tbuckley/cabot-search huggingface dataset:
Medical Financial Hardship in Survivors of Adolescent and Young Adult Cancer in the United States
Authors: Amy D Lu, Zhiyuan Zheng, Xuesong Han, Ruowen Qi, Jingxuan Zhao, K Robin Yabroff, Paul C Nathan
Journal: JNCI Journal of the National Cancer Institute (2021)

Cancer and its treatment can result in lifelong medical financial hardship, which we aimed to describe among adult survivors of adolescent and young adult (AYA) cancers in the United States.We identified adult (aged ≥18 years) survivors of AYA cancers (diagnosed ages 15-39 years) and adults without a cancer history from the 2010-2018 National Health Interview Surveys. Proportions of respondents reporting measures in different hardship domains (material [eg, problems paying bills], psychological [eg, distress], and behavioral [eg, forgoing care due to cost]) were compared between groups using multivariable logistic regression models and hardship intensity (cooccurrence of hardship domains) using ordinal logistic regression. Cost-related changes in prescription medication use were assessed separately.A total of 2588 AYA cancer survivors (median = 31 [interquartile range = 26-35] years at diagnosis; 75.0% more than 6 years and 50.0% more than 16 years since diagnosis) and 256 964 adults without a cancer history were identified. Survivors were more likely to report at least 1 hardship measure in material (36.7% vs 27.7%, P < .001) and behavioral (28.4% vs 21.2%, P < .001) domains, hardship in all 3 domains (13.1% vs 8.7%, P < .001), and at least 1 cost-related prescription medication nonadherence (13.7% vs 10.3%, P = .001) behavior.Adult survivors of AYA cancers are more likely to experience medical financial hardship across multiple domains compared with adults without a cancer history. Health-care providers must recognize this inequity and its impact on survivors' health, and multifaceted interventions are necessary to address underlying causes.
Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction
Authors: Kaspar Broch, Anne Kristine Anstensrud, Sindre Woxholt, Kapil Sharma, Ingvild Maria Tøllefsen, Bjørn Bendz, Svend Aakhus, Thor Ueland, Brage Høyem Amundsen, Jan Kristian Damås, Erlend Sturle Berg, Elisabeth Bjørkelund, Christina Bendz, Einar Hopp, Ola Kleveland, Knut Haakon Stensæth, Anders Opdahl, Nils-Einar Kløw, Ingebjørg Seljeflot, Geir Øystein Andersen, Rune Wiseth, Pål Aukrust, Lars Gullestad
Journal: Journal of the American College of Cardiology (2021)
Chemical Control of Pulmonary Ventilation
Authors: Hans Winterstein
Journal: New England Journal of Medicine (1956)

IN my first lecture I shall deal with chemoreceptors — that is, the nervous structures that control the lungs according to the chemical composition of the blood. Their discovery by Heymans and Bouckaert1 represents one of the greatest revolutions in the physiology of respiration. It is not as if the idea of a control of respiratory movements by peripheral nerves were something entirely new, since Hering and Breuer,2 nearly a hundred years ago, discovered the so-called self-regulation of respiration by proprioceptor reflexes. It seems that sixty years ago even the thought had been put forward by Speck3 that the influence . . .
A reporting and analysis framework for structured evaluation of COVID-19 clinical and imaging data
Authors: Gabriel Alexander Salg, Maria-Katharina Ganten, Andreas Michael Bucher, Hannes Goetz Kenngott, Matthias Alexander Fink, Constantin Seibold, Ricarda Elisabeth Fischbach, Kai Schlamp, Carlos Alberto Velandia, Philipp Fervers, Felix Doellinger, Anna Luger, Saif Afat, Uta Merle, Markus K. Diener, Philippe L. Pereira, Tobias Penzkofer, Thorsten Persigehl, Ahmed Othman, Claus Peter Heußel, Matthias Baumhauer, Gerlig Widmann, Konstantinos Stathopoulos, Bernd Hamm, Thomas J. Vogl, Konstantin Nikolaou, Hans-Ulrich Kauczor, Jens Kleesiek
Journal: npj Digital Medicine (2021)

