tbuckley/cabot-search huggingface dataset:
Relationship Between Residual Mitral Regurgitation and Clinical and Quality-of-Life Outcomes After Transcatheter and Medical Treatments in Heart Failure
Authors: Saibal Kar, Michael J. Mack, JoAnn Lindenfeld, William T. Abraham, Federico M. Asch, Neil J. Weissman, Maurice Enriquez-Sarano, D. Scott Lim, Jacob M. Mishell, Brian K. Whisenant, Jason H. Rogers, Suzanne V. Arnold, David J. Cohen, Paul A. Grayburn, Gregg W. Stone
Journal: Circulation (2021)

In the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation), among 614 patients with heart failure with 3+ or 4+ secondary mitral regurgitation (MR), transcatheter mitral valve repair (TMVr) with the MitraClip reduced MR, heart failure hospitalizations, and mortality and improved quality of life compared with guideline-directed medical therapy (GDMT) alone. We aimed to examine the prognostic relationship between MR reduction and outcomes after TMVr and GDMT alone.Outcomes in COAPT between 30 days and 2 years were examined on the basis of the severity of residual MR at 30 days.TMVr-treated patients had less severe residual MR at 30 days than GDMT-treated patients (0/1+, 2+, and 3+/4+: 72.9%, 19.9%, and 7.2% versus 8.2%, 26.1%, and 65.8%, respectively [P<0.0001]). The rate of composite death or heart failure hospitalizations between 30 days and 2 years was lower in patients with 30-day residual MR of 0/1+ and 2+ compared with patients with 30-day residual MR of 3+/4+ (37.7% versus 49.5% versus 72.2%, respectively [P<0.0001]). This relationship was consistent in the TMVr and GDMT arms (Pinteraction=0.92). The improvement in Kansas City Cardiomyopathy Questionnaire score from baseline to 30 days was maintained between 30 days and 2 years in patients with 30-day MR ≤2+ but deteriorated in those with 30-day MR 3+/4+ (-0.3±1.7 versus -9.4±4.6 [P=0.0008]) consistently in both groups (Pinteraction=0.95).In the COAPT trial, reduced MR at 30 days was associated with greater freedom from death or heart failure hospitalizations and improved quality of life through 2-year follow-up whether the MR reduction was achieved by TMVr or GDMT. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.
Clinicopathologic Features and Response to Therapy of<i>NRG1</i>Fusion–Driven Lung Cancers: The eNRGy1 Global Multicenter Registry
Authors: Alexander Drilon, Michael Duruisseaux, Ji-Youn Han, Masaoki Ito, Christina Falcon, Soo-Ryum Yang, Yonina R. Murciano-Goroff, Haiquan Chen, Morihito Okada, Miguel Angel Molina, Marie Wislez, Philippe Brun, Clarisse Dupont, Eva Branden, Giulio Rossi, Alexa Schrock, Siraj Ali, Valérie Gounant, Fanny Magne, Torsten Gerriet Blum, Alison M. Schram, Isabelle Monnet, Jin-Yuan Shih, Joshua Sabari, Maurice Pérol, Viola W. Zhu, Misako Nagasaka, Robert Doebele, D. Ross Camidge, Maria Arcila, Sai-Hong Ignatius Ou, Denis Moro-Sibilot, Rafael Rosell, Lucia Anna Muscarella, Stephen V. Liu, Jacques Cadranel
Journal: Journal of Clinical Oncology (2021)

