tbuckley/cabot-search huggingface dataset:
AB0243 THE SHORT DISEASE DURATION IS ASSOCIATED WITH WORSE MOOD DISORDER IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Y. Geng, T. Gao, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) is commonly associated with mood disorders, especially depression and anxiety. But the status of mood disorders in RA patients with different courses is unknown. Objectives: The aims of this study were to investigate the frequencies of depression and anxiety in patients with early RA and non-early RA, and further to identify the risk factors for mood disorders. Methods: Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were applied to all enrolled RA patients to assess their corresponding status of anxiety and depression. Besides clinical assessment, power Doppler and grey-scale ultrasound of 22 joints were also performed. The status of mood disorder was studied in early RA patients compared to non-early RA patients. Multivariate regression was used to identify the risk factor for mood disorders. Results: 201 RA patients were enrolled, with 76 early RA (disease duration ≤ 2 years) and 125 non-early RA (disease duration &gt; 2 years) patients. Mood disorder (depression and/or anxiety) was found in 20.9% (42/201) patients. Depression was more often observed in early RA patients than non-early RA patients (26.3% vs. 14.4%, P =0.036). The similar trend for anxiety was observed also in early RA patients compared to non-early RA patients, although the difference was insignificant (13.2% vs. 5.6%, P =0.062). Multivariate logistic regression analysis showed that disease duration (OR 0.991 [95% CI 0.985-0.998]), rheumatoid factor concentration (OR 2.697 [95% CI 1.165-6.241]), Health Assessment Questionnaire Disability Index (HAQ-DI) (OR 1.045 [95% CI 1.001-1.091]) and grey-scale synovitis score (GS score) (OR 1.092 [95% CI 1.032-1.156]) were independent risk factors for predicting depression in RA. Disease duration (OR 0.983 [95% CI 0.970-0.997]), HAQ-DI (OR 1.069 [95% CI 1.002-1.141]) and GS score (OR 1.073 [95% CI 1.005-1.141]) were independent risk factors for predicting anxiety in RA patients. Conclusion: Mood disorders were almost doubled in frequency in early RA patients than non-early RA patients. RA Patients with short disease duration, high HAQ-DI and high GS score were more likely to be in depression and anxiety. More attention is needed to the psychological status of RA patients, especially those at an early stage, with poor physical function and severe synovitis. References: [1]Sturgeon JA, Finan PH, Zautra AJ. Affective disturbance in rheumatoid arthritis: psychological and disease-related pathways. Nat Rev Rheumatol 2016;12(9):532-42. [2]Bacconnier L, Rincheval N, Flipo RM, et al. Psychological distress over time in early rheumatoid arthritis: results from a longitudinal study in an early arthritis cohort. Rheumatology (Oxford) 2015; 54(3): 520-7. Acknowledgments: The authors thank all the colleagues in our department. Disclosure of Interests: None declared
Artificial intelligence-based diagnostic system classifying gastric cancers and ulcers: comparison between the original and newly developed systems
Authors: Ken Namikawa, Toshiaki Hirasawa, Kaoru Nakano, Yohei Ikenoyama, Mitsuaki Ishioka, Sho Shiroma, Yoshitaka Tokai, Shoichi Yoshimizu, Yusuke Horiuchi, Akiyoshi Ishiyama, Toshiyuki Yoshio, Tomohiro Tsuchida, Junko Fujisaki, Tomohiro Tada
Journal: Endoscopy (2020)

