tbuckley/cabot-search huggingface dataset:
Abstract 9030: Effects of Edoxaban on Clinical Outcomes in Extremely Elderly Patients (aged ≥ 90 Years) With Atrial Fibrillation: A Subanalysis of Data from the ELDERCARE-AF Trial
Authors: Masaru Kuroda, Eiji Tamiya, Takahisa Nose, Akiyoshi Ogimoto, Junki Taura, Yuki Imamura, Masayuki Fukuzawa, Takuya Hayashi, Masaharu Akao, Takeshi Yamashita, Gregory Lip, Ken Okumura
Journal: Circulation (2021)

Introduction: Atrial fibrillation (AF) affects about 10% of the very elderly (≥ 80 years), and its prevalence increases exponentially with age. Data are lacking on the efficacy and safety of anticoagulants in extremely elderly AF patients (≥ 90 years). We tested the hypotheses that such patients are at increased risk of stroke or systemic embolism (SSE) and could benefit from low-dose edoxaban. Methods: This was a subanalysis of ELDERCARE-AF, a multicenter, double-blind, phase 3 study in which very elderly Japanese patients with non-valvular AF (NVAF) considered ineligible for standard anticoagulants were randomly allocated to low-dose edoxaban (15 mg once daily) or placebo. Outcomes were compared between the three prespecified subgroups of age at baseline 80-84, 85-89, and ≥ 90 years. Primary efficacy and safety endpoints were incidence of SSE and ISTH-defined major bleeding, respectively (% per patient-year). Results: A total of 984 patients were randomized. Mean (± SD) age and CHADS 2 score of the patients aged ≥ 90 years were 92.3 (2.1) years and 3.1 (1.1), respectively. SSE occurred in 14/354 (2.8%), 25/374 (5.0%), and 20/256 (6.1%) of patients aged 80-84, 85-89, and ≥ 90 years, respectively; its incidence was significantly higher in the ≥ 90 years vs 80-84 years group (HR = 2.16 [95% CI, 1.09-4.27], P = 0.03). Major bleeding occurred in 6/353 (1.3%), 12/373 (2.6%), and 13/256 (4.3%) of patients aged 80-84, 85-89, and ≥ 90 years, respectively; its incidence was significantly higher in the ≥ 90 years vs 80-84 years (HR = 3.42 [1.30-9.01], P = 0.01). In this patient group ≥ 90 years with higher SSE and major bleeding incidences, edoxaban showed a significantly lower SSE incidence than placebo (4/129 [2.4%] vs 16/127 [10.1%]; HR = 0.23 [0.08-0.68], P = 0.008); however, edoxaban showed a greater tendency toward major bleeding than placebo (10/129 [6.5%] vs 3/127 [2.1%]; HR = 3.02 [0.82-11.21], P = 0.10), and significantly higher incidence of gastrointestinal bleeding (9/129 [5.9%] vs 1/127 [0.7%]; HR = 8.37 [1.04-67.07], P &lt; 0.05). Conclusions: In extremely elderly Japanese NVAF patients, low-dose edoxaban may be an option for preventing SSE. The prophylactic benefit must be balanced against the increased risk of major bleeding, particularly gastrointestinal bleeding.
Comparative Study of Treosulfan Plus Fludarabine (FT14) with Busulfan Plus Fludarabine (FB4) for Acute Myeloid Leukemia in First or Second Complete Remission: An Analysis from the European Society for Blood and Marrow Transplantation (EBMT) Acute Leukemia Working Party (ALWP)
Authors: Eleni Gavriilaki, Ioanna Sakellari, Myriam Labopin, Urpu Salmenniemi, Ibrahim Yakoub-Agha, Victoria Potter, Anna Berceanu, Alessandro Rambaldi, Inken Hilgendorf, Nicolaus Kröger, Stephan Mielke, Tsila Zuckerman, Jaime Sanz, Alessandro Busca, Hakan Ozdogu, Bipin B. Savani, Sebastian Giebel, Ali Bazarbachi, Alexandros Spyridonidis, Arnon Nagler, Mohamad Mohty
Journal: Blood (2021)
Venetoclax in Combination with Gilteritinib Demonstrates Molecular Clearance of <i>FLT3</i> mutation in Relapsed/Refractory <i>FLT3</i>-Mutated Acute Myeloid Leukemia
Authors: Naval Daver, Alexander E. Perl, Joseph Maly, Mark Levis, Ellen Ritchie, Mark R. Litzow, James McCloskey, Catherine C. Smith, Gary J. Schiller, Terrence Bradley, Ramon V. Tiu, Kiran Naqvi, Monique Dail, Satya Siddani, Jing Wang, Brenda Chyla, Paul Lee, Jessica K. Altman
Journal: Blood (2021)
Risk of herpesvirus, serious and opportunistic infections in atopic dermatitis: a population‐based cohort study*
Authors: J. Wan, D.B. Shin, M.N. Syed, K. Abuabara, A.R. Lemeshow, J.M. Gelfand
Journal: British Journal of Dermatology (2021)

