tbuckley/cabot-search huggingface dataset:
Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic
Authors: Grégory Destras, Antonin Bal, Vanessa Escuret, Florence Morfin, Bruno Lina, Laurence Josset
Journal: The Lancet Microbe (2020)

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged since December, 2019, and spread worldwide, causing the COVID-19 pandemic. Despite COVID-19 being a respiratory tract infection, the pathophysiology in both adults and children is incompletely understood. Neurological signs and symptoms—from headache to meningitis—have been reported in hospitalised patients.1,2 SARS-CoV-2 can enter and replicate in neuronal cells in vitro,3 but the association between neurological manifestations and presence of SARS-CoV-2 in cerebrospinal fluid (CSF) has only been tested in a few cases, with one patient testing positive for SARS-CoV-2 in a case report4 and seven of seven patients testing negative in a case series.
Rituximab Plus Bortezomib Still Represents an Effective Treatment Option for Patients with Relapsed or Refractory Mantle Cell Lymphoma
Authors: Vittorio Ruggero Zilioli, Cristina Gabutti, Erika Meli, Periana Minga, Michelle Zancanella, Roberto Cairoli, Chiara Rusconi
Journal: Blood (2017)
Dynamic rewiring of the human interactome by interferon signaling
Authors: Craig H. Kerr, Michael A. Skinnider, Daniel D. T. Andrews, Angel M. Madero, Queenie W. T. Chan, R. Greg Stacey, Nikolay Stoynov, Eric Jan, Leonard J. Foster
Journal: Genome biology (2020)

Abstract Background The type I interferon (IFN) response is an ancient pathway that protects cells against viral pathogens by inducing the transcription of hundreds of IFN-stimulated genes. Comprehensive catalogs of IFN-stimulated genes have been established across species and cell types by transcriptomic and biochemical approaches, but their antiviral mechanisms remain incompletely characterized. Here, we apply a combination of quantitative proteomic approaches to describe the effects of IFN signaling on the human proteome, and apply protein correlation profiling to map IFN-induced rearrangements in the human protein-protein interaction network. Results We identify &gt; 26,000 protein interactions in IFN-stimulated and unstimulated cells, many of which involve proteins associated with human disease and are observed exclusively within the IFN-stimulated network. Differential network analysis reveals interaction rewiring across a surprisingly broad spectrum of cellular pathways in the antiviral response. We identify IFN-dependent protein-protein interactions mediating novel regulatory mechanisms at the transcriptional and translational levels, with one such interaction modulating the transcriptional activity of STAT1. Moreover, we reveal IFN-dependent changes in ribosomal composition that act to buffer IFN-stimulated gene protein synthesis. Conclusions Our map of the IFN interactome provides a global view of the complex cellular networks activated during the antiviral response, placing IFN-stimulated genes in a functional context, and serves as a framework to understand how these networks are dysregulated in autoimmune or inflammatory disease.
IL-15 superagonist RLI has potent immunostimulatory properties on NK cells: implications for antimetastatic treatment
Authors: Mélanie Desbois, Coralie Béal, Mélinda Charrier, Benjamin Besse, Guillaume Meurice, Nicolas Cagnard, Yannick Jacques, David Béchard, Lydie Cassard, Nathalie Chaput
Journal: Journal for ImmunoTherapy of Cancer (2020)

