tbuckley/cabot-search huggingface dataset:
78P Cardiotoxicity in cancer patients treated with immune-checkpoint inhibitors
Authors: F.F. Franco, Y. Garitaonaindía, M. Blanco Clemente, M. Torrente, V. Calvo de Juan, A. Collazo Lorduy, L. Gutierrez, J.C. Sánchez, M.A. Gonzalez del Alba Baamonde, A. Royuela, G. Visedo, S.C. González, M. Martinez Cutillas, C. Traseira Puchol, R. Aguado, C.D. Mitroi, M. Provencio
Journal: Annals of Oncology (2021)
10P Family history of cancer correlates with improved outcome from immunotherapy in NSCLC independent of somatic DNA damage response gene status
Authors: A. Cortellini, M. Filetti, F. Citarella, R. Giusti, M. Russano, F. Grossi, A.J. Gelibter, F. Pecci, M. De Tursi, M. Macerelli, O. Nigro, M.G. Ferrara, S. Buti, F. Mazzoni, L. Cantini, M.R. Migliorino, A. Addeo, V. Adamo, A. Russo, D.J. Pinato
Journal: Annals of Oncology (2021)
Analysis of Factors Associated with Conversion to CR in Patients with Large B-Cell Lymphoma Achieving Day 30 PR after CAR T-Cell Therapy
Authors: Ajlan Al Zaki, Jason R. Westin, Grace Watson, Lei Feng, Sairah Ahmed, Haleigh Mistry, Loretta Nastoupil, Misha Hawkins, Ranjit Nair, Swaminathan P Iyer, Hun Lee, Raphael E Steiner, Christopher R. Flowers, Elizabeth J. Shpall, Partow Kebriaei, Sattva S. Neelapu, Paolo Strati
Journal: Blood (2021)
Recognized Outstanding Reviewers for <i>Circulation</i> in 2021
Authors: Darren K. McGuire, James A. de Lemos, Joseph A. Hill, Eloisa Arbustini, Emelia Benjamin, Michael Blaha, Barry Borlaug, Khadijah Breathett, Robert Byrne, Alida Caforio, Edina Cenko, Richard Cheng, David Cohen, Nancy Cook, Leslie Cooper, Kieran Docherty, John Eikelboom, Assam El-Osta, Eva Gerdts, Bruna Gigante, Robert Giugliano, Shinichi Goto, Christopher Granger, Ziad Hijaz, Mark Hlatky, Michael Holmes, Priscilla Hsue, Sadiya Khan, Susan Kwon, Gregory Lewis, Douglas Mann, Erin Michos, Alanna Morris, Pradeep Natarajan, Chiadi Ndumele, Paul Ridker, Christianne Roumie, Michelle Schmiegelow, Loren Smith, Markella Zanni
Journal: Circulation (2021)
CircDOCK1 promotes the tumorigenesis and cisplatin resistance of osteogenic sarcoma via the miR-339-3p/IGF1R axis
Authors: Shenglong Li, Fei Liu, Ke Zheng, Wei Wang, Enduo Qiu, Yi Pei, Shuang Wang, Jiaming Zhang, Xiaojing Zhang
Journal: Molecular Cancer (2021)

Abstract Background Circular RNAs (circRNAs), a class of noncoding RNAs (ncRNAs), may modulate gene expression by binding to miRNAs. Additionally, recent studies show that circRNAs participate in some pathological processes. However, there is a large gap in the knowledge about circDOCK1 expression and its biological functions in osteogenic sarcoma (OS). Methods Differentially expressed circRNAs in OS cell lines and tissues were identified by circRNA microarray analysis and quantitative real-time PCR (qRT–PCR). To explore the actions of circDOCK1 in vivo and in vitro, circDOCK1 was knocked down or overexpressed. To assess the binding and regulatory associations among miR-339-3p, circDOCK1 and IGF1R, we performed rescue experiments, RNA immunoprecipitation (RIP), RNA pulldown assays and dual-luciferase assays. Moreover, we performed apoptosis assays to reveal the regulatory effects of the circDOCK1/miR-339-3p/IGF1R axis on cisplatin sensitivity. Results CircDOCK1 expression remained stable in the cytoplasm and was higher in OS tissues and cells than in the corresponding controls. Overexpression of circDOCK1 increased oncogenicity in vivo and malignant transformation in vitro. In the U2OS and MG63 cell lines, circDOCK1 modulated tumor progression by regulating IGF1R through sponging of miR-339-3p. Additionally, in the U2OS/DDP and MG63/DDP cell lines, cisplatin sensitivity was regulated by circDOCK1 via the miR-339-3p/IGF1R axis. Conclusions CircDOCK1 can promote progression and regulate cisplatin sensitivity in OS via the miR-339-3p/IGF1R axis. Thus, the circDOCK1/miR-339-3p/IGF1R axis may be a key mechanism and therapeutic target in OS.