Abstract Background We previously reported for the first time the usefulness of artificial intelligence (AI) systems in detecting gastric cancers. However, the “original convolutional neural network (O-CNN)” employed in the previous study had a relatively low positive predictive value (PPV). Therefore, we aimed to develop an advanced AI-based diagnostic system and evaluate its applicability for the classification of gastric cancers and gastric ulcers. Methods We constructed an “advanced CNN” (A-CNN) by adding a new training dataset (4453 gastric ulcer images from 1172 lesions) to the O-CNN, which had been trained using 13 584 gastric cancer and 373 gastric ulcer images. The diagnostic performance of the A-CNN in terms of classifying gastric cancers and ulcers was retrospectively evaluated using an independent validation dataset (739 images from 100 early gastric cancers and 720 images from 120 gastric ulcers) and compared with that of the O-CNN by estimating the overall classification accuracy. Results The sensitivity, specificity, and PPV of the A-CNN in classifying gastric cancer at the lesion level were 99.0 % (95 % confidence interval [CI] 94.6 %−100 %), 93.3 % (95 %CI 87.3 %−97.1 %), and 92.5 % (95 %CI 85.8 %−96.7 %), respectively, and for classifying gastric ulcers were 93.3 % (95 %CI 87.3 %−97.1 %), 99.0 % (95 %CI 94.6 %−100 %), and 99.1 % (95 %CI 95.2 %−100 %), respectively. At the lesion level, the overall accuracies of the O- and A-CNN for classifying gastric cancers and gastric ulcers were 45.9 % (gastric cancers 100 %, gastric ulcers 0.8 %) and 95.9 % (gastric cancers 99.0 %, gastric ulcers 93.3 %), respectively. Conclusion The newly developed AI-based diagnostic system can effectively classify gastric cancers and gastric ulcers.
Innate lymphoid cells in isocyanate-induced asthma: role of microRNA-155
Authors: Evy E. Blomme, Sharen Provoost, Erica Bazzan, Hannelore P. Van Eeckhoutte, Mirjam P. Roffel, Lore Pollaris, Annelies Bontinck, Matteo Bonato, Louise Vandenbroucke, Fien Verhamme, Guy F. Joos, Manuel G. Cosio, Jeroen A. J. Vanoirbeek, Guy G. Brusselle, Marina Saetta, Tania Maes
Journal: European Respiratory Journal (2020)

Background Occupational asthma, induced by workplace exposures to low molecular weight agents such as toluene 2,4-diisocyanate (TDI), causes a significant burden to patients and society. Little is known about innate lymphoid cells (ILCs) in TDI-induced asthma. A critical regulator of ILC function is microRNA-155, a microRNA associated with asthma. Objective To determine whether TDI exposure modifies the number of ILCs in the lung and whether microRNA-155 contributes to TDI-induced airway inflammation and hyperresponsiveness. Methods C57BL/6 wild-type and microRNA-155 knockout mice were sensitised and challenged with TDI or vehicle. Intracellular cytokine expression in ILCs and T-cells was evaluated in bronchoalveolar lavage (BAL) fluid using flow cytometry. Peribronchial eosinophilia and goblet cells were evaluated on lung tissue, and airway hyperresponsiveness was measured using the forced oscillation technique. Putative type 2 ILCs (ILC2) were identified in bronchial biopsies of subjects with TDI-induced occupational asthma using immunohistochemistry. Human bronchial epithelial cells were exposed to TDI or vehicle. Results TDI-exposed mice had higher numbers of airway goblet cells, BAL eosinophils, CD4 + T-cells and ILCs, with a predominant type 2 response, and tended to have airway hyperresponsiveness. In TDI-exposed microRNA-155 knockout mice, inflammation and airway hyperresponsiveness were attenuated. TDI exposure induced IL-33 expression in human bronchial epithelial cells and in murine lungs, which was microRNA-155 dependent in mice. GATA3 + CD3 − cells, presumably ILC2, were present in bronchial biopsies. Conclusion TDI exposure is associated with increased numbers of ILCs. The proinflammatory microRNA-155 is crucial in a murine model of TDI asthma, suggesting its involvement in the pathogenesis of occupational asthma due to low molecular weight agents.
