tbuckley/cabot-search huggingface dataset:
Publisher Correction: Microglial activation and tau propagate jointly across Braak stages
Authors: Tharick A. Pascoal, Andrea L. Benedet, Nicholas J. Ashton, Min Su Kang, Joseph Therriault, Mira Chamoun, Melissa Savard, Firoza Z. Lussier, Cécile Tissot, Thomas K. Karikari, Julie Ottoy, Sulantha Mathotaarachchi, Jenna Stevenson, Gassan Massarweh, Michael Schöll, Mony J. de Leon, Jean-Paul Soucy, Paul Edison, Kaj Blennow, Henrik Zetterberg, Serge Gauthier, Pedro Rosa-Neto
Journal: Nature Medicine (2021)
OA08.04 Validation of Scalable, Automated Data Extraction in an Advanced Lung Cancer Patient Population
Authors: M. Gauthier, J. Law, L. Le, J.J.n. Li, S. Zahir, M. Sung, C. Pettengell, L. Darwish, S. Aviv, R. Chu, A. Sacher, G. Liu, P. Bradbury, F.A. Shepherd, N. Leighl
Journal: Journal of Thoracic Oncology (2021)
Description of the inflammatory profile with 45 cytokines according to ABO blood group in COVID- 19 and its implications on severity and mortality
Authors: A. Tamayo-Velasco, I. De La Fuente Graciani, S. Pérez González, C. Bombín Canal, J. C. Caballero Berrocal, C. Pérez Martínez, R. Acevedo García, A. García Bacelar, K. Herrera Robles, M. Bourgeois, E. Golvano, M. J. Cebeira, A. García De Coca, R. Cuello, L. Gómez García, L. Rico, T. Jiménez, A. Sánchez, M. Hijas, H. Gonzalo Benito, P. Martínez-Paz, M. Martin-Fernández, M. J. Peñsarrubia
Journal: HemaSphere (2021)
Abstract 10904: Human Umbilical Cord Blood Stem Cells Secrete Specific Growth Factors and Anti-Inflammatory Cytokines That Limit Cardiomyopathy by Significantly Upregulating Myocyte Akt and Downregulating JNK and p38
Authors: Robert J Henning, Jose Burgos, Masood Shariff
Journal: Circulation (2018)

Introduction: Stem cell paracrine factors are beneficial in treatment of ischemic cardiomyopathies. However, specific stem cell paracrine factors, cardiomyopathy inflammatory cytokines and cytokine...
3D‐Printed Reinforcement Scaffolds with Targeted Biodegradation Properties for the Tissue Engineering of Articular Cartilage
Authors: Enrico Tosoratti, Philipp Fisch, Scott Taylor, Lee Ann Laurent‐Applegate, Marcy Zenobi‐Wong
Journal: Advanced Healthcare Materials (2021)

Abstract Achieving regeneration of articular cartilage is challenging due to the low healing capacity of the tissue. Appropriate selection of cell source, hydrogel, and scaffold materials are critical to obtain good integration and long‐term stability of implants in native tissues. Specifically, biomechanical stability and in vivo integration can be improved if the rate of degradation of the scaffold material matches the stiffening of the sample by extracellular matrix secretion of the encapsulated cells. To this end, a novel 3D‐printed lactide copolymer is presented as a reinforcement scaffold for an enzymatically crosslinked hyaluronic acid hydrogel. In this system, the biodegradable properties of the reinforced scaffold are matched to the matrix deposition of articular chondrocytes embedded in the hydrogel. The lactide reinforcement provides stability to the soft hydrogel in the early stages, allowing the composite to be directly implanted in vivo with no need for a preculture period. Compared to pure cellular hydrogels, maturation and matrix secretion remain unaffected by the reinforced scaffold. Furthermore, excellent biocompatibility and production of glycosaminoglycans and collagens are observed at all timepoints. Finally, in vivo subcutaneous implantation in nude mice shows cartilage‐like tissue maturation, indicating the possibility for the use of these composite materials in one‐step surgical procedures.
Gene editing to enhance the efficacy of cancer cell therapies
Authors: Tara Murty, Crystal L. Mackall
Journal: Molecular Therapy (2021)