123MO Monalizumab, cetuximab and durvalumab in first-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): A phase II trial
Authors: D.A. Colevas, K. Misiukiewicz, A.T. Pearson, J. Fayette, J.R. Bauman, D. Cupissol, E. Saada-Bouzid, D.R. Adkins, D.B. Marie, S.L. Cornen, P. André, F. Carrette, F. Rotolo, A. Boyer Chammard, R.B. Cohen
Journal: Annals of Oncology (2021)
Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR T-cell therapy
Authors: Allison Barz Leahy, Kaitlin J. Devine, Yimei Li, Hongyan Liu, Regina Myers, Amanda DiNofia, Lisa Wray, Susan R. Rheingold, Colleen Callahan, Diane Baniewicz, Maria Patino, Haley Newman, Stephen P. Hunger, Stephan A. Grupp, David M. Barrett, Shannon L. Maude
Journal: Blood (2021)
Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal study
Authors: Yves Dauvilliers, Isabelle Arnulf, Nancy Foldvary-Schaefer, Anne Marie Morse, Karel Šonka, Michael J Thorpy, Emmanuel Mignot, Patricia Chandler, Rupa Parvataneni, Jed Black, Amanda Sterkel, Dan Chen, Franck Skobieranda, Richard K Bogan
Journal: The Lancet Neurology (2021)
Abstract 10125: Continuous Heart Rate Dynamics Preceding In-Hospital Cardiac Arrest of Respiratory Etiology
Authors: Rongzi Shan, Xiao Hu, Noel G Boyle, Duc H Do
Journal: Circulation (2021)

Introduction: Respiratory failure is a common cause of pulseless electrical activity (PEA) arrest in hospitalized patients, but how pathophysiologic changes in these conditions affect heart rate (HR) pre-arrest is not well described. We describe HR dynamics prior to in-hospital cardiac arrest (IHCA) among PEA/asystole arrest patients with respiratory etiology. Methods: In this retrospective descriptive study, we evaluated 67 patients with ≥3 hours of continuous ECG data recorded immediately preceding PEA/asystole IHCA in a single institution from 2010-2014. We identified respiratory arrest cases (eg. pneumonia, aspiration, pulmonary embolism, acute respiratory distress syndrome) by chart review and evaluated ECG patterns up to 24 hours prior to arrest to identify patterns of HR increase, HR decrease, sinus arrest, and escape rhythms. Results: We identified 31/67 patients with respiratory etiology (age 59±17 years, 52% male, 83% return of spontaneous circulation, 41% survived to discharge); of these 23/31(74%) fit an a priori model of HR response (Figure). Twelve cases demonstrated clear onset of HR increase at a median of 44 (IQR 28-507) minutes prior to arrest, while the remaining 11 cases started the monitoring period in sinus tachycardia. The mean peak HR was 120±20 bpm. An abrupt onset of HR decrease occurred at a median of 3.4 (IQR 2.3-5.9) minutes prior to arrest. Sinus arrest occurred during the HR decrease phase in 18/23 cases; the first escape rhythm was atrial in 11 (61%), junctional in 2 (11%) and ventricular in 3 (17%) cases. Conclusion: The majority of IHCA due to respiratory etiology (74%) follow a typical model of HR increase due to physiologic compensation to hypoxia, followed by rapid HR decrease leading to PEA arrest, likely from the vagal effect of hypoxia and sinus node suppression from acidosis. Understanding HR trends can aid clinical management as well as development of artificial intelligence models for prediction of IHCA.
