tbuckley/cabot-search huggingface dataset:
Kupffer cells promote T-cell hepatitis by producing CXCL10 and limiting liver sinusoidal endothelial cell permeability
Authors: Shen Dai, Fengming Liu, Zhongnan Qin, Jinyan Zhang, Jiayi Chen, Wen-Xing Ding, Dechun Feng, Yong Ji, Xuebin Qin
Journal: Theranostics (2020)

Rationale: Kupffer cells (KCs) play a crucial role in liver immune homeostasis through interacting with other immune cells and liver sinusoidal endothelial cells (LSECs).However, how KCs exactly interact with these cells for maintaining the homeostasis still require the further investigation.CXCL10 is a chemokine that has been implicated in chemoattraction of monocytes, T cells, NK cells, and dendritic cells, and promotion of T cell adhesion to endothelial cells.Although CXCL10 is also known to participate in the pathogenesis of hepatic inflammation, the degree to which it is functionally involved in the crosstalk between immune cells and regulation of immune response is still unclear.Methods: To dynamically investigate the function of KCs, we used our recently developed rapid cell ablation model, intermedilysin (ILY)/human CD59 (hCD59)-mediated cell ablation tool, to selectively ablate KC pool under normal condition or concanavalin A (Con A)-induced hepatitis.At certain time points after KCs ablation, we performed flow cytometry to monitor the amount of hepatic infiltrating immune cells.mRNA array was used to detect the change of hepatic cytokines and chemokines levels.Cytokines and chemokines in the serum were further measured by LEGENDplex TM mouse proinflammatory chemokine panel and inflammation panel.Evans blue staining and transmission electron microscopy were used to investigate the interaction between KCs and LSECs in steady condition.CXCL10 neutralizing antibody and CXCL10 deficient mouse were used to study the role of CXCL10 in immune cell migration and pathogenesis of Con A-induced hepatitis.Results: At steady state, elimination of KCs results in a reduction of hepatic infiltrating monocytes, T, B, and NK cells and a list of cytokines and chemokines at transcriptional level.In the meantime, the depletion of KCs resulted in increased sinusoidal vascular permeability.In the pathological condition, the KCs elimination rescues Con A-induced acute hepatitis through suppressing proinflammatory immune responses by down-regulation of hepatitis-associated cytokines/chemokines in serum such as CXCL10, and recruitment of infiltrating immune cells (monocytes, T, B, and NK cells).We further documented that deficiency or blockade of CXCL10 attenuated the development of Con A-induced hepatitis associated with reduction of the infiltrating monocytes, especially inflammatory Ly6C hi monocytes.Conclusions: This study supports the notion that KCs actively interact with immune cells and LSECs for maintaining immune response and liver homeostasis.Our data indicate that the interplay between KCs and infiltrated monocytes via CXCL10 contribute to Con A-induced hepatitis.
Hospital-Wide SARS-CoV-2 Antibody Screening in 3056 Staff in a Tertiary Center in Belgium
Authors: Deborah Steensels, Els Oris, Laura Coninx, Dieter Nuyens, Marie-Luce Delforge, Pieter Vermeersch, Line Heylen
Journal: JAMA (2020)

This study characterizes the prevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among hospital staff of a Belgian tertiary care center tested over 1 week in April 2020, and risk factors for seropositivity.
KRAS Mutation-Responsive miR-139-5p inhibits Colorectal Cancer Progression and is repressed by Wnt Signaling
Authors: Feng Du, Tianyu Cao, Huahong Xie, Ting Li, Lina Sun, Hao Liu, Hao Guo, Xin Wang, Qi Liu, Taewan Kim, Jeffrey L Franklin, Ramona Graves-Deal, Weili Han, Zuhong Tian, Minghui Ge, Yongzhan Nie, Daiming Fan, Robert J Coffey, Yuanyuan Lu, Xiaodi Zhao
Journal: Theranostics (2020)

