tbuckley/cabot-search huggingface dataset:
Effects of Protein Source on Liposome Uptake by Cells: Corona Composition and Impact of the Excess Free Proteins
Authors: Keni Yang, Catharina Reker‐Smit, Marc C. A. Stuart, Anna Salvati
Journal: Advanced Healthcare Materials (2021)

Abstract Corona formation in biological fluids strongly affects nanomedicine interactions with cells. However, relatively less is known on additional effects from the free proteins in solution. Within this context, this study aims to gain a better understanding of nanomaterial–cell interactions in different biological fluids and, more specifically, to disentangle effects due to corona composition and those from the free proteins in solution. To this aim, the uptake of liposomes in medium with bovine and human serum are compared. Uptake efficiency in the two media differs strongly, as also corona composition. However, in contrast with similar studies on other nanomaterials, despite the very different corona, when the two corona‐coated liposomes are exposed to cells in serum free medium, their uptake is comparable. Thus, in this case, the observed differences in uptake depend primarily on the presence and source of the free proteins. Similar results are obtained when testing the liposomes on different human cells, as well as in murine cells and in the presence of murine serum. Overall, these results show that the protein source affects nanomedicine uptake not only due to effects on corona composition, but also due to the presence and composition of the free proteins in solution.
POS0851 IDENTIFICATION OF HUB GENES AND PATHWAYS IN DERMATOMYOSITIS BY BIOINFORMATICS ANALYSIS
Authors: C. Zheng, S. X. Zhang, R. Zhao, L. Cheng, T. Kong, X. Sun, S. Feng, Q. Wang, X. Li, Q. Yu, P. F. He
Journal: Annals of the Rheumatic Diseases (2021)

Background: Dermatomyositis (DM) is a chronic systemic autoimmune disease characterized by inflammatory infiltrates in the skin and muscle 1 . The genes and pathways in the inflamed myopathies in patients with DM are poorly understood 2 . Objectives: To identify the key genes and pathways associated with DM and further discover its pathogenesis. Methods: Muscle tissue gene expression profile (GSE143323) were acquired from the GEO database, which included 39 DM samples and 20 normal samples. The differentially expressed genes (DEGs) in DM muscle tissue were screened by adopting the R software. Gene ontology (GO) and Kyoto Encyclopedia of Genome (KEGG) pathway enrichment analysis was performed by Metascape online analysis tool. A protein-protein interaction (PPI) network was then constructed by STRING software using the genes in significantly different pathways. Network of DEGs was analyzed by Cytoscape software. And degree of nodes was used to screen key genes. Results: Totally, 126 DEGs were obtained, which contained 122 up-regulated and 4 down-regulated. GO analysis revealed that most of the DEGs were significantly enriched in type I interferon signaling pathway, response to interferon-gamma, collagen-containing extracellular matrix, response to interferon-alpha and bacterium, positive regulation of cell death, leukocyte chemotaxis. KEGG pathway analysis showed that upregulated DEGs enhanced pathways associated with the hepatitis C, complement and coagulation cascades, p53 signaling pathway, RIG-I-like receptor signaling, Osteoclast differentiation, and AGE-RAGE signaling pathway. Ten hub genes were identified in DM, they were ISG15, IRF7, STAT1, MX1, OASL, OAS2, OAS1, OAS3, GBP1, and IRF9 according to the Cytoscape software and cytoHubba plugin. Conclusion: The findings from this bioinformatics network analysis study identified the key hub genes that might provide new molecular markers for its diagnosis and treatment. References: [1]Olazagasti JM, Niewold TB, Reed AM. Immunological biomarkers in dermatomyositis. Curr Rheumatol Rep 2015;17(11):68. doi: 10.1007/s11926-015-0543-y [published Online First: 2015/09/26]. [2]Chen LY, Cui ZL, Hua FC, et al. Bioinformatics analysis of gene expression profiles of dermatomyositis. Mol Med Rep 2016;14(4):3785-90. doi: 10.3892/mmr.2016.5703 [published Online First: 2016/09/08]. [3]Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10(1):1523. doi: 10.1038/s41467-019-09234-6 [published Online First: 2019/04/05]. Acknowledgements: This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078). Disclosure of Interests: None declared
AB0703 THE COURSE OF COVID-19 INFECTION IN PATIENTS WITH ARTHRITIS RECEIVING TARGETED DMARDS
Authors: E. Koltsova, G. Lukina, E. Shmidt, K. Lytkina, E. Rozochkina, E. Zhilyaev
Journal: Annals of the Rheumatic Diseases (2021)

