tbuckley/cabot-search huggingface dataset:
OP0070 The role of individual and country-level socio-economic factors in work participation in patients with spondyloarthritis across 22 countries worldwide: results from the comospa study
Authors: S Rodrigues Manica, A Sepriano, S Ramiro, FM Pimentel-Santos, P Putrik, E Nikiphorou, A Moltό, M Dougados, D van der Heijde, R Landewé, F Van den Bosch, A Boonen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Spondyloarthritis (SpA) carries substantial financial costs, including direct costs (use of medical services and treatments) and indirect costs (loss of work productivity). While disease related factors have been repeatedly shown to be associated with work outcomes, information on the role of educational attainment and the economic wealth of the patients9 country of residence is scarce. <h3>Objectives</h3> To explore the role of individual and country level socio-economic (SE) factors on employment, absenteeism and presenteeism across 22 countries. <h3>Methods</h3> Patients with a clinical diagnosis of SpA, fulfilling the ASAS SpA criteria and in working age (≤65 years old) from COMOSPA were included. Outcomes explored were employment-status, absenteeism and presenteeism according to the Work Productivity and Activity Impairment Specific Health Problem (WPAI-SHP) questionnaire. Absenteeism and presenteeism were assessed in employed patients. Multilevel logistic (for work status) and linear (for absenteeism and presenteeism) regression models with random intercept for country were constructed. Independent contribution of individual (education) and country level socio-economic factors (country healthcare expenditures and gross domestic product (GDP) (all low vs medium/high tertiles) were assessed in models adjusted for clinical factors. <h3>Results</h3> In total 3,114 patients from 22 countries were included (mean (SD) age 40.9 (11.8) years; 66% males; and 63% employed). Of these, 89% had axial SpA and 11% a peripheral SpA. Unadjusted employment rates ranged from 28% (Colombia) to 83% (Canada). After adjustment for relevant socio-demographic and clinical variables, differences between countries in work status persisted (Figure). High healthcare expenditures were associated with higher employment (OR=2.42; 95% CI=1.53;3.81) and lower presenteeism (β=-4.53;CI=-8.90;-0.17). Similarly, higher GDP was associated with higher employment (OR=1.70; 95% CI=1.02;2.83), and in the same direction with presenteeism but without reaching statistical significance (β=-3.42;CI=-13.07;6.23). No significant association between any country SE indicators and absenteeism was found. At individual level, higher education was positively associated with employment-status, presenteeism and absenteeism. <h3>Conclusions</h3> Individual- and country-level SE factors affect work participation in SpA, and this varies significantly across countries. Better socio-economic welfare seems to support SpA patients to stay employed and productive. <h3>Disclosure of Interest</h3> None declared
Reconsidering Reliance on Confirmatory Drug Testing in a Patient With Repeated Positive Urine Drug Screen Results
Authors: Stephanie T. Weiss, Mark Chinn, Laura Veach
Journal: JAMA Internal Medicine (2021)

This Teachable Moment illustrates the repercussions of misinterpreted drug testing results and advocates for reconsideration of routine urine drug screening in the absence of other indicators of relapse.
Weekly SARS-CoV-2 screening of asymptomatic kindergarten to grade 12 students and staff helps inform strategies for safer in-person learning
Authors: Shira Doron, Robin R. Ingalls, Anne Beauchamp, Jesse S. Boehm, Helen W. Boucher, Linda H. Chow, Linda Corridan, Katey Goehringer, Doug Golenbock, Liz Larsen, David Lussier, Marcia Testa, Andrea Ciaranello
Journal: Cell Reports Medicine (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in K-12 schools was rare during in 2020-2021; few studies included Centers for Disease Control and Prevention (CDC)-recommended screening of asymptomatic individuals. We conduct a prospective observational study of SARS-CoV-2 screening in a mid-sized suburban public school district to evaluate the incidence of asymptomatic coronavirus disease 2019 (COVID-19), document frequency of in-school transmission, and characterize barriers and facilitators to asymptomatic screening in schools. Staff and students undergo weekly pooled testing using home-collected saliva samples. Identification of >1 case in a school prompts investigation for in-school transmission and enhancement of safety strategies. With layered mitigation measures, in-school transmission even before student or staff vaccination is rare. Screening identifies a single cluster with in-school staff-to-staff transmission, informing decisions about in-person learning. The proportion of survey respondents self-reporting comfort with in-person learning before versus after implementation of screening increases. Costs exceed $260,000 for assays alone; staff and volunteers spend 135-145 h per week implementing screening.