Staphylococcal and herpes simplex virus (HSV) infections are commonly recognized in atopic dermatitis (AD), but less is known about other types of infections.To determine the risk of herpesvirus infections, serious infections and opportunistic infections in patients with AD.We conducted a population-based cohort study using UK-based electronic medical records data. Patients with AD were each matched to up to five unaffected patients on age, practice and index date. AD severity was defined using treatments as a proxy. Outcomes were incident herpesvirus infections [cytomegalovirus (CMV), Epstein-Barr virus (EBV), HSV or varicella zoster virus (VZV)], serious infections and opportunistic infections.Among 409 431 children and 625 083 adults with AD matched to 1 809 029 children and 2 678 888 adults without AD, respectively, adjusted Cox regression models showed children and adults with AD had a 50-52% greater risk of HSV and 18-33% greater risk of VZV, with risk increasing in parallel with AD severity. CMV risk was elevated among children with AD [hazard ratio (HR) 2·50, 95% confidence interval (95% CI) 1·38-4·54] and adults with severe AD (HR 4·45, 95% CI 1·76-11·25). Patients with AD had a 26-40% increase in risk of serious infections, with severe AD carrying the greatest risk. Although rare, opportunistic infections were associated with all severities of AD in adults (overall HR 1·31, 95% CI 1·20-1·42), but were not associated with AD in children. All estimates remained consistent after excluding patients receiving immunosuppressive treatments for AD.AD is significantly associated with herpesvirus infections, serious infections and opportunistic infections in a 'dose-dependent' manner with increasing severity. AD may increase susceptibility to infections exclusive of immunosuppressive medications.
Correlations between Mutations in Cancer-Related Genes, Therapy Responses and Outcomes of the 3 rd Generation Tyrosine Kinase-Inhibitor (TKI) in Persons with Chronic Myeloid Leukemia Failing Prior TKI-Therapy
Authors: Xiaoshuai Zhang, Zongru Li, Yazhen Qin, Robert Peter Gale, Xiaojun Huang, Qian Jiang
Journal: Blood (2021)
Clinical Characteristics and Contemporary Outcomes of Acute Myeloid Leukemia Evolving from Chronic Myelomonocytic Leukemia
Authors: Danielle Hammond, Tapan M. Kadia, Courtney D. DiNardo, Marina Konopleva, Nicholas J. Short, Naval Daver, Farhad Ravandi, Naveen Pemmaraju, Elias J. Jabbour, Kelly S. Chien, Sherry A. Pierce, Hagop Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban-Bravo
Journal: Blood (2021)
Cost and Value in Contemporary Heart Failure Clinical Guidance Documents
Authors: John W. Ostrominski, Sameer Hirji, Ankeet S. Bhatt, Javed Butler, Mona Fiuzat, Gregg C. Fonarow, Paul A. Heidenreich, James L. Januzzi, Carolyn S.P. Lam, Thomas M. Maddox, Christopher M. O’Connor, Muthiah Vaduganathan
Journal: JACC Heart Failure (2021)