Background: WHO declared the COVID-19 outbreak as a pandemic on March 12th, 2020. Assessing the risk of severe course in patients with rheumatic diseases, especially those who receive targeted immunosuppressive treatment, is an urgent problem for rheumatologists. Objectives: determine the relationship between used targeted biologic and synthetic DMARDs (tDMARDs) and the severity of course of COVID-19 infection. Methods: The analysis included the data of patients with chronic arthritis and COVID-19, used tDMARDs. COVID-19 infection was confirm by serology tests or immune system molecules (immunoglobulins/antibodies). The presence of symptoms, the need for hospitalization, and the need for oxygen therapy were considered as indicators of the severity of the infection. We also analyzed the spread of the lung involvement according to CT data, symptoms during the disease (fever, cough, anosmia, diarrhea). Results: Analyses included 78 patients, among them 32 patients has ankylosing spondylitis, 31 patients - rheumatoid arthritis, 12 patients has psoriatic arthritis, 3 patients - juvenile arthritis. The average age of the included patients was 51,8 ± 11,69. Most of patients used TNF inhibitors - 43 (Adalimumab -10, Golimumab -4, Infliximab – 4, Certolizumab pegol -3, Etanercept – 22), JAK inhibitor tofacitinib used 13 patients, 5 patients each was treated with Abatacept and Tocilizumab, 3 patients used Rituximab and 2 patients each used Netakimab and Ustekinumab (Table 1). None of the patients included in the analysis required treatment in the ICU and/or mechanical ventilation. The course of the disease in patients treated with tDMARDs did not seem to be more severe than in 5 patients with arthritis who stopped treatment with tDMARDs before the onset of the pandemic. There was a direct correlation between the severity of the infection and the age of the patients (p=0.007). There were no significant differences in the severity of the infection depending on the drug, including when adjusting for age. Conclusion: COVID-19 does not look extremely dangerous in patients with rheumatic diseases, used target DMARDs. Used of tsDMARDs doesn’t reliably increase the risk of COVID-19 severity. There is reliable correlation between age and COVID-19 severity. Table 1. Cohort characteristics Drugs Mean age Number of patients Patients with symptoms Hospitalized patients Asymptomatic course Adalimumab 41,0±11,4 10 9 2 1 Golimumab 51,0±11,03 4 4 0 0 Infliximab 42,7±11,8 4 0 0 4 Certolizumab 41,6±11,7 3 3 0 0 Etanercept 50,7±11,4 22 20 6 2 Tofacitinib 56,8±10,4 13 12 2 1 Abatacept 57,4±10,9 5 4 1 1 Tocilizumab 48,8±10.9 5 3 1 2 Rituximab 55,6±10,7 3 3 1 0 Netakimab 44,0±15,8 2 2 1 0 Ustekinumab 48,0±10,5 2 1 0 1 Disclosure of Interests: None declared
Effect of Opt-In vs Opt-Out Framing on Enrollment in a COVID-19 Surveillance Testing Program
Authors: Allison H. Oakes, Jonathan A. Epstein, Arupa Ganguly, Sae-Hwan Park, Chalanda N. Evans, Mitesh S. Patel
Journal: JAMA Network Open (2021)

This randomized clinical trial examines the effect of an opt-out recruitment strategy vs a conventional opt-in strategy on enrollment and initial adherence to a COVID-19 surveillance testing program.
POS0340 VASCULAR IMAGING IN PATIENTS WITH REFRACTORY TAKAYASU ARTERITIS TREATED WITH TOCILIZUMAB: ANALYSIS FROM A RANDOMIZED CONTROLLED TRIAL
Authors: Y. Nakaoka, M. Yanagawa, A. Hata, K. Yamashita, N. Okada, S. Yamakido, H. Hayashi, D. Jayne
Journal: Annals of the Rheumatic Diseases (2021)