Yields and Immunomodulatory Effects of Pneumococcal Membrane Vesicles Differ with the Bacterial Growth Phase
Authors: Mina Mehanny, Tobias Kroniger, Marcus Koch, Jessica Hoppstädter, Dörte Becher, Alexandra K. Kiemer, Claus‐Michael Lehr, Gregor Fuhrmann
Journal: Advanced Healthcare Materials (2021)

Streptococcus pneumoniae infections are a leading cause of death worldwide. Bacterial membrane vesicles (MVs) are promising vaccine candidates because of the antigenic components of their parent microorganisms. Pneumococcal MVs exhibit low toxicity towards several cell lines, but their clinical translation requires a high yield and strong immunogenic effects without compromising immune cell viability. MVs are isolated during either the stationary phase (24 h) or death phase (48 h), and their yields, immunogenicity and cytotoxicity in human primary macrophages and dendritic cells have been investigated. Death-phase vesicles showed higher yields than stationary-phase vesicles. Both vesicle types displayed acceptable compatibility with primary immune cells and several cell lines. Both vesicle types showed comparable uptake and enhanced release of the inflammatory cytokines, tumor necrosis factor and interleukin-6, from human primary immune cells. Proteomic analysis revealed similarities in vesicular immunogenic proteins such as pneumolysin, pneumococcal surface protein A, and IgA1 protease in both vesicle types, but stationary-phase MVs showed significantly lower autolysin levels than death-phase MVs. Although death-phase vesicles produced higher yields, they lacked superiority to stationary-phase vesicles as vaccine candidates owing to their similar antigenic protein cargo and comparable uptake into primary human immune cells.
Analysis of Surgical Volume in Military Medical Treatment Facilities and Clinical Combat Readiness of US Military Surgeons
Authors: Michael K. Dalton, Kyle N. Remick, Michael Mathias, Quoc-Dien Trinh, Zara Cooper, Eric A. Elster, Joel S. Weissman
Journal: JAMA Surgery (2021)

<h3>Importance</h3> Low surgical volume in the US Military Health System (MHS) has been identified as a challenge to military surgeon readiness. The Uniformed Services University of Health Sciences, in partnership with the American College of Surgeons, developed the Knowledge, Skills, and Abilities (KSA) Clinical Readiness Program that includes a tool for quantifying the clinical readiness value of surgeon workload, known as the KSA metric. <h3>Objective</h3> To describe changes in US military general surgeon procedural volume and readiness using the KSA metric. <h3>Design, Setting, and Participants</h3> This cohort study analyzed general surgery workload performed across the MHS, including military and civilian facilities, between fiscal year 2015 and 2019 and the calculated KSA metric value. The surgeon-level readiness among military general surgeons was calculated based on the KSA metric readiness threshold. Data were obtained from TRICARE, the US Department of Defense health insurance product. <h3>Main Outcomes and Measures</h3> The main outcomes were general surgery procedural volumes and the KSA metric point value of those procedures across the MHS as well as the number of military general surgeons meeting the KSA metric readiness threshold. Aggregate facility and regional market-level claims data were used to calculate the procedural volumes and KSA metric readiness value of those procedures. Annual adjusted KSA metric points earned were used to determine the number of individual US military general surgeons meeting the readiness threshold. <h3>Results</h3> The number of general surgery procedures generating KSAs in military hospitals decreased 25.6%, from 128 377 in 2015 to 95 461 in 2019, with a 19.1% decrease in the number of general surgeon KSA points (from 7 155 563 to 5 790 001). From 2015 to 2019, there was a 3.2% increase in both the number of procedures (from 419 980 to 433 495) and KSA points (from 21 071 033 to 21 748 984) in civilian care settings. The proportion of military general surgeons meeting the KSA metric readiness threshold decreased from 16.7% (n = 97) in 2015 to 10.1% (n = 68) in 2019. <h3>Conclusions and Relevance</h3> This study noted that the number of KSA metric points and procedural volume in military hospitals has been decreasing since 2015, whereas both measures have increased in civilian facilities. The findings suggest that loss of surgical workload has resulted in further decreases in military surgeon readiness and may require substantial changes in patient care flow in the MHS to reverse the change.
