tbuckley/cabot-search huggingface dataset:
AB0898 Course of ankylosing spondylitis in pregnancy
Authors: Z. Gandaloeva, O. Kritchevskaya, T. Dubinina, S. Erdes
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To study the effect of pregnancy on ankylosing spondylitis (AS) course. <h3>Methods</h3> 86 AS patients having pregnancy in the course of the disease were included into questionnaire survey. Patients' mean age was 34 [30:37] years, mean disease duration was 120 [72:180] month. The questionnaire items were designed to elucidate modifications in AS course during the last pregnancy with live birth outcome. The study is based on patient's self-reported health (SRH) status (improvement, worsening, no change). <h3>Results</h3> All responders reported delivery of full-term babies at mean 39 weeks [38:40] of gestation, vaginal delivery was documented by 46 (53,5%) responders, Caesarean section – by 40 (46,5%). AS worsening or improvement during all three trimesters is shown in the table 1. Worsening of underlying disease (as compared to the condition 3 months prior to pregnancy) during whole pregnancy was reported by 3 (3,5%) women, absence of noticeable changes was reported by 13 (15,1%) patients, and AS improvement – by 9 (10,4%) participants. 61 (71%) of responders reported fluctuating AS activity during pregnancy. AS worsening was associated with exacerbation of back pain in 44 (51%), emergence and/or recurrence of arthritis – in 15 (17,4%), or uveitis – in 9 (10,4%), and other symptoms – in 11 (12,8%) patients. <h3>Conclusions</h3> Therefore, the majority of participants reported the diverse fluctuations in AS course during pregnancy, although 50% of responders reported the improvement in the course of the disease at least during one trimester (more often in the first). Nevertheless, almost 70% of responders reported AS worsening with exacerbations rates increasing in parallel with increasing gestation age. 50% of participants noticed worsening back pain, although special attention should be given to correct evaluation of AS activity in these patients keeping in mind the increased physiological load on the backbone during the second half of pregnancy. <h3>Disclosure of Interest</h3> None declared
Identifying facial phenotypes of genetic disorders using deep learning
Authors: Yaron Gurovich, Yair Hanani, Omri Bar, Guy Nadav, Nicole Fleischer, Dekel Gelbman, Lina Basel-Salmon, Peter M. Krawitz, Susanne B. Kamphausen, Martin Zenker, Lynne M. Bird, Karen W. Gripp
Journal: Nature Medicine (2018)
Deep and Durable Responses with Selinexor, Daratumumab, and Dexamethasome (SDd) in Patients with Multiple Myeloma (MM) Previously Exposed to Proteasome Inhibitors and Immunomodulatory Drugs: Results of Phase 1b Study of SDd
Authors: Cristina J Gasparetto, Suzanne Lentzsch, Gary J. Schiller, William Bensinger, Nizar Bahlis, Heather J. Sutherland, Darrell J. White, Michael Sebag, Rami Kotb, Christopher P. Venner, Richard Leblanc, Christine I Chen, Aldo Del Col, Jatin J. Shah, Jacqueline Jeha, Jean-Richard Saint-Martin, Michael G. Kauffman, Sharon Shacham, Joel G. Turner, Daniel M Sullivan, Brea Lipe
Journal: Blood (2018)
Abstract P374: Trends in Hypertension Prevalence, Awareness, Treatment, and Control: The National Health and Nutrition Examination Survey, 1999-2014
Authors: Kathryn Foti, Dan Wang, Elizabeth Selvin
Journal: Circulation (2018)