This study sought to evaluate the frequency and nature of cost/value statements in contemporary heart failure (HF) clinical guidance documents (CGDs).In an era of rising health care costs and expanding therapeutic options, there is an increasing need for formal consideration of cost and value in the development of HF CGDs.HF CGDs published by major professional cardiovascular organizations between January 2010 and February 2021 were reviewed for the inclusion of cost/value statements.Overall, 33 documents were identified, including 5 (15%) appropriate use criteria, 7 (21%) clinical practice guidelines, and 21 (64%) expert consensus documents. Most CGDs (27 of 33; 82%) included at least 1 cost/value statement, and 20 (61%) CGDs included at least 1 cost/value-related citation. Most of these statements were found in expert consensus documents (77.7%). Three (9%) documents reported estimated costs of recommended interventions, but only 1 estimated out-of-pocket cost. Of 179 cost/value-related statements observed, 116 (64.8%) highlighted the economic impact of HF or HF-related care, 6 (3.4%) advocated for cost/value issues, 15 (8.4%) reported gaps in cost/value evidence, and 42 (23.5%) supported clinical guidance recommendations. Over time, patterns of inclusion of statements and citations of cost/value have been largely stable.Although most contemporary HF CGDs contain at least 1 cost/value statement, most CGDs focus on the high economic impact of HF and its related care; explicit inclusion of cost/value to support clinical guidance recommendations remains infrequent. These results highlight key opportunities for the integration of formalized cost/value considerations in future HF-focused CGDs.
EXTH-22. NEOADJUVANT IMMUNOTHERAPY WITH ANTI-PD1 ALTERS THE TUMOR MICROENVIRONMENT POST SURGERY IN A MODEL OF RECURRENT GLIOBLASTOMA
Authors: Lan Hoang-Minh, Bently Doonan, Christina von Roemeling, Changlin Yang, David Shin, Vrunda Trivedi, Aida Karachi, Yu Wang, Duane Mitchell
Journal: Neuro-Oncology (2021)

Abstract SIGNIFICANCE New promising clinical trials for glioblastoma are evaluating the efficacy of neoadjuvant immunotherapy in the context of recurrent tumor surgery. OBJECTIVE We investigated the effects of neoadjuvant PD1 blockade on the glioma tumor microenvironment in a clinically relevant murine model of recurrent tumor. RESULTS Using an orthotopic mouse KR158 resection model of glioblastoma that we have established, we show that neoadjuvant anti-PD1 and surgery enhance animal survival and increase the recruitment of CD8+ and CD4+ T cells at recurrent tumor sites following bulk tumor resection compared to surgery followed by adjuvant immunotherapy. Transcriptome and spatial genomic analyses reveal alterations in immune exhaustion and activation pathway signaling after neoadjuvant anti-PD1treatment when compared with adjuvant anti-PD1-treatment or surgery alone. CONCLUSIONS These results provide insights into the effects of neoadjuvant PD1 blockade on the tumor microenvironment and uncover additional treatment targets.
Infusion of iPSC-Derived CD34 + Hematopoietic Progenitors Following Myeloablative HSC Transplantation and Assessment of Their Immunogenicity in MHC-Defined Nonhuman Primate Model
Authors: Saritha S D'souza, Akhilesh Kumar, John P Maufort, Nick Strelchenko, Mathew Raymond, Jason Weinfurter, Jennifer Coonen, Matt Reynolds, James A. Thomson, Igor I Slukvin
Journal: Blood (2021)
Central Nervous System Involvement By Mantle Cell Lymphoma
Authors: Nicole McLaughlin, Jonas Paludo, Yucai Wang, David J. Inwards, Nora Bennani, Gita Thanarajasingam, Jose C. Villasboas, Grzegorz S. Nowakowski, Luis F. Porrata, Carrie A. Thompson, Ivana N. Micallef, Patrick B. Johnston, Thomas E. Witzig, Thomas M. Habermann, Stephen M. Ansell
Journal: Blood (2021)
Practice Patterns Pre-CART for Aggressive B-Cell Lymphomas: Patient Selection and Real World Salvage and Bridging Practices
Authors: Imran Nizamuddin, Kevin A. David, Jonathon B. Cohen, Vaishalee P. Kenkre, Geoffrey Shouse, Brian T. Hess, Thomas A. Ollila, Deborah M. Stephens, Sayan Mullick Chowdhury, Robert Ferdman, Kaitlyn O'Shea, Jieqi Liu, Jason T. Romancik, Joanna C. Zurko, Rahul S. Bhansali, Elyse I. Harris, McKenzie Sorrell, Rebecca Masel, Lindsey Fitzgerald, Carlos Galvez, Shuo Ma, Jane N. Winter, Barbara Pro, Leo I. Gordon, Alexey V. Danilov, Nirav N. Shah, Stefan K. Barta, Narendranath Epperla, Pallawi Torka, Reem Karmali
Journal: Blood (2021)
TMOD-27. IDENTIFYING ONCOGENIC C-MYC AND MYCN COMPLEXES IN HIGH-RISK PEDIATRIC CANCERS
Authors: Bo Qiu, Bo Qiu, Bo Qiu
Journal: Neuro-Oncology (2021)