Background: In the TAKT study, a randomized controlled trial of tocilizumab (TCZ) in patients with refractory Takayasu arteritis (TAK) in Japan, the primary end point of time to relapse after induction of remission with glucocorticoid (GC) treatment showed a trend favoring TCZ over placebo (hazard ratio 0.41 [95.41% confidence interval, 0.15-1.10; p =0.0596]), 1 but the double-blind period was too short for imaging evaluation. Objectives: To independently evaluate vascular imaging in a post hoc analysis of radiographs from the TAKT study. Methods: Computed tomography images from patients in the TAKT study were evaluated by three independent radiologists who were not involved in the original trial. Patients who received TCZ and had computed tomography images available (n=28) were included. Assessments were made in 22 arteries for the change from baseline in wall thickness (primary end point), dilatation/aneurysm, stenosis/occlusion, or wall enhancement for at least 96 weeks after the start of tocilizumab treatment. Patient-level assessments were also conducted. Results: Among 28 patients who received at least one dose of TCZ and for whom images were available, 86.7% of 22 arteries had improved/stable (no progression) wall thickness at week 96. The proportions of patients with no progressed, partially progressed, or newly progressed lesions were 57.1%, 10.7%, and 28.6% for wall thickness, and the proportions without progressed lesions were 92.9% for dilatation/aneurysm and 85.7% for stenosis/occlusion (Figure 1). Patients with newly progressed lesions, reflecting more refractory disease, were receiving glucocorticoid doses that could not be reduced below 0.1 mg/kg/day at week 96. Conclusion: Approximately 60% of patients with TAK treated with tocilizumab did not experience progression in wall thickness. Few patients experienced progressive dilatation/aneurysm or stenosis/occlusion. Wall thickness progression likely resulted from refractory TAK. Patients who experience this should be monitored regularly by imaging, and additional glucocorticoid or immunosuppressive treatment should be considered to avoid vascular progression. References: [1]Nakaoka Y et al. Ann Rheum Dis. 2018;77:348-354. Disclosure of Interests: Yoshikazu Nakaoka Consultant of: Roche/Genentech, Grant/research support from: Roche/Genentech, Masahiro Yanagawa Consultant of: Roche/Genentech, Akinori Hata Consultant of: Roche/Genentech, Katsuhisa Yamashita Employee of: Chugai Pharmaceutical Co., Ltd., Norihiro Okada Employee of: Chugai Pharmaceutical Co., Ltd., Shinji Yamakido Employee of: Chugai Pharmaceutical Co., Ltd., Hiromitsu Hayashi Consultant of: Roche/Genentech, David Jayne Consultant of: Roche/Genentech, Grant/research support from: Roche/Genentech
The European Association of Urology COVID Intermediate-priority Group is Poorly Predictive of Pathological High Risk Among Patients with Renal Tumours
Authors: Pranav Satish, Teele Kuusk, Nick Campain, Yasmin Abu-Ghanem, Joana Neves, Ravi Barod, Soha El-Sheikh, Faiz Mumtaz, Prasad Patki, Maxine Tran, My-Anh Tran-Dang, Lee Grant, Tobias Klatte, Axel Bex
Journal: European Urology (2021)
Dynamic regulation of B cell complement signaling is integral to germinal center responses
Authors: Arun Cumpelik, David Heja, Yuan Hu, Gabriele Varano, Farideh Ordikhani, Mark P. Roberto, Zhengxiang He, Dirk Homann, Sergio A. Lira, David Dominguez-Sola, Peter S. Heeger
Journal: Nature Immunology (2021)
FDA Approval Summary: Pembrolizumab for the Treatment of Tumor Mutational Burden–High Solid Tumors
Authors: Leigh Marcus, Lola A. Fashoyin-Aje, Martha Donoghue, Mengdie Yuan, Lisa Rodriguez, Pamela S. Gallagher, Reena Philip, Soma Ghosh, Marc R. Theoret, Julia A. Beaver, Richard Pazdur, Steven J. Lemery
Journal: Clinical Cancer Research (2021)

Abstract The FDA approved pembrolizumab on June 16, 2020, for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden–high [TMB-H; ≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. FDA granted the approval based on a clinically important overall response rate (29%; 95% confidence interval, 21–39) and duration of response (57% of responses lasting ≥ 12 months) in the subset of patients with TMB-H solid tumors (n = 102) spanning nine different tumor types enrolled in a multicenter single-arm trial (KEYNOTE-158). The efficacy of pembrolizumab was supported by the results of whole-exome sequencing (WES) analyses of TMB in additional patients enrolled across multiple pembrolizumab clinical trials, and a scientific understanding of the effects of PD-1 inhibition. Overall, the adverse event profile of pembrolizumab was similar to the adverse event profile observed in prior trials that supported the approval of pembrolizumab in other indications. This approval of pembrolizumab is the first time that the FDA has approved a cancer treatment for an indication based on TMB, and the fourth based on the presence of a biomarker rather than the primary site of origin.
AB0466 RETENTION RATE AND EFFECTIVENESS OF SECUKINUMAB VERSUS TNF INHIBITOR SWITCHING IN ANKYLOSING SPONDYLITIS PATIENTS WITH A HISTORY OF TNF INHIBITOR TREATMENT: DATA FROM A KOREAN NATIONWIDE REGISTRY
Authors: H. K. Min, K. Y. Kang
Journal: Annals of the Rheumatic Diseases (2021)

