tbuckley/cabot-search huggingface dataset:
Dissecting the Stromal Signaling and Regulation of Myeloid Cells and Memory Effector T Cells in Pancreatic Cancer
Authors: Alex B. Blair, Victoria M. Kim, Stephen T. Muth, May Tun Saung, Nathalie Lokker, Barbara Blouw, Todd D. Armstrong, Elizabeth M. Jaffee, Takahiro Tsujikawa, Lisa M. Coussens, Jin He, Richard A. Burkhart, Christopher L. Wolfgang, Lei Zheng
Journal: Clinical Cancer Research (2019)

Myeloid cells are a prominent immunosuppressive component within the stroma of pancreatic ductal adenocarcinoma (PDAC). Previously, targeting myeloid cells has had limited success. Here, we sought to target the myeloid cells through modifying a specific stromal component.A murine model of metastatic PDAC treated with an irradiated whole-cell PDAC vaccine and PDAC specimens from patients treated with the same type of vaccine were used to assess the immune-modulating effect of stromal hyaluronan (HA) degradation by PEGPH20.Targeting stroma by degrading HA with PEGPH20 in combination with vaccine decreases CXCL12/CXCR4/CCR7 immunosuppressive signaling axis expression in cancer-associated fibroblasts, myeloid, and CD8+ T cells, respectively. This corresponds with increased CCR7- effector memory T-cell infiltration, an increase in tumor-specific IFNγ, and improved survival. In the stroma of human PDACs treated with the same vaccine, decreased stromal CXCR4 expression significantly correlated with decreased HA and increased cytotoxic activities, suggesting CXCR4 is an important therapeutic target.This study represents the first to dissect signaling cascades following PDAC stroma remodeling via HA depletion, suggesting this not only overcomes a physical barrier for immune cell trafficking, but alters myeloid function leading to downstream selective increases in effector memory T-cell infiltration and antitumor activity.
Psoriatic lesions are characterized by higher bacterial load and imbalance between Cutibacterium and Corynebacterium
Authors: Cheng Quan, Xiao-Ying Chen, Xia Li, Feng Xue, Li-Hong Chen, Na Liu, Bo Wang, Lan-Qi Wang, Xiao-Pan Wang, Hui Yang, Jie Zheng
Journal: Journal of the American Academy of Dermatology (2019)
Prognostic Implications of Right Ventricular Remodeling and Function in Patients With Significant Secondary Tricuspid Regurgitation
Authors: Marlieke F. Dietz, Edgard A. Prihadi, Pieter van der Bijl, Laurien Goedemans, Bart J.A. Mertens, Erhan Gursoy, Olton S. van Genderen, Nina Ajmone Marsan, Victoria Delgado, Jeroen J. Bax
Journal: Circulation (2019)

Background: In patients with significant (moderate and severe) tricuspid regurgitation (TR), the decision to intervene is influenced by right ventricular (RV) size and function. RV remodeling in significant secondary TR has been underexplored. The aim of this study was to characterize RV remodeling in patients with significant secondary TR and to investigate its prognostic implications. Methods: RV remodeling was characterized by transthoracic echocardiography in 1292 patients with significant secondary TR (median age 71 [62–78]; 50% male). Four patterns of RV remodeling were defined according to the presence of RV dilation (tricuspid annulus≥40 mm) and RV systolic dysfunction (tricuspid annulus systolic excursion plane&lt;17 mm): pattern 1, normal RV size and systolic function; pattern 2, dilated RV with preserved systolic function; pattern 3, normal RV size with systolic dysfunction; and pattern 4, dilated RV systolic dysfunction. The primary end point was all-cause mortality and the event rates were compared across the 4 patterns of RV remodeling. Results: A total of 183 (14%) patients showed pattern 1 RV remodeling; 256 (20%) showed pattern 2; 304 (24%) presented with pattern 3; and 549 (43%) had pattern 4 RV remodeling. Patients with pattern 4 RV remodeling were more frequently male; more often had coronary artery disease, worse renal function, and impaired left ventricular ejection fraction; and were more often symptomatic. Only 98 (8%) patients underwent tricuspid valve annuloplasty during follow-up. During a median follow-up of 34 (interquartile range, 0–60) months, 510 (40%) patients died. The 5-year survival rate was significantly worse in patients presenting with patterns 3 and 4 RV remodeling in comparison with pattern 1 (52% and 49% versus 70%; P =0.002 and P &lt;0.001, respectively), and were independently associated with poor outcome on multivariable analysis. Conclusions: In patients with significant secondary TR, patients with RV systolic dysfunction have worse clinical outcome regardless of the presence of RV dilation.
