tbuckley/cabot-search huggingface dataset:
Discovering in vivo cytokine-eQTL interactions from a lupus clinical trial
Authors: Emma E. Davenport, Tiffany Amariuta, Maria Gutierrez-Arcelus, Kamil Slowikowski, Harm-Jan Westra, Yang Luo, Ciyue Shen, Deepak A. Rao, Ying Zhang, Stephen Pearson, David von Schack, Jean S. Beebe, Nan Bing, Sally John, Michael S. Vincent, Baohong Zhang, Soumya Raychaudhuri
Journal: Genome biology (2018)

Cytokines are critical to human disease and are attractive therapeutic targets given their widespread influence on gene regulation and transcription. Defining the downstream regulatory mechanisms influenced by cytokines is central to defining drug and disease mechanisms. One promising strategy is to use interactions between expression quantitative trait loci (eQTLs) and cytokine levels to define target genes and mechanisms.
STRetch: detecting and discovering pathogenic short tandem repeat expansions
Authors: Harriet Dashnow, Monkol Lek, Belinda Phipson, Andreas Halman, Simon Sadedin, Andrew Lonsdale, Mark Davis, Phillipa Lamont, Joshua S. Clayton, Nigel G. Laing, Daniel G. MacArthur, Alicia Oshlack
Journal: Genome biology (2018)

Short tandem repeat (STR) expansions have been identified as the causal DNA mutation in dozens of Mendelian diseases. Most existing tools for detecting STR variation with short reads do so within the read length and so are unable to detect the majority of pathogenic expansions. Here we present STRetch, a new genome-wide method to scan for STR expansions at all loci across the human genome. We demonstrate the use of STRetch for detecting STR expansions using short-read whole-genome sequencing data at known pathogenic loci as well as novel STR loci. STRetch is open source software, available from github.com/Oshlack/STRetch .
Correction to: Infliximab associated with faster symptom resolution compared with corticosteroids alone for the management of immune-related enterocolitis
Authors: Daniel H. Johnson, Chrystia M. Zobniw, Van A. Trinh, Junsheng Ma, Roland L. Bassett Jr, Noha Abdel-Wahab, Jaime Anderson, Jennifer E. Davis, Jocelyn Joseph, Marc Uemura, Ali Noman, Hamzah Abu-Sbeih, Cassian Yee, Rodabe Amaria, Sapna Patel, Hussein Tawbi, Isabella C. Glitza, Michael A. Davies, Michael K. Wong, Scott Woodman, Wen-Jen Hwu, Patrick Hwu, Yinghong Wang, Adi Diab
Journal: Journal for ImmunoTherapy of Cancer (2019)

Following publication of the original article [1], the authors reported an error in their listed affiliations.
Abstract 10834: Post-Ischemic Angiogenic Therapy Using In Vivo Pre-Vascularized Ascorbic Acid-Enriched Myocardial Artificial Grafts Improves Heart Function in a Rat Model
Authors: Eliana C Martinez, Jing Wang, Shera Lilyanna, Lieng H Ling, Shu U Gan, Rajeev Singh, Chuen N Lee, Theo Kofidis
Journal: Circulation (2010)