Background: The choice of second-line biologics for ankylosing spondylitis (AS) patients previously treated with a tumour necrosis factor inhibitor (TNFi) remains unclear Objectives: Here, we compared drug retention and clinical efficacy between AS patients who switched biologics to secukinumab and those who switched to a different TNFi. Methods: AS patients enrolled in the Korean College of Rheumatology BIOlogics registry were included. Patients with previous TNFi exposure were divided into the secukinumab group and the TNFi switching group. Drug retention and clinical efficacy (BASDAI50, ASAS20, ASAS40, ASDAS &lt;2.1, ASDAS clinically important improvement, and ASDAS major improvement) were assessed at the 1 year follow-up. Propensity score (PS)-matched and covariate-adjusted logistic regression analyses were performed. Results: 246 had available 1 year follow-up data. Secukinumab as third- or later-line biologics was more frequent than alternative TNFi (54% vs. 14%). PS-matched and multiple covariate-adjusted analyses showed that the odds ratio (OR) for drug discontinuation was comparable between the secukinumab and TNFi switching groups (OR=1.136; 95% CI, 0.843–1.531 and OR=1.000; 95% CI, 0.433–2.308, respectively). The proportion of patients who achieved BASDAI50 was also comparable between the two groups (OR=0.833; 95% CI, 0.481–1.441 in PS-matched analysis). Other clinical efficacy parameters were also comparable. In the subgroup analysis of AS patients with previous TNFi discontinuation due to ineffectiveness, all clinical efficacy parameters were comparable between the two groups. Conclusion: In AS patients with previous exposure to a TNFi, switching biologics to secukinumab and switching to an alternative TNFi resulted in comparable drug retention and clinical efficacy. References: [1]Micheroli R, Tellenbach C, Scherer A, et al. Effectiveness of secukinumab versus an alternative TNF inhibitor in patients with axial spondyloarthritis previously exposed to TNF inhibitors in the Swiss Clinical Quality Management cohort. Ann Rheum Dis 2020;79:1203-9. Disclosure of Interests: None declared.
Abstract 17349: The Biomimetic Cardiac Tissue Model (BCTM) Reproduces the Pathological Remodeling Seen in Hypertrophic and Dilated Cardiomyopathy
Authors: Aaron J Rogers, Jessica M Miller, Ram Kannappan, Palaniappan Sethu
Journal: Circulation (2018)

Introduction: Cardiovascular research and regenerative strategies have been significantly limited by the lack of relevant cell culture systems that can recreate complex hemodynamic stresses associated with pressure-volume changes in the heart. To address this issue, we designed a Biomimetic Cardiac Tissue Model (BCTM) where encapsulated cardiac cells can be cultured in 3D fibers and subjected to hemodynamic loading to mimic pressure-volume changes seen in the left ventricle. Hypothesis: We tested the hypothesis that stimulation under hemodynamic loads as seen in pressure and volume overload is capable of reproducing the pathological remodeling seen in vivo. Methods: The 3D fibers are suspended between two posts within a pumping chamber that is integrated within a flow loop. Various parameters associated with heart function like heart rate, peak-systolic pressure, end-diastolic pressure and volume, end-systolic pressure and volume, and duration ratio between systolic and diastolic can all be precisely manipulated allowing culture of various cardiac cell types under developmental, normal, and disease states. Using the BCTM we reproduced the pathophysiological mechanical stresses of pressure overload and volume overload. Results: Using H9c2 cells, a cardiomyogenic cell line, our results clearly show that culture within the BCTM under pathological hemodynamic loads accurately induces morphological and gene expression changes similar to those seen in both hypertrophic and dilated cardiomyopathies in vivo . Cells within the BCTM under pressure overload see increased hypertrophic remodeling and fibrosis whereas cells subject to prolonged volume overload experience significant changes to cellular aspect ratio through thinning and elongation of the engineered tissue. Conclusions: These results clearly demonstrate that the BCTM can accurately reproduce pathological remodeling and create highly relevant models for cardiovascular disease modeling.
Large-scale genetic analyses in an understudied disease: haemorrhoidal disease
Authors: Eleonora A M Festen, Rinse K Weersma
Journal: Gut (2021)