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Trailblazing precision medicine in Europe: A joint view by Genomic Medicine Sweden and the Centers for Personalized Medicine, ZPM, in Germany
Authors: Albrecht Stenzinger, Anders Edsjö, Carolin Ploeger, Mikaela Friedman, Stefan Fröhling, Valtteri Wirta, Thomas Seufferlein, Johan Botling, Justus Duyster, Michael Akhras, Robert Thimme, Thoas Fioretos, Michael Bitzer, Lucia Cavelier, Peter Schirmacher, Nisar Malek, Richard Rosenquist, Anna Lindstrand, Anna Wedell, David Gisselsson, Erik Melén, Gisela Helenius, Hans Ehrencrona, Lars Engstrand, Lars Palmqvist, Lars-Åke Levin, Lovisa Lovmar, Maréne Landström, Martin Hallbeck, Mia Wadelius, Per Sikora, Ambros J. Beer, Anna L. Illert, Jan Budczies, Konstantin Nikolaou, Oliver Kohlbacher, Peter Horak, Peter Kuhn, Christopher Schroeder, Melanie Boerries, Silke Lassmann, Verena I. Gaidzik
Journal: Seminars in Cancer Biology (2021)
Incidental Finding of Hibernoma in Prostate-Specific Membrane Antigen PET/CT
Authors: Aurélie Moreau, Thierry Cruel, Anne Laure Giraudet, Philippe Derolland, David Kryza
Journal: Clinical Nuclear Medicine (2021)

We reported the case of a 76-year-old man followed up since 2008 for a prostatic adenocarcinoma with pelvic and retroperitoneal nodes. He was initially treated by hormonotherapy with a good biological response. Twelve years after, he demonstrated an increased PSA level up to 10.2 ng/mL. He underwent a 68Ga-PSMA PET/CT, which shown an intense uptake by a left iliac extern mass, suspected of recurrence. The histology concluded in a hibernoma.
Immunogenicity of Pfizer-BioNTech COVID-19 vaccine in patients with inborn errors of immunity
Authors: David Hagin, Tal Freund, Michal Navon, Tami Halperin, Dikla Adir, Rotem Marom, Inbar Levi, Shira Benor, Yifat Alcalay, Natalia T. Freund
Journal: Journal of Allergy and Clinical Immunology (2021)

In mid-December 2020, Israel started a nationwide mass vaccination campaign against coronavirus disease 2019 (COVID-19). In the first few weeks, medical personnel, elderly citizens, and patients with chronic diseases were prioritized. As such, patients with primary and secondary immunodeficiencies were encouraged to receive the vaccine. Although the efficacy of RNA-based COVID-19 vaccines has been demonstrated in the general population, little is known about their efficacy and safety in patients with inborn errors of immunity (IEI).Our aim was to evaluate the humoral and cellular immune response to COVID-19 vaccine in a cohort of patients with IEI.A total of 26 adult patients were enrolled, and plasma and peripheral blood mononuclear cells were collected from them 2 weeks following the second dose of Pfizer-BioNTech COVID-19 vaccine. Humoral response was evaluated by testing anti-SARS-CoV-2 spike (S) receptor-binding domain and antinucleocapsid antibody titers and evaluating neutralizing ability by inhibition of receptor-binding domain-angiotensin-converting enzyme 2 binding. Cellular immune response was evaluated by using ELISpot, estimating IL-2 and IFN-γ secretion in response to pooled SARS-CoV-2 S- or M-peptides.Our cohort included 18 patients with a predominantly antibody deficiency, 2 with combined immunodeficiency, 3 with immune dysregulation, and 3 with other genetically defined diagnoses. Twenty-two of them were receiving immunoglobulin replacement therapy. Of the 26 patients, 18 developed specific antibody response, and 19 showed S-peptide-specific T-cell response. None of the patients reported significant adverse events.Vaccinating patients with IEI is safe, and most patients were able to develop vaccine-specific antibody response, S-protein-specific cellular response, or both.
Smart Asymmetric Hydrogel with Integrated Multi‐Functions of NIR‐Triggered Tunable Adhesion, Self‐Deformation, and Bacterial Eradication
Authors: Lan Feng, Wenbin Shi, Qin Chen, Huitong Cheng, Jianxu Bao, Chunji Jiang, Weifeng Zhao, Changsheng Zhao
Journal: Advanced Healthcare Materials (2021)