Abstract The MYC family of proto-oncogenes is activated in a variety of cancers, including multiple high-risk pediatric malignancies. c-MYC (MYC) is ubiquitously expressed in human tissues, while MYCN (MYCN) has tissue and developmentally restricted expression patterns. In both neuroblastoma and medulloblastoma, enhanced activity of either MYCN or c-MYC drives high-risk disease. As transcription factors, MYC proteins exert oncogenic functions through protein-protein interaction networks that alter gene expression, but also mediate a growing list of target-gene independent nuclear functions (transcriptional elongation, chromatin changes throughout the cell cycle, etc…). While c-MYC and MYCN share many functions, they also regulate distinct cellular processes, and within medulloblastoma, they are activated in distinct molecular sub-groups (i.e. MYCN amplification is found in aggressive sonic hedge hog (SHH) subgroup tumors, while MYC amplification is found in aggressive group 3 and group 4 tumors). Here, we present an approach to identify oncogenic functions of c-MYC and MYCN in medulloblastoma and neuroblastoma using human induced pluripotent stem cell (iPSCO based orthotopic model systems. We hypothesize that the protein interaction networks and oncogenic functions of c-MYC and MYCN are impacted by cellular context, which are recapitulated in our orthotopic models (cell transcriptional and epigenetic landscape, tumor microenvironment). This premise is supported by recent single cell sequencing efforts in medulloblastoma and neuroblastoma, where primary human tumor cells are found to recapitulate specific transcriptional cell states found in normal hindbrain and sympathetic nervous system development, respectively. Through proximity labeling and quantitative mass spectrometry, we aim to identify tumor and oncogene specific protein interaction networks. This information will guide functional screening approaches to identify tumor-specific vulnerabilities. * Note MYC(N) refers to c-MYC and MYCN.
Progress in reaching unvaccinated (zero-dose) children in India, 1992–2016: a multilevel, geospatial analysis of repeated cross-sectional surveys
Authors: Mira Johri, Sunil Rajpal, S V Subramanian
Journal: The Lancet Global Health (2021)