Meta-analysis of Aspirin for Primary Prevention of Cardiovascular Events—Reply
Authors: Sean L. Zheng, Alistair J. Roddick
Journal: JAMA (2019)

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AB0204 THE CLINICAL FEATURES OF ANTI-TIF1GAMMA ANTIBODY POSITIVE DERMATOMYOSITIS
Authors: Yoshikazu Fujikawa, Kengo Akashi, Motoko Katayama, Mai Yamashita, Yoko Nose, Takaichi Okano, Yo Ueda, Sho Sendo, Akira Onishi, Jun Saegusa, Akio Morinobu
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Anti-TIF1gamma antibody positive dermatomyositis(TIF1γ-DM) has greater risk of complication with cancer. <h3>Objectives</h3> We aimed to analyze the clinical features of TIF1γ-DM and find the difference between cancer-associated TIF1γ-DM (CA-TIF1γ-DM) and non-cancer-associated TIF1γ-DM (nCA-TIF1γ-DM). <h3>Methods</h3> We investigated the clinical data of idiopathic inflammatory myositis (IIM) patients received remission induction therapy in out hospital between January 2006 and December 2018. <h3>Results</h3> We treated 148 patients with IIM in this period, 9 cases of them were TIF1γ-DM. Patients with CA-TIF1γ-DM and nCA-TIF1γ-DM were 4 and 5 cases, respectively. Average age at onset of 9 patients with TIF1γ-DM was 63 years old. CA-TIF1γ-DM was significantly older than nCA-TIF1γ-DM (average:78.0 vs 57.4). All of 9 TIF1γ-DM had distinctive skin rash and muscle weakness. Seven cases of them suffered from dysphagia. Interstitial lung disease was not seen in all patients with TIF1γ-DM. Serum creatine kinase (CK) levels of CA-TIF1γ-DM was significantly higher than those of nCA-TIF1γ-DM (average: 3405.5IU/L vs 719.8IU/L) (Fig 1.). Among the TIF1γ-DM patients, we administered glucocorticoid (GCs) for 8 cases, immunosuppresants for 4 cases, and intravenous immunoglobulins (IVIG) for 7 cases. All 4 cases of CA-TIF1γ-DM were treated with GC and IVIG. All TIF1γ-DM patients, especially 4 CA-TIF1γ-DM patients, seemed to have good response to treatment in serum CK levels. Although serum CK levels of these 4 cases were normalized within a month (Fig1.), their muscle weakness, skin rash and dysphagia which was associated with quality of life and the prognosis were poorly improved. <h3>Conclusion</h3> In our investigation, the age of onset and serum CK levels were significantly different between CA-TIF1γ-DM and nCA-TIF1γ-DM. We report our investigation of the phenotype and treatment of anti TIF1gamma antibody positive dermatomyositis. TIF1γ-DM with high serum CK levels, we should perform appropriate tests to check for cancer throughout our treatment, and the improvement of serum CK levels is not equal to the success of our treatment. <h3>Disclosure of Interests</h3> None declared
Abstract 14514: Cardiac Magnetic Resonance Myocardial Feature Tracking for Optimized Prediction of Cardiovascular Events Following Myocardial Infarction
Authors: Ingo Eitel, Thomas Stiermaier, Torben Lange, Johannes Kowallick, Joachim Lotz, Gerd Hasenfuß, Holger Thiele, Andreas Schuster
Journal: Circulation (2017)

Introduction: Cardiac magnetic resonance myocardial feature tracking (CMR-FT) is a new method that allows accurate assessment of global and regional circumferential, radial and longitudinal myocard...