Adoptive T cell therapies have shown impressive signals of activity, but their clinical impact could be enhanced by technologies to increase T cell potency and diminish the cost and labor involved in manufacturing these products. Gene editing platforms are under study in this arena to (1) enhance immune cell potency by knocking out molecules that inhibit immune responses; (2) deliver genetic payloads into precise genomic locations and thereby enhance safety and/or improve the gene expression profile by leveraging physiologic promoters, enhancers, and repressors; and (3) enable off-the-shelf therapies by preventing alloreactivity and immune rejection. This review discusses gene editing approaches that have been the best studied in the context of human T cells and adoptive T cell therapies, summarizing their current status and near-term potential for translation. Adoptive T cell therapies have shown impressive signals of activity, but their clinical impact could be enhanced by technologies to increase T cell potency and diminish the cost and labor involved in manufacturing these products. Gene editing platforms are under study in this arena to (1) enhance immune cell potency by knocking out molecules that inhibit immune responses; (2) deliver genetic payloads into precise genomic locations and thereby enhance safety and/or improve the gene expression profile by leveraging physiologic promoters, enhancers, and repressors; and (3) enable off-the-shelf therapies by preventing alloreactivity and immune rejection. This review discusses gene editing approaches that have been the best studied in the context of human T cells and adoptive T cell therapies, summarizing their current status and near-term potential for translation.
Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures
Authors: Arutha Kulasinghe, Chin Wee Tan, Anna Flavia Ribeiro dos Santos Miggiolaro, James Monkman, Habib SadeghiRad, Dharmesh D. Bhuva, Jarbas da Silva Motta Junior, Caroline Busatta Vaz de Paula, Seigo Nagashima, Cristina Pellegrino Baena, Paulo Souza-Fonseca-Guimaraes, Lucia de Noronha, Timothy McCulloch, Gustavo Rodrigues Rossi, Caroline Cooper, Benjamin Tang, Kirsty R. Short, Melissa J. Davis, Fernando Souza-Fonseca-Guimaraes, Gabrielle T. Belz, Ken O'Byrne
Journal: European Respiratory Journal (2021)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19). A better definition of the pulmonary host response to SARS-CoV-2 infection is required to understand viral pathogenesis and to validate putative COVID-19 biomarkers that have been proposed in clinical studies.Here, we use targeted transcriptomics of formalin-fixed paraffin-embedded tissue using the NanoString GeoMX platform to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19, pandemic H1N1 influenza and uninfected control patients.Host transcriptomics showed a significant upregulation of genes associated with inflammation, type I interferon production, coagulation and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs (emphasising the advantages of spatial transcriptomics) with the areas of high viral load associated with an increased type I interferon response. Once the dominant cell type present in the sample, within patient correlations and patient-patient variation, had been controlled for, only a very limited number of genes were differentially expressed between the lungs of fatal influenza and COVID-19 patients. Strikingly, the interferon-associated gene IFI27, previously identified as a useful blood biomarker to differentiate bacterial and viral lung infections, was significantly upregulated in the lungs of COVID-19 patients compared to patients with influenza.Collectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment.
Building health system resilience through policy development in response to COVID-19 in Ireland: From shock to reform
Authors: Sara Burke, Sarah Parker, Padraic Fleming, Sarah Barry, Steve Thomas
Journal: The Lancet Regional Health - Europe (2021)

Health systems worldwide are experiencing profound shocks resulting from the COVID-19 pandemic, with increased attention to health system resilience and researching ways to endure shocks. Pre-COVID-19, Ireland had begun a ten-year programme of reform, Sláintecare, aiming to deliver universal, timely access to integrated care. This study examines whether and how the Irish government's pandemic response contributed to health system reform and increased resilience including delivering universal healthcare. Documentary analysis identified and critiqued relevant government, health system and budgetary documents, published March 2020 - May 2021. Thirteen national policy documents were found, showing increased policy rhetoric and intent to implement reform, demonstrated by increased policy alignment with and budgetary allocation to Sláintecare, alongside implementation of key innovations. Ireland's health system response to COVID-19 offers a unique opportunity to advance understanding of government efforts to reform amidst a global pandemic. It indicated policy intent and funding to manage the Irish COVID-19 crisis, but to also build health system resilience through implementing Sláintecare. This case study has international significance, enabling policy development with potential for long-term health system transformation.
IL-6 trans-signalling: how <i>Haemophilus</i> surfs the NET to amplify inflammation in COPD
Authors: Holly R. Keir, James D. Chalmers
Journal: European Respiratory Journal (2021)