Colorectal cancer (CRC) frequently harbors KRAS mutations that result in chemoresistance and metastasis. MicroRNAs (miRNAs) are usually dysregulated and play important regulatory roles in tumor progression. However, the KRAS mutation-responsive miRNA profile in CRC remains uninvestigated.
Bacterial citrullinated epitopes generated by <i>Porphyromonas gingivalis</i> infection—a missing link for ACPA production
Authors: Madeleine Jenning, Bianka Marklein, Jimmy Ytterberg, Roman A Zubarev, Vijay Joshua, Dirkjan van Schaardenburg, Lotte van de Stadt, Anca Irinel Catrina, Ute Nonhoff, Thomas Häupl, Zoltán Konthur, Gerd R Burmester, Karl Skriner
Journal: Annals of the Rheumatic Diseases (2020)

Porphyromonas gingivalis (P.g.) is discussed to be involved in triggering self-reactive immune responses. The aim of this study was to investigate the autocitrullinated prokaryotic peptidylarginine deiminase (PPAD) from P.g. CH2007 (RACH2007-PPAD) from a rheumatoid arthritis (RA) patient and a synthetic citrullinated PPAD peptide (CPP) containing the main autocitrullination site as potential targets for antibody reactivity in RA and to analyse the possibility of citrullinating native human proteins by PPAD in the context of RA.Recombinant RACH2007-PPAD was cloned and expressed in Escherichia coli. Purified RACH2007-PPAD and its enzymatic activity was analysed using two-dimensional electrophoresis, mass spectrometry, immunoblot and ELISA. Autoantibody response to different modified proteins and peptides was recorded and bioinformatically evaluated.RACH2007-PPAD was capable to citrullinate major RA autoantigens, such as fibrinogen, vimentin, hnRNP-A2/B1, histone H1 and multiple peptides, which identify a common RG/RGG consensus motif. 33% of RA patients (n=30) revealed increased reactivity for α-cit-RACH2007-PPAD before RA onset. 77% of RA patients (n=99) presented α-cit-specific signals to CPP amino acids 57-71 which were positively correlated to α-CCP2 antibody levels. Interestingly, 48% of the α-CPP-positives were rheumatoidfactor IgM/anti-citrullinated peptide/protein antibodies (ACPA)-negative. Anti-CPP and α-RACH2007-PPAD antibody levels increase with age. Protein macroarrays that were citrullinated by RACH2007-PPAD and screened with RA patient sera (n=6) and controls (n=4) uncovered 16 RACH2007-PPAD citrullinated RA autoantigens and 9 autoantigens associated with lung diseases. We showed that the α-CPP response could be an important determinant in parenchymal changes in the lung at the time of RA diagnosis (n=106; p=0.018).RACH2007-PPAD induced internal citrullination of major RA autoantigens. Anti-RACH2007-PPAD correlates with ACPA levels and interstitial lung disease autoantigen reactivity, supporting an infection-based concept for induction of ACPAs via enzymatic mimicry.
The Tumour Suppressor TMEM127 Is a Nedd4-Family E3 Ligase Adaptor Required by Salmonella SteD to Ubiquitinate and Degrade MHC Class II Molecules
Authors: Eric Alix, Camilla Godlee, Ondrej Cerny, Samkeliso Blundell, Romina Tocci, Sophie Matthews, Mei Liu, Jonathan N. Pruneda, Kirby N. Swatek, David Komander, Tabitha Sleap, David W. Holden
Journal: Cell Host & Microbe (2020)