Precision Cancer Medicine: Large Studies Indicate Steady Progress
Authors: Alexander Eggermont, Birgit Geoerger, Giuseppe Curigliano
Journal: Cancer Discovery (2021)

Abstract Summary: Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions provide the basis of precision cancer medicine. In this issue of Cancer Discovery, continued progress in this field is demonstrated by two large collaborative studies: Horak and colleagues in the MASTER trial for patients with rare cancers and Van Tilburg and colleagues in the INFORM registry in pediatric tumors. See related article by van Tilburg et al., p. 2764. See related article by Horak et al., p. 2780.
TCT-429 Clinical Outcomes of Percutaneous Coronary Intervention in Left Main Coronary Artery Disease at Long-Term Follow-Up: Real-Life Experience at a Single-Center Without On-Site Cardiac Surgery
Authors: Ignacio Sanchez-Perez, Ricardo Concepcion-Suárez, Fernando Lozano, Ariana Gonzálvez-García, Manuel Muñoz Garcia, Alfonso Morón Alguacil, Jorge Martinez del Río, Martin Negreira, Jesus Piqueras-Flores, Alfonso Freites Esteves
Journal: Journal of the American College of Cardiology (2021)
C-MORE: A high-content single-cell morphology recognition methodology for liquid biopsies toward personalized cardiovascular medicine
Authors: Jennifer Furkel, Maximilian Knoll, Shabana Din, Nicolai V. Bogert, Timon Seeger, Norbert Frey, Amir Abdollahi, Hugo A. Katus, Mathias H. Konstandin
Journal: Cell Reports Medicine (2021)

Cellular morphology has the capacity to serve as a surrogate for cellular state and functionality. However, primary cardiomyocytes, the standard model in cardiovascular research, are highly heterogeneous cells and therefore impose methodological challenges to analysis. Hence, we aimed to devise a robust methodology to deconvolute cardiomyocyte morphology on a single-cell level: C-MORE (cellular morphology recognition) is a workflow from bench to data analysis tailored for heterogeneous primary cells using our R package cmoRe. We demonstrate its utility in proof-of-principle applications such as modulation of canonical hypertrophy pathways and linkage of genotype-phenotype in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). In our pilot study, exposure of cardiomyocytes to blood plasma prior to versus after aortic valve replacement allows identification of a disease fingerprint and reflects partial reversibility following therapeutic intervention. C-MORE is a valuable tool for cardiovascular research with possible fields of application in basic research and personalized medicine.