<b><i>Haemophilus</i> infection in COPD induces neutrophil extracellular traps which amplify inflammation through multiple mechanisms, including NET mediated IL-6 trans-signalling</b>https://bit.ly/3yFI2b7
Variation in response to VEGFR inhibitor AV-951 across a population of genetically engineered breast tumors reveals distinct phenotypic classes of resistance
Authors: Jie Lin, karrupiah Kannan, Joerg Heyer, Hongmei Yang, nan Liu, Gaoyuan Meng, Yinghui Zhou, William Rideout, Angela Bressel, Tong Zi, Sireesha Yalavarthi, Ruojie Wang, Murray Robinson
Journal: Cancer Research (2008)

2499  Variation in drug response is a hallmark of human tumor populations. For example, with VEGF/ VEGFR inhibitors in Renal Cell Carcinoma_the one tumor type with robust single agent activity_even the most active molecules elicit responses in less than half of patients treated. A better understanding of the molecular underpinnings of this variation in response could significantly enhance the speed and success of clinical development in oncology.  AV-951 (formerly KRN951) is a small molecule VEGFR inhibitor currently in phase 2 clinical trials. AV-951 inhibits VEGFR 1, 2 and 3 activity at picomolar concentrations (IC50¬ of 0.21, 0.16 and 0.24 nM respectively), while it inhibits c-Kit and PDGFR at 10-times higher concentrations (IC50¬ of 1.63 and 1.72 nM respectively).  To support the development of AV-951 and to better understand molecular mechanisms of sensitivity and resistance to AV-951 therapy, we created an alternate approach for preclinical antiangiogenic response prediction and biomarker discovery. Using novel ES cell based chimeric approach, a large population of more than 100 genetically engineered murine breast tumors were generated, in which defined genetic alterations, i.e., HER2 overexpression & INK4A-/-, are allowed to be combined with spontaneous genetic alterations to more accurately model human cancer populations. Characterization of this tumor population revealed a surprising degree of variation in key parameters such as angiogenesis, microvasculature, VEGF expression, microarray gene expression and chromosomal gain/loss by array CGH.  Having developed methodology to expand and archive these tumors, we have now conducted drug efficacy studies of AV-951 across multiple tumors of this population. These efforts have revealed significant variation in drug response to AV-951, identifying both responsive and resistant tumors. Among resistant tumors, we observed two different phenotypes. One resistant class exhibits reduction in vascularity while continuing to proliferate, whereas another class appears to maintain angiogenenic features despite treatment with AV-951.  Because each tumor of the archive has been characterized for both comprehensive RNA expression by microarray and DNA copy number alteration by array CGH, these studies provide an opportunity to correlate drug sensitivity in vivo with RNA and DNA signatures to identify molecular mechanisms of the resistant phenotypes and ultimately biomarkers of response to AV-951.
Response to COVID-19 mRNA vaccination in multiple myeloma is conserved but impaired compared to controls
Authors: Samuel Bitoun, Julien Henry, Christelle Vauloup-Fellous, Nicolas Dib, Rakiba Belkhir, Lina Mouna, Candie Joly, Delphine Desjardins, Marie Bitu, Roger Le Grand, Raphaèle Seror, Anne-Marie Roque Afonso, Xavier Mariette
Journal: Journal of Hematology & Oncology (2021)