Abstract The COVID-19 pandemic has worldwide individual and socioeconomic consequences. Chest computed tomography has been found to support diagnostics and disease monitoring. A standardized approach to generate, collect, analyze, and share clinical and imaging information in the highest quality possible is urgently needed. We developed systematic, computer-assisted and context-guided electronic data capture on the FDA-approved mint Lesion TM software platform to enable cloud-based data collection and real-time analysis. The acquisition and annotation include radiological findings and radiomics performed directly on primary imaging data together with information from the patient history and clinical data. As proof of concept, anonymized data of 283 patients with either suspected or confirmed SARS-CoV-2 infection from eight European medical centers were aggregated in data analysis dashboards. Aggregated data were compared to key findings of landmark research literature. This concept has been chosen for use in the national COVID-19 response of the radiological departments of all university hospitals in Germany.
Intratumoral Plasmid IL12 Expands CD8
Authors: Melinda L Telli, Hiroshi Nagata, Irene Wapnir, Chaitanya R Acharya, Kaitlin Zablotsky, Bernard A Fox, Carlo Bifulco, Shawn M Jensen, Carmen Ballesteros-Merino, Mai Hope Le, Robert H Pierce, Erica Browning, Reneta Hermiz, Lauren Svenson, Donna Bannavong, Kim Jaffe, Jendy Sell, Kellie Malloy Foerter, David A Canton, Christopher G Twitty, Takuya Osada, H Kim Lyerly, Erika J Crosby
Journal: Clinical Cancer Research (2021)
More Evidence From a US Nationwide Cohort Study for the Survival Benefit of END in Early Mouth Cancer: Time for a Change in Guidelines
Authors: Iain Hutchison
Journal: Journal of the National Comprehensive Cancer Network (2021)

"More Evidence From a US Nationwide Cohort Study for the Survival Benefit of END in Early Mouth Cancer: Time for a Change in Guidelines" published on 01 Apr 2021 by National Comprehensive Cancer Network.
Epicardial placement of human MSC-loaded fibrin sealant films for heart failure: Preclinical efficacy and mechanistic data
Authors: Laura Fields, Tomoya Ito, Kazuya Kobayashi, Yuki Ichihara, Mihai-Nicolae Podaru, Mohsin Hussain, Kizuku Yamashita, Vanessa Machado, Fiona Lewis-McDougall, Ken Suzuki
Journal: Molecular Therapy (2021)