AB0130 SERUM ATHEROGENICITY IN WOMEN WITH UNTREATED SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: H. Gerasimova, T. Popkova, D. Gerasimova, I. Sobenin, A. Lila
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic lupus erythematosus (SLE) is associated with an unexplained increase cardiovascular risk. The nature of the factors that contribute to progression of atherosclerosis were identified using the method for determining the atherogenicity of blood serum in cell culture in cell culture (in vitro). The term “atherogenicity” is meant as the ability of the serum and/or its components to induce intracellular accumulation of cholesterol in cultured cells. Objectives: To compare atherogenicity of blood serum in women with untreated SLE and healthy women. Methods: Thirty seven women (median age 30[21;39] years) with active SLE (median disease duration 45[3;102] months; SLADAI 17 [8;34]) were enrolled in the study. Lupus nephritis are defined in 15 (41%), Antiphospholipid syndrome (APS) – in 8 (22%) of 37 SLE patients (pts). The control group consisted of 30 women, median age 31[25;39] years. Atherogenicity of blood serum was determined in the culture of murine macrophages. Peritoneal macrophages were isolated from the ascitic fluid of the line mice according to the generally accepted method J. Goldstein et al (1979y). Serum atherogenicity was determined by the accumulation of intracellular cholesterol induced by 10% of the blood serum of the patients, and expressed as a percentage of the content of cholesterol in the control cells. Results: Elevated atherogenicity of blood serum was detected more frequently in SLE pts (24/72 (65%) vs healthy controls (5/30 (17%), p&lt;0,01). The blood serum of SLE pts caused a 3-7-fold accumulation of intracellular cholesterol, which significantly differed from healthy women (203±136% vs 127±42%, p&lt;0,001). The ability to stimulate the accumulation of cholesterol esters in murine macrophages was not associated with age, duration of the disease, lipid spectrum and was the highest in pts with nephritis (305±141% vs 180±52%, p&lt;0,05) and APS (253±130% vs 119±75%, p&lt;0,05). Conclusion: Serums of women with untreated SLE may stimulate the accumulation of cholesterol in mouse macrophages unlike of healthy women. The highest atherogenicity was found in blood serum of SLE pts with nephritis and APS. Disclosure of Interests: None declared
Modulating the function of ABCB1: <i>in vitro</i> and <i>in vivo</i> characterization of sitravatinib, a tyrosine kinase inhibitor
Authors: Yuqi Yang, Ning Ji, Chao‐Yun Cai, Jing‐Quan Wang, Zi‐Ning Lei, Qiu‐Xu Teng, Zhuo‐Xun Wu, Qingbin Cui, Yihang Pan, Zhe‐Sheng Chen
Journal: Cancer Communications (2020)

Abstract Background Overexpression of ATP‐binding cassette (ABC) transporter is a major contributor to multidrug resistance (MDR), in which cancer cells acquire resistance to a wide spectrum of chemotherapeutic drugs. In this work, we evaluated the sensitizing effect of sitravatinib, a broad‐spectrum tyrosine kinase inhibitor (TKI), on ATP‐binding cassette subfamily B member 1 (ABCB1)‐ and ATP‐binding cassette subfamily C member 10 (ABCC10)‐mediated MDR. Methods MTT assay was conducted to examine cytotoxicity and evaluate the sensitizing effect of sitravatinib at non‐toxic concentrations. Tritium‐labeled paclitaxel transportation, Western blotting, immunofluorescence analysis, and ATPase assay were carried out to elucidate the mechanism of sitravatinib‐induced chemosensitization. The in vitro findings were translated into preclinical evaluation with the establishment of xenograft models. Results Sitravatinib considerably reversed MDR mediated by ABCB1 and partially antagonized ABCC10‐mediated MDR. Our in silico docking simulation analysis indicated that sitravatinib strongly and stably bound to the transmembrane domain of ABCB1 human‐mouse chimeric model. Furthermore, sitravatinib inhibited hydrolysis of ATP and synchronously decreased the efflux function of ABCB1. Thus, sitravatinib could considerably enhance the intracellular concentration of anticancer drugs. Interestingly, no significant alterations of both expression level and localization of ABCB1 were observed. More importantly, sitravatinib could remarkably restore the antitumor activity of vincristine in ABCB1‐mediated xenograft model without observable toxic effect. Conclusions The findings in this study suggest that the combination of sitrvatinib and substrate antineoplastic drugs of ABCB1 could attenuate the MDR mediated by the overexpression of ABCB1.
