tbuckley/cabot-search huggingface dataset:
Message from the new EULAR President and Steering Group
Authors: Annamaria Iagnocco, Daniel Aletaha, Xenofon Baraliakos, Iain B McInnes
Journal: Annals of the Rheumatic Diseases (2021)

The last decade witnessed the ascendancy of rheumatology to become one of the most dynamic and progressive across the fields of medicine. During the COVID-19 pandemic our discipline emerged at the forefront of molecular medicine with the rapid uptake of immune-modulatory therapeutics and depth of immune pathogenesis understanding contributing fundamentally to the COVID-19 response. The European Alliance of Associations for Rheumatology (EULAR) played a fundamental and vital role in this response in guiding rheumatic and musculoskeletal disease (RMD) therapeutics, vaccine use and even treatment innovations in the context of COVID-19 itself. Given this remarkable contribution, it is timely to reflect on EULAR-what is it and for what does it stand? At its core, EULAR represents people with RMDs, including their national societies, health professionals in rheumatology and scientific societies of rheumatology across the European nations. Our mission is to reduce the burden of RMDs on individuals and society and improve the treatment and prevention of RMDs. In this message from the new EULAR President and Steering Group, we present the most relevant activities of EULAR, its strategic aims and the concept of the EULAR family, a fantastic team of people working together across the three pillars of medical, health professional and patient societies.
Ginseng-derived nanoparticles potentiate immune checkpoint antibody efficacy by reprogramming the cold tumor microenvironment
Authors: Xuan Han, Qin Wei, Yan Lv, Ling Weng, Haoying Huang, Qingyun Wei, Mengyuan Li, Yujie Mao, Di Hua, Xueting Cai, Meng Cao, Peng Cao
Journal: Molecular Therapy (2021)

Cold tumor microenvironment (TME) marked with low effector T cell infiltration leads to weak response to immune checkpoint inhibitor (ICI) treatment. Thus, switching cold to hot TME is critical to improve potent ICI therapy. Previously, we reported extracellular vesicle (EV)-like ginseng-derived nanoparticles (GDNPs) that were isolated from Panax ginseng C.A. Mey and can alter M2 polarization to delay the hot tumor B16F10 progression. However, the cold tumor is more common and challenging in the real world. Here, we explored a combinatorial strategy with both GDNPs and PD-1 (programmed cell death protein-1) monoclonal antibody (mAb), which exhibited the ability to alter cold TME and subsequently induce a durable systemic anti-tumor immunity in multiple murine tumor models. GDNPs enhanced PD-1 mAb anti-tumor efficacy in activating tumor-infiltrated T lymphocytes. Our results demonstrated that GDNPs could reprogram tumor-associated macrophages (TAMs) to increase CCL5 and CXCL9 secretion for recruiting CD8+ T cells into the tumor bed, which have the synergism to PD-1 mAb therapy with no detected systemic toxicity. In situ activation of TAMs by GDNPs may broadly serve as a facile platform to modulate the suppressive cold TME and optimize the PD-1 mAb immunotherapy in future clinical application. Cold tumor microenvironment (TME) marked with low effector T cell infiltration leads to weak response to immune checkpoint inhibitor (ICI) treatment. Thus, switching cold to hot TME is critical to improve potent ICI therapy. Previously, we reported extracellular vesicle (EV)-like ginseng-derived nanoparticles (GDNPs) that were isolated from Panax ginseng C.A. Mey and can alter M2 polarization to delay the hot tumor B16F10 progression. However, the cold tumor is more common and challenging in the real world. Here, we explored a combinatorial strategy with both GDNPs and PD-1 (programmed cell death protein-1) monoclonal antibody (mAb), which exhibited the ability to alter cold TME and subsequently induce a durable systemic anti-tumor immunity in multiple murine tumor models. GDNPs enhanced PD-1 mAb anti-tumor efficacy in activating tumor-infiltrated T lymphocytes. Our results demonstrated that GDNPs could reprogram tumor-associated macrophages (TAMs) to increase CCL5 and CXCL9 secretion for recruiting CD8+ T cells into the tumor bed, which have the synergism to PD-1 mAb therapy with no detected systemic toxicity. In situ activation of TAMs by GDNPs may broadly serve as a facile platform to modulate the suppressive cold TME and optimize the PD-1 mAb immunotherapy in future clinical application.
27380 Bimekizumab efficacy in patients with moderate to severe plaque psoriasis during the randomized withdrawal and retreatment phase of BE READY, a phase 3 trial
Authors: Andrew Blauvelt, Jashin J. Wu, Kristian Reich, Melinda Gooderham, Mark Lebwohl, Katy White, Nancy Cross, Christopher Cioffi, Kim A. Papp
Journal: Journal of the American Academy of Dermatology (2021)
Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials
Authors: Naveed Sattar, Matthew M Y Lee, Søren L Kristensen, Kelley R H Branch, Stefano Del Prato, Nardev S Khurmi, Carolyn S P Lam, Renato D Lopes, John J V McMurray, Richard E Pratley, Julio Rosenstock, Hertzel C Gerstein
Journal: The Lancet Diabetes & Endocrinology (2021)
Targeting Depressive Symptoms in Younger Breast Cancer Survivors: The Pathways to Wellness Randomized Controlled Trial of Mindfulness Meditation and Survivorship Education
Authors: Julienne E. Bower, Ann H. Partridge, Antonio C. Wolff, Elissa D. Thorner, Michael R. Irwin, Hadine Joffe, Laura Petersen, Catherine M. Crespi, Patricia A. Ganz
Journal: Journal of Clinical Oncology (2021)