Non-invasive evaluation of response to obeticholic acid in patients with NASH: Results from the REGENERATE study
Authors: Mary E. Rinella, Jean-Francois Dufour, Quentin M. Anstee, Zachary Goodman, Zobair Younossi, Stephen A. Harrison, Rohit Loomba, Arun J. Sanyal, Martin Bonacci, Aldo Trylesinski, Macky Natha, Reshma Shringarpure, Tanya Granston, Aditya Venugopal, Vlad Ratziu
Journal: Journal of Hepatology (2021)
TCT-498 Pre-PCI Sudden Cardiac Arrest in ST-Segment Elevation Myocardial Infarction: Incidence, Predictors, and Related Outcomes
Authors: André Theobald, Rodrigo Wainstein, Marco Wainstein, Mauricio Pimentel, Gustavo Araújo, Guilherme Pinheiro Machado, Sandro Goncalves, Julia Luchese Custódio, Luiz Carlos Bergoli
Journal: Journal of the American College of Cardiology (2021)
Clinical progress of nanomedicine-based RNA therapies
Authors: Siyoung A. Lim, Alysia Cox, Madelynn Tung, Eun Ji Chung
Journal: Bioactive Materials (2021)

The clinical application of nanoparticles (NPs) to deliver RNA for therapy has progressed rapidly since the FDA approval of Onpattro® in 2018 for the treatment of polyneuropathy associated with hereditary transthyretin amyloidosis. The emergency use authorization or approval and widespread global use of two mRNA-NP based vaccines developed by Moderna Therapeutics Inc. and Pfizer-BioNTech in 2021 has highlighted the translatability of NP technology for RNA delivery. Furthermore, in clinical trials, a wide variety of NP formulations have been found to extend the half-life of RNA molecules such as microRNA, small interfering RNA, and messenger RNA, with limited safety issues. In this review, we discuss the NP formulations that are already used in the clinic to deliver therapeutic RNA and highlight examples of RNA-NPs which are currently under evaluation for human use. We also detail NP formulations that failed to progress through clinical trials, in hopes of guiding future successful translation of nanomedicine-based RNA therapeutics into the clinic.
TCT-287 National Trends and Age Differences in Treatment and Outcomes of Patients With Mitral Regurgitation in the United States
Authors: Alexis Okoh, Setri Fugar, Ankur Sethi, Molly Szerlip, Isaac George, Tom Nguyen, Tsuyoshi Kaneko, Michael Mack, Vinod Thourani, Leonard Lee, Mark Russo
Journal: Journal of the American College of Cardiology (2021)
Isotype-specific binding patterns of serum antibodies to multiple conformational epitopes of Bet v 1
Authors: Stefanie Schmalz, Vanessa Mayr, Alexandra Shosherova, Barbara Gepp, Daniela Ackerbauer, Gunter Sturm, Barbara Bohle, Heimo Breiteneder, Christian Radauer
Journal: Journal of Allergy and Clinical Immunology (2021)

Birch pollen is an important elicitor of respiratory allergy. The major allergen, Bet v 1, binds IgE exclusively via conformational epitopes.We identified Bet v 1-specific epitope repertoires of IgE and IgG from birch pollen-allergic and nonallergic subjects.Chimeric proteins were created by grafting individual epitope-sized, contiguous surface patches of Bet v 1 onto a nonallergenic structural homolog and expressed in Escherichia coli. Binding of IgE, IgG1, and IgG4 from sera of 30 birch pollen-allergic and 11 nonallergic subjects to Bet v 1, 13 chimeric proteins, and 4 bacterial Bet v 1 homologs were measured by ELISA. The proportion of epitope-specific in-total Bet v 1-specific IgE and the cross-reactivity of Bet v 1-specific IgE with bacterial homologs were determined by competitive ELISA.Thirteen soluble, correctly folded chimeric proteins were produced. IgE from 27 of 30 birch pollen-allergic patients bound to 1 to 12 chimeric proteins (median, 4.0), with patient-specific patterns evident. Three chimeras binding IgE from the majority of sera were identified, the grafted patches of which overlapped with previously published epitopes. Patterns of IgG1 and IgG4 binding to the chimeric proteins did not correspond to the binding patterns of IgE. Sera of 19 of 30 birch pollen-allergic patients contained low amounts of IgE to bacterial homologs. Bacterial proteins were able to partially inhibit IgE binding to Bet v 1.Epitopes recognized by Bet v 1-specific antibodies from birch pollen-allergic patients are specific to each patient and differ between IgE, IgG1, and IgG4.