Abstract Multifunctional hydrogels acting as wound dressing have received extensive attention in soft tissue repair; however, it is still a challenge to develop a non‐antibiotic‐dependent antibacterial hydrogel that has tunable adhesion and deformation to achieve on‐demand removal. Herein, an asymmetric adhesive hydrogel with near‐infrared (NIR)‐triggered tunable adhesion, self‐deformation, and bacterial eradication is designed. The hydrogel is prepared by the crosslinking polymerization of N ‐isopropylacrylamide and acrylic acid, during the sedimentation of conductive PPy‐PDA nanoparticles based on the polymerization of pyrrole (Py) and dopamine (DA). Due to the conversion capacity from NIR light into heat for PPy‐PDA NPs, the formed temperature‐sensitive hydrogel exhibits tissue adhesive as well as NIR‐triggered tunable adhesion and self‐deformation property, which can achieve an on‐demand dressing refreshing. Systematically in vitro / in vivo antibacterial experiments indicate that the hydrogel shows excellent disinfection capability to both Gram‐negative and Gram‐positive bacteria. The in vivo experiments in a full‐layer cutaneous wound model demonstrate that the hydrogel has a good treatment effect to promote wound healing. Overall, the asymmetric hydrogel with tunable adhesion, self‐deformation, conductive, and photothermal antibacterial activity may be a promising candidate to fulfill the functions of adhesion on skin tissue, easy removing on‐demand, and accelerating the wound healing process.
Social Connectedness Among Medicare Beneficiaries Following the Onset of the COVID-19 Pandemic
Authors: Wesley J. Talcott, James B. Yu, Cary P. Gross, Henry S. Park
Journal: JAMA Internal Medicine (2021)

Social Connectedness Among Medicare Beneficiaries Following the Onset of the COVID-19 PandemicSocial distancing is an effective strategy to limit contagion and mortality from the COVID-19 pandemic.However, these measures may also decrease perceived social connectedness and conversely increase social isolation, states which are associated with psychologic and physiologic morbidity. 1-5Patients who are elderly or have disabilities are particularly encouraged to practice social distancing given their higher risk of severe COVID-19 infection, but they also have a higher baseline risk for reporting social isolation. 5,6We hypothesized that the pandemic and social distancing measures have negatively affected perceptions of social connectedness among these high-risk patients.
Abstract 16209: Safety and Efficacy of Percutaneous Groin Access Closure vs. Surgical Cutdown for Thoracic Endovascular Aortic Repair and Transcatheter Aortic Valve Replacement: A Single-Center Retrospective Analysis
Authors: Adam M Carroll, T. B Reece, Christian V Ghincea, Yuki Ikeno, Kaitlin Roth, Dominik M Wiktor, John C Messenger, John D Carroll, Joseph C Cleveland, David A Fullerton, Muhammad Aftab
Journal: Circulation (2019)