Younger women are at risk for depression and related symptoms following breast cancer. The Pathways to Wellness study, a randomized, multi-institution, three-arm trial, tested the efficacy of two behavioral interventions for younger breast cancer survivors with elevated depressive symptoms: mindful awareness practices (MAPs) and survivorship education (SE) (Clincaltrials.gov identifier: NCT03025139).
Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome
Authors: Makhloufi Zoulikha, Qingqing Xiao, George Frimpong Boafo, Marwa A. Sallam, Zhongjian Chen, Wei He
Journal: Acta Pharmaceutica Sinica B (2021)

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The properties such as clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the translation of siRNA is restricted by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic.
Polymeric and lipid nanoparticles for delivery of self-amplifying RNA vaccines
Authors: Anna K. Blakney, Paul F. McKay, Kai Hu, Karnyart Samnuan, Nikita Jain, Andrew Brown, Anitha Thomas, Paul Rogers, Krunal Polra, Hadijatou Sallah, Jonathan Yeow, Yunqing Zhu, Molly M. Stevens, Andrew Geall, Robin J. Shattock
Journal: Journal of Controlled Release (2021)

Self-amplifying RNA (saRNA) is a next-generation vaccine platform, but like all nucleic acids, requires a delivery vehicle to promote cellular uptake and protect the saRNA from degradation. To date, delivery platforms for saRNA have included lipid nanoparticles (LNP), polyplexes and cationic nanoemulsions; of these LNP are the most clinically advanced with the recent FDA approval of COVID-19 based-modified mRNA vaccines. While the effect of RNA on vaccine immunogenicity is well studied, the role of biomaterials in saRNA vaccine effectiveness is under investigated. Here, we tested saRNA formulated with either pABOL, a bioreducible polymer, or LNP, and characterized the protein expression and vaccine immunogenicity of both platforms. We observed that pABOL-formulated saRNA resulted in a higher magnitude of protein expression, but that the LNP formulations were overall more immunogenic. Furthermore, we observed that both the helper phospholipid and route of administration (intramuscular versus intranasal) of LNP impacted the vaccine immunogenicity of two model antigens (influenza hemagglutinin and SARS-CoV-2 spike protein). We observed that LNP administered intramuscularly, but not pABOL or LNP administered intranasally, resulted in increased acute interleukin-6 expression after vaccination. Overall, these results indicate that delivery systems and routes of administration may fulfill different delivery niches within the field of saRNA genetic medicines.
Randomized Clinical Trials in the Era of Precision Oncology—The Role of End Points, Industry Funding, and Medical Writing Integrity
Authors: Thomas M. Schindler, Jacqueline M. Marchington, Gail V. Flores
Journal: JAMA Oncology (2021)

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The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children
Authors: Rebecca A. Porritt, Aleksandra Binek, Lisa Paschold, Magali Noval Rivas, Angela McArdle, Lael M. Yonker, Galit Alter, Harsha K. Chandnani, Merrick Lopez, Alessio Fasano, Jennifer E. Van Eyk, Mascha Binder, Moshe Arditi
Journal: Journal of Clinical Investigation (2021)