Inhaled Isotonic Saline for Bronchiolitis
Authors: Clement L. Ren
Journal: JAMA Pediatrics (2020)

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Early administered antibiotics do not impact mortality in critically ill patients with COVID-19.
Authors: Niccolò Buetti, Timothy Mazzuchelli, Elia Lo Priore, Carlo Balmelli, Michael Llamas, Micol Pallanza, Luigia Elzi, Vera Consonni, Pierpaolo Trimboli, Valentina Forni-Ogna, Enos Bernasconi
Journal: Journal of Infection (2020)
Letter by Coscia et al Regarding Article, “High-Sensitivity Cardiac Troponin and the Universal Definition of Myocardial Infarction”
Authors: Tania Coscia, Thomas Nestelberger, Christian Mueller
Journal: Circulation (2020)

We congratulate Chapman and colleagues 1 for their highly relevant study showing important information on the effect of implementing a high-sensitivity cardiac troponin I assay and the recommendations of the Fourth Universal Definition of Myocardial Infarction (MI) 2 on the investigation, treatment, and outcomes of patients.We would like to ask the authors to provide additional information that will help to better put their findings into perspective.First, please report the median time and interquartile range between the first and second measurement of high-sensitivity cardiac troponin I with information on which absolute or relative concentration change was chosen to qualify for MI.Second, please clarify how the number of patients with type 1 or 2 MI could decrease after the implementation of the Fourth Universal Definition of MI instead of the third definition used during the study enrollment (Figure I in the Data Supplement).Third, please clarify the low rate of coronary angiography (59%) and percutaneous coronary intervention (41%) in the type 1 MI group. 2 Fourth, for many readers, it would be very interesting to know the percentage of type 2 MI with a previously known or new diagnosis of coronary artery disease because this has been found to substantially affect the outcome of type 2 MI. 3,4Fifth, please report the percentage of patients with dual antiplatelet therapy at hospital discharge.Finally, it would be interesting to know the percentage of patients with non-ST-segment-elevation MI or ST-segment-elevation MI in the different groups.
Risky Business: lessons from covid-19
Authors: Mun-Keat Looi, Rebecca Coombes
Journal: BMJ (2020)

Clinical professionals are at the forefront of learning and innovation about, and sparked by, the pandemic. <b>Mun-Keat Looi</b> and <b>Rebecca Coombes</b> report from the first virtual Risky Business conference, held on 2 June
Avelumab in patients with gestational trophoblastic tumors resistant to monochemotherapy: Final outcomes of TROPHIMMUN phase II trial, cohort A.
Authors: Benoit You, Pierre-Adrien Bolze, Jean-Pierre Lotz, Jerome Massardier, Laurence Gladieff, Florence Joly, Touria Hajri, Delphine Maucort-Boulch, Sylvie Bin, Pascal Rousset, Laurent Villeneuve, Adeline Roux, Marine Alves-Ferreira, Daniele Grazziotin, Catherine Mercier, Gilles Freyer, Francois Golfier
Journal: Journal of Clinical Oncology (2020)

LBA6008 Background: Patients with gestational trophoblastic tumors (GTT) resistant to monochemotherapy are treated with historic chemotherapy regimens known to be effective, but toxic. PD-L1 is constitutively expressed in all GTT subtypes (Bolze et al. Int J Gynecol Cancer 2017). HLA-G and natural killer (NK) cells are involved in GTT immune-surveillance. The anti-PD-L1 monoclonal antibody avelumab (Pfizer &amp; Merck KGaA) triggers cytotoxicity through NK cells. The objective of TROPHIMMUN trial was to assess the efficacy of avelumab in patients with chemoresistant GTT. Methods: In the cohort A of this academic multicenter trial (NCT03135769), avelumab was given at 10 mg/kg Q2W in patients with GTT resistant to monochemotherapy. Avelumab was prescribed until hCG normalization, and then for 3 consolidation cycles. The primary objective was the rate of patients with hCG normalization, with a 2 step Simon design. Results: 15 patients (median 34 y old) followed by the French Gestational Trophoblastic Center were treated from Dec 2016 to Sept 2019 (stage I/III: 53%/47%; FIGO score 0-4: 33%; score 5-6: 47%; score &gt;6: 20%). They all had progressed with previous methotrexate, and 1 patient with actinomycin-D. They received median 8 avelumab cycles (range: 2-11). The tolerability was favorable. 