Introduction: Thoracic endovascular aortic repair (TEVAR) and transcatheter aortic valve replacement (TAVR) necessitate large-bore arterial access for stent/valve delivery. With improvement of devi...
Practices and Attitudes of Swiss Stakeholders Regarding Investigator-Initiated Clinical Trial Funding Acquisition and Cost Management
Authors: Stuart McLennan, Alexandra Griessbach, Matthias Briel
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Randomized clinical trials (RCTs) are an essential method of evaluating health care interventions and a cornerstone for evidence-based health care. However, RCTs have become increasingly complex and costly, which is particularly challenging for independent investigator-initiated clinical trials (IICTs). IICTs have an essential role in clinical research, and it is important that efforts are made to ensure IICTs are adequately funded and are conducted cost-effectively. <h3>Objective</h3> To examine the practices and attitudes of Swiss stakeholders regarding IICT funding acquisition and cost management. <h3>Design, Setting, and Participants</h3> For this qualitative study, interviews were conducted in Switzerland between February and August 2020. The purposive sample comprised 48 stakeholders from 4 different groups: primary investigators (n = 27), funders and sponsors (n = 9), clinical trial support organizations (n = 6), and ethics committee members (n = 6). <h3>Main Outcomes and Measures</h3> Practices and attitudes of stakeholders regarding IICT funding acquisition and cost management were assessed using individual semistructured qualitative interviews. Interviews were analyzed using conventional content analysis. <h3>Results</h3> After interviews with 48 IICT stakeholders (75% male presenting), these participants identified a systemic problem of IICTs being underfunded, which can lead to compromises being made regarding the quality and conduct of IICTs. Participants identified 2 overarching and interconnected groups of reasons why IICTs in Switzerland are regularly underfunded. First, it was reported that IICT budget estimations are often inaccurate because of poor planning and preparation, unforeseeable events, investigators intentionally underestimating budgets, and limited budget assessment and oversight. Second, with the exception of a specific IICT funding program by the Swiss National Science Foundation, it was reported that limited funding sources and unrealistic expectation of funders led to underlying challenges in getting IICTs fully funded. A number of measures that could help reduce the underfunding of IICTs were identified, including improving the support of investigators and IICTs, strengthening networking and guidance, harmonizing and simplifying bureaucracy, and increasing public funding of IICTs. <h3>Conclusions and Relevance</h3> This study highlights the inadequate expertise of Swiss stakeholders to correctly, systematically, and reproducibly calculate RCT budgets and the need for transparency on trial costs as well as training in budgeting practices. Limited financial resources for academic clinical research and issues regarding the professional planning and conduct of IICTs are persistent issues that many other countries also face.
Accurate construction of cell membrane biomimetic graphene nanodecoys via purposeful surface engineering to improve screening efficiency of active components of traditional Chinese medicine
Authors: Qi Hu, Lanlan Jia, Xiaolin Zhang, Aihong Zhu, Sicen Wang, Xiaoyu Xie
Journal: Acta Pharmaceutica Sinica B (2021)

Biomimetic nanoengineering presents great potential in biomedical research by integrating cell membrane (CM) with functional nanoparticles. However, preparation of CM biomimetic nanomaterials for custom applications that can avoid the aggregation of nanocarriers while maintaining the biological activity of CM remains a challenge. Herein, a high-performance CM biomimetic graphene nanodecoy was fabricated via purposeful surface engineering, where polyethylene glycol (PEG) was used to modifying magnetic graphene oxide (MGO) to improve its stability in physiological solution, so as to improve the screening efficiency to active components of traditional Chinese medicine (TCM). With this strategy, the constructed PEGylated MGO (PMGO) could keep stable at least 10 days, thus improving the CM coating efficiency. Meanwhile, by taking advantage of the inherent ability of HeLa cell membrane (HM) to interact with specific ligands, HM-camouflaged PMGO showed satisfied adsorption capacity (116.2 mg/g) and selectivity. Finally, three potential active components, byakangelicol, imperatorin, and isoimperatorin, were screened from Angelica dahurica, whose potential antiproliferative activity were further validated by pharmacological studies. These results demonstrated that the purposeful surface engineering is a promising strategy for the design of efficient CM biomimetic nanomaterials, which will promote the development of active components screening in TCM.
POS0430 EXPRESSION AND CLINICAL SIGNIFICANCE OF AUTOPHAGY-RELATED GENES IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF SYSTEMIC SCLEROSIS
Authors: Y. F. Qing, J. Zheng, S. B. Wang, F. Dai, Y. Jiang, Y. X. He, Q. B. Zhang
Journal: Annals of the Rheumatic Diseases (2021)

