tbuckley/cabot-search huggingface dataset:
Dual PET Imaging of an H3K27M-Mutant Glioma With 18F-GE-180 and 18F-FET PET
Authors: Franziska J. Vettermann, Marcus Unterrainer, Viktoria Ruf, Daniel F. Fleischmann, Rainer Rupprecht, Robert Forbrig, Jochen Herms, Joerg C. Tonn, Claus Belka, Peter Bartenstein, Maximilian Niyazi, Nathalie L. Albert
Journal: Clinical Nuclear Medicine (2020)

Abstract A 25-year-old man presented with headache and intracranial pressure symptoms. On MRI, an intracranial lesion was detected in the right thalamus with exophytic growth into the third ventricle and inhomogeneous contrast enhancement without necrosis. Dual amino acid ( 18 F-FET) and TSPO ( 18 F-GE-180) PET imaging showed high tumor-to-background ratios in both scans and a short time-to-peak in 18 F-FET uptake dynamics. Biopsy revealed a diffuse midline glioma, H3K27M-mutant (WHO grade IV), a novel entity in the 2016 WHO classification with poor clinical outcome. Our case shows that the highly aggressive features of this tumor entity can be visualized in vivo by both PET modalities.
Stereotactic Radiotherapy and Resection of Brain Metastases
Authors: Debra Nana Yeboa, Iris C. Gibbs
Journal: JAMA Oncology (2020)

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Efficacy and safety of tafamidis doses in the <scp>Tafamidis in Transthyretin Cardiomyopathy Clinical Trial</scp> (<scp>ATTR‐ACT</scp>) and long‐term extension study
Authors: Thibaud Damy, Pablo Garcia‐Pavia, Mazen Hanna, Daniel P. Judge, Giampaolo Merlini, Balarama Gundapaneni, Terrell A. Patterson, Steven Riley, Jeffrey H. Schwartz, Marla B. Sultan, Ronald Witteles
Journal: European Journal of Heart Failure (2020)

Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM) in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). While ATTR-ACT was not designed for a dose-specific assessment, further analysis from ATTR-ACT and its long-term extension study (LTE) can guide determination of the optimal dose.In ATTR-ACT, patients were randomized (2:1:2) to tafamidis 80 mg, 20 mg, or placebo for 30 months. Patients completing ATTR-ACT could enrol in the LTE (with placebo-treated patients randomized to tafamidis 80 or 20 mg; 2:1) and all patients were subsequently switched to high-dose tafamidis. All-cause mortality was assessed in ATTR-ACT combined with the LTE (median follow-up 51 months). In ATTR-ACT, the combination of all-cause mortality and cardiovascular-related hospitalizations over 30 months was significantly reduced with tafamidis 80 mg (P = 0.0030) and 20 mg (P = 0.0048) vs. placebo. All-cause mortality vs. placebo was reduced with tafamidis 80 mg [Cox hazards model (95% confidence interval): 0.690 (0.487-0.979), P = 0.0378] and 20 mg [0.715 (0.450-1.137), P = 0.1564]. The mean (standard error) change in N-terminal pro-B-type natriuretic peptide from baseline to Month 30 was -1170.51 (587.31) (P = 0.0468) with tafamidis 80 vs. 20 mg. In ATTR-ACT combined with the LTE there was a significantly greater survival benefit with tafamidis 80 vs. 20 mg [0.700 (0.501-0.979), P = 0.0374]. Incidence of adverse events in both tafamidis doses were comparable to placebo.Tafamidis, both 80 and 20 mg, effectively reduced mortality and cardiovascular-related hospitalizations in patients with ATTR-CM. The longer-term survival data and the lack of dose-related safety concerns support tafamidis 80 mg as the optimal dose.ClinicalTrials.gov NCT01994889; NCT02791230.
OATargets: a knowledge base of genes associated with osteoarthritis joint damage in animals
Authors: Jamie Soul, Matthew J Barter, Christopher B Little, David A Young
Journal: Annals of the Rheumatic Diseases (2020)