Approximately 20% of the US population have ever been diagnosed with haemorrhoidal disease, and out of those individuals, one in five reports to have had surgery for his or her haemorrhoids. Outpatient and emergency department visits to gastroenterologists and surgeons for haemorrhoids outnumber those for colon cancer, inflammatory bowel disease or irritable bowel syndrome. Historically accepted notions that constipation and a low-fibre diet contribute to disease development have not been confirmed in large US and UK survey and registry data studies.1 Moreover, these studies found that generally accepted symptoms of haemorrhoids, like pruritus, pain, mucus discharge and bleeding, occur just as frequently in individuals without haemorrhoids. Haemorrhoidal disease is a classic example of a disease that has a large burden within the population, but for which scientific knowledge and research efforts are nonetheless very limited. A recent narrative review by Sandler and Peery thoroughly exposed the large gaps in our understanding of the underlying disease mechanisms and the lack of evidence-based treatment options in haemorrhoidal disease.2 

In Gut , Zheng et al focused on the mechanisms underlying haemorrhoidal disease and set out to study the genetic components in its development.3 The study is noteworthy and laudable for two reasons. First of all, it represents a state-of-the-art genome-wide association study (GWAS) making use of available data from (population based) biobanks resulting in a massive study involving just under a million participants. …
Apatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706)
Authors: Hongyun Zhao, Wenxiu Yao, Xuhong Min, Kangsheng Gu, Guohua Yu, Zhonghan Zhang, Jiuwei Cui, Liyun Miao, Li Zhang, Xia Yuan, Yong Fang, Xiuhua Fu, Chengping Hu, Xiaoli Zhu, Yun Fan, Qitao Yu, Gang Wu, Ou Jiang, Xiuping Du, Jiwei Liu, Wei Gu, Zhiguo Hou, Quanren Wang, Rongrong Zheng, Xianfeng Zhou, Li Zhang
Journal: Journal of Thoracic Oncology (2021)
Difficult biliary cannulation in ERCP procedures with or without trainee involvement: a comparative study
Authors: Xu Wang, Hui Luo, Qin Tao, Gui Ren, Xiangping Wang, Shuhui Liang, Linhui Zhang, Long Chen, Xin Shi, Xuegang Guo, Yanglin Pan
Journal: Endoscopy (2021)

Abstract Background The 5–5–1 criteria (&gt; 5 minutes – 5 cannulation attempts – 1 unintended pancreas duct cannulation) were proposed by the European Society of Gastrointestinal Endoscopy to define difficult biliary cannulation. However, the criteria may be inappropriate for trainee-involved procedures. We developed criteria for difficult cannulation in trainee-involved procedures. Methods Patients undergoing biliary cannulation with or without trainee involvement were eligible. Procedures that might be too easy (e. g. fistula) or too difficult (e. g. altered anatomy) were excluded. The primary outcome was difficult cannulation, defined as cannulation time, attempts, or inadvertent pancreatic duct (PD) cannulation exceeding the 75 % percentile of each variable. Propensity score matching (PSM) analysis was used. Results After PSM, there were 1596 patients in each group. Trainee-involved procedures had longer median (interquartile range [IQR]) cannulation time (7.5 [2.2–15.3] vs. 2.0 [0.6–5.2] minutes), and more attempts (5 [2–10] vs. 2 [1–4]) and inadvertent PD cannulation (0 [0–2] vs. 0 [0–1]) vs. procedures without trainee involvement (all P &lt; 0.001). The 15–10–2 criteria for difficult cannulation were proposed for trainee-involved cannulation and the 5–5-1 criteria were nearly confirmed for cannulation without trainee involvement. The proportions of difficult cannulation using these respective criteria were 35.5 % (95 % confidence interval [CI] 33.2 %–37.9 %) and 31.8 % (95 %CI 29.5 %–34.2 %), respectively (odds ratio 1.18 [95 %CI 1.02–1.37]). Incidences of post-ERCP pancreatitis following difficult cannulation were comparable (7.8 % [95 %CI 5.7 %–10.3 %] vs. 9.8 % [95 %CI 7.4 %–12.8 %], respectively). Conclusion By using the 75 % percentiles as cutoffs, the proposed 15–10–2 criteria for difficult cannulation could be appropriate in trainee-involved procedures.