As the immune system is compromised in patients with cancer, therapeutic strategies to stimulate immunity appear promising, to avoid relapse and increase long-term overall survival. Interleukin-15 (IL-15) has similar properties to IL-2, but does not cause activation-induced cell death nor activation and proliferation of regulatory T cells (Treg), which makes it a serious candidate for anticancer immunotherapy. However, IL-15 has a short half-life and high doses are needed to achieve responses. Designed to enhance its activity, receptor-linker-IL-15 (RLI) (SO-C101) is a fusion molecule of human IL-15 covalently linked to the human IL-15Rα sushi+ domain currently assessed in a phase I/Ib clinical trial on patients with advanced/metastatic solid cancer.We investigated the antimetastatic activity of RLI in a 4T1 mouse mammary carcinoma that spontaneously metastasizes and evaluated its immunomodulatory role in the metastatic lung microenvironment. We further characterized the proliferation, maturation and cytotoxic functions of natural killer (NK) cells in tumor-free mice treated with RLI. Finally, we explored the effect of RLI on human NK cells from healthy donors and patients with non-small cell lung cancer (NSCLC).RLI treatment displayed antimetastatic properties in the 4T1 mouse model. By characterizing the lung microenvironment, we observed that RLI restored the balance between NK cells and neutrophils (CD11b+ Ly6Ghigh Ly6Clow) that massively infiltrate lungs of 4T1-tumor bearing mice. In addition, the ratio between NK cells and Treg was strongly increased by RLI treatment. Further pharmacodynamic studies in tumor-free mice revealed superior proliferative and cytotoxic functions on NK cells after RLI treatment compared with IL-15 alone. Characterization of the maturation stage of NK cells demonstrated that RLI favored accumulation of CD11b+ CD27high KLRG1+ mature NK cells. Finally, RLI demonstrated potent immunostimulatory properties on human NK cells by inducing proliferation and activation of NK cells from healthy donors and enhancing cytotoxic responses to NKp30 crosslinking in NK cells from patients with NSCLC.Collectively, our work demonstrates superior activity of RLI compared with rhIL-15 in modulating and activating NK cells and provides additional evidences for a therapeutic strategy using RLI as antimetastatic molecule.
AB0217 IMPACT OF THE BODY-MASS-INDEX ON DISEASE ACTIVITY, FUNCTIONAL ABILITY AND QUALITY OF LIFE IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: L. Medjedovic, J. Mrdja, P. Ostojic
Journal: Annals of the Rheumatic Diseases (2020)

Objectives: This study aims to assess differences in disease activity, functional ability and quality of life among underweight, normal weight, overweigth and obese patients with rheumatoid arthritis (RA). Methods: 715 patients with RA (609 women and 106 men) were included in this study. According to their Body-Mass-Index, all patients were divided into four subgroups: underweight (BMI &lt;18,5), normal weight (BMI between 18,5 and 24,9), overweight (BMI between 25,0 and 29,9) and obesitas (BMI ≥ 30,0). Mean values of DAS 28 , CDAI and SDAI (measures of disease activity), HAQ-disability index (measure of functional ability) and RAQoL index (measure of qualitiy of life) were compared among four subgroups of patients. Results: 28 (3,9%) RA patients were underweight, 310 (43,4%) had normal weight, 268 (37,5%) were overweight, whilst 109 (15,2%) patients were obese. Among these subgroups, no difference in mean age, disease duration, percentage of seropositive patients, and patients treated with glucocorticoids, csDMARDs or biologics, was noticed. There were no statistically significant differences in mean values of DAS 28 , CDAI und SDAI in four subgroups of patients. However, mean value of the HAQ disability index was significantly higher (p&lt;0.05) in underweight (1.32) and obese patients (1.27), compared to normal (0.87) and overweigth patients (1.08). The mean value of the RAQoL-Index was also somewhat higher in underweight and obese patients (8.8 and 8.1, respectively) than patients who are overweight or have normal weigth (7.0 and 6.5, respectively), but the difference was not statistically significant. Conclusion: Underweight and obese RA patients have worse physical function than normal and overweight patients. However, worse disability can not be explained by higher disease activity. Disclosure of Interests: None declared
Ligand-Induced Degradation of a CAR Permits Reversible Remote Control of CAR T Cell Activity In Vitro and In Vivo
Authors: Sarah A. Richman, Liang-Chuan Wang, Edmund K. Moon, Uday R. Khire, Steven M. Albelda, Michael C. Milone
Journal: Molecular Therapy (2020)