FRI0567 ABATACEPT THERAPY EXPERIENCE IN THE CASE SERIES OF PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS ASSOCIATED WITH OVERLAP SYNDROME AND/OR SJOGREN’S SYNDROME
Authors: Irina Nikishina, Svetlana Arsenyeva, Olga Kostareva, Maria Kaleda
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The choice of Biologics in patients with juvenile idiopathic arthritis (JIA) who have overlap syndrome with juvenile onset of systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM), juvenile systemic sclerosis (jSSc) and juvenile Sjogren's syndrome (jSS) is difficult. TNF inhibitors are limited in this kind of disorders and abatacept (ABA) seems to be the favorable option for children, but there are not enough studies in pediatric overlap syndrome and jSS. <h3>Objectives</h3> The evaluation of the abatacept therapy in case series of patients with JIA associated with overlap syndrome and/or jSS. <h3>Methods</h3> Patients who fulfilled the criteria for JIA and the criteria of above mentioned rheumatic disorders and received abatacept therapy according to JIA indication in real clinical practice of our rheumatological clinic. <h3>Results</h3> 11 patients included in the retrospective study (8 girls, 3 boys). The average age of patients was 15.1 years (from 7 to 18 years). Mean duration of disease was 5.4 years. 9 patients were RF positive, 4 patients had ACCP. All of the patients had antinuclear antibody (from 1:320 to 1:2560), 3 patients had positive anti-Ro antibody. Sjogren's syndrome was the most common concomitant autoimmune disorder (<b>n</b> = 8), JDM (<b>n</b> = 2), jSSc (<b>n</b> = 2), JSLE (<b>n</b> = 1). 7 patients were treated by a low dose of prednisolone (median 5.7 mg/day). All patients received methotrexate in dose 10-15 mg/m<sup>2</sup>/week. ABA was indicated as first line of biology therapy in 10 patients, in one patient after adalimumab withdrawn due to severe flare. Mean duration of abatacept treatment was 23.7 month (from 6 to 78). The most of the patients (82%) had excellent stable effect of ABA treatment, but two patients needed to be switched to rituximab due to secondary inefficacy. We observed wonderful result of treatment with full remission of arthritis, calcinosis regression and resolving of Sjogren's syndrome in the boy with overlap syndrome treated by ABA for 78 months. The seroconversion from initial levels of RF 32.9 IU/ml (&gt;2N), antinuclear antibody 1:640, anti-Ro antibody 200 U/ml (&gt;9N) to negative results was registered. The ABA was good tolerated in all patients. In one case it was canceled due to pregnancy. <h3>Conclusion</h3> ABA is efficacy and safety option in patients with pediatric overlap syndrome and jSS. ABA is good alternative to anti-B cell therapy and preferable choice among Biologics in such category of patients. <h3>Disclosure of Interests</h3> None declared
Abstract 3450: Mutations in Cardiac Myosin-Binding Protein C (MYBPC3) and α-Tropomyosin (TPM1) in Left Ventricular Noncompaction
Authors: Sabine Klaassen, Susanne Probst, Erwin Oechslin, Pia Schuler, Felix Berger, Rolf Jenni, Ludwig Thierfelder
Journal: Circulation (2008)

Left ventricular noncompaction (LVNC) constitutes a primary cardiomyopathy characterized by a severely thickened, two-layered myocardium, numerous prominent trabeculations, and deep intertrabecular...