Objectives To collate the genes experimentally modulated in animal models of osteoarthritis (OA) and compare these data with OA transcriptomics data to identify potential therapeutic targets. Methods PubMed searches were conducted to identify publications describing gene modulations in animal models. Analysed gene expression data were retrieved from the SkeletalVis database of analysed skeletal microarray and RNA-Seq expression data. A network diffusion approach was used to predict new genes associated with OA joint damage. Results A total of 459 genes were identified as having been modulated in animal models of OA, with ageing and post-traumatic (surgical) models the most prominent. Ninety-eight of the 143 genes (69%) genetically modulated more than once had a consistent effect on OA joint damage severity. Several discrepancies between different studies were identified, providing lessons on interpretation of these data. We used the data collected along with OA gene expression data to expand existing annotations and prioritise the most promising therapeutic targets, which we validated using the latest reported associations. We constructed an online database OATargets to allow researchers to explore the collated data and integrate it with existing OA and skeletal gene expression data. Conclusions We present a comprehensive survey and online resource for understanding gene regulation of animal model OA pathogenesis.
Association of outcomes in acute flaccid myelitis with identification of enterovirus at presentation: a Canadian, nationwide, longitudinal study
Authors: Carmen Yea, Ari Bitnun, Helen M Branson, Beyza Ciftci-Kavaklioglu, Mubeen F Rafay, Olivier Fortin, Paola Moresoli, Guillaume Sébire, Myriam Srour, Hélène Decaluwe, Louis Marois, Félixe Pelletier, Michelle Barton, Maryam Nabavi Nouri, Jason Brophy, Sunita Venkateswaran, Daniela Pohl, Kathryn Selby, Kevin Jones, Joan Robinson, Aleksandra Mineyko, Christoph Licht, Birgit Ertl-Wagner, E Ann Yeh
Journal: The Lancet Child & Adolescent Health (2020)
Interleukin‐7/Interferon Axis Drives T Cell and Salivary Gland Epithelial Cell Interactions in Sjögren’s Syndrome
Authors: Elodie Rivière, Juliette Pascaud, Alexandre Virone, Anastasia Dupré, Bineta Ly, Audrey Paoletti, Raphaèle Seror, Nicolas Tchitchek, Michael Mingueneau, Nikaïa Smith, Darragh Duffy, Lydie Cassard, Nathalie Chaput, Sabrina Pengam, Vanessa Gauttier, Nicolas Poirier, Xavier Mariette, Gaetane Nocturne
Journal: Arthritis & Rheumatology (2020)

Objective Primary Sjögren’s syndrome (SS) is characterized by a lymphocytic infiltration of salivary glands (SGs) and the presence of an interferon (IFN) signature. SG epithelial cells (SGECs) play an active role in primary SS pathophysiology. We undertook this study to examine the interactions between SGECs and T cells in primary SS and the role of the interleukin‐7 (IL‐7)/IFN axis. Methods Primary cultured SGECs from control subjects and patients with primary SS were stimulated with poly(I‐C), IFNα, or IFNγ. T cells were sorted from blood and stimulated with IL‐7. CD25 expression was assessed by flow cytometry. SG explants were cultured for 4 days with anti–IL‐7 receptor (IL‐7R) antagonist antibody (OSE‐127), and transcriptomic analysis was performed using the NanoString platform. Results Serum IL‐7 level was increased in patients with primary SS compared to controls and was associated with B cell biomarkers. IL7R expression was decreased in T cells from patients with primary SS compared to controls. SGECs stimulated with poly(I‐C), IFNα, or IFNγ secreted IL‐7. IL‐7 stimulation increased the activation of T cells, as well as IFNγ secretion. Transcriptomic analysis of SG explants showed a correlation between IL7 and IFN expression. Finally, explants cultured with anti–IL‐7R antibody showed decreased IFN‐stimulated gene expression. Conclusion These results suggest the presence of an IL‐7/IFNγ amplification loop involving SGECs and T cells in primary SS. IL‐7 was secreted by SGECs stimulated with type I or type II IFN and, in turn, activated T cells that secrete type II IFN. An anti–IL‐7R antibody decreased the IFN signature in T cells in primary SS and could be of therapeutic interest.
A global benchmark of algorithms for segmenting the left atrium from late gadolinium-enhanced cardiac magnetic resonance imaging
Authors: Zhaohan Xiong, Qing Xia, Zhiqiang Hu, Ning Huang, Cheng Bian, Yefeng Zheng, Sulaiman Vesal, Nishant Ravikumar, Andreas Maier, Xin Yang, Pheng-Ann Heng, Dong Ni, Caizi Li, Qianqian Tong, Weixin Si, Elodie Puybareau, Younes Khoudli, Thierry Géraud, Chen Chen, Wenjia Bai, Daniel Rueckert, Lingchao Xu, Xiahai Zhuang, Xinzhe Luo, Shuman Jia, Maxime Sermesant, Yashu Liu, Kuanquan Wang, Davide Borra, Alessandro Masci, Cristiana Corsi, Coen de Vente, Mitko Veta, Rashed Karim, Chandrakanth Jayachandran Preetha, Sandy Engelhardt, Menyun Qiao, Yuanyuan Wang, Qian Tao, Marta Nuñez-Garcia, Oscar Camara, Nicolo Savioli, Pablo Lamata, Jichao Zhao
Journal: Medical Image Analysis (2020)
The epidemiology of rubella, 2007–18: an ecological analysis of surveillance data
Authors: Minal K Patel, Sébastien Antoni, M Carolina Danovaro-Holliday, Shalini Desai, Marta Gacic-Dobo, Yoann Nedelec, Katrina Kretsinger
Journal: The Lancet Global Health (2020)