Aged neutrophils form mitochondria-dependent vital NETs to promote breast cancer lung metastasis
Authors: Chenghui Yang, Zhen Wang, Lili Li, Zhigang Zhang, Xiaoyan Jin, Pin Wu, Shanshan Sun, Jun Pan, Ke Su, Fang Jia, Leyi Zhang, Haijun Wang, Xiuyan Yu, Xuan Shao, Ke Wang, Fuming Qiu, Jun Yan, Jian Huang
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Neutrophils-linked premetastatic niche plays a key role in tumor metastasis, but not much is known about the heterogeneity and diverse role of neutrophils in niche formation. Our study focuses on the existence and biological function of a rarely delved subset of neutrophils, named as tumor-associated aged neutrophils (Naged, CXCR4 + CD62L low ), involved in premetastatic niche formation during breast cancer metastasis. Methods We explored the distributions of Naged in 206 patients and mice models (4T1 and MMTV-PyMT) by flow cytometry. The ability of Naged to form neutrophil extracellular traps (NETs) and promote tumor metastasis in patients and mice was determined by polychromatic immunohistochemistry, scanning electron microscopy and real-time video detection. Furthermore, the differences among tumor-associated Naged, Non-Naged and inflammation-associated aged neutrophils were compared by transcriptome, the biological characteristics of Naged were comprehensively analyzed from the perspectives of morphology, the metabolic capacity and mitochondrial function were investigated by Seahorse, co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP) and transmission electron microscopy (TEM). Finally, 120 patients’ sample were applied to confirm the acceleration of Naged formation through secreted NAMPT, and the importance of blocking this pathway in mice was evaluated. Results We find that Naged accumulate in the lung premetastatic niche at early stage of breast tumorigenesis in multiple mice models and also exist in peripheral blood and metastatic lung of patients with breast cancer. Naged exhibit distinct cell marker and morphological feature of oversegmented nuclei. Further transcriptome reveals that Naged are completely different from those of Non-Aged or inflammation-associated aged neutrophils and illustrates that the key transcription factor SIRT1 in Naged is the core to maintain their lifespan via mitophagy for their function. The responsible mechanism is that SIRT1 can induce the opening of mitochondrial permeability transition pore channels to release mitochondrial DNA and lead to the mitochondria-dependent vital NETs formation, rather than traditional Cit-Histone H3 dependent fatal-NETs. Further mechanically investigation found tumor derived NAMPT could induce Naged formation. Additionally, therapeutic interventions of Naged and its formation-linked pathways could effectively decrease breast cancer lung metastasis. Conclusions Naged exerts a vital role in breast cancer lung metastasis, and strategies targeting SIRT1-Naged-NETs axis show promise for translational application.
First Prospective Data on Minimal Residual Disease (MRD) Outcomes after Fixed-Duration Ibrutinib Plus Venetoclax (Ibr+Ven) Versus Chlorambucil Plus Obinutuzumab (Clb+O) for First-Line Treatment of CLL in Elderly or Unfit Patients: The Glow Study
Authors: Tahla Munir, Carol Moreno, Carolyn Owen, George A Follows, Ohad Benjamini, Ann Janssens, Mark-David Levin, Anders Österborg, Tadeusz Robak, Martin Simkovic, Don Stevens, Sergey Voloshin, Vladimir I. Vorobyev, Munchi Yagci, Loic Ysebaert, Qianaya Qi, Andrew Steele, Natasha Schuier, Kurt Baeten, Donne Bennett Caces, Carsten Utoft Niemann, Arnon P. Kater
Journal: Blood (2021)