Background: Growing evidences have demonstrated that autophagy is a powerful regulators in the pathogenesis of fibrosis and autoimmune diseases. Autophagy abnormalities in SSc involve abnormal autophagy-related protein and autophagy-related gene polymorphism [1-2] , however there is a few reports on the expression and clinical significance of autophagy-related genes. Objectives: To investigate the expression and clinical significance of autophagy-related genes LC-3 mRNA, Becline-1 mRNA, Agt-3 mRNA, Agt-5 mRNA, Agt-12 mRNA and Agt-16L1 mRNA in peripheral blood mononuclear cells (PBMC) of systemic sclerosis (SSc). Methods: 51 cases of SSc and 60 cases of normal control were received from the Affiliated Hospital of North Sichuan Medical College, and autophagy-related genes were detected by RT-PCR. SPSS19.0 statistical software was used to compare the expression of autophagy-related genes between groups and analyze the relationship between autophagy-related genes and clinical data, P&lt;0.05 was considered statistically significant Results: LC-3, Becline-1, and Agt-3 were highly expressed in SSc compared with normal control [LC-3: 0.78(0.60) ×10 -3 vs. 0.52(0.54) ×10 -3 ; Beclin-1: 6.68(3.56)×10 -3 vs. 5.22(3.54)×10 -3 ; Agt-3: 17.58(12.33)×10 -3 vs. 11.00(4.56)×10 -3 , P&lt;0.05], however Agt-5, Agt-12 and Agt-16L1 of autophagy-related genes were not statistically significant [AGT-5: 6.67(3.58) ×10 -3 vs. 6.67(2.64) ×10 -3 ; AGT-12: 8.64(5.56)×10 -3 vs. 8.57(4.66)×10 -3 ; Agt-16L1: 2.69(2.19)×10 -3 vs. 2.52(2.26)×10 -3 ] (Figure 1). Beclin-1 and Agt-5 high expressed in SSc with the positive of anti-SSA/Ro antibody. LC-3 was positively correlated with Age(r=0.662) and ESR(r=0.355) (all P&lt;0.05). Conclusion: Autophagy-related genes were increased in PBMC of SSc, and were correlated with Age, ESR and autoantibody, suggested that autophagy is a key feature in the pathogenesis of systemic sclerosis. Figure 1. The relative expression of autophagy-related genes References: [1]LIU C, ZHOU X, LU J, et al. Autophagy mediates 2-methoxyestradiol-inhibited scleroderma collagen synthesis and endothelial-to-mesenchymal transition induced by hypoxia[J]. Rheumatology, 2019;58(11):1966–1975. [2]Mayes M D, Bossini-Castillo L, Gorlova O, et al. Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis[J]. The American Journal of Human Genetics, 2014,94(1):47-61.DOI:10.1016/j.ajhg.2013.12.002. Disclosure of Interests: None declared
Skeletal Muscle Metastases in HCC Revealed by 18F-Choline PET/CT
Authors: Laura Evangelista, Francesco Giacomuzzi, Fernando Di Gregorio, Marco Rensi
Journal: Clinical Nuclear Medicine (2021)

We present a case of a 68-year-old woman undergoing 18F-choline PET/CT due to a history of hepatocellular cancer treated with multimodal therapies and with a rapid increase in α-fetoprotein. 18F-Choline PET/CT showed multiple uptakes in the skeletal muscles compatible with the recurrence of disease. The interpretation of 18F-choline PET/CT in this cancer should be careful and discussed in a multidisciplinary team.
Histone deficiency and accelerated replication stress in T cell aging
Authors: Chulwoo Kim, Jun Jin, Zhongde Ye, Rohit R. Jadhav, Claire E. Gustafson, Bin Hu, Wenqiang Cao, Lu Tian, Cornelia M. Weyand, Jörg J. Goronzy
Journal: Journal of Clinical Investigation (2021)

With increasing age, individuals are more vulnerable to viral infections such as with influenza or the SARS-CoV-2 virus. One age-associated defect in human T cells is the reduced expression of miR-181a. miR-181ab1 deficiency in peripheral murine T cells causes delayed viral clearance after infection, resembling human immune aging. Here we show that naive T cells from older individuals as well as miR-181ab1–deficient murine T cells develop excessive replication stress after activation, due to reduced histone expression and delayed S-phase cell cycle progression. Reduced histone expression was caused by the miR-181a target SIRT1 that directly repressed transcription of histone genes by binding to their promoters and reducing histone acetylation. Inhibition of SIRT1 activity or SIRT1 silencing increased histone expression, restored cell cycle progression, diminished the replication-stress response, and reduced the production of inflammatory mediators in replicating T cells from old individuals. Correspondingly, treatment with SIRT1 inhibitors improved viral clearance in mice with miR-181a–deficient T cells after LCMV infection. In conclusion, SIRT1 inhibition may be beneficial to treat systemic viral infection in older individuals by targeting antigen-specific T cells that develop replication stress due to miR-181a deficiency.
POS0829 SPECIFICITY OF PANCA AUTOANTIBODIES IN AUTOIMMUNE DISEASES
Authors: O. Argyropoulou, A. Tsirogianni, C. Sfontouris, G. Boutzios, P. Vlachoyiannopoulos, A. Tzioufas, E. Kapsogeorgou
Journal: Annals of the Rheumatic Diseases (2021)