Multisystem inflammatory syndrome in children (MIS-C) manifests as a severe and uncontrolled inflammatory response with multiorgan involvement, occurring weeks after SARS-CoV-2 infection. Here, we utilized proteomics, RNA sequencing, autoantibody arrays, and B cell receptor (BCR) repertoire analysis to characterize MIS-C immunopathogenesis and identify factors contributing to severe manifestations and intensive care unit admission. Inflammation markers, humoral immune responses, neutrophil activation, and complement and coagulation pathways were highly enriched in MIS-C patient serum, with a more hyperinflammatory profile in severe than in mild MIS-C cases. We identified a strong autoimmune signature in MIS-C, with autoantibodies targeted to both ubiquitously expressed and tissue-specific antigens, suggesting autoantigen release and excessive antigenic drive may result from systemic tissue damage. We further identified a cluster of patients with enhanced neutrophil responses as well as high anti-Spike IgG and autoantibody titers. BCR sequencing of these patients identified a strong imprint of antigenic drive with substantial BCR sequence connectivity and usage of autoimmunity-associated immunoglobulin heavy chain variable region (IGHV) genes. This cluster was linked to a TRBV11-2 expanded T cell receptor (TCR) repertoire, consistent with previous studies indicating a superantigen-driven pathogenic process. Overall, we identify a combination of pathogenic pathways that culminate in MIS-C and may inform treatment.
25792 Improvements in BSA associate with improvements in itch and quality of life in patients with moderate-to-severe psoriasis treated with ixekizumab or guselkumab through 24 weeks
Authors: Alice Gottlieb, Melinda Gooderham, Bruce Konicek, Russel Burge, So Young Park, Andrew Blauvelt
Journal: Journal of the American Academy of Dermatology (2021)
26874 Long-term efficacy and safety of tildrakizumab in patients with moderate-to-severe psoriasis who were partial responders or nonresponders to etanercept: Post hoc analysis through 5 years from the reSURFACE 2 phase 3 trial
Authors: Diamant Thaçi, Christopher E.M. Griffiths, Lars Iversen, Andrea Peserico, Ignasi Pau-Charles, Andrew Blauvelt, Kristian Reich
Journal: Journal of the American Academy of Dermatology (2021)
AB0654 TOCILIZUMAB IS PROTECTIVE AGAINST SARS-COV2 INFECTION OR NOT?
Authors: F. Fayed, E. Abdelkarim
Journal: Annals of the Rheumatic Diseases (2021)

Background: SARS-COV2 (Covid19) pandemic has a scaring burden on hospitals and health care providers all over the world. Unfortunately, after one year of pandemic, millions of persons are infected either mild symptoms or critical ones and unexplained deaths. Till now, No effective treatment or vaccination. Researches showed that Covid 19 associated with elevated interleukin-6. Subsequently, Studies reported that tocilizumab (IL-6 antagonist) may be effective in critical patients even though other were shown that it is not associated with reduction in the mortality. (1,2) Therefore the question is that patients with rheumatic diseases who are already receiving tocilizumab having a primary protection against infection of Covid 19 in comparing to other receiving the other biologicals or conventional Therapy or not. Objectives: Our objective was to determine if tocolizumab had a primary protection against SARS-COV2 in comparing to patients were on other biologics. Methods: A Retrospective study was done among 100 patients with rheumatic diseases (Group 1: 10 on tocilizumab, Group2: 40 (30 on antiTNF and 10 on IL17 antagonist), Group3: on cDMARDs) from March to Dec 2020. Detailed history, clinical presentation, laboratory, computed tomography of chest and PCR for covid 19 if presented among infected patients. Results: Among 100 patients of median age 21, 19 patient (19%) had infected with Covid 19 (2 on tocilizumab, 6 on antiTNF, 1 on IL17 antagonist, 10 on cDMARDs). Symptoms were reported fever (89.4%), Fatigue (78.9%), myalgia (78.9%), Headache (73.7%), Dyspnea (52.6%), Cough (47.3%), chest pain (26.3%) and hypoxia (5%). CT findings were positive in 10 patients (52.63%) while PCR was done and positive in 15 out of 19 (78.94%). Nevertheless, there was no significant statistically difference between groups according to infection with SARS-COV2. (p=0.704) Conclusion: Tocilizumab is not shown to be protective against SARS-COV2 (COVID 19) infection compared to other biological or cDMARDs in patients with rheumatic diseases. References: [1]Tleyjeh IM, Kashour Z, Damlaj M, et al. Efficacy and safety of tocilizumab in COVID-19 patients: A living systematic review and meta-analysis. Clinical Microbiology and Infection. 2020 Nov 5. [2]Tsai, A., Diawara, O., Nahass, R.G. et al. Impact of tocilizumab administration on mortality in severe COVID-19. 2020; Sci Rep 10: 19131 Disclosure of Interests: None declared.
27374 Bimekizumab efficacy in patients with moderate to severe plaque psoriasis receiving continuous bimekizumab or switching from adalimumab: Results from the phase 3 BE SURE trial
Authors: Bruce E. Strober, Andreas Pinter, Richard B. Warren, Andrew Blauvelt, Michael Sebastian, Dirk De Cuyper, Veerle Vanvoorden, Maggie Wang, Cynthia Madden, Melinda Gooderham
Journal: Journal of the American Academy of Dermatology (2021)
Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (ITCC-050): a multicentre, open-label, multicohort, phase 1/2 study
Authors: Nathalie Gaspar, Rajkumar Venkatramani, Stefanie Hecker-Nolting, Soledad Gallego Melcon, Franco Locatelli, Francisco Bautista, Alessandra Longhi, Cyril Lervat, Natacha Entz-Werle, Michela Casanova, Isabelle Aerts, Sandra J Strauss, Estelle Thebaud, Bruce Morland, Adela Cañete Nieto, Perrine Marec-Berard, Marion Gambart, Claudia Rossig, Chinyere E Okpara, Cixin He, Lea Dutta, Quentin Campbell-Hewson
Journal: The Lancet Oncology (2021)
26860 Secukinumab treatment demonstrated high efficacy and safety in pediatric patients with moderate-to-severe plaque psoriasis: 52-week results from a randomized trial
Authors: Nina Magnolo, Külli Kingo, Vivian Laquer, John Browning, Adam Reich, Jacek C. Szepietowski, Deborah Keefe, Rafal Mazur, Prayashi Ghelani, Pascal Forrer, Manmath Patekar
Journal: Journal of the American Academy of Dermatology (2021)
A Review of Neuroimaging-Driven Brain Age Estimation for Identification of Brain Disorders and Health Conditions
Authors: Shiwangi Mishra, Iman Beheshti, Pritee Khanna
Journal: IEEE Reviews in Biomedical Engineering (2021)

<italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Background:</i> Neuroimage analysis has made it possible to perform various anatomical analyses of the brain regions and helps detect different brain conditions/ disorders. Recently, neuroimaging-driven estimation of brain age is introduced as a robust biomarker for detecting different diseases and health conditions. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Objective:</i> To present a comprehensive review of brain age frameworks concerning: i) designing view: an overview of brain age frameworks based on image modality and methods used, and ii) clinical aspect: an overview of the application of brain age frameworks for detection of neurological disorders or health conditions. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Methods:</i> PubMed is explored to collect 136 articles from January 2010 to June 2021 using "Brain Age Estimation" and "Brain Imaging," along with combinations of other radiological terms. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Results &amp; Conclusion:</i> The studies presented in this review are evidence of using brain age estimation methods in detecting various brain diseases/conditions. The survey also highlights tools and methods for brain age estimation and addresses some future research directions.
26313 Efficacy and safety of dupilumab for up to 1 year in a phase 3 open-label extension (OLE) trial (LIBERTY AD PED-OLE) in adolescents with uncontrolled, moderate-to-severe atopic dermatitis (AD)
Authors: Andrew Blauvelt, Emma Guttman-Yassky, Amy S. Paller, Eric L. Simpson, John Browning, Zhen Chen, Dimittri Delevry, Puneet Mahajan, John T. O’Malley, Ashish Bansal
Journal: Journal of the American Academy of Dermatology (2021)
The Pharmacokinetic Evaluation Of Oral Administered Carbon Monoxide Instilled In a Liquid Formulation (CO-LF) To Rats To Determine Carbon Monoxide Hemoglobin Levels With Potential Efficacy In Patients With Sickle Cell Disease (SCD)
Authors: Edward D. Gomperts, Martin I Lee, Henry J Forman, Honglei Liu
Journal: Blood (2013)
Platinum-resistant ovarian cancer: From drug resistance mechanisms to liquid biopsy-based biomarkers for disease management
Authors: Mohammad Aslam Khan, Kunwar Somesh Vikramdeo, Sarabjeet Kour Sudan, Seema Singh, Annelise Wilhite, Santanu Dasgupta, Rodney Paul Rocconi, Ajay Pratap Singh
Journal: Seminars in Cancer Biology (2021)
COVID-19 Vaccines Complicate Mammograms
Journal: Cancer Discovery (2021)