Introduction: Angiogenesis plays a key role in post-ischemic myocardial repair and remains a challenge in myocardial tissue engineering. We assessed the hypothesis that ascorbic acid (AA)-enriched ...
THU0028 COMPARISON OF IL-17A AND TNF INDUCED CYTOKINE SECRETION BY RHEUMATOID AND PSORIATIC ARTHRITIS SYNOVIAL FIBROBLASTS AND THEIR INHIBITION BY BIOLOGICS
Authors: Klaus Frommer, Stefan Rehart, Ulf Müller-Ladner, Elena Neumann
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis (RA) and psoriatic arthritis (PsA), although similar in several respects, display clinical as well as therapeutic differences. This includes, for example, the higher effectiveness of the anti-IL17A biologic secukinumab in PsA than in RA patients. Synovial fibroblasts (SF) are one of the key effector cell types in the pathophysiology of RA and PsA. We hypothesized that RASF and PsASF respond differentially to IL-17A and its biologic secukinumab and that this might contribute to the difference seen in the therapeutic response. <h3>Objectives</h3> To examine the effect of the two cytokines IL-17A and TNF-α on RASF in comparison to PsASF as well as the effect of their corresponding biologics. To analyze the effect of the IL-17A homolog IL-17F. <h3>Methods</h3> SF were isolated from synovium from PsA or RA patients undergoing surgery. SF from RA and PsA patients were stimulated with recombinant IL-17A, IL-17F and TNF-α alone or with respective combinations. Dose-response curve analysis was performed with IL-17A. The biologics secukinumab and adalimumab were used to block the effects on the SF. As a measure of the proinflammatory response, secretion of the cytokine IL–6 was quantified using an immunoassay. <h3>Results</h3> IL-6 secretion was induced by IL-17A in RASF as well as PsASF (IL-17A: 13.7-fold ↑ vs 6.9–fold ↑; n=3). Although sharing the same receptor, the IL-17A homolog IL-17F alone caused no induction of IL-6 secretion in SF. However, when combined with TNF-α, both IL-17 isoforms, IL–17A and IL-17F, increased IL-6 secretion due to a strong synergistic effect with TNF-α. RASF (n=3) responded more strongly than PsASF (n=3) to the combined stimulation (IL-17A: 544-fold ↑ vs 127-fold ↑, IL-17F: 54-fold ↑ vs 27-fold ↑). Adalimumab and secukinumab were similarly effective in abolishing the synergistic effect of IL-17A + TNF-α in RASF and PsASF. <h3>Conclusion</h3> According to our data, the differences in the therapeutic effectiveness of the anti-IL17A biologic secukinumab cannot be attributed to differential SF responses since the response to IL-17A alone and IL-17A together with TNF–α is not stronger for PsASF than for RASF and since secukinumab was similarly effective for both SF types. Furthermore, in a proinflammatory milieu with increased TNF levels, both IL-17A and IL-17F can contribute to promoting inflammation in the pathophysiology of PsA and RA. <h3>Acknowledgement</h3> Supported by an unrestricted educational grant from Celgene GmbH. <h3>Disclosure of Interests</h3> Klaus Frommer: None declared, Stefan Rehart: None declared, Ulf Müller-Ladner Grant/research support from: Projekt supported by an unrestricted educational grant from Celgene GmbH., Elena Neumann: None declared
AB0136 EVALUATION OF ANALGESIC ACTIVITY OF ALLOPURINOL AND FEBUXOSTAT IN EXPERIMENTAL ANALGESIC MODELS IN MICE
Authors: S Pal
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Allopurinol and febuxostat are xanthine oxidase inhibitor which are used in the treatment of hyperuricemia and gout. Pain is one of the important symptoms in gout patients. <h3>Objectives:</h3> The present study is to evaluate the analgesic activity of allopurinol and febuxostat in two analgesic models in mice. <h3>Methods:</h3> The analgesic activity of allopurinol (39 mg/kg) and febuxostat (15.6 mg/kg) was evaluated by using central analgesic model of Eddy's hot plate and peripheral analgesic model of acetic acid induced writhing. Both drugs were compared with the positive control, pentazocin for hot plate method &amp; aspirin for the Writhing method. Also both allopurinol and febuxostat were compared with each other. <h3>Results:</h3> Both allopurinol and febuxostat showed significant increase in reaction time at various time periods in hot plate method &amp; also showed significant delay in onset of writhing as well as decrease in number of writhes in writhing method. As compared to positive control result allopurinol and febuxostat result were lower. Febuxostat shows better analgesic activity as compared to that of allopurinol. <h3>Conclusion:</h3> Allopurinol and febuxostat exhibited analgesic activity in both central and peripheral models of pain. <h3>Disclosure of Interests:</h3> None declared
AB0567 DISEASE PATTERN IN EARLY AND NON-EARLY SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Sadovici-Bobeica Victoria, Maria Garabajiu, Lucia Mazur-Nicorici, Mariana Cebanu, Virginia Salaru, Minodora Mazur
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease with a high degree of variability at onset, creating challenges in the accurate estimation of it's pattern in early stages<sup>1</sup>. <h3>Objectives:</h3> To evaluate the pattern of the disease in patients with early and non-early systemic lupus erythematosus from physician's perspective. <h3>Methods:</h3> Performed case-control study included SLE patients that fulfilled SLICC classification criteria, 2012. The research included two groups: patients with early SLE – 1<sup>st</sup> group (disease duration ≤24 months) and non-early SLE – 2<sup>nd</sup> group (disease duration ≤24 months). The pattern of the disease activity was assessed by SLEDAI-2K, SLAM, PGA and PhGA for SLE activity, SLICC/ACR DI for disease irreversible changes and SF-8 for the quality of life (QoL). We correlated disease activity scores within groups and activity indices with the QoL using intra- and inter-class correlation coefficients <h3>Results:</h3> A total of 101 SLE patients was analyzed. First group (early SLE) included 34 patients while the second group (non-early SLE) included 67 patients. The disease duration ± SD (range) was 12,42±8,70 (0.1-24) and 146,41±81,64 (31-432) months, respectively. The disease activity was high in both groups. The QoL was appreciated as low, compared to general population, by both components, in 2 groups. The damage index was higher in the 2nd group, which can be explained by longer disease duration and development of irreversible changes during the course of lupus. The PhGA showed stronger and higher correlation with disease activity and QoL in patients with longer disease duration. These can be explained by the more accurate assessment of patients that have longer disease duration, while the unpredictable evolution and the assessment of early SLE is being challenging for the physician. Also, physician's judgment was influenced by the presence of irreversible organ damage in patient with longer disease, while in early disease course they where concerned mostly about disease activity. <h3>Conclusion:</h3> The clinical picture of SLE was characterized by high disease activity and low QoL in both, early and non-early lupus, while occurrence of irreversible organ changes was more characteristic for the longer disease. The disease parameters (activity, damage and QoL) correlated with PhGA mostly in patients with non-early SLE, the appreciation of the disease pattern being challenging in the early disease course. <h3>References</h3> [1] Cervera R. et al. Lessons from the "Euro-Lupus Cohort". Ann Med Interne, 2012 Dec;153(8):530-6 <h3>Disclosure of Interests:</h3> None declared
SP0069 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
Abstract 161: β-Arrestin-Biased Agonism of β-Adrenergic Receptor Regulates Dicer-mediated MicroRNA Maturation to Promote Cardioprotective Signaling
Authors: Jian-Peng Teoh, Il-man Kim
Journal: Circulation Research (2017)

