Erwei Li, Haili Shan, Liqun Chen, Aijun Long, Yuanyuan Zhang, Yang Liu, Liangjie Jia, Fangchao Wei, Jinbo Han, Tong Li, Xiaohui Liu, Haiteng Deng, Yiguo Wang
Journal: Cell Metabolism (2019)
PB2140 IMPACT OF EXTRAMEDULLARY DISEASE IN THE OUTCOMES OF MEXICAN PATIENTS WITH MULTIPLE MYELOMA
Authors: C. Vargas‐Serafin, J. Rangel‐Patino, D. Perez‐Samano, A. Acosta‐Medina, I. Ordonez‐Perez, C. Bourlon
Journal: HemaSphere (2019)

Background: Extramedullary myeloma (EMM) is the synchronous presence of clonal plasma cells (CPC) at bone marrow and distant sites. Its frequency is reported among 6‐20% of multiple myeloma (MM) patients and manifest as bone‐dependent plasmocitoma (BP) or tissue‐dependent plasmocitoma (TP). Previous reports state a more aggressive clinical course, whether at diagnosis or relapse. There is no data regarding the clinical course and prognosis in Mexican patients with EMM. Aims: To analyze and describe the impact of EMM on overall survival (OS) and progression free survival (PFS) of Mexican patients diagnosed and treated at monoclonal gammapathies clinic of our institution. Methods Retrospective analysis including &gt;18 year‐old patients with MM diagnosis according to IMWG criteria. EMM was defined as presence of CPC corroborated by immunohistochemistry in BP or TP or demonstration of a synchronous tumor by imaging method and no accessible to biopsy. Results: A total of 199 patients were included. Sixty‐three patients had EMM (31.8%), 45 cases (71.4%) presented at diagnosis and 18 (28.6%) at progression. Forty‐eight cases (76.2%) were diagnosed by biopsy and 15 (23.8%) by imaging. Fifty‐four percent ( n = 34) cases presented BP and 46% ( n = 29) TP. Most frequently involved sites were abdomen (34.5%), thorax (27.6%) and lymph nodes (13.8%) in TP and spine (50%), chest wall (26.3%) and head/neck (13.2%) in BP. EMM was associated with lower comorbidity rate and higher renal failure. Population characteristics are shown in Table 1. Mean PFS and OS was 22.9 and 43.7 months, respectively. EMM at any time of disease resulted on lower PFS and OS ( p = 0.03, p = 0.04), while TP showed lower OS ( p &lt; 0.01). A higher ECOG PS and lower deep response was associated with worse PFS (HR 1.05‐2.60 (p = 0.03) and HR 0.20‐0.38 (p &lt; 0.01), respectively) while ISS and lower deep response resulted on worse OS (HR 1.0‐2.2 (p = 0.02) and HR 0.37‐0.73 (p &lt; 0.01)) at multivariate regression. Summary/Conclusion: A higher EMM rate was found in the studied population. EMM was associated to higher renal failure and low incidence of comorbidities, as shorter PFS and OS, particularly in TP. Identification of this high risk myeloma population allows an attempt for more intensive treatment with intention to improve prognosis. image
Abstract MP75: Geographic Variation in Stroke Rates and Oral Anticoagulation Use among Medicare Beneficiaries with Atrial Fibrillation
Authors: Inmaculada Hernandez, Samir Saba, Yuting Zhang
Journal: Circulation (2018)

Background: Recent studies have shown strong geographic variation in oral anticoagulation (OAC) use in atrial fibrillation (AF); however, it remains unknown how this contributes to the geographic variation in ischemic stroke observed across the US. The objective of the present study was to evaluate the relationship between the geographic variation in the initiation of OAC and the incidence of ischemic stroke in a cohort of Medicare beneficiaries newly diagnosed with AF. Methods: Using 2013-2014 claims data from a 5% random sample of Medicare beneficiaries, we identified patients newly diagnosed with AF in 2013-2014 and categorized them according to their initiation of OAC. Our sample included 21,226 OAC initiators and 20,068 patients who did not initiate OAC therapy. We assigned each patient to one of the 9 US Census Divisions using the zip code, and collected their medical claims with a diagnosis of ischemic stroke. We constructed logistic regression models to estimate the average adjusted probability of OAC initiation and Poisson models to estimate the average adjusted rate of ischemic stroke, in each Census Division. Both estimates were adjusted for demographics, eligibility for Medicaid coverage and for low-income subsidy, enrollment in a Medicare Advantage Part D plan, and a comprehensive list of clinical characteristics. We computed the correlation between the average adjusted probability of OAC initiation and the average adjusted rate of ischemic stroke at the Census Division level. Results: The probability of OAC initiation was lowest in the West South Central (0.47) and highest in the West North Central (0.54) and New England (0.54). The average adjusted rate of ischemic stroke was lowest in the West North Central (0.09) and highest in the South Atlantic (0.14) and South West Central (0.14). The average adjusted probability of OAC initiation at the Census Division level and the average adjusted rate of ischemic stroke were inversely correlated, with R=-0.576, p-value=0.10. This suggests that variation in OAC initiation likely explains at least a third of geographic variation in ischemic stroke [R 2 =(-0.576) 2 =0.332]. Conclusions: Our results suggest that geographic variations in OAC initiation within the U.S. explain, in part, variations in the incidence of ischemic stroke among AF patients. Further mechanistic research using advanced causal mediation models is warranted.
SP0016 YOUR VERY FIRST STEPS ON SYSTEMATIC REVIEW
Authors: Loreto Carmona
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Systematic reviews (SR) are a type of clinical research, and thus they follow the hypothetical-deductive or scientific method. Their objective is to answer clinical questions and they do it based on a specific structure (protocol) and working through inferences. Interestingly, a SR is a type of study design that can answer all types of questions, from efficacy to incidence. They manage the information from previous studies in a pre-established reproducible way, as unbiased as possible. They provide quick answers. However, they should be performed and interpreted with caution: a poor systematic review is much worse than a narrative review, as it gives the false impression of "science". This is even worse if the studies were combined in a meta-analysis. In this lecture, we will review the protocol of a SR, the importance of rephrasing the question, the search strategy, selection criteria, and procedures of studies selection, primary endpoints, and quality and risk of bias. The last part of any SR is the analysis, which is always qualitative, supported by the evidence table, and following a synthetic discourse with the PICO order, and sometimes quantitative (meta-analysis). We will review some methods to evaluate publication bias, to combine results, and to explore heterogeneity. In this sense, it is essential to note that if we cannot find a valid explanation for heterogeneity, our results may not be valid. <h3>Disclosure of Interests:</h3> Loreto Carmona Grant/research support from: Abbvie, Actelion, Astellas, BMS, Eisay, Gebro Pharma, Grünenthal, Leo Pharma, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis and UCB Pharma, Paid instructor for: Novartis
PF793 FUNCTIONAL ACTIVITY OF PLATELETS IN THE APPLICATION OF OLIGOPEPTIDES CONTAINING PROLINE AND ARGININE
Authors: M. Grigorjeva, L. Lyapina, T. Obergan, T. Shubina
Journal: HemaSphere (2019)