BackgroundAs of 2018, the rubella vaccine had been incorporated into the national immunisation schedule of 168 countries, representing 87% of the world's population. Countries have used different strategies to reduce the burden of congenital rubella syndrome (CRS), such as vaccinating only females. Given the different strategies, and that 26 countries still had not introduced the vaccine, we analysed global rubella surveillance data to understand rubella epidemiology and the effect of vaccination.MethodsIn this ecological analysis, we evaluated surveillance data on rubella cases that had been reported to WHO from 2007 to 2018, by age, vaccination history, and onset year. Cases were classified as either being vaccine eligible or ineligible on the basis of the country's vaccination strategy and the birth year of the person. We required all cases be confirmed by laboratory testing or that they were epidemiologically linked, and we excluded cases defined only by clinical symptoms. Incidence per million people was calculated by use of World Population Prospects data.FindingsBetween Jan 1, 2007, and Dec 31, 2018, from data reported to WHO as of Jan 3, 2020, there were 139 486 reported rubella cases, of which 15 613 (11%) were vaccine eligible. Annual incidence ranged from 13·9 cases per million in 2007 to 1·7 cases per million in 2018. In all years, absolute and proportional global incidence were higher among vaccine ineligible cohorts than eligible cohorts. In vaccine ineligible cohorts, 87 666 (74%) of 118 308 cases were in children younger than 15 years, compared with 8423 (54%) of 15 613 cases in vaccine eligible cohorts. Vaccine ineligible women of reproductive age (WRA) had a higher incidence than vaccine eligible WRA, except in 2011–12.InterpretationVaccination has been successful in decreasing the burden of rubella, regardless of the strategy used. WRA remain at risk, but the risk is higher in those countries that have yet to introduce the vaccine. These countries should introduce the rubella-containing vaccine as soon as possible, to eliminate rubella, and to prevent the morbidity and mortality associated with CRS.FundingNone.
AB0138 INCREASED CD38 EXPRESSION LEVELS ON IMMUNE CELL SUBSETS IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: L. Ostendorf, P. Enghard, P. Durek, F. Heinrich, M. F. Mashreghi, G. R. Burmester, A. Radbruch, F. Hiepe, T. Alexander
Journal: Annals of the Rheumatic Diseases (2020)