Patients with multiple myeloma are at high risk of severe forms of COVID-19. Despite data showing diminished response to vaccine, the era of highly efficient mRNA vaccine might be a gamechanger. We sought to examine response to mRNA vaccine between healthy controls (n = 28) and multiple myeloma (MM) patients (n = 27). Response was analyzed 1 month after the second dose of anti-SARS-CoV-2 BNT162b2 vaccine. Multiple myeloma patients showed diminished levels of Anti-Spike IgG levels compared to controls, but with a high proportion of patients achieving a humoral response (89% vs. 97% in controls). Neutralizing antibodies were present in 74% of patients versus 96% of controls. Patients under current daratumumab treatment had neutralizing activity of anti-SARS-CoV-2 antibodies. Multiple myeloma patients show diminished response to SARS-COV-2 vaccine but with still high response rate. The main potential risk factor of non-response to COVID-19 vaccine was uncontrolled disease under treatment.
Biomarker signatures for progressive idiopathic pulmonary fibrosis
Authors: Britt Clynick, Tamera J. Corte, Helen E. Jo, Iain Stewart, Ian N. Glaspole, Christopher Grainge, Toby M. Maher, Vidya Navaratnam, Richard Hubbard, Peter M.A. Hopkins, Paul N. Reynolds, Sally Chapman, Christopher Zappala, Gregory J. Keir, Wendy A. Cooper, Annabelle M. Mahar, Samantha Ellis, Nicole S. Goh, Emma De Jong, Lilian Cha, Dino B.A. Tan, Lucy Leigh, Christopher Oldmeadow, E. Haydn Walters, R. Gisli Jenkins, Yuben Moodley
Journal: European Respiratory Journal (2021)

Background Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers have the potential for guiding management in clinical practice. We assessed the prognostic role of serum biomarkers in three independent IPF cohorts: Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE). Methods In the AIPFR cohort, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. LASSO (least absolute shrinkage and selection operator) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at 1 year in the AIPFR cohort, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in the PROFILE cohort. Four significantly replicating biomarkers were aggregated into a progression index model based on tertiles of circulating concentrations. Results 189 participants were included in the AIPFR cohort, 205 participants from the TLF cohort and 122 participants from the PROFILE cohort. Differential biomarker expression was observed by ELISA and replicated for osteopontin, matrix metallopeptidase-7, intercellular adhesion molecule-1 and periostin for those with a progressor phenotype at 1 year. Proteomic data did not replicate. The progression index in the AIPFR, TLF and PROFILE cohorts predicted risk of progression, mortality and progression-free survival. A statistical model incorporating the progression index demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP (gender, age and physiology) score model alone in all cohorts, and significantly so within the incidence-based TLF and PROFILE cohorts. Conclusion A panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.
Point-of-Care Ultrasonography
Authors: Eden Bernstein, Tracy Y. Wang
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Abstract 17422: The Role of Changes in IgG-glycosylation in the Pathogenesis of DCM: A Link Between Terminal Sialic Acid and the Negative Inotropic Activity of DCM-IgG
Authors: Yvonne Reinke, Marcus Dörr, Stephan B Felix
Journal: Circulation (2013)

Background: There is evidence that circulating cardiodepressive antibodies play a role in cardiac dysfunction of patients with dilated cardiomyopathy (DCM). We have previously demonstrated that pur...
Abstract 15433: Thrombin Activation of Platelet Protease-activated Receptor 4 Augments Atherosclerosis
Authors: Adrien Mann, Deborah A Howatt, Debra L Rateri, Alan Daugherty, Nigel Mackman, A. Phillip Owens
Journal: Circulation (2015)