Background: The clinical significance of pANCA by indirect immunofluorescence is well-established. However, their clinical utility is sometimes hindered by the fact that pANCA are also detected in various autoimmune diseases. Myeloperoxidase (MPO) is considered as the major autoantigen recognized by pANCA in ANCA-associated vasculitides (AAV) and predominantly in microscopic polyangiitis (MPA). However, information regarding the targets of pANCA in other autoimmune diseases is still elusive. Objectives: To investigate the specific autoantigens recognized by pANCA in autoimmune diseases. Methods: Sera from all patients that were found positive for pANCA in the diagnostic laboratories of the Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens and the Department of Immunology and Histocompatibility, Evangelismos General Hospital, Athens, Greece during the last two years were studied. The pANCA+ sera were evaluated for reactivity with the major antigens that are recognized by pANCA [MPO, lactoferrin, neutrophil elastase, cathepsin G and bactericidal/permeability increasing protein (BPI)] by a commercially available multiplex ELISA (ANCA profile ELISA, Euroimmun, Lubeck, Germany). Results: A total of 82 patients were included in the study. All patients had positive pANCA by indirect immunofluorescence with a title ranging from 1/160 to 1/640. According to respective classification criteria, 21 patients had systemic vasculitides (15 MPA, 1 granulomatosis with polyangiitis; GPA, 1 Behcet’s disease; BD, 1 aortitis, 2 Henoch-Schonlein purpura; HSP and 1 cryoglobulinemic vasculitis; CV), 29 had systemic lupus erythematosus (SLE), 6 antiphospholipid syndrome (APS), 8 Sjögren’s syndrome (SS), 2 rheumatoid arthritis (RA), 1 systemic scleroderma (SScl), 14 Hashimoto thyroiditis and 1 sarcoidosis. The specificities of pANCA in each entity are shown in the following table. Autoimmune Diseases Antigens recognized by pANCA+ sera MPO Elastase Cathepsin G BPI Lactoferrin Vasculitides MPA 66.7 (10/15) 0 (0/15) 0 (0/15) 0 (0/15) 0 (0/15) GPA 100 (1/1) 0 (0/1) 0 (0/1) 0 (0/1) 0 (0/1) BD 100 (1/1) 0 (0/1) 0 (0/1) 0 (0/1) 0 (0/1) Aortitis 0 (0/1) 0 (0/1) 0 (0/1) 0 (0/1) 0 (0/1) HSP 0 (0/2) 0 (0/2) 0 (0/2) 0 (0/2) 0 (0/2) CV 0 (0/1) 0 (0/1) 0 (0/1) 0(0/1) 100 (1/1) SLE 6.9 (2/29) 0 (0/29) 0 (0/29) 0 (0/29) 6.9 (2/29) APS 16.6 (1/6) 16.6 (1/6) 0 (0/6) 0 (0/6) 0 (0/6) SS 0 (0/8) 12.5 (1/8) 0 (0/8) 12.5 (1/8) 0 (0/8) RA 50 (1/2) 0 (0/2) 0 (0/2) 0 (0/2) 0 (0/2) SScl 100 (1/1) 0 (0/1) 0 (0/1) 0 (0/1) 0 (0/1) Hashimoto 0 (0/14) 0 (0/14) 0 (0/14) 0 (0/14) 0 (0/14) Sarcoidosis 0 (0/1) 0 (0/1) 0 (0/1) 0 (0/1) 0 (0/1) Conclusion: pANCA positive staining in AAVs is highly restricted to MPO specificity. On the contrary, pANCA staining pattern in other autoimmune diseases, involves unknown autoantigens that are under investigation in our laboratory. Disclosure of Interests: None declared