Chimeric antigen receptor (CAR)-modified T cells are endowed with novel antigen specificity and are most often administered to patients without an engineered mechanism to control the CAR T cells once infused. "Suicide switches" such as the small molecule-controlled, inducible caspase-9 (iCas9) system afford the ability to selectively eliminate engineered T cells; however, these approaches are designed for all-or-none, irreversible termination of an ongoing immune response. In order to permit reversible and adjustable modulation, we have created a CAR that is capable of on-demand downregulation by fusing the CAR to a previously developed ligand-induced degradation (LID) domain. Addition of a small molecule ligand triggers exposure of a cryptic degron within the LID domain, resulting in proteasomal degradation of the CAR-LID fusion protein and loss of CAR on the surface of T cells. This fusion construct allowed for reversible and "tunable" inhibition of CAR T cell activity in vitro. Delivery of the triggering molecule in CAR-LID-treated tumor-bearing mice temporarily reduced CAR activity through modulation of CAR surface expression. The ability to more flexibly modulate CAR T cell expression through a small molecule provides a platform for controlling possible adverse side effects, as well as preclinical investigations of CAR T cell biology. Chimeric antigen receptor (CAR)-modified T cells are endowed with novel antigen specificity and are most often administered to patients without an engineered mechanism to control the CAR T cells once infused. "Suicide switches" such as the small molecule-controlled, inducible caspase-9 (iCas9) system afford the ability to selectively eliminate engineered T cells; however, these approaches are designed for all-or-none, irreversible termination of an ongoing immune response. In order to permit reversible and adjustable modulation, we have created a CAR that is capable of on-demand downregulation by fusing the CAR to a previously developed ligand-induced degradation (LID) domain. Addition of a small molecule ligand triggers exposure of a cryptic degron within the LID domain, resulting in proteasomal degradation of the CAR-LID fusion protein and loss of CAR on the surface of T cells. This fusion construct allowed for reversible and "tunable" inhibition of CAR T cell activity in vitro. Delivery of the triggering molecule in CAR-LID-treated tumor-bearing mice temporarily reduced CAR activity through modulation of CAR surface expression. The ability to more flexibly modulate CAR T cell expression through a small molecule provides a platform for controlling possible adverse side effects, as well as preclinical investigations of CAR T cell biology.
Abstract 13154: Reparative Macrophages Contribute to Development of Solid Replacement Fibrosis Through Protecting Cardiac Fibroblasts
Authors: Manabu Shiraishi, Atsushi Yamaguchi, Ken Suzuki
Journal: Circulation (2019)

We have recently reported that CD206+cardiac macrophages play the central role in cardiac repair post myocardial infarction (MI). These reparative macrophages increase and activate cardiac fibrobla...
Chlorin e6 and CRISPR-Cas9 dual-loading system with deep penetration for a synergistic tumoral photodynamic-immunotherapy
Authors: Chengli Yang, Yuyin Fu, Cheng Huang, Danrong Hu, Kai Zhou, Ying Hao, Bingyang Chu, Yun Yang, Zhiyong Qian
Journal: Biomaterials (2020)
Vaping-Associated Pulmonary Injury
Authors: Matthew R. Norris
Journal: Annals of Internal Medicine (2020)