MicroRNAs (miRs) are small, non-coding RNAs that function to post-transcriptionally regulate gene expression. First transcribed as primary miR transcripts (pri-miRs), they are enzymatically processed by Drosha into premature miRs (pre-miRs) and further processed by Dicer into mature miRs. Initially discovered to desensitize β-adrenergic receptor (βAR) signaling, β-arrestins are now well-appreciated to modulate multiple effector pathways independent of G protein-mediated signaling, a concept known as biased signaling. Using the β-arrestin-biased βAR ligand carvedilol (Carv), we previously showed that β-arrestin1-biased β1AR cardioprotective signaling stimulates Drosha-mediated processing of a subset of miRs. Here, we investigate whether Carv could regulate Dicer-mediated miR maturation, thereby providing a novel mechanism for its cardioprotective effects. In mouse hearts, Carv indeed upregulates 3 mature miRs, but not their pre-miRs and pri-miRs, in a β-arrestin1/2-dependent manner. Interestingly, Carv-mediated activation of miR-466g and miR-532 is dependent on β2AR, while the activation of miR-674 by Carv is β1AR-dependent. Mechanistically, β-arrestins regulate maturation of 3 newly identified βAR/β-arrestin-responsive miRs (β-miRs) by associating with the Dicer complex as well as hnRNPK and dyskerin on 3 pre-miRs (Fig. A). Cardiac cell approaches uncover that β-miRs act as gatekeepers of cardiac cell function by repressing detrimental target genes (Fig. B). In conclusion, our findings indicate a novel role for βAR-mediated β-arrestin signaling activated by Carv in miR maturation, which may be linked, in part, to its protective mechanism.
Cockroach allergen component analysis of children with or without asthma and rhinitis in an inner-city birth cohort
Authors: Anna Pomés, Jill Glesner, Agustin Calatroni, Cindy M. Visness, Robert A. Wood, George T. O'Connor, Meyer Kattan, Leonard B. Bacharier, Lisa M. Wheatley, James E. Gern, William W. Busse, P. Gergen, A. Togias, E. Smartt, K. Thompson
Journal: Journal of Allergy and Clinical Immunology (2019)
PB2452 DISTRIBUTION OF ABO AND RH BLOOD GROUP IN NEPALESE POPULATION
Authors: B. Nepal
Journal: HemaSphere (2019)