The Salmonella enterica effector SteD depletes mature MHC class II (mMHCII) molecules from the surface of infected antigen-presenting cells through ubiquitination of the cytoplasmic tail of the mMHCII β chain. Here, through a genome-wide mutant screen of human antigen-presenting cells, we show that the NEDD4 family HECT E3 ubiquitin ligase WWP2 and a tumor-suppressing transmembrane protein of unknown biochemical function, TMEM127, are required for SteD-dependent ubiquitination of mMHCII. Although evidently not involved in normal regulation of mMHCII, TMEM127 was essential for SteD to suppress both mMHCII antigen presentation in mouse dendritic cells and MHCII-dependent CD4
Hematological features of persons with COVID-19
Authors: Qiubai Li, Yulin Cao, Lei Chen, Di Wu, Jianming Yu, Hongxiang Wang, Wenjuan He, Li Chen, Fang Dong, Weiqun Chen, Wenlan Chen, Lei Li, Qijie Ran, Qiaomei Liu, Wenxiang Ren, Fei Gao, Zhichao Chen, Robert Peter Gale, Yu Hu
Journal: Leukemia (2020)
Clinical outcomes in adult athletes with hypertrophic cardiomyopathy: a 7-year follow-up study
Authors: Antonio Pelliccia, Stefano Caselli, Matteo Pelliccia, Maria Beatrice Musumeci, Erika Lemme, Fernando M Di Paolo, Viviana Maestrini, Domitilla Russo, Luca Limite, Cristian Borrazzo, Camillo Autore
Journal: British Journal of Sports Medicine (2020)

Objective Current guidelines recommend precautionary disqualification from competitive sports in patients with hypertrophic cardiomyopathy (HCM). We assessed the incidence of cardiovascular events in a cohort of patients with HCM engaged in long-term exercise programmes and competitive sport. Methods We reviewed data on 88 consecutive athletes diagnosed with HCM, from 1997 to 2017; 92% male, 98% Caucasian, median age 31 (IQR: 19–44) years. All participated in regular exercise programmes and competitive sport at study entry. We performed follow-up evaluation after 7±5 (1–21) years. 61 (69%) of the athletes had substantially reduced or stopped exercise and sport (ie, HCM-detrained), and 27 had continued with regular training and sport competitions (HCM-trained). At baseline evaluation, both groups were similar for age, gender balance, symptoms, ECG abnormalities, extent of left ventricular hypertrophy, arrhythmias and risk profile for sudden cardiac death/arrest. Results During the follow-up period, two participants suffered sudden cardiac arrest or death (0.3% per year) both outside of sport participation. In addition, 19 (22%) reported symptoms (syncope in 3, palpitations in 10, chest pain in 4 and dyspnoea in 2). The Kaplan-Meier analyses of freedom from combined sudden cardiac arrest/death and symptoms (log-rank test p=0.264) showed no differences between HCM-trained and detrained patients. Conclusion In this adult cohort of low-risk HCM athletes, voluntary decision to pursue in participation in competitive sport events was not associated with increased risk for major cardiac events or clinical worsening compared with decision to reduce or withdraw from exercise programmes and sport. Similar results may not be seen in younger or racially diverse athlete populations, or in patients with more severe HCM phenotypes.
Position statement of the Royal Spanish Football Federation for the resumption of football activities after the COVID-19 pandemic (June 2020)
Authors: Helena Herrero-Gonzalez, Rafael Martín-Acero, Juan Del Coso, Carlos Lalín-Novoa, Rafel Pol, Pilar Martín-Escudero, Ana Isabel De la Torre, Christopher Hughes, Magni Mohr, Francisco Biosca, Rafael Ramos
Journal: British Journal of Sports Medicine (2020)