LYVE1+ macrophages of murine peritoneal mesothelium promote omentum-independent ovarian tumor growth
Authors: Nan Zhang, Seung Hyeon Kim, Anastasiia Gainullina, Emma C. Erlich, Emily J. Onufer, Jiseon Kim, Rafael S. Czepielewski, Beth A. Helmink, Joseph R. Dominguez, Brian T. Saunders, Jie Ding, Jesse W. Williams, Jean X. Jiang, Brahm H. Segal, Bernd H. Zinselmeyer, Gwendalyn J. Randolph, Ki-Wook Kim
Journal: The Journal of Experimental Medicine (2021)

Two resident macrophage subsets reside in peritoneal fluid. Macrophages also reside within mesothelial membranes lining the peritoneal cavity, but they remain poorly characterized. Here, we identified two macrophage populations (LYVE1hi MHC IIlo-hi CX3CR1gfplo/− and LYVE1lo/− MHC IIhi CX3CR1gfphi subsets) in the mesenteric and parietal mesothelial linings of the peritoneum. These macrophages resembled LYVE1+ macrophages within surface membranes of numerous organs. Fate-mapping approaches and analysis of newborn mice showed that LYVE1hi macrophages predominantly originated from embryonic-derived progenitors and were controlled by CSF1 made by Wt1+ stromal cells. Their gene expression profile closely overlapped with ovarian tumor-associated macrophages previously described in the omentum. Indeed, syngeneic epithelial ovarian tumor growth was strongly reduced following in vivo ablation of LYVE1hi macrophages, including in mice that received omentectomy to dissociate the role from omental macrophages. These data reveal that the peritoneal compartment contains at least four resident macrophage populations and that LYVE1hi mesothelial macrophages drive tumor growth independently of the omentum.
Therapeutic antibodies – natural and pathological barriers and strategies to overcome them
Authors: Yara Al Ojaimi, Timothée Blin, Juliette Lamamy, Matthieu Gracia, Aubin Pitiot, Caroline Denevault-Sabourin, Nicolas Joubert, Jean-Pierre Pouget, Valérie Gouilleux-Gruart, Nathalie Heuzé-Vourc’h, Débora Lanznaster, Sophie Poty, Thomas Sécher
Journal: Pharmacology & Therapeutics (2021)
TCT-440 Long-Term Outcomes of Left Atrial Appendage Occlusion: 10-Year Results of a Single-Center Registry
Authors: Moniek Maarse, Marina Huijboom, Errol Aarnink, Bob Abeln, Diederik Staal, Benno Rensing, Joost Kerklaan, Vincent van Dijk, Martin Swaans, Lucas Boersma
Journal: Journal of the American College of Cardiology (2021)
TCT-35 One-Month Dual Antiplatelet Therapy After PCI With Resolute Onyx DES: Final 2-Year Results From Onyx ONE Clear
Authors: David Kandzari, Ajay Kirtane, Roxana Mehran, Matthew Price, Daniel Simon, Azeem Latib, Elvin Kedhi, Alexandre Abizaid, Stephen G. Worthley, Azfar Zaman, Maria Parke, Amanda Mahoney, Te-Hsin Lung, Stephan Windecker, Gregg Stone
Journal: Journal of the American College of Cardiology (2021)
TCT-455 Preprocedural ATI Score (Age–Thrombus Burden–Index of Microcirculatory Resistance) Predicts Long-Term Clinical Outcomes in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention
Authors: Claudio Montalto, Rafail Kotronias, Federico Marin, Dimitrios Terentes-Printzios, Mayooran Shanmuganathan, Maria Emfietzoglou, Riccardo Scalamera, Italo Porto, Jeremy Langrish, Andrew Lucking, Rajesh Kharbanda, Keith Channon, Giovanni Luigi De Maria, Adrian Banning
Journal: Journal of the American College of Cardiology (2021)
Lintuzumab-Ac225 in Combination with CLAG-M Yields High MRD (-) Responses in R/R AML with Adverse Features: Interim Results of a Phase I Study
Authors: Sameem Abedin, Guru Subramanian Guru Murthy, Mehdi Hamadani, Laura C. Michaelis, Lyndsey Runaas, Karen Carlson, Ehab L. Atallah
Journal: Blood (2021)