Critical role of <i>Lama4</i> for hematopoiesis regeneration and acute myeloid leukemia progression
Authors: Huan Cai, Makoto Kondo, Lakshmi Sandhow, Pingnan Xiao, Anne-Sofie Johansson, Takako Sasaki, Joanna Zawacka-Pankau, Karl Tryggvason, Johanna Ungerstedt, Julian Walfridsson, Marja Ekblom, Hong Qian
Journal: Blood (2021)

Impairment of normal hematopoiesis and leukemia progression are 2 well-linked processes during leukemia development and are controlled by the bone marrow (BM) niche. Extracellular matrix proteins, including laminin, are important BM niche components. However, their role in hematopoiesis regeneration and leukemia is unknown. Laminin α4 (Lama4), a major receptor-binding chain of several laminins, is altered in BM niches in mice with acute myeloid leukemia (AML). So far, the impact of Lama4 on leukemia progression remains unknown. We here report that Lama4 deletion in mice resulted in impaired hematopoiesis regeneration following irradiation-induced stress, which is accompanied by altered BM niche composition and inflammation. Importantly, in a transplantation-induced MLL-AF9 AML mouse model, we demonstrate accelerated AML progression and relapse in Lama4-/- mice. Upon AML exposure, Lama4-/- mesenchymal stem cells (MSCs) exhibited dramatic molecular alterations, including upregulation of inflammatory cytokines that favor AML growth. Lama4-/- MSCs displayed increased antioxidant activities and promoted AML stem cell proliferation and chemoresistance to cytarabine, which was accompanied by increased mitochondrial transfer from the MSCs to AML cells and reduced reactive oxygen species in AML cells in vitro. Similarly, we detected lower levels of reactive oxygen species in AML cells from Lama4-/- mice post-cytarabine treatment. Notably, LAMA4 inhibition or knockdown in human MSCs promoted human AML cell proliferation and chemoprotection. Together, our study for the first time demonstrates the critical role of Lama4 in impeding AML progression and chemoresistance. Targeting Lama4 signaling pathways may offer potential new therapeutic options for AML.
14P Circulating tumor DNA (ctDNA) residual and dynamics of ctDNA clonality indicated therapeutic efficacy of sintilimab plus docetaxel in previously treated advanced non-small cell lung cancer
Authors: Z. Wang, X. Han, J. Guo, X. Tang, C. Zhu, H. Zhu, D. Zhu, X. Zhang, X. Meng
Journal: Annals of Oncology (2021)
NAVIGATE 24-Month Results: Electromagnetic Navigation Bronchoscopy for Pulmonary Lesions at 37 Centers in Europe and the United States
Authors: Erik E. Folch, Mark R. Bowling, Michael A. Pritchett, Septimiu D. Murgu, Michael A. Nead, Javier Flandes, William S. Krimsky, Amit K. Mahajan, Gregory P. LeMense, Boris A. Murillo, Sandeep Bansal, Kelvin Lau, Thomas R. Gildea, Merete Christensen, Douglas A. Arenberg, Jaspal Singh, Krish Bhadra, D. Kyle Hogarth, Christopher W. Towe, Bernd Lamprecht, Michela Bezzi, Jennifer S. Mattingley, Kristin L. Hood, Haiying Lin, Jennifer J. Wolvers, Sandeep J. Khandhar
Journal: Journal of Thoracic Oncology (2021)