Abstract In a small number of people, an unexpected side effect of the COVID-19 vaccine has emerged: swollen lymph nodes on the same side of the body as the shot was given. For women who undergo breast screening soon after vaccination, such swelling can show up on a mammogram, so clinicians may need to take extra steps to educate patients about this possibility and assess the need for follow-up testing.
Mogamulizumab efficacy is underscored by its associated rash that mimics cutaneous T-cell lymphoma: a retrospective single-centre case series
Authors: N.A. Trum, J. Zain, X.U. Martinez, V. Parekh, M. Afkhami, F. Abdulla, K.R. Carson, S.T. Rosen, C.L. Bennett, C. Querfeld
Journal: British Journal of Dermatology (2021)

Summary Background Mogamulizumab is a humanized antibody against chemokine receptor type 4. It was recently approved by the US Food and Drug Administration for relapsed or refractory mycosis fungoides (MF) and Sézary syndrome (SS). The most commonly reported adverse event in the phase III licensing trial was drug eruption (28%), now termed mogamulizumab-associated rash (MAR). Clinical recommendations about MAR and its treatment differ between the current package insert and postapproval insights reported from two single-centre studies that focused on its characterization, but less so on outcomes and clinicopathological differentiation from cutaneous T-cell lymphoma (CTCL). Objectives To describe our experience in the diagnosis of MAR and treatment of patients with CTCL with mogamulizumab. Methods This is a single-centre retrospective case series study. Results We found a higher incidence of MAR in patients with CTCL (17 of 24, 68%) than previously reported. MAR development is associated with complete (11 of 17) or partial (four of 17) responses, with an overall response rate of 88%, compared with 29% (two of seven) in patients without MAR. Diagnosis of MAR may be obscured by its ability to mimic key CTCL features both clinically and histologically, but an absence of T-cell-receptor clonality and relatively decreased CD4 : CD8 ratio compared with baseline lesions strongly favour MAR over recurrent disease. Conclusions MAR has the potential to create a significant management problem for patients on mogamulizumab. Misidentification of MAR as recurrent CTCL may detrimentally result in the premature discontinuation of mogamulizumab in patients whose disease is historically hard to treat. Thorough clinicopathological investigation of new lesions during treatment with mogamulizumab is required to inform ideal treatment decisions and achieve better outcomes.
27915 Rapid skin improvement with upadacitinib with or without topical corticosteroids (TCS) in moderate-to-severe atopic dermatitis (AD): Results from 3 phase 3 studies (Measure Up 1, Measure Up 2, and AD Up)
Authors: Eric L. Simpson, Richard B. Warren, Lawrence F. Eichenfield, Norito Katoh, Xiaofei Hu, Jiewei Zeng, Brian M. Calimlim, Allan R. Tenorio, Henrique D. Teixeira, Marjolein De Bruin-Weller
Journal: Journal of the American Academy of Dermatology (2021)
Corrigendum to “Layered double hydroxides as effective carrier for anticancer drugs and tailoring of release rate through interlayer anions” [Journal of Controlled Release 224 (2106) 186–198]
Authors: Sudipta Senapati, Ravi Thakur, Shiv Prakash Verma, Shivali Duggal, Durga Prasad Mishra, Parimal Das, T. Shripathi, Mohan Kumar, Dipak Rana, Pralay Maiti
Journal: Journal of Controlled Release (2021)
Abstract 12593: Growth Stunting Persists in Single Ventricle Patients After Heart Transplantation Even When Nutritional Weight Gain is Achieved
Authors: Alyssa Power, Lisa Schultz, Katelin Dennis, Sandra Rizzuto, Amanda M Hollander, David N Rosenthal, Christopher S Almond, Seth A Hollander
Journal: Circulation (2018)

Introduction: Malnutrition is common in children with single ventricle (SV) physiology and may take on the form of wasting (low weight) and/or stunting (short stature). The impact of heart transpla...
BMP/TGFβシグナル伝達におけるプロスタサイクリン類似体による平衡作用:肺動脈高血圧症におけるPG12の新規抗増殖機構
Authors: Ogo Takeshi, Ogo Keiko, Tsuji Akihiro, Takagi Yaemi, Demachi Jun, Morisaki Hiroko, Morisaki Takayuki, Morrell Nick, Trembath Richard, Nakanishi Norifumi
Journal: Circulation (2013)
Beyond the Front Line: Emerging Data for Maintenance Therapy in Pancreatic Cancer
Authors: Harshabad Singh, Kimberly Perez, Brian M. Wolpin, Andrew J. Aguirre
Journal: Journal of Clinical Oncology (2021)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.