PF698 LUSUTROMBOPAG RELIABLY INCREASES PLATELETS REGARDLESS OF BASELINE PLATELET COUNTS IN THROMBOCYTOPENIC CHRONIC LIVER DISEASE PATIENTS UNDERGOING PLANNED INVASIVE PROCEDURES: RESULTS OF 2 PHASE 3 TRIALS
Authors: R.S. Brown, M. Imawari, N. Izumi, Y. Osaki, R. Bentley, T. Baykal, T. Ochiai, T. Kano
Journal: HemaSphere (2019)

Background: Lusutrombopag is an oral, small molecule thrombopoietin receptor agonist approved in Japan and US for improvement of thrombocytopenia, and in EU for severe thrombocytonia, associated with chronic liver disease in patients undergoing planned invasive procedures. The degree of thrombocytopenia may impact the treatment response to lusutrombopag and need for platelet transfusion. Aims: This analysis evaluates the increase in platelet count and maximum platelet count achieved according to baseline platelet count. Methods: L‐PLUS 1 and L‐PLUS 2 were two similar phase 3 multicenter, randomized, double‐blind, placebo‐controlled studies; L‐PLUS 1 (JapicCTI‐132323) was conducted in Japan and L–PLUS 2 (NCT02389621) was conducted globally. Patients with thrombocytopenia due to chronic liver disease received lusutrombopag 3 mg or placebo for up to 7 days prior to an invasive procedure scheduled 9–14 days after randomization. Patients were adults with platelet count (x10 9 /L) &lt;50 at baseline. Platelet transfusion was mandated if the platelet count remained &lt;50 no more than two days prior to the planned invasive procedure. The change in platelet count over time was a key efficacy endpoint. A per‐protocol population from the two trials was integrated for this analysis; post‐platelet transfusion platelet counts were excluded from the analysis when calculating the proportion of patients who met a criterion and summary statistics for maximum platelet counts. Results: 312 patients were randomized. Of the 270 patients in the per‐protocol population, 78.1% of patients in the lusutrombopag group (n = 137) achieved a platelet count ≥50 at least once during the study versus 30.1% of patients in the placebo group (n = 133). The platelet count increased by double or more in 47.4% and 3.8% in the lusutrombopag and placebo groups, respectively, and increased by 50% or more in 77.4% and 12.8%, respectively. The average maximum platelet count in the lusutrombopag group stratified according to baseline platelet count of &lt;20, ≥20‐&lt;30, ≥30‐&lt;35, ≥35‐&lt;40, and ≥40‐&lt;50 was 56, 45, 64, 82, and 87, respectively ( Figure ). The average maximum change in platelet count in these strata were +41, 21, 32, 45, and 42, respectively. Summary/Conclusion: Patients on lusutrombopag experienced a clinically meaningful response in platelet count regardless of whether the baseline platelet count was above or below 35x10 9 /L, thereby avoiding the need for use of platelet transfusion. image
Positron-Emission Tomographic Imaging of a Fluorine 18–Radiolabeled Poly(ADP-Ribose) Polymerase 1 Inhibitor Monitors the Therapeutic Efficacy of Talazoparib in SCLC Patient–Derived Xenografts
Authors: James Laird, Benjamin H. Lok, Brandon Carney, Susanne Kossatz, Elisa de Stanchina, Thomas Reiner, John T. Poirier, Charles M. Rudin
Journal: Journal of Thoracic Oncology (2019)
5 The motivators and barriers to physical activity in primary prevention of chronic disease
Authors: A Pavitt
Journal: British Journal of Sports Medicine (2019)