135P First-in-human phase I trial of SRF617, a potent inhibitor of CD39 activity, as monotherapy or in combination, in patients (pts) with advanced solid tumors
Authors: A. Patnaik, I. Mehmi, J. Strauss, Y. Xing, R. Jamal, A. O'Neill, A.C. Lake, S. Koseoglu, M.C. Warren, J-K. Chung, A. Alika, R. Lis, D. Rasco, A.T. Salawu, W. Chow, A. Spreafico
Journal: Annals of Oncology (2021)
45S rDNA Repeats of Turtles and Crocodiles Harbor a Functional 5S rRNA Gene Specifically Expressed in Oocytes
Authors: Asya G Davidian, Alexander G Dyomin, Svetlana A Galkina, Nadezhda E Makarova, Sergey E Dmitriev, Elena R Gaginskaya
Journal: Molecular Biology and Evolution (2021)

In most eukaryotic genomes, tandemly repeated copies of 5S rRNA genes are clustered outside the nucleolus organizer region (NOR), which normally encodes three other major rRNAs: 18S, 5.8S, and 28S. Our analysis of turtle rDNA sequences has revealed a 5S rDNA insertion into the NOR intergenic spacer in antisense orientation. The insertion (hereafter called NOR-5S rRNA gene) has a length of 119 bp and coexists with the canonical 5S rDNA clusters outside the NOR. Despite the ∼20% nucleotide difference between the two 5S gene sequences, their internal control regions for RNA polymerase III are similar. Using the turtle Trachemys scripta as a model species, we showed the NOR-5S rDNA specific expression in oocytes. This expression is concurrent with the NOR rDNA amplification during oocyte growth. We show that in vitellogenic oocytes, the NOR-5S rRNA prevails over the canonical 5S rRNA in the ribosomes, suggesting a role of modified ribosomes in oocyte-specific translation. The orders Testudines and Crocodilia seem to be the only taxa of vertebrates with such a peculiar rDNA organization. We speculate that the amplification of the 5S rRNA genes as a part of the NOR DNA during oogenesis provides a dosage balance between transcription of all the four ribosomal RNAs while producing a maternal pool of extra ribosomes. We further hypothesize that the NOR-5S rDNA insertion appeared in the Archelosauria clade during the Permian period and was lost later in the ancestors of Aves.
Alzheimer’s disease modification mediated by bone marrow-derived macrophages via a TREM2-independent pathway in mouse model of amyloidosis
Authors: Raz Dvir-Szternfeld, Giulia Castellani, Michal Arad, Liora Cahalon, Sarah Phoebeluc Colaiuta, Hadas Keren-Shaul, Tommaso Croese, Chiara Burgaletto, Kuti Baruch, Tyler Ulland, Marco Colonna, Assaf Weiner, Ido Amit, Michal Schwartz
Journal: Nature Aging (2021)
Treatment of experimental anthrax with pegylated circularly permuted capsule depolymerase
Authors: Patricia M. Legler, Stephen F. Little, Jeffrey Senft, Rowena Schokman, John H. Carra, Jaimee R. Compton, Donald Chabot, Steven Tobery, David P. Fetterer, Justin B. Siegel, David Baker, Arthur M. Friedlander
Journal: Science Translational Medicine (2021)

Pegylated circularly permuted capsule depolymerase removes capsule from Bacillus anthracis and protects anthrax-infected mice.
Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial
Authors: Marwan G Fakih, Scott Kopetz, Yasutoshi Kuboki, Tae Won Kim, Pamela N Munster, John C Krauss, Gerald S Falchook, Sae-Won Han, Volker Heinemann, Kei Muro, John H Strickler, David S Hong, Crystal S Denlinger, Gustavo Girotto, Myung-Ah Lee, Haby Henary, Qui Tran, Joseph K Park, Gataree Ngarmchamnanrith, Hans Prenen, Timothy J Price
Journal: The Lancet Oncology (2021)
Pink Ribbons
Authors: Elizabeth Prsic
Journal: JAMA Oncology (2021)

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Changes in Calorie Content of Menu Items at Large Chain Restaurants After Implementation of Calorie Labels
Authors: Anna H. Grummon, Joshua Petimar, Mark J. Soto, Sara N. Bleich, Denise Simon, Lauren P. Cleveland, Anjali Rao, Jason P. Block
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Calorie labeling on menus is required in US chain food establishments with 20 or more locations. This policy may encourage retailers to offer lower-calorie items, which could lead to a public health benefit by reducing customers' calorie intake from prepared foods. However, potential reformulation of restaurant menu items has not been examined since nationwide enforcement of this policy in 2018. <h3>Objective</h3> To examine the calorie content of menu items at large chain restaurants before and after implementation of federally mandated menu calorie labels. <h3>Design, Setting, and Participants</h3> This pre-post cohort study used restaurant menu data from MenuStat, a database of nutrition information for menu items offered in the largest chain restaurants in the US, collected annually from 2012 to 2019. The study comprised 35 354 menu items sold at 59 large chain restaurants in the US. Statistical analysis was conducted from February 4 to October 8, 2021. <h3>Intervention</h3> Nationwide implementation of menu calorie labeling. <h3>Main Outcomes and Measures</h3> Changes in menu items' calorie content after restaurant chains implemented calorie labels were estimated, adjusting for prelabeling trends. All menu items, continuously available items, items newly introduced to menus, and items removed from menus were examined separately. <h3>Results</h3> Among the 59 restaurant chains included in the study, after labeling, there were no changes in mean calorie content for all menu items (change = −2.0 calories; 95% CI, −8.5 to 4.4 calories) or continuously available items (change = −2.3 calories; 95% CI, −11.5 to 6.3 calories). Items that were newly introduced after labeling, however, had a lower mean calorie content than items introduced before labeling (change = −112.9 calories; 95% CI, −208.6 to −25.2 calories), although there was heterogeneity by restaurant type. Items removed from menus after labeling had similar calorie content as items removed before labeling (change = 0.5 calories; 95% CI, −79.4 to 84.0 calories). <h3>Conclusions and Relevance</h3> In this cohort study of large chain restaurants, implementing calorie labels on menus was associated with the introduction of lower-calorie items but no changes in continuously available or removed items.
159P Pembrolizumab, SBRT, and immunomodulation for recurrent and/or refractory cervical or endometrial carcinoma
Authors: E.A. De Jaeghere, S. Tuyaerts, A.M.T. Van Nuffel, L. Lippens, A. Hendrix, P. Vuylsteke, S. Henry, X.B. Trinh, P.A. Van Dam, S. Aspeslagh, A. De Caluwe, E. Naert, K. Van de Vijver, F. Amant, K. Vandecasteele, H.G. Denys
Journal: Annals of Oncology (2021)
Family Functioning When a Child Has a Serious Illness: All for One and One for All
Authors: Lauren M. Yagiela, Mary E. Hartman
Journal: JAMA Network Open (2021)

Chris Feudtner, MD, PhD, MPH; Russell T. Nye, PhD; Jackelyn Y. Boyden, PhD, MPH, RN; Katherine E. Schwartz, MD; Emilie R. Korn, MD; Aaron G. Dewitt, MD; Amy T. Waldman, MD, MSCE; Lisa A. Schwartz, PhD; Yuming A. Shen, PhD; Michael Manocchia, PhD; Rui Xiao, PhD; Blyth T. Lord, EdM; Douglas L. Hill, PhD
Adherence of Clinical Practice Guidelines for Pharmacologic Treatments of Hospitalized Patients With COVID-19 to Trustworthy Standards
Authors: Karen E. A. Burns, Matthew Laird, James Stevenson, Kimia Honarmand, David Granton, Michelle E. Kho, Deborah Cook, Jan O. Friedrich, Maureen O. Meade, Mark Duffett, Dipayan Chaudhuri, Kuan Liu, Frederick D’Aragon, Arnav Agarwal, Neill K. J. Adhikari, Hayle Noh, Bram Rochwerg, David Lightfoot, Karen Choong, Andrea Lucas, Joanna Dionne, Colungo Lozano, Erick Duan, Emilie Belley-Cote, Melissa Parker, John Basmaji, Vincent Lau, Samantha Arora