<h3>Abstract</h3> IKAROS family zinc finger 1 (<i>IKZF1</i>) alterations represent a diverse group of genetic lesions that are associated with an increased risk of relapse in B-lymphoblastic leukemia (B-ALL). Due to the heterogeneity of concomitant lesions it remains unclear how <i>IKZF1</i> abnormalities directly affect cell function and therapy resistance and whether their consideration as a prognostic indicator is valuable in improving outcome. We used CRISPR/Cas9 to engineer multiple panels of isogeneic lymphoid leukemia cell lines with a spectrum of <i>IKZF1</i> lesions in order to measure changes in chemosensitivity, gene expression, cell cycle, and in vivo engraftment dynamics that can be directly linked to loss of IKAROS protein. <i>IKZF1</i> knockout and heterozygous null cells displayed relative resistance to a number of commonly employed therapies for B-ALL including dexamethasone, vincristine, asparaginase, and daunorubicin. Transcription profiling revealed a stem/myeloid cell-like phenotype and JAK/STAT upregulation after IKAROS loss. We also used a CRISPR homology-directed repair (HDR) strategy to knock-in the dominant-negative IK6 isoform tagged with GFP into the endogenous locus and observed a similar drug resistance profile with the exception of retained sensitivity to dexamethasone. Interestingly, <i>IKZF1</i> knockout and IK6 knock-in cells both have significantly increased sensitivity to cytarabine, suggesting intensification of nucleoside analog therapy may be specifically effective for <i>IKZF1</i>-deleted B-ALL. Both types of <i>IKZF1</i> lesions decreased survival time of xenograft mice, with higher numbers of circulating blasts and increased organ infiltration. Given these findings, exact specification of <i>IKZF1</i> status in patients may be a beneficial addition to risk stratification and could inform therapy. <h3>Key points</h3> Engineered <i>IKZF1</i> perturbations result in a stem-cell like expression signature, enhanced engraftment in vivo, and multi-drug resistance Loss of IKAROS may result in new vulnerabilities due to increased sensitivity to cytarabine and upregulation of JAK/STAT and mAb targets
Increased antiviral response in circulating lymphocytes from hypogammaglobulinemia patients
Authors: Oliver F. Wirz, Öykü Üzülmez, Kirstin Jansen, Willem van de Veen, Auli Lammela, Leena Kainulainen, Tytti Vuorinen, Heimo Breiteneder, Cezmi A. Akdis, Tuomas Jartti, Mübeccel Akdis
Journal: Allergy (2020)