Introduction: The decline in cardiovascular disease mortality in the US has stalled in recent years, though patterns have varied by age and sociodemographic characteristics. Trends in prevalence of hypertension, as well as awareness, treatment, and control in population subgroups can shed light on opportunities for improving hypertension management and CVD prevention. Hypothesis: There has been greater improvement in hypertension control among adults aged ≥65 years than in middle- and younger-age (45-64 and 25-44 years) adults and that race and socioeconomic disparities may be narrower among adults aged ≥65 years. Methods: We analyzed data for adults aged ≥25 years from the 1999-2014 National Health and Nutrition Examination Survey (NHANES). We examined mean systolic blood pressure (SBP), prevalence of hypertension, and among those with hypertension, prevalence of awareness, treatment, and control by age category and survey cycle. We fit linear regression models for trends with interaction terms for age category and time. Results: Among those aged ≥65, mean SBP decreased 10.4 mmHg, from 143.2 to 132.9 mmHg, a significantly greater decrease than among those aged 45-64 (-3.1 mmHg) or 25-44 (-0.1 mmHg), though absolute SBP values are highest among those aged ≥65 ( Table ). Hypertension awareness, treatment, and control increased significantly each age category, but to a lesser extent among those 45-64 than those ≥65 (p-values for interaction: 0.031, 0.054, 0.051, respectively). Differences in hypertension control and mean SBP among whites and blacks were greater among those 45-64 than those ≥65. Within age categories, there were few significant differences in trends over time by race/ethnicity, education, or poverty to income ratio. Conclusions: Our findings highlight the need to address hypertension management among middle- and younger-age adults. Persistent disparities in hypertension control over time demonstrate that prevention and management of hypertension is a priority health equity issue.
Development and validation of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis
Authors: Nava Ferdowsi, Molla Huq, Wendy Stevens, Marie Hudson, Mianbo Wang, Tien Tay, Jodie L Burchell, Sam Mancuso, Candice Rabusa, Vijaya Sundararajan, David Prior, Susanna M Proudman, Murray Baron, Mandana Nikpour
Journal: Annals of the Rheumatic Diseases (2019)

Objective We sought to develop the first Damage Index (DI) in systemic sclerosis (SSc). Methods The conceptual definition of ‘damage’ in SSc was determined through consensus by a working group of the Scleroderma Clinical Trials Consortium (SCTC). Systematic literature review and consultation with patient partners and non-rheumatologist experts produced a list of potential items for inclusion in the DI. These steps were used to reduce the items: (1) Expert members of the SCTC (n=331) were invited to rate the appropriateness of each item for inclusion, using a web-based survey. Items with &gt;60% consensus were retained; (2) Using a prospectively acquired Australian cohort data set of 1568 patients, the univariable relationships between the remaining items and the endpoints of mortality and morbidity (Physical Component Summary score of the Short Form 36) were analysed, and items with p&lt;0.10 were retained; (3) using multivariable regression analysis, coefficients were used to determine a weighted score for each item. The DI was externally validated in a Canadian cohort. Results Ninety-three (28.1%) complete survey responses were analysed; 58 of 83 items were retained. The univariable relationships with death and/or morbidity endpoints were statistically significant for 22 items, with one additional item forced into the multivariable model by experts due to clinical importance, to create a 23-item weighted SCTC DI (SCTC-DI). The SCTC-DI was predictive of morbidity and mortality in the external cohort. Conclusions Through the combined use of consensus and data-driven methods, a 23-item SCTC-DI was developed and retrospectively validated.
Abstract 20908: Notch Signalling in Pathogenesis of Calcified Aortic Valve
Authors: Anna Malashicheva, Anastasia Shishkova, Vladimir Uspenskiy, Olga Irtyuga, Olga Moiseeva, Eugeniy Shlyakhto
Journal: Circulation (2016)

Introduction: Calcific aortic valve stenosis (CAVS) is the most common form of acquired valvular disease. A progressive mineralization of aortic valve leaflets is a major culprit in the development...
Optimising TNFRSF agonism and checkpoint blockade with a novel CD137/PD-L1 bispecific antibody
Authors: M.A. Lakins, J. Munoz-Olaya, D. Jones, R. Giambalvo, C. Hall, A. Knudsen, N. Masque Soler, S. Pechouckova, E. Goodman, C. Gradinaru, A. Koers, S. Marshall, M. Wydro, F. Wollerton, S. Batey, D. Gliddon, M. Davies, M. Morrow, M. Tuna, N. Brewis
Journal: Annals of Oncology (2018)