Background: The previous studies have shown that Tumor Educated Platelets (TEPs) RNA may complement currently used biosources and biomolecules employed for liquid biopsy diagnosis. RT-PCR is a regular method to measure gene expression levels to stage the patients and evaluate their prognosis. As there are little research on reference mRNA in platelets, especially in cancer. Aims: Our study is to find the proper internal controls for RT-PCR in platelet study. Methods: Firstly, based on dataset GSE68086, we found 285 genes with relatively equal expression in 4 kinds of high incidence cancer (non-small cell lung cancer (NSCLC), colorectal cancer (CC), breast cancer (BC) and liver cancer (LC)) and healthy control (HC). 95 genes left after screening with the criteria of mean>1 and coefficient of variation (cv) <1. Secondly, we gained 73 common reference genes from previous reported studies. Thirdly, we obtained 7 candidate reference genes (ACTB, B2 M, GAPDH, GNAS, OAZ1, PTMA and YWHAZ) after intersected the 95 genes and 73 genes. At last, we extracted total RNA from 1.5 ml blood in 30 unselected persons, including 6 NSCLC, 6 CC, 6 LC, 6 BC, and 6 HC, and performed RT-PCR with equal quantity of RNA to measure the expression levels of the candidate reference genes. Results: All of 7 candidate reference genes performed well in 5 tested groups with a cv<0.1. Both B2 M and GAPDH were the most stably expressed with a cv<0.05, but the expression of B2 M was much higher than GAPDH in platelets.Summary/Conclusion: We have found 7 platelets mRNA with relatively same expression levels among several solid tumors and healthy people, which can be used as reference genes for mRNA measuring of platelets. Among them, B2 M may be the best reference control gene.
New reference genome sequences of hot pepper reveal the massive evolution of plant disease-resistance genes by retroduplication
Authors: Seungill Kim, Jieun Park, Seon-In Yeom, Yong-Min Kim, Eunyoung Seo, Ki-Tae Kim, Myung-Shin Kim, Je Min Lee, Kyeongchae Cheong, Ho-Sub Shin, Saet-Byul Kim, Koeun Han, Jundae Lee, Minkyu Park, Hyun-Ah Lee, Hye-Young Lee, Youngsill Lee, Soohyun Oh, Joo Hyun Lee, Eunhye Choi, Eunbi Choi, So Eui Lee, Jongbum Jeon, Hyunbin Kim, Gobong Choi, Hyeunjeong Song, JunKi Lee, Sang-Choon Lee, Jin-Kyung Kwon, Hea-Young Lee, Namjin Koo, Yunji Hong, Ryan W. Kim, Won-Hee Kang, Jin Hoe Huh, Byoung-Cheorl Kang, Tae-Jin Yang, Yong-Hwan Lee, Jeffrey L. Bennetzen, Doil Choi
Journal: Genome biology (2017)

Transposable elements are major evolutionary forces which can cause new genome structure and species diversification. The role of transposable elements in the expansion of nucleotide-binding and leucine-rich-repeat proteins (NLRs), the major disease-resistance gene families, has been unexplored in plants.We report two high-quality de novo genomes (Capsicum baccatum and C. chinense) and an improved reference genome (C. annuum) for peppers. Dynamic genome rearrangements involving translocations among chromosomes 3, 5, and 9 were detected in comparison between C. baccatum and the two other peppers. The amplification of athila LTR-retrotransposons, members of the gypsy superfamily, led to genome expansion in C. baccatum. In-depth genome-wide comparison of genes and repeats unveiled that the copy numbers of NLRs were greatly increased by LTR-retrotransposon-mediated retroduplication. Moreover, retroduplicated NLRs are abundant across the angiosperms and, in most cases, are lineage-specific.Our study reveals that retroduplication has played key roles for the massive emergence of NLR genes including functional disease-resistance genes in pepper plants.