Background Regular physical activity is protective against many chronic diseases. Despite this, 39% of adults in the UK are insufficiently active with an increased risk of chronic disease. Moving Medicine is an online resource developed by the FSEM to facilitate clinician-led conversations to reduce the risk of chronic disease through increased physical activity. Aim This is the first review to categorise and understand the principle motivators for and barriers against physical activity, for the primary prevention of chronic disease. It has informed the development of a national Moving Medicine resource. Methods A structured search of MEDLINE and OpenGrey, augmented by handsearching of reference lists and contents of key journals. Qualitative evidence was then synthesised thematically. Results Thirteen papers were selected as being of good quality (structured interviews and focus groups rather than questionnaires) and relevant to the aims of this review. Motivators identified were grouped into: anticipated positive effects, support/encouragement, social aspects, environmental aspects, goal-setting, and the use of feedback. Barriers to physical activity were grouped into: time constraints, physical health problems, environmental aspects, cost and poor communication. Building results into the resource The results of this review were presented to an expert panel of SEM doctors, GPs, nurses, physiotherapists, and patients. This multidisciplinary team then helped shape the primary prevention resource on the Moving Medicine website. See examples from the resource below. Conclusion Good quality conversations on physical activity in healthcare require an understanding of the key motivators and barriers reported by patients. Combining this qualitative review with the knowledge, skills and the experience of a multidisciplinary expert panel has enabled the development of a unique patient-centred primary prevention resource. Delivering this information through MovingMedicine.ac.uk is a vital step in using these important findings to inform routine clinical practice across the NHS. This should facilitate an increase in the proportion of adults meeting recommended physical activity levels and therefore reduce the rates of chronic disease.
SCARNA10, a nuclear-retained long non-coding RNA, promotes liver fibrosis and serves as a potential biomarker
Authors: Kun Zhang, Yawei Han, Zhimei Hu, Zhen Zhang, Shuai Shao, Qingbin Yao, Lina Zheng, Jingzhao Wang, Xiaohui Han, Yu Zhang, Ting Chen, Zhi Yao, Tao Han, Wei Hong
Journal: Theranostics (2019)

Long non-coding RNAs (lncRNAs) are involved in numerous biological functions and pathological processes.However, the clinical significance of lncRNAs and their functions in liver fibrosis remain largely unclear.Methods: The transcript of lncRNA SCARNA10 in serum and liver samples from patients with advanced hepatic fibrosis, liver tissues from two fibrosis mouse models, and cultured hepatic stellate cells (HSCs) was determined by real-time RT-PCR.The effects of lentivirus-mediated knockdown or over-expression of SCARNA10 in liver fibrosis were examined in vitro and in vivo.Moreover, the effects and mechanisms of down-regulation or over-expression of SCARNA10 on the expression of the genes involved in TGFβ pathway were determined.Results: It was found lncRNA ENSMUST00000158992, named as Scarna10, was remarkably up-regulated in mouse fibrotic livers according to the microarray data.We observed that the transcript of SCARNA10 was increased in the serum and liver from patients with advanced hepatic fibrosis.Furthermore, we found that SCARNA10 promoted liver fibrosis both in vitro and in vivo through inducing hepatocytes (HCs) apoptosis and HSCs activation.Mechanistically, RNA immunoprecipitation (RIP) assays demonstrated that SCARNA10 physically associated with polycomb repressive complex 2 (PRC2).Additionally, our results demonstrated that SCARNA10 functioned as a novel positive regulator of TGFβ signaling in hepatic fibrogenesis by inhibiting the binding of PRC2 to the promoters of the genes associated with ECM and TGFβ pathway, thus promoting the transcription of these genes.Conclusions: Our study identified a crucial role of SCARNA10 in liver fibrosis, providing a proof of this molecule as a potential diagnostic marker and a possible therapeutic target against liver fibrosis.