Reaching zero-dose children (infants who receive no routine vaccinations) is a global strategic priority. We studied zero-dose children in India over 24 years to clarify aggregate trends and the contribution of large-scale social, economic, and geographical inequalities to these.We did a multilevel, geospatial analysis of repeated cross-sectional surveys of all four rounds (1992-2016) of India's National Family Health Survey to study the prevalence, distribution, and drivers of zero-dose (no first dose of diphtheria, tetanus, and pertussis) vaccination status. We included all children born to participating women who were aged 12-23 months at the time of the survey, as this is the standard age at which immunisation data are assessed. Children who died before the survey and those missing data on key outcomes or correlates were excluded. The outcome was child zero-dose vaccination status. We also compared the prevalence of nutritional deficits among zero-dose versus vaccinated children. For the most recent survey, we produced geospatial estimates identifying the prevalence of zero-dose children across states and districts and used these to project head count.We examined 393 167 children for eligibility. 72 848 children were included in the final analytic data set. The proportion of zero-dose children in India declined from 33·4% (95% CI 32·5-34·2) in 1992 to 10·1% (9·8-10·4) in 2016. Progress notwithstanding, in 2016, zero-dose children remained concentrated among disadvantaged groups (prevalence in the bottom wealth quintile 15·3%, 95% CI 14·6-16·0; prevalence among mothers with no education 16·8%, 16·1-17·4). Compared with vaccinated children, zero-dose children were more likely to suffer from malnutrition in all survey rounds (prevalence of severe stunting in 1992: zero dose 41·3%, 95% CI 39·2-43·8 vs vaccinated 28·5%, 27·2-29·7; 2016: zero dose 24·9%, 23·6-26·2 vs vaccinated 18·7%, 18·3-19·1). In 2016, there were an estimated 2·88 (95% CI 2·86-2·89) million zero-dose children in India, concentrated in less developed states and districts and several urban areas.Over a 24-year period in India, child zero-dose status was shaped by large-scale social inequalities and remained a consistent marker of generalised vulnerability. Interventions that address this cycle of intergenerational inequities should be prioritised.None.For the French, Spanish, and Hindi translations of the abstract see Supplementary Materials section.
Incidential Findings of Mutations in the PIGA Gene Are Highly Specific for the Presence of PNH Clones
Authors: Gregor Hoermann, Niroshan Nadarajah, Constance Baer, Frank Dicker, Kristina Loy, Sabit Delic, Frauke Bellos, Claudia Haferlach, Manja Meggendorfer, Torsten Haferlach, Wolfgang Kern
Journal: Blood (2021)
Locus-Conserved Circular RNA cZNF292 Controls Endothelial Cell Flow Responses
Authors: Andreas W. Heumüller, Alisha N. Jones, André Mourão, Marius Klangwart, Chenyue Shi, Ilka Wittig, Ariane Fischer, Marion Muhly-Reinholz, Giulia K. Buchmann, Christoph Dieterich, Michael Potente, Thomas Braun, Phillip Grote, Nicolas Jaé, Michael Sattler, Stefanie Dimmeler
Journal: Circulation Research (2021)

Circular RNAs (circRNAs) are generated by back splicing of mostly mRNAs and are gaining increasing attention as a novel class of regulatory RNAs that control various cellular functions. However, their physiological roles and functional conservation in vivo are rarely addressed, given the inherent challenges of their genetic inactivation. Here, we aimed to identify locus conserved circRNAs in mice and humans, which can be genetically deleted due to retained intronic elements not contained in the mRNA host gene to eventually address functional conservation. Combining published endothelial RNA-sequencing data sets with circRNAs of the circATLAS databank, we identified locus-conserved circRNA retaining intronic elements between mice and humans. CRISPR/Cas9 mediated genetic depletion of the top expressed circRNA cZfp292 resulted in an altered endothelial morphology and aberrant flow alignment in the aorta in vivo. Consistently, depletion of cZNF292 in endothelial cells in vitro abolished laminar flow-induced alterations in cell orientation, paxillin localization and focal adhesion organization. Mechanistically, we identified the protein SDOS (syndesmos) to specifically interact with cZNF292 in endothelial cells by RNA-affinity purification and subsequent mass spectrometry analysis. Silencing of SDOS or its protein binding partner Syndecan-4, or mutation of the SDOS-cZNF292 binding site, prevented laminar flow-induced cytoskeletal reorganization thereby recapitulating cZfp292 knockout phenotypes. Together, our data reveal a hitherto unknown role of cZNF292/cZfp292 in endothelial flow responses, which influences endothelial shape.
Multipolar traction with homemade “spider” device to improve submucosal dissection of gastric superficial lesions is safe and effective
Authors: Martin Bordet, Thomas Lambin, Timothée Wallenhorst, Jérôme Rivory, Jérémie Jacques, Lucile Héroin, Mathieu Pioche
Journal: Endoscopy (2021)