Letters16 June 2020Vaping-Associated Pulmonary InjuryMatthew R. Norris, MDMatthew R. Norris, MDOverlook Medical Center, Summit, New Jersey (M.R.N.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-0279 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I have seen several cases of vaping-associated pulmonary injury at my institution and read Hooper and Garfield's commentary (1) with great enthusiasm. As the authors highlight, the patients at my institution also presented with 3 to 5 days of nonspecific constitutional and gastrointestinal symptoms followed by rapidly progressive pulmonary symptoms often requiring admission to the intensive care unit and mechanical ventilation. All of my institution's known cases had negative results on infectious work-up; had computed tomography showing multilobar ground-glass opacities before (or concurrent with) respiratory symptoms; and were related to heavy, long-term marijuana vaporization. Since the Centers ...References1. Hooper RW, Garfield JL. An emerging crisis: vaping-associated pulmonary injury. Ann Intern Med. 2020; 172:57-58. [PMID: 31590182]. doi:10.7326/M19-2908 LinkGoogle Scholar2. Laughlen GF. Studies on pneumonia following naso-pharyngeal injections of oil. Am J Pathol. 1925;1:407-414. [PMID: 19969662] MedlineGoogle Scholar3. Cannon PR. The problem of lipid pneumonia: a brief review. JAMA. 1940;115:2176-2179. CrossrefGoogle Scholar4. Kameswaran M, Annobil SH, Benjamin B, et al. Bronchoscopy in lipoid pneumonia. Arch Dis Child. 1992;67:1376-1377. [PMID: 1471891] CrossrefMedlineGoogle Scholar5. Perrine CG, Pickens CM, Boehmer TK, et al; Lung Injury Response Epidemiology/Surveillance Group. Characteristics of a multistate outbreak of lung injury associated with E-cigarette use, or vaping—United States, 2019. MMWR Morb Mortal Wkly Rep. 2019;68:860-864. [PMID: 31581168] doi:10.15585/mmwr.mm6839e1 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Overlook Medical Center, Summit, New Jersey (M.R.N.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L20-0279. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAn Emerging Crisis: Vaping-Associated Pulmonary Injury Randol W. Hooper II and Jamie L. Garfield Vaping-Associated Pulmonary Injury Randol W. Hooper II and Jamie L. Garfield Metrics 16 June 2020Volume 172, Issue 12Page: 841KeywordsInfectious disease surveillanceIntensive care unitsLungsMarijuanaNicotineOilsPneumoniaPulmonary diseasesUpper respiratory tract infectionsVentilators ePublished: 16 June 2020 Issue Published: 16 June 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Modulation of Donor Graft By the Steroidal Lactone Withaferin A Alleviates Post-Transplant Acute GVHD Via Nrf-2 Independent T-Reg Induction
Authors: Vikram Gota, Miten Mehta, Dievya Gohil, Dhruv Jha, Rajiv Kumar, Beamon Agarwal, Deepak Sharma, Santosh Sandur, Navin Khattry, Anuradha Majumdar
Journal: Blood (2017)
Synapse and Active Zone Assembly in the Absence of Presynaptic Ca2+ Channels and Ca2+ Entry
Authors: Richard G. Held, Changliang Liu, Kunpeng Ma, Austin M. Ramsey, Tyler B. Tarr, Giovanni De Nola, Shan Shan H. Wang, Jiexin Wang, Arn M.J.M. van den Maagdenberg, Toni Schneider, Jianyuan Sun, Thomas A. Blanpied, Pascal S. Kaeser
Journal: Neuron (2020)
Annals Graphic Medicine - Fire Extinguishers
Authors: Sara Twadell
Journal: Annals of Internal Medicine (2020)

Web Exclusives4 August 2020Annals Graphic Medicine - Fire ExtinguishersFREESara Twadell, BASara Twadell, BACharles E. Schmidt College of Medicine, Boca Raton, Florida (S.T.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0058 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Charles E. Schmidt College of Medicine, Boca Raton, Florida (S.T.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G20-0058.Author/Illustrator Information: Sara Twadell, BA; e-mail, [email protected]fau.edu.This article was published at Annals.org on 16 June 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFabrication of a microcapsule extinguishing agent with a core–shell structure for lithium-ion battery fire safety 4 August 2020Volume 173, Issue 3Page: W59-W63KeywordsDisclosureHealth care ePublished: 16 June 2020 Issue Published: 4 August 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Variations in killer-cell immunoglobulin-like receptor and human leukocyte antigen genes and immunity to malaria
Authors: Stephen Tukwasibwe, Annettee Nakimuli, James Traherne, Olympe Chazara, Jyothi Jayaraman, John Trowsdale, Ashley Moffett, Prasanna Jagannathan, Philip J. Rosenthal, Stephen Cose, Francesco Colucci
Journal: Cellular and Molecular Immunology (2020)
Adversarial attack vulnerability of medical image analysis systems: Unexplored factors
Authors: Gerda Bortsova, Cristina González-Gonzalo, Suzanne C. Wetstein, Florian Dubost, Ioannis Katramados, Laurens Hogeweg, Bart Liefers, Bram van Ginneken, Josien P.W. Pluim, Mitko Veta, Clara I. Sánchez, Marleen de Bruijne
Journal: Medical Image Analysis (2021)