Background: PD-1/L1 axis blockade shows durable responses and extended overall survival across cancer types in a subset of patients. Tumour Necrosis Factor Receptor (TNFR) superfamily activation is also being tested clinically to improve patient responses. Current interventions using therapeutic CD137 agonists to activate T cells are limited by adverse safety effects and poor efficacy as monotherapies. The generation of a bispecific agonist of CD137 following PD-L1 crosslinking allows a greater therapeutic window with improved safety and efficacy. Methods: An anti-CD137/PD-L1 mAb2 was generated by introducing a CD137-binding specificity into the Fc-region of a human IgG1 targeting PD-L1 mAb. FcgR binding was decreased by introducing a LALA mutation. Binding characterisation was assessed and in vitro activity measured in a mouse primary OT-1 CD8+ T cell assay. The anti-tumour activity and PK/PD of anti-CD137/PD-L1 mAb2 was tested in mouse tumour models. Results: An anti-CD137/PD-L1 mAb2 was developed, which binds to mouse PD-L1 enabling CD137 agonism (in vitro EC50: 3 pM in primary antigen-specific OT-1 assay). The mAb2 significantly reduced tumour growth in 3 syngeneic mouse tumour models (MC38, CT26 and B16-F10) with dose-dependent inhibition seen in CT26, resulting in a significant survival benefit at concentrations of 0.3 mg/kg or above. This growth inhibition was coincident with increases in tumour and peripheral activated CD8 T cells. Liver pharmacology was minimal as defined by histopathology. Conclusions: We report intra-tumoural and peripheral PD changes leading to an increase in the proliferative CD8+ T cell response following dosing with an anti-CD137/PD-L1 bispecific mAb2. These changes were dose dependent and coincident with tumour growth inhibition. In in vitro T cell activation assays the bispecific was superior to control antibodies and relevant combinations. Minimal liver pharmacology and no toxicity was observed with the anti-CD137/PD-L1 mAb2 unlike with other monoclonal antibodies targeting CD137. This warrants the development of a first-in-class anti-human CD137/PD-L1 bispecific antibody with a novel mode of action and improved therapeutic index for the treatment of human cancer. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Abstract 14882: Interpretable Machine Learning Identifies Risk Predictors in Patients With Heart Failure
Authors: William Zame, Jinsung Yoon, Folkert Asselbergs, Mihaela van der Schaar
Journal: Circulation (2018)

Introduction: Accurate identification of mortality risk and risk predictors is vital to optimize the management and treatment of patients with heart failure. Our goals were to predict risk of 1-yea...
Abstract 19261: The Mechanism and Predictive Value of QRS Shortening in Cardiac Resynchronization Therapy in Patients With Heart Failure
Authors: Ning Jiang, Anyu Zhou, Guangbin Shi, Hafiz Imran, Jharendra Rijal, Malcolm Kirk, David Donaldson, Michael Orlov, Antony Chu, Samuel C Dudley
Journal: Circulation (2017)

Introduction: Cardiac resynchronization therapy (CRT) improves systolic function and decreases arrhythmic events in heart failure (HF). HF is known to be associated with a reduction in Sarco/Endopl...
Abstract 17412: Practice Leadership, Quality Improvement and Use of Statins for Secondary Prevention of Atherosclerotic Cardiovascular Disease: The Heart Health NOW Study
Authors: Kamal Henderson, Jacquie Halladay, Darren Dewalt, Samuel Cykert
Journal: Circulation (2017)

Introduction: Primary care practice re-design through improving quality of care delivery for chronic disease management is at the forefront for improving cardiovascular care in the United States. E...
Abstract 14192: Iron Deficiency and Risk of One-year Adverse Events Following a Hospitalization for Acute Heart Failure
Authors: Hiroki Nakano, Toshiyuki Nagai, Michikazu Nakai, Kunihiro Nishimura, Varun Sundaram, Yasuyuki Honda, Satoshi Honda, Naotsugu Iwakami, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
Journal: Circulation (2017)