In recent years, endoscopic submucosal dissection (ESD) has been a revolution for en bloc resection of large superficial tumors of the digestive tract including the stomach. The European Society of Gastrointestinal Endoscopy recommends ESD as the treatment of choice for most gastric superficial neoplastic lesions [1]. However, it remains a time-consuming technique with a long learning curve. Several suggestions have been made in order to improve the technique [2] [3] [4] [5], but the lateral and distal edges of the incision remain tricky sections.
Post-Transplantation Cyclophosphamide for Graft-Versus-Host Disease Prophylaxis in Allogeneic Hematopoietic Cell Transplantation for Higher-Risk Myelodysplastic Syndrome
Authors: Eun-Ji Choi, Han-Seung Park, Jung-Hee Lee, Kyoo Hyung Lee, Youngshin Lee, Young-Ah Kang, Mijin Jeon, Ji Min Woo, Hyeran Kang, Je-Hwan Lee
Journal: Blood (2021)
GA4GH Passport standard for digital identity and access permissions
Authors: Craig Voisin, Mikael Linden, Stephanie O.M. Dyke, Sarion R. Bowers, Pinar Alper, Maxmillian P. Barkley, David Bernick, Jianpeng Chao, Mélanie Courtot, Francis Jeanson, Melissa A. Konopko, Martin Kuba, Jonathan Lawson, Jaakko Leinonen, Stephanie Li, Vivian Ota Wang, Anthony A. Philippakis, Kathy Reinold, Gregory A. Rushton, J. Dylan Spalding, Juha Törnroos, Ilya Tulchinsky, Jaime M. Guidry Auvil, Tommi H. Nyrönen
Journal: Cell Genomics (2021)

The Global Alliance for Genomics and Health (GA4GH) supports international standards that enable a federated data sharing model for the research community while respecting data security, ethical and regulatory frameworks, and data authorization and access processes for sensitive data. The GA4GH Passport standard (Passport) defines a machine-readable digital identity that conveys roles and data access permissions (called "visas") for individual users. Visas are issued by data stewards, including data access committees (DACs) working with public databases, the entities responsible for the quality, integrity, and access arrangements for the datasets in the management of human biomedical data. Passports streamline management of data access rights across data systems by using visas that present a data user's digital identity and permissions across organizations, tools, environments, and services. We describe real-world implementations of the GA4GH Passport standard in use cases from ELIXIR Europe, National Institutes of Health, and the Autism Sharing Initiative. These implementations demonstrate that the Passport standard has provided transparent mechanisms for establishing permissions and authorizing data access across platforms.
Abstract 11219: Evaluate The Incidence of Hypertension in Patients With Rheumatoid Arthritis Treated by Tnf Alpha Inhibitors
Authors: Hetavi Mahida, Ana Gubeladze, Dawn M Calderon
Journal: Circulation (2019)

Introduction: Etanercept, Infliximab, Adalimumab and Certolizumab are the Tumor Necrosis factor alpha inhibitors (TNF inhibitors) used in the treatment of Rheumatoid arthritis(RA) Methods: Meta-ana...
Helen Salisbury: To level up, we need to top up GPs
Authors: Helen Salisbury
Journal: BMJ (2021)

Poverty is a deadly condition. We don’t need to look to faraway countries ravaged by war, climate disaster, and famine to know this—it stares us in the face here at home. A rich man in England can expect to live nearly a decade longer than a poor man and to spend 19 more years in good health. In women the gap in life expectancy is slightly less, but disadvantaged women spend even more of their lives in poor health.1

Many factors contribute to health and longevity, but access to medical care is one. Doctors cannot prevent or cure all …
Correlative Biological Studies Related to the Response, Peak and Persistence of ARI0002h, an Academic BCMA-Directed CAR-T Cell, with Fractionated Initial Infusion and Booster Dose for Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM)
Authors: Aina Oliver-Caldés, Marta Español-Rego, Aintzane Zabaleta, Susana Inogés, Ascensión López-Diaz de Cerio, Veronica Gonzalez-Calle, Valentin Cabañas, Beatriz Martin-Antonio, Lorena Pérez-Amill, Juan Luis Reguera, Juan Roberto Rodriguez-Madoz, Paula Rodríguez-Otero, Daniel Benítez-Ribas, Mari-Pau Mena, Marta Lasa, Luis Gerardo Rodríguez-Lobato, Azucena González, Laura Rosinol, Jose Maria Moraleda, Felipe Prósper, Álvaro Urbano-Ispizua, Maria-Victoria Mateos, Manel Juan, Bruno Paiva, Mariona Pascal, Carlos Fernandez de Larrea
Journal: Blood (2021)
Gene Expression after Hemarthrosis Differs between FVIII-Deficient Mice Treated with Recombinant FVIII or FVIII-Fc Fusion Protein
Authors: Bilgimol Chumappumkal Joseph, Esther Cooke, Jenny Y Zhou, Sonha Nguyen, Samantha Ruiz, Annette von Drygalski
Journal: Blood (2021)