Do you understand the words that are comin outta my mouth? Voice assistant comprehension of medication names
Authors: Adam Palanica, Anirudh Thommandram, Andrew Lee, Michael Li, Yan Fossat
Journal: npj Digital Medicine (2019)

Abstract This study investigated the speech recognition abilities of popular voice assistants when being verbally asked about commonly dispensed medications by a variety of participants. Voice recordings of 46 participants (12 of which had a foreign accent in English) were played back to Amazon’s Alexa, Google Assistant, and Apple’s Siri for the brand- and generic names of the top 50 most dispensed medications in the United States. A repeated measures ANOVA indicated that Google Assistant achieved the highest comprehension accuracy for both brand medication names ( M = 91.8%, SD = 4.2) and generic medication names ( M = 84.3%, SD = 11.2), followed by Siri (brand names M = 58.5%, SD = 11.2; generic names M = 51.2%, SD = 16.0), and the lowest accuracy by Alexa (brand names M = 54.6%, SD = 10.8; generic names M = 45.5%, SD = 15.4). An interaction between voice assistant and participant accent was also found, demonstrating lower comprehension performance overall for those with a foreign accent using Siri ( M = 48.8%, SD = 11.8) and Alexa ( M = 41.7%, SD = 12.7), compared to participants without a foreign accent (Siri M = 57.0%, SD = 11.7; Alexa M = 53.0%, SD = 10.9). No significant difference between participant accents were found for Google Assistant. These findings show a substantial performance lead for Google Assistant compared to its voice assistant competitors when comprehending medication names, but there is still room for improvement.
THU0479 SAFETY AND EFFICACY OF MEDICAL CANNABIS IN FIBROMYALGIA
Authors: Iftach Sagy, Lihi Bar-Lev Schleider, Mahmoud Abu-Shakra, Victor Novack
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Although chronic pain is a well established indication for medical cannabis therapy, there is scarce evidence to support the role of medical cannabis in the treatment of fibromyalgia. <h3>Objectives:</h3> The aim of the study was to investigate the characteristics, safety and effectiveness of medical cannabis therapy for fibromyalgia. <h3>Methods:</h3> A prospective study with 6 months follow-up period based on fibromyalgia patients who were willing to answer questionnaire in a specialized medical cannabis clinic between 2015 and 2017. <h3>Results:</h3> Among the 367 fibromyalgia patients the mean age was 52.9±15.1, of whom 301 (82.0%) were women. 28 patients (7.6%) stopped the treatment prior to the six months follow-up. The six months response rate was 70.8%. Pain intensity (scale 0-10) reduced from a median of 9.0 at baseline to 5.0 (p&lt;0.001), and 194 patients (81.1%) achieved treatment response. In a multivariate analysis age above 60 years (Odds ratio [OR] 0.34, 95% C.I 0.16-0.72), concerns about cannabis treatment (OR 0.36, 95% C.I 0.16-0.80), spasticity (OR 2.26, 95% C.I 1.08-4.72) and previous use of cannabis (OR 2.46 95% C.I 1.06-5.74) were associated with treatment outcome. The most common adverse effects were mild and included dizziness (7.9%), dry mouth (6.7%) and gastrointestinal symptoms (5.4%). <h3>Conclusion:</h3> Medical cannabis appears to be safe and effective alternative for the treatment of fibromyalgia symptoms. Standardization of treatment compounds and regimens are required. <h3><b>Disclosure of Interests:</b>&nbsp;:</h3> Iftach Sagy: None declared, Lihi Bar-Lev Schleider Employee of: employee of Tikun-Olam Ltd. without shares or options, Mahmoud Abu-Shakra: None declared, Victor Novack Consultant for: paid member of the Tikun Olam Ltd. scientific advisory board&nbsp;
Review: E-health interventions improve blood pressure level and control in hypertension
Authors: Jeffery Gray, Patrick O’Malley
Journal: Annals of Internal Medicine (2019)

Source Citation Ma Y, Cheng HY, Cheng L, Sit JWH. The effectiveness of electronic health interventions on blood pressure control, self-care behavioural outcomes and psychosocial well-being in patients with hypertension: a systematic review and meta-analysis. Int J Nurs Stud. 2018;92:27-46. 30690164