Background: Plasma Cells (PCs) are implicated in the pathogenesis of Systemic Lupus erythematosus (SLE) and their targeting proved a promising treatment modality. As there is a monoclonal therapeutic antibody targeting CD38 licensed for clinical use in multiple myeloma, plasma cell depletion via CD38 seems to represent a promising path in SLE treatment. While CD38 Is highly expressed on plasmacells, it is present on the surface of subsets of T and B lymphocytes as well as myeloid cells. Objectives: Here we aim to identify the differential expression of CD38 on peripheral blood leukocytes in SLE compared to healthy controls (HC) investigate the function of CD38+ T lymphocytes Methods: We performed flow cytometry to investigate the expression of CD38 on peripheral blood mononuclear cells of SLE patients (n=36) and HCs (n=20). We additionally analyzed the expression of T lymphocytes within the urine of patients with lupus nephritis as well as the skin of SLE patients. We investigated the inflammatory potential of CD38 positive memory T lymphocytes after stimulation and performed single-cell RNA sequencing analyses. Results: CD38 Expression is increased on certain immune cell subsets: Plasmablasts and unswitched Memory B cells, as well as plasmacytoid dendritic cells and CD16+ non-classical monocytes. We observed a drastic increase CD38 in both memory CD4 and CD8 T lymphocytes in SLE patients. These cells were mostly effector T cells (and not regulatory T cells) and expressed other markers of T cell activation and proliferation. We found an enrichment of CD38+ memory T cells in the urine of patients with lupus nephritis. After polyclonal stimulation of T cells, CD38+ produced less inflammatory cytokines. Preliminary single-cell sequencing results indicate that CD38+ CD8+ T-lymphocytes have decreased clonal diversity and that these cells express genes associated with exhaustion and type 1 interferon response. Conclusion: Increased CD38 expression on various lymphocyte subsets provides an additional rationale for investigating CD38-directed therapies in SLE. Targeting CD38 could not only deplete plasma cells but also has the potential to target interferon alpha producing plasmacytoid dendritic cells and modulate inflammatory T cell functions. Disclosure of Interests: Lennard Ostendorf: None declared, Philipp Enghard: None declared, Pawel Durek: None declared, Frederik Heinrich: None declared, Mir-Farzin Mashreghi: None declared, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Andreas Radbruch: None declared, Falk Hiepe: None declared, Tobias Alexander: None declared
Quantitative Analysis of Von Willebrand Factor (VWF) Multimers in Von Willebrand Disease (VWD) Patients Recruited through the Zimmerman Program for the Molecular and Clinical Biology of VWD
Authors: Sandra L Haberichter, Pamela A Christopherson, Veronica H Flood, Joan Cox Gill, Kenneth Dale Friedman, Robert R. Montgomery
Journal: Blood (2017)
Tissue Engineered Vascular Graft Recipient Interleukin 10 Status Is Critical for Preventing Thrombosis
Authors: Gabriel J. M. Mirhaidari, Jenny C. Barker, Jacob C. Zbinden, Brevan M. Santantonio, Yu‐Chun Chang, Cameron A. Best, James W. Reinhardt, Kevin M. Blum, Tai Yi, Christopher K. Breuer
Journal: Advanced Healthcare Materials (2020)

Abstract Tissue engineered vascular grafts (TEVGs) are a promising technology, but are hindered by occlusion. Seeding with bone‐marrow derived mononuclear cells (BM‐MNCs) mitigates occlusion, yet the precise mechanism remains unclear. Seeded cells disappear quickly and potentially mediate an anti‐inflammatory effect through paracrine signaling. Here, a series of reciprocal genetic TEVG implantations plus recombinant protein treatment is reported to investigate what role interleukin‐10, an anti‐inflammatory cytokine, plays from both host and seeded cells. TEVGs seeded with BM‐MNCs from wild‐type and IL‐10 KO mice, plus unseeded grafts, are implanted into wild‐type and IL‐10 KO mice. Wild‐type mice with unseeded grafts also receive recombinant IL‐10. Serial ultrasound evaluates occlusion and TEVGs are harvested at 14 d for immunohistochemical analysis. TEVGs in IL‐10 KO mice have significantly higher occlusion incidence compared to wild‐type mice attributed to acute (&lt;3 d) thrombosis. Cell seeding rescues TEVGs in IL‐10 KO mice comparable to wild‐type patency. IL‐10 from the host and seeded cells do not significantly influence graft inflammation and macrophage phenotype, yet IL‐10 treatment shows interesting biologic effects including decreasing cell proliferation and increasing M2 macrophage polarization. IL‐10 from the host is critical for preventing TEVG thrombosis and seeded BM‐MNCs exert a significant anti‐thrombotic effect in IL‐10 KO mice.
What Next after Biologic Therapy Fails in Rheumatoid Arthritis?
Authors: Guro L. Goll, Tore K. Kvien
Journal: New England Journal of Medicine (2020)

Treatment of rheumatoid arthritis and other inflammatory joint diseases has been transformed by the use of biologic medicines. These targeted therapies are usually added to the treatment regimen when background conventional disease-modifying antirheumatic drugs (DMARDs) are insufficient. With these newer drugs, remission is now an achievable goal, especially for patients with newly diagnosed rheumatoid arthritis. Furthermore, the availability of biosimilar tumor necrosis factor α (TNF-α)–blocking agents has contributed to lower drug prices and improved access for patients. In addition to TNF-α inhibitors, current therapies for rheumatoid arthritis target B cells, interleukin-6, or T-cell costimulation. Despite the large number of available . . .
Small interfering RNA for cancer treatment: overcoming hurdles in delivery
Authors: Nitin Bharat Charbe, Nikhil D. Amnerkar, B. Ramesh, Murtaza M. Tambuwala, Hamid A. Bakshi, Alaa A.A. Aljabali, Saurabh C. Khadse, Rajendran Satheeshkumar, Saurabh Satija, Meenu Metha, Dinesh Kumar Chellappan, Garima Shrivastava, Gaurav Gupta, Poonam Negi, Kamal Dua, Flavia C. Zacconi
Journal: Acta Pharmaceutica Sinica B (2020)