Adversarial attacks are considered a potentially serious security threat for machine learning systems. Medical image analysis (MedIA) systems have recently been argued to be vulnerable to adversarial attacks due to strong financial incentives and the associated technological infrastructure. In this paper, we study previously unexplored factors affecting adversarial attack vulnerability of deep learning MedIA systems in three medical domains: ophthalmology, radiology, and pathology. We focus on adversarial black-box settings, in which the attacker does not have full access to the target model and usually uses another model, commonly referred to as surrogate model, to craft adversarial examples. We consider this to be the most realistic scenario for MedIA systems. Firstly, we study the effect of weight initialization (ImageNet vs. random) on the transferability of adversarial attacks from the surrogate model to the target model. Secondly, we study the influence of differences in development data between target and surrogate models. We further study the interaction of weight initialization and data differences with differences in model architecture. All experiments were done with a perturbation degree tuned to ensure maximal transferability at minimal visual perceptibility of the attacks. Our experiments show that pre-training may dramatically increase the transferability of adversarial examples, even when the target and surrogate's architectures are different: the larger the performance gain using pre-training, the larger the transferability. Differences in the development data between target and surrogate models considerably decrease the performance of the attack; this decrease is further amplified by difference in the model architecture. We believe these factors should be considered when developing security-critical MedIA systems planned to be deployed in clinical practice.
Accelerated diagnostic algorithms with hs-cTn have ≥ 92% sensitivity but lower specificity for diagnosing AMI
Authors: Heather Murray, Erin Slaunwhite
Journal: Annals of Internal Medicine (2020)

Lee CC, Huang SS, Yeo YH, et al. High-sensitivity-cardiac troponin for accelerated diagnosis of acute myocardial infarction: a systematic review and meta-analysis. Am J Emerg Med. 2019. [Epub ahead of print]. 31932131.
Restoration of the Lost Obscured Coronal Sulcus: A Novel Surgical Technique for Penile Lichen Sclerosus with Severe Preputial Adhesions
Authors: Marta Skrodzka, Wiliam Britnell, Jennifer Ayers, Amanda Rea, Saskia Morgenstern, Paul Hadway, Asif Muneer, Peter R. Malone
Journal: European Urology (2020)
AB0451 PRIMARY SJOGREN’S SYNDROME IN MEN
Authors: S. Wafa, A. Kefi, M. Ach, F. Jaziri, K. Ben Abdelghani, S. Turki, T. Ben Abdallah
Journal: Annals of the Rheumatic Diseases (2020)

Background: Primary Sjogren’s syndrome (PSS) is characterized as an autoimmune exocrinopathy, but this disorder also may involve extraglandular organs, giving rise to multisystem disease. Although the first case reported by Dr Mikulicz was a 42 year old man [1], there are only few reports describing the clinical picture of Sjogren’s Syndrome in males Objectives: To determine whether there were any clinical and biological differences between male and female tunisian patients with primary Sjogren’s syndrome (PSS). Methods: We studied 60 patients with pSS according to American-European Consensus Group (AECG), attending an Internal Medicine departement in Tunisia. The nine (15%) male patients in this cohort comprised the male group described in this study Results: The average age of men at diagnosis was 53.2 years [31 to 73 years]. Male SSp was revealed by sicca symptoms (55.5%), by extra glandular manifestations (33.3%). Fourty-four percent of our male patients had a positive result for a minor salivary gland biopsy (grade III or IV). Extraglandular manifestations during the course of the disease were present in 6 cases (66%) of our male patients with pSS. weight loss and raynaud’s phenomenon were more common in men. a significantly greater percentage of men had neurological involvement (66.6%vs 23,7) and and pulmonary involvement, notably a restrictive syndrome (66.6% vs 31,1%, p=0.043). The positivity of Anti-nuclear antibodies, anti-SSb and rheumatoid factor were significantly less common in males. Anemia was significanty more common in the male patients (p=0,049). No cases of Lymphoma in the male patients in our series. Eighty-eight percent of the men were treated with corticosteroids. In our series, the use of immunosuppressants was not necessary in male patients. Conclusion: Although pSS is typically a disease affecting women, clinicians should be aware that it may be diagnosed in male patients. Although men were at the same risk for the development of extraglandular complications, there were significant serologic and immunogenetic differences. In Sharp contrast to women with Sjogren’s syndrome, men with Sjogren’s syndrome were more seronegative in our series. References: [1]Mikulicz J. Discussion at Verein fur wissenschaftliche Heilkunde zu königsberg. Berl Klin Wocchenschr 1888; 25:759. [2]Gondran G, Fauchais A, Lambert M, Ly K, Launay D, Queyrel V, et al. Primary Sjogren’s syndrome in men. Scandinavian journal of rheumatology. 2008;37(4):300-5. [3]Virdee S, Greenan-Barrett J, Ciurtin C. A systematic review of primary Sjogren’s syndrome in male and paediatric populations. 2017;36(10):2225-36 Disclosure of Interests: None declared