Backgrounds: Iron deficiency (ID) is commonly observed in chronic heart failure (HF) patients and is associated with worse clinical outcomes. While ID is a frequent finding in acute HF (AHF), its i...
Anti-MUC1 CAR-T cells combined with PD-1 knockout engineered T cells for patients with non-small cell lung cancer (NSCLC): A pilot study
Authors: S. Chen, Y. Lin, S. Zhong, H. An, Y. Lu, M. Yin, W. Liang, E.M. McGowan
Journal: Annals of Oncology (2018)

Background: Despite CAR-T cell therapy achieving remarkable results in the treatment of lymphoma, treatment of solid tumor using CAR-T remains an enormous challenge. It has been proposed that combinational immune-therapy may be a more efficacious approach to solid tumors. In this study, we combined anti-MUC1 CAR-T cell with PD-1 knockout (KO) T cells to treat advanced NSCLC. This represents the first attempt in the treatment of human solid cancer using PD-1 (KO) technology. Methods: Patients were recruited according to the criteria in NCT03525782. MUC1-specific CARs were constructed using the SM3 scFv. Following lenti-MUC1 CAR retroviral transduction, efficiency of transgenic expression was assessed by flow cytometry. PD-1 gene KO in the CAR positive T cells was achieved using the CRISPR-Cas9 system and validated by sequencing. MUC1-CAR+/PD-1- KO engineered T cells at a dose of 2.5x106/KG were infused over 60 mins. Following treatment, patients' general condition, levels of lymphocytes, IL-6, hs-CRP, PCT, CYFRA21, NSE(E), and SCC were monitored at regular intervals. Changes in tumor size were examined by MRI scans. Results: 8 patients (aged 36 to 84) diagnosed with NSCLC (IIIb to IV), were recruited for this study. Data from 6 patients are included in this report. All patients had significant symptom improvements in the first 2 weeks after infusion. Serum CYFRA 21 declined following infusion and subsequently increased 4 weeks after treatment. Changes in tumor size varied between patients. In 2/6 patients, lung tumor size shrunk significantly within 4 weeks after treatment (one reduced from 25x19x22mm to 14x10x26mm). The effect on metastasis was limited. No CRS was observed although cytokine levels increased in 3/6 patients. No other adverse effects were recorded in all patients. Conclusions: Our data suggests that combined MUC1-CAR+/PD-1-KO therapy is safe and well tolerated by all patients and importantly no CRS was indicated in all cases. The efficacy of the combined therapy was case specific: some NSCLC patients responded well, while no noticeable response observed in others. This marked individual patient response to treatment indicates that other unknown factors, confer more sensitivity in a sub-set of patients. Clinical trial identification: NCT03525782. Legal entity responsible for the study: Guangzhou Anjie Biomedical Technology Co. Ltd. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Abstract 11870: The -174 G>C Interleukin-6 Gene Polymorphism is Associated With Angiographic Progression of Non-culprit Coronary Plaques in a Mid-term Period
Authors: Nikolaos Anousakis-Vlachochristou, Dimitrios Klettas, Konstantinos Melidis, Zeta Azilazian, Maria Asimomiti, Antonios Karanasos, Anastasios Spanos, Eleftherios Tsiamis, Konstantinos Toutouzas, Petros Nihoyannopoulos, Dimitris Tousoulis
Journal: Circulation (2016)

Hypothesis: Inflammation is the key process underlying the course of CAD. Interleukin-6 (IL-6) is an upstream key regulator of inflammation. Single nucleotide polymorphisms (SNPs) of inflammatory g...
Assessment of Frequency and Reporting of Changes in Cancer Trial Design After Initiation of Patient Accrual
Authors: Daniel Shepshelovich, Ariadna Tibau, Consolación Molto, Hadar Goldvaser, Alberto Ocana, Bostjan Šeruga, Eitan Amir
Journal: JAMA Oncology (2018)