Mesenchymal stromal cell (MSC) transplantation has been investigated as an advanced treatment of heart failure; however, further improvement of the therapeutic efficacy and mechanistic understanding are needed. Our previous study has reported that epicardial placement of fibrin sealant films incorporating rat amniotic membrane-derived (AM)-MSCs (MSC-dressings) could address limitations of traditional transplantation methods. To progress this finding toward clinical translation, this current study aimed to examine the efficacy of MSC-dressings using human AM-MSCs (hAM-MSCs) and the underpinning mechanism for myocardial repair. Echocardiography demonstrated that cardiac function and structure were improved in a rat ischemic cardiomyopathy model after hAM-MSC-dressing therapy. hAM-MSCs survived well in the rat heart, enhanced myocardial expression of reparative genes, and attenuated adverse remodeling. Copy number analysis by qPCR revealed that upregulated reparative genes originated from endogenous rat cells rather than hAM-MSCs. These results suggest hAM-MSC-dressing therapy stimulates a secondary release of paracrine factors from endogenous cells improving myocardial repair ("secondary paracrine effect"), and cardiac M2-like macrophages were identified as a potential cell source of repair. We demonstrated hAM-MSCs increased M2-like macrophages through not only enhancing M2 polarization but also augmenting their proliferation and migration capabilities via PGE2, CCL2, and TGF-β1, resulting in enhanced cardiac function after injury.
<i>SASH3</i>variants cause a novel form of X-linked combined immunodeficiency with immune dysregulation
Authors: Ottavia M. Delmonte, Jenna R. E. Bergerson, Tomoki Kawai, Hye Sun Kuehn, David H. McDermott, Irene Cortese, Michael T. Zimmermann, A. Kerry Dobbs, Marita Bosticardo, Danielle Fink, Shamik Majumdar, Boaz Palterer, Francesca Pala, Nikita R. Dsouza, Marie Pouzolles, Naomi Taylor, Katherine R. Calvo, Stephen R. Daley, Daniel Velez, Anahita Agharahimi, Katherine Myint-Hpu, Lesia K. Dropulic, Jonathan J. Lyons, Steven M. Holland, Alexandra F. Freeman, Rajarshi Ghosh, Morgan B. Similuk, Julie E. Niemela, Jennifer Stoddard, Douglas B. Kuhns, Raul Urrutia, Sergio D. Rosenzweig, Magdalena A. Walkiewicz, Philip M. Murphy, Luigi D. Notarangelo
Journal: Blood (2021)
Efficacy and safety of suvratoxumab for prevention of Staphylococcus aureus ventilator-associated pneumonia (SAATELLITE): a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial
Authors: Bruno François, Hasan S Jafri, Jean Chastre, Miguel Sánchez-García, Philippe Eggimann, Pierre-François Dequin, Vincent Huberlant, Lucia Viña Soria, Thierry Boulain, Cédric Bretonnière, Jérôme Pugin, Josep Trenado, Ana Catalina Hernandez Padilla, Omar Ali, Kathryn Shoemaker, Pin Ren, Frank E Coenjaerts, Alexey Ruzin, Olivier Barraud, Leen Timbermont, Christine Lammens, Vadryn Pierre, Yuling Wu, Julie Vignaud, Susan Colbert, Terramika Bellamy, Mark T Esser, Filip Dubovsky, Marc J Bonten, Herman Goossens, Pierre-François Laterre, Didier Chochrad, Alain Dive, Frédéric Foret, Marc Simon, Herbert Spapen, Jacques Creteur, Yves Bouckaert, Patrick Biston, Marc Bourgeois, Martin Novacek, Tomas Vymazal, Petr Svoboda, Jan Pachl, Vladimir Sramek, Michal Hanauer, Tomas Hruby, Martin Balik, Tomas Suchy, Alain Lepape, Laurent Argaud, Frédéric Dailler, Arnaud Desachy, Christophe Guitton, Alain Mercat, Ferhat Meziani, Jean-Christophe Navellou, Rene Robert, Bertrand Souweine, Jean-Marc Tadie, Adel Maamar, Djillali Annane, Fabienne Tamion, Antoine Gros, Saad Nseir, Carole Schwebel, Gilles Francony, Jean-Yves Lefrant, Francis Schneider, Matthias Gründling, Johann Motsch, Lorenz Reill, Caroline Rolfes, Tobias Welte, Oliver Cornely, Frank Bloos, Maria Deja, Katrin Schmidt, Frank Wappler, Andreas Meier-Hellmann, Apostolos Komnos, Vasileios Bekos, Vasilios Koulouras, Ioanna Soultati, Georgios Baltopoulos, Georgios Filntisis, Epaminondas Zakynthinos, Spyros Zakynthinos, Ioannis Pnevmatikos, Ildikó Krémer, Zoltán Szentkereszty, Agnes Sarkany, Zsuzsa Marjanek, Pedro Moura, Maria Consuelo Pintado Delgado, Juan Carlos Montejo González, Paula Ramirez, Antonio Torres Marti, Juan Carlos Valia, Jose Lorente, Ana Loza Vazquez, Raúl De Pablo Sanchez, Dolores Escudero, Ricard Ferrer Roca, Jean-Luc Pagani, Marco Maggiorini
Journal: The Lancet Infectious Diseases (2021)
Moving Toward the Ideal Autologous Adoptive T-cell Therapy for Cancer
Authors: Brian H. Ladle
Journal: Cancer Research (2021)

Abstract Despite being one of the earliest immunotherapies to prove that the immune system can effectively recognize and eradicate cancer, autologous adoptive T-cell therapies remain largely limited to academic centers and research trials. The highly individualized protocols and the heterogeneous nature of the expanded T-cell products hinder effectiveness, commercial development, and regulatory approvals. The report by Li and colleagues details a novel method of generating cancer-specific autologous T cells from patients receiving anti-PD-1 checkpoint blockade immunotherapy. Their method achieved promising results in four initial patients treated in a pilot study. While further studies are required to characterize the autologous T-cell products generated and their effectiveness in larger cohorts of patients, the protocol they describe addresses several of the roadblocks that have prevented more wide-spread use of autologous adoptive T-cell therapy. See related article by Li et al., p. 2184
Tenascin-C-mediated suppression of extracellular matrix adhesion force promotes entheseal new bone formation through activation of Hippo signalling in ankylosing spondylitis
Authors: Zihao Li, Siwen Chen, Haowen Cui, Xiang Li, Dongying Chen, Wenjun Hao, Jianru Wang, Zemin Li, Zhaomin Zheng, Zhongping Zhang, Hui Liu
Journal: Annals of the Rheumatic Diseases (2021)