Objective: Platelet activation has been shown to play a critical role in both formation and propagation of atherosclerosis. Protease-activated receptors (PARs) 1 and 4 mediate signaling by the coagulation protease thrombin. While PAR1 and 4 mediate thrombin activation on human platelets, mouse platelets contain PAR4 with PAR3 acting as a cofactor. Recent studies have demonstrated direct thrombin inhibitors (DTIs) reduced atherosclerosis in hypercholesterolemic mice. In this study, we examined the effect of PAR1 and 4 deficient on atherosclerosis using low-density lipoprotein receptor deficient (Ldlr -/- ) mice. Methods and Results: Ldlr -/- mice that were PAR1 +/+ , PAR1 -/- , PAR4 +/+ , or PAR4 -/- (n = 5-20 each group) were fed a fat and cholesterol-enriched diet for 12 weeks. PAR4 deficiency attenuated aortic root (65% decrease; P = 0.001) and aortic arch (71% decrease; P = 0.001) atherosclerosis with no effects on total plasma cholesterol concentrations or lipoprotein distributions. These reductions were attributable to hematopoietic-derived PAR4 from analysis of bone marrow experiments. To determine if PAR4 mediated all effects of thrombin signaling, Ldlr -/- /PAR4 +/+ or Ldlr -/- /PAR4 -/- mice were fed a fat and cholesterol-enriched diet, supplemented with placebo or the DTI dabigatran etexilate (30 g/kg diet) for 12 weeks. Dabigatran etexilate administration reduced atherosclerosis in PAR4 +/+ mice but not in PAR4 -/- mice. PAR1 deficiency had no effect on atherosclerotic burden. Conclusion: We demonstrated whole body and hematopoietic PAR4 deficiency resulted in decreased aortic root and sinus atherosclerosis. PAR1 deficiency had no effects on atherosclerosis. Thrombin inhibition did not alter atherosclerosis in PAR4 deficient mice. Together, these results suggest that thrombin activation of PAR4 on platelets contributes to atherosclerosis.
Association between warfarin and COVID-19-related outcomes compared with direct oral anticoagulants: population-based cohort study
Authors: Angel Y. S. Wong, Laurie A. Tomlinson, Jeremy P. Brown, William Elson, Alex J. Walker, Anna Schultze, Caroline E. Morton, David Evans, Peter Inglesby, Brian MacKenna, Krishnan Bhaskaran, Christopher T. Rentsch, Emma Powell, Elizabeth Williamson, Richard Croker, Seb Bacon, William Hulme, Chris Bates, Helen J. Curtis, Amir Mehrkar, Jonathan Cockburn, Helen I. McDonald, Rohini Mathur, Kevin Wing, Harriet Forbes, Rosalind M. Eggo, Stephen J. W. Evans, Liam Smeeth, Ben Goldacre, Ian J. Douglas
Journal: Journal of Hematology & Oncology (2021)

Abstract Background Thromboembolism has been reported as a consequence of severe COVID-19. Although warfarin is a commonly used anticoagulant, it acts by antagonising vitamin K, which is low in patients with severe COVID-19. To date, the clinical evidence on the impact of regular use of warfarin on COVID-19-related thromboembolism is lacking. Methods On behalf of NHS England, we conducted a population-based cohort study investigating the association between warfarin and COVID-19 outcomes compared with direct oral anticoagulants (DOACs). We used the OpenSAFELY platform to analyse primary care data and pseudonymously linked SARS-CoV-2 antigen testing data, hospital admissions and death records from England. We used Cox regression to estimate hazard ratios (HRs) for COVID-19-related outcomes comparing warfarin with DOACs in people with non-valvular atrial fibrillation. We also conducted negative control outcome analyses (being tested for SARS-CoV-2 and non-COVID-19 death) to assess the potential impact of confounding. Results A total of 92,339 warfarin users and 280,407 DOAC users were included. We observed a lower risk of all outcomes associated with warfarin versus DOACs [testing positive for SARS-CoV-2, HR 0.73 (95% CI 0.68–0.79); COVID-19-related hospital admission, HR 0.75 (95% CI 0.68–0.83); COVID-19-related deaths, HR 0.74 (95% CI 0.66–0.83)]. A lower risk of negative control outcomes associated with warfarin versus DOACs was also observed [being tested for SARS-CoV-2, HR 0.80 (95% CI 0.79–0.81); non-COVID-19 deaths, HR 0.79 (95% CI 0.76–0.83)]. Conclusions Overall, this study shows no evidence of harmful effects of warfarin on severe COVID-19 disease.
MA16.01 Subsequent Systemic Therapy After Lurbinectedin Discontinuation in Patients With Small-cell Lung Cancer
Authors: V. Subbiah, L. Paz-Ares, B. Besse, K. Zaman, M.A. Sala, C. Fernández, M. Siguero, C. Kahatt, J.A. Lopez-Vilariño, A. Zeaiter, J. Arrondeau, J. Delord, M. Martínez, L. Wannesson, A. Antón, J.M. Trigo
Journal: Journal of Thoracic Oncology (2021)