Background: ABO and RH are the major blood grouping system .which can effective transfusion compatibility .The distribution of blood group ABO and RH varies across the world according to the population Aims: To get the knowledge of distribution of ABO and RH blood group for effective management of inventory Methods: This is retrospective study conducted at Nepal Red Cross Society Central Blood Transfusion Service. Data from January 2010 to January 2016 were collected from donor management software .The data includes socio demographic data and Transfusion Transmissible infectious and other laboratory defects of blood donors. Results: Out of 440720 blood donor, 384308 (87.20%) were male and 56412 (12.8%) were female. The commonest ABO blood group present was A (31.64 %) followed by O (30.79 %), B (25.94 %) and AB (8.88 %) in blood donors; while in Rhesus system, 428600 (97.25%) donors were Rh-Positive and 12120 (2.75%) donors were Rh-Negative. Among the various ABO blood group “A” is the commonest and Rh Positive nearly equal to 97%. Summary/Conclusion: Similarity of distribution of ABO and Rh blood group were reported in south Asian countries. This indicates the influence factor of genetic drift and ancestral link with Indian sub continent. These studies has a important proposition regarding the inventory management of blood bank and transfusion services.
PB1993 EFFICACY OF ANTI-NEUTROPHIL ANTIBODIES TESTING IN PREDICTING CLINICAL OUTCOMES AND SPONTANEOUS RESOLUTION OF NEUTROPENIA IN CHILDREN: A SINGLE CENTER EXPERIENCE
Authors: Y.T. Lim, E.J. Yang, K.M. Park
Journal: HemaSphere (2019)

Background: Autoimmune neutropenia (AIN) is common form of neutropenia in children. AIN presents with absolute neutrophil count (ANC) of less than 0.5 x 109/L, but mild infection and spontaneous resolution. AIN is caused by anti-neutrophil antibodies (ANA). Detection of ANA is usually helpful in the diagnosis of AIN, but is controversy about the exclusion of congenital neutropenia or the prediction of outcome. Aims: The purpose of this study was to demonstrate the efficacy of the ANA testing for predicting clinical outcomes and spontaneous resolution of neutropenia in children with neutropenia. Methods: We reviewed the records of 62 patients with neutropenia of less than 1.5 x 109/L who were tested for ANA (positive or negative) in Department of Pediatrics, Pusan National University Children's Hospital, from February 2013 to January 2018. Patients with ANC > 1.5 x 109/L at presentation, alternative clinical diagnosis such as marrow failure or malignancy, and patients who were lost to follow-up were excluded. Blood samples for immunoglobulin G (IgG) and immunoglobulin M (IgM) ANA were tested by immunofluorescent flow cytometric technique. Results: For total of 62 pediatric patients with neutropenia, the mean age was 18.69 months (range, 3-96 months), 31 of the patients were boys and 31 was girl. All 62 patients had neutropenia, the mean ANC was 0.38 x 109/L (range, 0-1.39 x 109/L). Positive ANA were detected in 18 cases (29.0%) and absent in 44 (71.0%). Fifteen of 18 patients (83.3%) in ANA positive and 23 of 44 patients (52.3%) in ANA negative showed recovery from neutropenia, statistically significant (P = 0.022). The median age at recovery for those with resolving neutropenia was 26.8 months for the ANA positive and 20.48 months for ANA negative patients, respectively. The frequency of admission to the tertiary hospital with recurrent fevers and infections after the ANA testing (2.52, range, 0–23) in ANA negative was significantly higher than those (0.72, range, 0–3) in ANA positive (P = 0.008). Summary/Conclusion: Our study documents that ANA testing in children with neutropenia is helpful in establishing the diagnosis of AIN and effective in predicting clinical prognosis and spontaneous resolution of neutropenia. We also recommend that you consider to the results of ANA testing when treat of neutropenic children with recurrent fever and infection.
Abstract 16512: Malignancy Type Impacts Coronary Lesion Severity and Location: Multivariable Regression With Concurrent Machine Learning-Backed Case-Control Analysis
Authors: David L Boone, Dominique J Monlezun, Frances Cervoni-Curet, Jawad Chohan, Jennifer Sunny, Karan Bhatti, Dinu V Balanescu, Teodora Donisan, Gloria Iliescu, Nicolas Palaskas, Juan Lopez-Mattei, Saamir Hassan, Peter Kim, Jean-Bernard Durand, Serban M Balanescu, Konstantinos Marmagkiolis, Ezequiel D Muñoz Gonzalez, Tochukwu M Okwuosa, Cezar Iliescu
Journal: Circulation (2018)