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.
What Should Clinicians Tell Patients about Placebo and Nocebo Effects? Practical Considerations Based on Expert Consensus
Authors: Andrea W.M. Evers, Luana Colloca, Charlotte Blease, Jens Gaab, Karin B. Jensen, Lauren Y. Atlas, Chris J. Beedie, Fabrizio Benedetti, Ulrike Bingel, Christian Büchel, Jet Bussemaker, Ben Colagiuri, Alia J. Crum, Damien G. Finniss, Andrew L. Geers, Jeremy Howick, Regine Klinger, Stefanie H. Meeuwis, Karin Meissner, Vitaly Napadow, Keith J. Petrie, Winfried Rief, Ionica Smeets, Tor D. Wager, Vishvarani Wanigasekera, Lene Vase, John M. Kelley, Irving Kirsch
Journal: Psychotherapy and Psychosomatics (2020)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Clinical and laboratory studies demonstrate that placebo and nocebo effects influence various symptoms and conditions after the administration of both inert and active treatments. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; There is an increasing need for up-to-date recommendations on how to inform patients about placebo and nocebo effects in clinical practice and train clinicians how to disclose this information. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Based on previous clinical recommendations concerning placebo and nocebo effects, a 3-step, invitation-only Delphi study was conducted among an interdisciplinary group of internationally recognized experts. The study consisted of open- and closed-ended survey questions followed by a final expert meeting. The surveys were subdivided into 3 parts: (1) informing patients about placebo effects, (2) informing patients about nocebo effects, and (3) training clinicians how to communicate this information to the patients. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; There was consensus that communicating general information about placebo and nocebo effects to patients (e.g., explaining their role in treatment) could be beneficial, but that such information needs to be adjusted to match the specific clinical context (e.g., condition and treatment). Experts also agreed that training clinicians to communicate about placebo and nocebo effects should be a regular and integrated part of medical education that makes use of multiple formats, including face-to-face and online modalities. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; The current 3-step Delphi study provides consensus-based recommendations and practical considerations for disclosures about placebo and nocebo effects in clinical practice. Future research is needed on how to optimally tailor information to specific clinical conditions and patients’ needs, and on developing standardized disclosure training modules for clinicians.
A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics
Authors: Daniela Amann-Zalcenstein, Luyi Tian, Jaring Schreuder, Sara Tomei, Dawn S. Lin, Kirsten A. Fairfax, Jessica E. Bolden, Mark D. McKenzie, Andrew Jarratt, Adrienne Hilton, Jacob T. Jackson, Ladina Di Rago, Matthew P. McCormack, Carolyn A. de Graaf, Olivia Stonehouse, Samir Taoudi, Warren S. Alexander, Stephen L. Nutt, Matthew E. Ritchie, Ashley P. Ng, Shalin H. Naik
Journal: Nature Immunology (2020)
SPEG: a key regulator of cardiac calcium homeostasis
Authors: Hannah Campbell, Yuriana Aguilar-Sanchez, Ann P Quick, Dobromir Dobrev, Xander H T Wehrens
Journal: Cardiovascular Research (2020)

Abstract Proper cardiac Ca2+ homeostasis is essential for normal excitation–contraction coupling. Perturbations in cardiac Ca2+ handling through altered kinase activity has been implicated in altered cardiac contractility and arrhythmogenesis. Thus, a better understanding of cardiac Ca2+ handling regulation is vital for a better understanding of various human disease processes. ‘Striated muscle preferentially expressed protein kinase’ (SPEG) is a member of the myosin light chain kinase family that is key for normal cardiac function. Work within the last 5 years has revealed that SPEG has a crucial role in maintaining normal cardiac Ca2+ handling through maintenance of transverse tubule formation and phosphorylation of junctional membrane complex proteins. Additionally, SPEG has been causally impacted in human genetic diseases such as centronuclear myopathy and dilated cardiomyopathy as well as in common acquired cardiovascular disease such as heart failure and atrial fibrillation. Given the rapidly emerging role of SPEG as a key cardiac Ca2+ regulator, we here present this review in order to summarize recent findings regarding the mechanisms of SPEG regulation of cardiac excitation–contraction coupling in both physiology and human disease. A better understanding of the roles of SPEG will be important for a more complete comprehension of cardiac Ca2+ regulation in physiology and disease.