This study matches entries in ClinicalTrials.gov for cancer drug trials at initiation of the trial with later entries and with journal reports of the trials to assess modifications in trial design, external factors associated with such modifications, and transparency in reporting them.
P066 A Phase I Study of Apatinib Combined with Pemetrexed and Carboplatin in Untreated EGFR-Negative Stage IV Non-Squamous NSCLC
Authors: M. Huang, Y. Gong, J. Zhu, Y. Qin, F. Peng, L. Ren, Z. Ding, Y. Liu, Y. Wang, Y. Lu
Journal: Journal of Thoracic Oncology (2018)
Controversies in drug allergy: In vitro testing
Authors: Cristobalina Mayorga, Didier G. Ebo, David M. Lang, Werner J. Pichler, Vito Sabato, Miguel A. Park, Joanna Makowska, Marina Atanaskovic-Markovic, Patrizia Bonadonna, Edgardo Jares
Journal: Journal of Allergy and Clinical Immunology (2018)
Effective NY-ESO-1–specific MHC II–restricted T cell receptors from antigen-negative hosts enhance tumor regression
Authors: Lucia Poncette, Xiaojing Chen, Felix K.M. Lorenz, Thomas Blankenstein
Journal: Journal of Clinical Investigation (2018)

Adoptive transfer of T cell receptor–engineered (TCR-engineered) T cells is a promising approach in cancer therapy but needs improvement for more effective treatment of solid tumors. While most clinical approaches have focused on CD8+ T cells, the importance of CD4+ T cells in mediating tumor regression has become apparent. Regarding shared (self) tumor antigens, it is unclear whether the human CD4+ T cell repertoire has been shaped by tolerance mechanisms and lacks highly functional TCRs suitable for therapy. Here, TCRs against the tumor-associated antigen NY-ESO-1 were isolated either from human CD4+ T cells or from mice that express a diverse human TCR repertoire with HLA-DRA/DRB1*0401 restriction and are NY-ESO-1 negative. NY-ESO-1–reactive TCRs from the mice showed superior recognition of tumor cells and higher functional activity compared with TCRs from humans. We identified a candidate TCR, TCR-3598_2, which was expressed in CD4+ T cells and caused tumor regression in combination with NY-ESO-1–redirected CD8+ T cells in a mouse model of adoptive T cell therapy. These data suggest that MHC II–restricted TCRs against NY-ESO-1 from a nontolerant nonhuman host are of optimal affinity and that the combined use of MHC I– and II–restricted TCRs against NY-ESO-1 can make adoptive T cell therapy more effective.
THU0071 Muscle lipotoxicity on sarcopenia development in a model of collagen-induced arthritis
Authors: G. Vial, A. Pinel, D. Bechet, F. Wauquier, Y. Wittrant, C. Chevenet, M. Soubrier, A. Tournadre, F. Capel
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Alterations of body composition in Rheumatoid arthritis (RA) may contribute to the development of cardiometabolic disorders. RA patients have a decrease in muscle mass with a preserved or increased fat mass, notably accumulation of ectopic fat in the muscles, witch define the sarcopenic obesity. The mechanisms leading to this sarcopenic obesity phenotype remain poorly understood. Accumulation of intramuscular lipids and the formation of lipotoxic compounds may affect intracellular signalling pathways and energy production, alter protein synthesis and thus promote sarcopenia. <h3>Objectives</h3> Our objective was to determine if muscular lipotoxicity promotes the development of sarcopenia in joint inflammatory condition, using rats with collagen-induced arthritis. <h3>Methods</h3> Male Sprague Dawley rats were divided into a control group (CO, n=12) and a collagen-induced arthritis group (CIA, n=11). After 5 weeks, hind leg muscles and epididymal adipose tissue were removed. Tissues were weighed at sacrifice and stored for histological analyses and evaluation of mitochondrial function, lipotoxicity, protein and gene expression levels. Statistical analyses were performed with t-test. <h3>Results</h3> Animals, adipose tissue and muscle weights tended to be lower in the CIA group. Only EDL muscle weight was significantly lower in the CIA group (p=0.05). Muscle histological analyses showed larger CSA (cross sectional area) in CO group. In the CIA group we observed a nonhomogeneous distribution of muscle fibre CSA with a predominance of small fibres (figure 1). Mean perimeter and mean diameter were also significantly decrease in CIA group but the shape of fibres remained similar between groups. Furthermore, there was an increased expression of MAFBx (a marker of catabolism) mRNA (40%, p=0.04) in the CIA group, while MyoD (a myogenesis marker) mRNA was decreased by 18% (p=0.01), indicating a catabolic state. Lipid content analysis showed an accumulation of intramuscular TAG (x 1.5, p=0.05), as well as an increased expression of cellular fatty acid transporter FATP1 (about 35%, p=0.01) and mitochondrial fatty acid transporter CPT1b (about 27%, p=0.02). Mitochondrial DNA copy number was decreased by 27% in CIA rats (p=0.01) and complex IV activity of mitochondrial respiratory chain also tended to be reduced in CIA group (−20%, p=0.18). <h3>Conclusions</h3> Collagen-induced arthritis induced fibres alterations in skeletal muscle. The association of increased muscle protein catabolism, mitochondrial dysfunction and fatty acid accumulation in skeletal muscle of animals with arthritis supports the hypothesis that lipotoxicity is involved in sarcopenia development during joint inflammation. <h3>Disclosure of Interest</h3> None declared
Second Attempt of TKI Discontinuation with Dasatinib for Treatment-Free Remission after Failing First Attempt with Imatinib: Treatment-Free Remission Accomplished By Dasatinib (TRAD) Trial
Authors: Dennis Dong Hwan Kim, Lambert Busque, Donna L. Forrest, Lynn Savoie, Isabelle Bence-Bruckler, Stephen Couban, Robert Delage, Anargyros Xenocostas, Elena Liew, Pierre Laneuville, Kristjan Paulson, Jeffrey H. Lipton, Suzanne Kamel-Reid, Brian Leber
Journal: Blood (2018)
Genetic classification of grade 3 and grade 4 astrocytoma with DNA microarrays
Authors: Anjan Misra, Janice Nigro, Ivan Smirnov, Edward Pan, Sherwin Kamkar, Scott Vandenberg, Kathleen Lamborn, Ken Aldape, Burt G. Feuerstein
Journal: Cancer Research (2004)