The aim of this study was to identify the role of tenascin-C (TNC) in entheseal new bone formation and to explore the underlying molecular mechanism.Ligament tissue samples were obtained from patients with ankylosing spondylitis (AS) during surgery. Collagen antibody-induced arthritis and DBA/1 models were established to observe entheseal new bone formation. TNC expression was determined by immunohistochemistry staining. Systemic inhibition or genetic ablation of TNC was performed in animal models. Mechanical properties of extracellular matrix (ECM) were measured by atomic force microscopy. Downstream pathway of TNC was analysed by RNA sequencing and confirmed with pharmacological modulation both in vitro and in vivo. Cellular source of TNC was analysed by single-cell RNA sequencing (scRNA-seq) and confirmed by immunofluorescence staining.TNC was aberrantly upregulated in ligament and entheseal tissues from patients with AS and animal models. TNC inhibition significantly suppressed entheseal new bone formation. Functional assays revealed that TNC promoted new bone formation by enhancing chondrogenic differentiation during endochondral ossification. Mechanistically, TNC suppressed the adhesion force of ECM, resulting in the activation of downstream Hippo/yes-associated protein signalling, which in turn increased the expression of chondrogenic genes. scRNA-seq and immunofluorescence staining further revealed that TNC was majorly secreted by fibroblast-specific protein-1 (FSP1)+fibroblasts in the entheseal inflammatory microenvironment.Inflammation-induced aberrant expression of TNC by FSP1+fibroblasts promotes entheseal new bone formation by suppressing ECM adhesion forces and activating Hippo signalling.
Computational models of atrial fibrillation: achievements, challenges, and perspectives for improving clinical care
Authors: Jordi Heijman, Henry Sutanto, Harry J G M Crijns, Stanley Nattel, Natalia A Trayanova
Journal: Cardiovascular Research (2021)

Abstract Despite significant advances in its detection, understanding and management, atrial fibrillation (AF) remains a highly prevalent cardiac arrhythmia with a major impact on morbidity and mortality of millions of patients. AF results from complex, dynamic interactions between risk factors and comorbidities that induce diverse atrial remodelling processes. Atrial remodelling increases AF vulnerability and persistence, while promoting disease progression. The variability in presentation and wide range of mechanisms involved in initiation, maintenance and progression of AF, as well as its associated adverse outcomes, make the early identification of causal factors modifiable with therapeutic interventions challenging, likely contributing to suboptimal efficacy of current AF management. Computational modelling facilitates the multilevel integration of multiple datasets and offers new opportunities for mechanistic understanding, risk prediction and personalized therapy. Mathematical simulations of cardiac electrophysiology have been around for 60 years and are being increasingly used to improve our understanding of AF mechanisms and guide AF therapy. This narrative review focuses on the emerging and future applications of computational modelling in AF management. We summarize clinical challenges that may benefit from computational modelling, provide an overview of the different in silico approaches that are available together with their notable achievements, and discuss the major limitations that hinder the routine clinical application of these approaches. Finally, future perspectives are addressed. With the rapid progress in electronic technologies including computing, clinical applications of computational modelling are advancing rapidly. We expect that their application will progressively increase in prominence, especially if their added value can be demonstrated in clinical trials.
Paul Cosford: public health supremo
Authors: John Illman
Journal: BMJ (2021)

“I love my job,” said Paul Cosford in a post reflecting his highly honed communication skills, eloquent writing, and disarming honesty about living with an incurable cancer. What was it that he loved so much about being medical director of Public Health England? He explained, “There is nothing more fascinating than taking scientific advice, converting it into practical action, and encouraging the public to understand and support that action.”

The words “communication” and “information” are often used interchangeably, but Cosford knew that they were not synonymous; and that information involves “giving out,” while communication involves “getting through.” Critically, Cosford “got through” to politicians as well as to the wider public.

Cosford had “a wisdom and emotional intelligence that is given to few,” according to Duncan Selbie, founding director of PHE and president of the International Association of National Public Health Institutes.