93 % of patients developed drug-related grade 1-2 toxicities (86% grade 1), mainly including fatigue (33% patients); nausea-vomiting (33%); infusion-related reactions (27%); thyroid disorder (20%); dry eyes (20%) &amp; diarrhea (20%). A grade 3 uterus bleeding (treatment unrelated) was observed in 1 patient. Median follow-up was 30 months. Successful hCG normalizations were obtained in 8 patients (53%, median 9 avelumab cycles), either during avelumab treatment in 7 patients, or after avelumab discontinuation in 1 patient. None presented relapse afterwards, and 1 patient had a subsequent healthy pregnancy. Avelumab resistances requiring switch to chemotherapy were observed in 7 patients (47%), who normalized hCG with subsequent actinomycin-D (42%), or surgery/polychemotherapy (57%). The likelihood of success with avelumab was not related to the FIGO score, or disease stages. Conclusions: TROPHIMMUN is the first trial of immunotherapy in GTT patients. The anti-PD-L1 monoclonal antibody avelumab was effective, with a favorable safety profile compared to chemotherapy, in patients with resistance to mono-chemotherapy. About 50 % patients could be cured of their chemoresistant diseases. Avelumab may be a new therapeutic option. Clinical trial information: NCT03135769 .
Abstract IA19: Role of autophagy in cancer metabolism
Authors: Eileen P. White
Journal: Cancer Research (2020)

Abstract Autophagy captures intracellular components and delivers them to lysosomes, where they are degraded and recycled to sustain metabolism and enable survival in starvation. Acute, whole-body deletion of the essential autophagy gene Atg7 in adult mice causes a systemic metabolic defect manifested by starvation intolerance and gradual loss of white adipose tissue, liver glycogen, and muscle mass. Cancer cells benefit from autophagy as deletion of essential autophagy genes impairs spontaneous tumor growth in autochthonous cancer models. Tumor cell autonomous autophagy is required to recycle macromolecules to sustain mitochondrial substrate supply and thereby energy and nucleotide pools essential for survival during nutrient limitation. In addition to promoting tumor cell survival, autophagy in the host also promotes tumorigenesis. Host-specific Atg7 or Atg5 deletion impairs growth of multiple different allografted tumors, by preventing the release of Arginase 1 from hepatocytes. Arginase 1 degrades circulating arginine that is essential for the growth of tumors, most of which are auxotrophic for arginine. Thus, autophagy sustains both tumor cell and host metabolism to enable tumor growth. In tumors with a high neoantigen load that can be recognized and killed by T cells, autophagy suppresses an antitumor T-cell response. Autophagy prevents tumor killing by T cells by suppressing production of interferon gamma in a T cell-dependent manner. Thus, autophagy promotes tumorigenesis by promoting intrinsic and extrinsic tumor metabolism and by suppressing the ability of the immune system to eliminate tumors. This suggests that autophagy inhibitors may be especially useful for cancer therapy when combined with immunotherapy. To better understand the toxicity of autophagy inhibition to normal tissues, we have examined the functional consequence of conditional Atg7 or Atg5 deletion in adult mice. Whereas Atg7 deletion causes neurodegeneration in 2-3 months, Atg5 deletion causes very specific loss of telocytes and stem cells in the ileum part of the intestine and rapid death due to a more abrupt loss of autophagy function. This indicates that there is a difference in the sensitivity of cell types and tissues to the loss of autophagy and that there are discrete functional dependencies on different ATGs. Citation Format: Eileen P. White. Role of autophagy in cancer metabolism [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA19.