B cells play a crucial role during rhinovirus (RV) infections by production of virus-neutralizing antibodies. A main feature of common variable immunodeficiency (CVID) is hypogammaglobulinemia (HG). HG patients have severely reduced levels of antibody-producing B cells and suffer from prolonged virus infections. Here, we addressed whether antiviral response of peripheral blood lymphocytes differs between HG patients and healthy individuals during natural RV infection.Using fluorescence-activated cell sorting, B-cell subsets were analyzed. Simultaneously, CD19 + B cells, CD14 + monocytes, and CD3 + T cells were sorted from frozen peripheral blood mononuclear cells from 11 RV-infected hypogammaglobulinemia patients, 7 RV-infected control subjects, and 14 noninfected control subjects. Real-time PCR was used to study expression of antiviral genes. A pan-RV PCR was used to detect RV genome in all samples.In HG patients, total B-cell numbers, as well as IgA + and IgG + switched memory B cells, were reduced while naïve B cells and T cells were increased. STAT1 expression was increased in HG patients compared to controls in all lymphocyte subsets analyzed. The expression of antiviral genes IFITM1 and MX1 correlated with STAT1 expression in B cells and monocytes. RV RNA was found in 88.9% of monocytes from infected HG patients, 85.7% of monocytes from infected controls, and 7.1% of monocytes from uninfected controls.We demonstrate an increased antiviral response in B cells and monocytes in HG patients and their correlation with STAT1 expression. Monocytes of infected HG patients and infected non-HG controls carry RV RNA.
AB0088 N6-METHYLADENOSINE-MODIFIED CIRC_0088194 PROMOTES MIGRATION AND INVASION OF RHEUMATOID ARTHRITIS FIBROBLAST-LIKE SYNOVIOCYTES THROUGH MIR-766-3P/MMP2 AXIS
Authors: Y. Cai, M. Yang, Q. Ouyang, Q. Huang, R. Liang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Circular RNAs (circRNAs) participate in the initiation and progression of various diseases by miRNA sponges including postmenopausal osteoporosis[1], bladder cancer[2], and osteoarthritis (OA)[3]. However, the activity of circRNAs as “miRNA sponges” in rheumatoid arthritis (RA) has not been studied. Objectives: To investigate whether circRNA acts as competing endogenous RNA to regulate pathological processes of RA, and whether the N6-methyladenosine (m 6 A) modification affects Circ_0088194 stability in RA fibroblast-like synoviocytes (RA-FLSs). Methods: CircRNA microarray analysis was conducted to characterize the expression profiles of circRNAs in 3 RA-FLSs and 3 osteoarthritis fibroblast-like synoviocytes (OA-FLSs). Methylated RNA immunoprecipitation was performed to validate the level of m 6 A modification on Circ_0088194 in RA-FLSs and OA-FLSs. Dual-luciferase reporter assay, bioinformatics analysis, protein array analysis, and fluorescence in situ hybridization were employed to evaluate the interaction between Circ_0088194 and miR-766-3p, and between target miR-766-3p and matrix metalloproteinase 2 (MMP2). Results: Overexpression of Circ_0088194 promoted the migration and invasion of RA-FLSs and increased MMP2 expression. The expression and function of miR-766-3p were inversely correlated with Circ_0088194, which sponged miR-766-3p to upregulate MMP2 expression. Although m 6 A modification of Circ_0088194 exists in RA-FLSs and OA-FLSs, their level did not differ. Conclusion: This study presents an important role of this novel circRNA as a sponge of miR-766-3p to promote RA-FLS migration and invasion by targeting MMP2. However, the modification might not affect Circ_0088194 stability in RA-FLSs and OA-FLSs. Therefore, Circ_0088194 may contribute to RA development and represent as an auspicious therapeutic target. References: [1]Yu, L., and Liu, Y. (2019). circRNA_0016624 could sponge miR-98 to regulate BMP2 expression in postmenopausal osteoporosis. Biochem Biophys Res Commun 516: 546-550. [2]Yang, C., et al. (2018). Circular RNA circ-ITCH inhibits bladder cancer progression by sponging miR-17/miR-224 and regulating p21, PTEN expression. MOL CANCER 17. [3]Shen, S., et al. (2019). CircSERPINE2 protects against osteoarthritis by targeting miR-1271 and ETS-related gene. ANN RHEUM DIS 78: 826-836. Disclosure of Interests: None declared
Artificial intelligence for breast cancer detection in mammography and digital breast tomosynthesis: State of the art
Authors: Ioannis Sechopoulos, Jonas Teuwen, Ritse Mann
Journal: Seminars in Cancer Biology (2020)

Screening for breast cancer with mammography has been introduced in various countries over the last 30 years, initially using analog screen-film-based systems and, over the last 20 years, transitioning to the use of fully digital systems. With the introduction of digitization, the computer interpretation of images has been a subject of intense interest, resulting in the introduction of computer-aided detection (CADe) and diagnosis (CADx) algorithms in the early 2000's. Although they were introduced with high expectations, the potential improvement in the clinical realm failed to materialize, mostly due to the high number of false positive marks per analyzed image. In the last five years, the artificial intelligence (AI) revolution in computing, driven mostly by deep learning and convolutional neural networks, has also pervaded the field of automated breast cancer detection in digital mammography and digital breast tomosynthesis. Research in this area first involved comparison of its capabilities to that of conventional CADe/CADx methods, which quickly demonstrated the potential of this new technology. In the last couple of years, more mature and some commercial products have been developed, and studies of their performance compared to that of experienced breast radiologists are showing that these algorithms are on par with human-performance levels in retrospective data sets. Although additional studies, especially prospective evaluations performed in the real screening environment, are needed, it is becoming clear that AI will have an important role in the future breast cancer screening realm. Exactly how this new player will shape this field remains to be determined, but recent studies are already evaluating different options for implementation of this technology. The aim of this review is to provide an overview of the basic concepts and developments in the field AI for breast cancer detection in digital mammography and digital breast tomosynthesis. The pitfalls of conventional methods, and how these are, for the most part, avoided by this new technology, will be discussed. Importantly, studies that have evaluated the current capabilities of AI and proposals for how these capabilities should be leveraged in the clinical realm will be reviewed, while the questions that need to be answered before this vision becomes a reality are posed.
Cardiac Tamponade as the First Manifestation of Erdheim-Chester Disease
Authors: Isabela B.S. da S. Costa, Fernanda A. de S. Costa, Cristina S. Bittar, Stéphanie I. Rizk, André N.R. Abdo, Sheila A.C. Siqueira, Vanderson Rocha, Juliana Pereira, Bonnie Ky, Ludhmila A. Hajjar
Journal: JACC CardioOncology (2020)