Selbie said, “Public health is …
ROBO1 Promotes Homing, Dissemination, and Survival of Multiple Myeloma within the Bone Marrow Microenvironment
Authors: Giada Bianchi, Peter G. Czarnecki, Matthew Ho, Aldo M. Roccaro, Antonio Sacco, Yawara Kawano, Annamaria Gullà, Anil Aktas Samur, Tianzeng Chen, Kenneth Wen, Yu-Tzu Tai, Maria Moscvin, Xinchen Wu, Gulden Camci-Unal, Matteo C. Da Vià, Niccolo' Bolli, Tomasz Sewastianik, Ruben D. Carrasco, Irene M. Ghobrial, Kenneth C. Anderson
Journal: Blood Cancer Discovery (2021)

The bone marrow (BM) microenvironment actively promotes multiple myeloma (MM) pathogenesis and therapies targeting both cancer cells and the niche are highly effective. We were interested in identifying novel signaling pathways supporting MM-BM crosstalk. Mutations in the transmembrane receptor Roundabout 1 (ROBO1) were recently identified in MM patients, however their functional consequences are uncertain. Through protein structure-function studies, we discovered that ROBO1 is necessary for MM adhesion to BM stromal and endothelial cells and ROBO1 knock out (KO) compromises BM homing and engraftment in a disseminated mouse model. ROBO1 KO significantly decreases MM proliferation in vitro and intra- and extramedullary tumor growth, in vivo. Mechanistically, ROBO1 C-terminus is cleaved in a ligand-independent fashion and is sufficient to promote MM proliferation. Viceversa, mutants lacking the cytoplasmic domain, including the human-derived G674* truncation, act dominantly negative. Interactomic and RNA sequencing studies suggest ROBO1 may be involved in RNA processing, supporting further studies.
Abstract 15966: Effect of Race and Geography on Rates of Durable Ventricular Assist Device (VAD) Use in the U.S. a Combined Medicare and Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS) Analysis
Authors: Joshua Bourque, Qixing Laing, Frances D Pagani, Michael P Thompson, Raymond Strobel, Keith D Aaronson, Robert L Kormos, Jeffrey S McCullough, Donald S Likosky
Journal: Circulation (2018)

Introduction: Durable ventricular assist device (VAD) therapy is a highly specialized surgical treatment that has experienced rapid growth. To date, there is limited understanding of its disseminat...
Receptor-Mediated Endocytosis and Differentiation in Proximal Tubule Cell Systems
Authors: Marine Berquez, Patrick Krohn, Alessandro Luciani, Olivier Devuyst
Journal: Journal of the American Society of Nephrology (2021)

The epithelial cells lining the proximal tubule (PT) of the kidney rely on multiligand receptors and vesicular membrane pathways to efficiently reabsorb essential nutrients and low–mol wt proteins ([Figure 1A][1]).[1][2] The endolysosome stands at the crossroads of this network, processing
Intravenous high‐dose methotrexate based systemic therapy in the treatment of isolated primary vitreoretinal lymphoma: An <scp>LOC</scp> network study
Authors: Marion Lam, Valérie Touitou, Sylvain Choquet, Nathalie Cassoux, Hervé Ghesquières, Laurent Kodjikian, Anna Schmitt, Sarra Gattoussi, Émeline Tabouret, Magali Sampo, Marie Blonski, Karine Angioi‐Duprez, Roch Houot, Frédéric Mouriaux, Emmanuel Gyan, Marie‐Laure Le Lez, Marie‐Pierre Moles, Fabien Croisé, Adrien Chauchet, Claire Schwartz, Guido Ahle, Laurent Meyer, Rémy Gressin, Christophe Chiquet, Lucie Oberic, Priscille Ollé, Jean‐Pierre Marolleau, Benjamin Jany, Adrian Tempescul, Béatrice Cochener, Gandhi Damaj, Jean‐Claude Quintyn, Cécile Moluçon‐Chabrot, Eve Rousseau, Paul Franciane, Christelle Schneider, Hélène Massé, Jérôme Tamburini‐Bonnefoy, Antoine Brézin, Luc‐Matthieu Fornecker, Laurent Ballonzoli, Magali Le Garff‐Tavernier, Khê Hoang‐Xuan, Bahram Bodaghi, Carole Soussain, Caroline Houillier
Journal: American Journal of Hematology (2021)

Abstract The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high‐dose methotrexate (IV HD‐MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first‐line treatment with HD‐MTX between 2011 and 2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL‐10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL‐10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow‐up of 61 months, 42/59 (71%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression‐free survival, ocular‐free survival and brain‐free survival were 75, 18, 29 and 73 months, respectively. IV HD‐MTX based systemic therapy as a first‐line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL‐10.