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The COVID-19 pandemic created the need for rapid and urgent guidance for clinicians to manage COVID-19 among patients and prevent transmission. <h3>Objective</h3> To appraise the quality of clinical practice guidelines (CPGs) using the National Academy of Medicine (NAM) criteria. <h3>Evidence Review</h3> A search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to December 14, 2020, and a search of related articles to February 28, 2021, that included CPGs developed by societies or by government or nongovernment organizations that reported pharmacologic treatments of hospitalized patients with COVID-19. Teams of 2 reviewers independently abstracted data and assessed CPG quality using the 15-item National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards (NEATS) instrument. <h3>Findings</h3> Thirty-two CPGs were included in the review. Of these, 25 (78.1%) were developed by professional societies and emanated from a single World Health Organization (WHO) region. Overall, the CPGs were of low quality. Only 7 CPGs (21.9%) reported funding sources, and 12 (37.5%) reported conflicts of interest. Only 5 CPGs (15.6%) included a methodologist, described a search strategy or study selection process, or synthesized the evidence. Although 14 CPGs (43.8%) made recommendations or suggestions for or against treatments, they infrequently rated confidence in the quality of the evidence (6 of 32 [18.8%]), described potential benefits and harms (6 of 32 [18.8%]), or graded the strength of the recommendations (5 of 32 [15.6%]). External review, patient or public perspectives, or a process for updating were rare. High-quality CPGs included a methodologist and multidisciplinary collaborations involving investigators from 2 or more WHO regions. <h3>Conclusions and Relevance</h3> In this review, few COVID-19 CPGs met NAM standards for trustworthy guidelines. Approaches that prioritize engagement of a methodologist and multidisciplinary collaborators from at least 2 WHO regions may lead to the production of fewer, high-quality CPGs that are poised for updates as new evidence emerges. <h3>Trial Registration</h3> PROSPERO Identifier:CRD42021245239
Immediate and Longer-Term Changes in the Mental Health and Well-being of Older Adults in England During the COVID-19 Pandemic
Authors: Paola Zaninotto, Eleonora Iob, Panayotes Demakakos, Andrew Steptoe
Journal: JAMA Psychiatry (2021)

Despite the emphasis placed on the psychological impact of the COVID-19 pandemic, evidence from representative studies of older adults including pre-COVID-19 data and repeated assessments during the pandemic is scarce.To examine changes in mental health and well-being before and during the initial and later phases of the COVID-19 pandemic and test whether patterns varied with sociodemographic characteristics in a representative sample of older adults living in England.This longitudinal cohort study analyzed data from 5146 older adults participating in the English Longitudinal Study of Ageing who provided data before the COVID-19 pandemic (2018 and 2019) and at 2 occasions in 2020 (June or July as well as November or December).The COVID-19 pandemic and sociodemographic characteristics, including sex, age, partnership status, and socioeconomic position.Changes in depression (8-item Centre for Epidemiological Studies Depression scale), anxiety (7-item Generalized Anxiety Disorder scale), quality of life (12-item Control, Autonomy, Self-realization, and Pleasure scale), and loneliness (3-item Revised University of California, Los Angeles, loneliness scale) were tested before and during the COVID-19 pandemic using fixed-effects regression models.Of 5146 included participants, 2723 (52.9%) were women, 4773 (92.8%) were White, and the mean (SD) age was 67.7 (10.6) years. The prevalence of clinically significant depressive symptoms increased from 12.5% (95% CI, 11.5-13.4) before the COVID-19 pandemic to 22.6% (95% CI, 21.6-23.6) in June and July 2020, with a further rise to 28.5% (95% CI, 27.6-29.5) in November and December 2020. This was accompanied by increased loneliness and deterioration in quality of life. The prevalence of anxiety rose from 9.4% (95% CI, 8.8-9.9) to 10.9% (95% CI, 10.3-11.5) from June and July 2020 to November and December 2020. Women and nonpartnered people experienced worse changes in mental health. Participants with less wealth had the lowest levels of mental health before and during the COVID-19 pandemic. Higher socioeconomic groups had better mental health overall but responded to the COVID-19 pandemic with more negative changes.In this longitudinal cohort study of older adults living in England, mental health and well-being continued to worsen as the COVID-19 pandemic progressed, and socioeconomic inequalities persisted. Women and nonpartnered people experienced greater deterioration in mental health.