Erdheim-Chester disease (ECD) is classified as an inflammatory myeloid neoplasia that has an unknown origin and low incidence (∼600 cases described in the literature) ([1][1],[2][2]). ECD is multisystemic, affecting the bones, skin, ocular tissue, lungs, brain, pituitary gland, and other tissues
문맥압 항진증의 진단: 침습적 방법
Authors: 박승하
Journal: Clinical and Molecular Hepatology (2009)

The hallmark of portal hypertension is a pathologic increase in hepatic venous pressure gradient (HVPG) which reflects portal pressure accurately and, if measured precisely, has a very low variability. HVPG has been established as a predictor for the development of varices, the risk of variceal hemorrhage, clinical decompensation, and death. Furthermore, recent international consensuses have adopted the HVPG as the best surrogate marker in both portal hypertension trial and trials assessing progression of fibrosis in chronic liver disease. Although it is somewhat questionable that HVPG measurement is worthwhile in clinical decision making because of its cost and invasive nature, we have no doubt of the importance that it played and is still playing in advancing our knowledge of the portal hypertension. The main advantages of HVPG measurement are its simplicity, reproducibility, and safety. This article provides practical viewpoints to ensure that the technique is performed properly.
Zeb2 drives invasive and microbiota-dependent colon carcinoma
Authors: Karolina Slowicka, Ioanna Petta, Gillian Blancke, Esther Hoste, Emilie Dumas, Mozes Sze, Hanna Vikkula, Enrico Radaelli, Jody J. Haigh, Sven Jonckheere, Joachim Taminau, Niels Vandamme, Andy Wullaert, Eugene Tulchinsky, David Nittner, Pieter Van Vlierberghe, Gert De Hertogh, Pamela Baldin, Emre Etlioglu, Pratyaksha Wirapati, Louis Boon, Bart N. Lambrecht, Chris Callewaert, Sabine Tejpar, Steven Goossens, Geert Berx, Lars Vereecke, Geert van Loo
Journal: Nature Cancer (2020)
Convalescent Plasma and COVID-19
Authors: Anurag N. Malani, John P. Sherbeck, Preeti N. Malani
Journal: JAMA (2020)

Chenguang Shen, PhD; Zhaoqin Wang, PhD; Fang Zhao, PhD; Yang Yang, MD; Jinxiu Li, MD; Jing Yuan, MD; Fuxiang Wang, MD; Delin Li, PhD; Minghui Yang, PhD; Li Xing, MM; Jinli Wei, MM; Haixia Xiao, PhD; Yan Yang, MM; Jiuxin Qu, MD; Ling Qing, MM; Li Chen, MD; Zhixiang Xu, MM; Ling Peng, MM; Yanjie Li, MM; Haixia Zheng, MM; Feng Chen, MM; Kun Huang, MM; Yujing Jiang, MM; Dongjing Liu, MD; Zheng Zhang, MD; Yingxia Liu, MD; Lei Liu, MD