Introduction: Data-driven guidelines for the optimal medical and interventional management of cancer patients according to the primary malignancy are absent. Hypothesis: We aimed to assess whether ...
Concurrent chemoradiotherapy with S-1 plus cisplatin for advanced cervical esophageal carcinoma: Long-term results of a phase II trial.
Authors: Hiroaki Iwase, Masaaki Shimada, Tomoyuki Tsuzuki, Noboru Hirashima, Masayuki Okeya, Nobumitsu Ryuge, Yuichi Kida, Takeshi Kuno, Yusaku Tanaka, Eriko Kato
Journal: Journal of Clinical Oncology (2013)

e15159 Background: Carcinoma of the advanced cervical esophagus is a highly virulent disease. Although surgery is considered the standard therapy, the results of surgery alone remain poor. The present study analyzes the efficacy of concurrent chemoradiotherapy (CCRT) with S-1 and cisplatin for advanced cervical esophageal carcinoma (ACEC). Methods: CCRT comprised two courses, 30-Gy radiotherapy over 3 weeks (2 Gy per fraction, 5 times a week) accompanied by daily oral S-1 powder (80 mg/m 2 /day) for 2 weeks and a 24-hr cisplatin infusion (70 mg/m 2 ) on Day 8. An identical course was administered after a 2-week break. Responders received a 5-week cycle of chemotherapy with S-1 and cisplatin. Results: Twenty-one subjects, 3 with Stage II, 14 with Stage III, and 4 with Stage IV ACEC participated, and all completed the CCRT courses. Eighteen subjects received a total of 59 cycles of chemotherapy after CCRT and a median of 3 cycles per subject was administered (range: 1 to 9 cycles). Complete response rates in subjects with Stage II, Stage III, and Stage IV diseases were 100%, 85.7%, and 25%, respectively, and a dysphagia-free status was found in 80.9%. The most serious toxicity was myelosuppression; Grades 3 and 4 neutropenia occurred in 33.3% and 9.5%, of subjects, respectively. Non-hematologic toxicities were moderate. The most common were Grade 2 nausea (38.0%), esophageal pain, and oral mucositis (19.0% each) and renal dysfunction (9.5%). Adverse events from the first course of CCRT resolved during the 2-week treatment break. Overall median progression-free survival was 1.5 years and the median survival time was 2.5 years. The 1- and 5-year survival rates were 75.0 and 27.7%, respectively. Conclusions: This regimen showed favorable antitumor activity, improving survival and quality of life with tolerable toxicity, and could become an alternative to conventional surgery for the treatment of ACEC.