1673  We used a DNA microarray to map DNA copy number aberrations at high resolution in >50 grade 3 and >100 grade 4 primary human astrocytomas. The BAC array detects DNA copy number changes at ∼1.4Mb average resolution. We analyzed the data with unsupervised clustering to visualize possible genetic subgroups and supervised clustering methods (Significance Analysis of Microarrays (SAM), shrunken centroid analysis (PAM), linear discriminant analysis) to distinguish between histological tumor grades and between different genetic groups within a tumor grade. Along with previously known amplifications and homozygous deletions, the arrays identified candidate amplifications on chromosomes 1, 2, 3, 4, 7, 9, 10, 11, 12, 14, 15, and 17; candidate homozygous deletions on chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 22. Unsupervised cluster analysis of the cases suggests there are at least two groups of grade 3 and three groups of grade 4 astrocytomas; one group of grade 4 astrocytomas clusters better with grade 3 than with grade 4 tumors. Supervised cluster analyses suggest that grade 3 and grade 4 astrocytomas can be genetically distinguished. PAM analysis suggests that 30 BAC clones located on chromosomes 7 and 10 correctly classify over 80% of tumors into histological grade 3 and grade 4 astrocytoma. Linear discriminant analysis using the top ranked 25 of these clones improved correct classification to 92%. In a random subset of grade 4 astrocytomas, gain of chromosome 7 and loss on chromosome 10 are associated with average/short term grade 4 survivors. We are studying these regions in further detail and validating our results in a second set of tumors.This work was supported by NIH (NS42927 and CA85799) and the National Brain Tumor Foundation