tbuckley/cabot-search huggingface dataset:
Obstructive sleep apnoea and cognitive decline in mild-to-moderate Alzheimer's disease
Authors: Carmen Jorge, Adriano Targa, Iván David Benítez, Faride Dakterzada, Gerard Torres, Olga Minguez, Anna Carnes, Montse Pujol, Aurora Gibert, Ricard López, Anna Michela Gaeta, Mireia Dalmases, Ramón Farré, Manuel Sánchez-de-la-Torre, Ferran Barbé, Gerard Piñol-Ripoll
Journal: European Respiratory Journal (2020)

We evaluated the influence of untreated obstructive sleep apnoea (OSA) on the magnitude of cognitive decline and on several cognitive subdomains in patients with mild-to-moderate Alzheimer's disease. In this single-centre study, 144 patients were recruited prospectively from a cognitive impairment unit and underwent overnight polysomnography. The mean± sd change in the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) score at 12 months was 3.19±5.61 in the non-OSA group and 0.08±5.62 in the OSA group, with an intergroup difference of −3.36 (95% CI 0.19–0.16; p=0.002). We did not observe a significant difference in any cognitive subdomains at 12 months. Regarding Mini-Mental State Examination scores at 36 months, the mean change was 1.69 (95% CI −1.26–4.64; p=0.445). No significant differences were found among different OSA severity groups. We observed that ADAS-cog scores were better in the OSA group than in the non-OSA group by a statistically but not clinically significant margin. We did not find differences in the different cognitive subdomains after 1 year or in global cognition after 3 years of follow-up.
Precision Medicine in Diabetes: A Consensus Report From the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
Authors: Wendy K. Chung, Karel Erion, Jose C. Florez, Andrew T. Hattersley, Marie-France Hivert, Christine G. Lee, Mark I. McCarthy, John J. Nolan, Jill M. Norris, Ewan R. Pearson, Louis Philipson, Allison T. McElvaine, William T. Cefalu, Stephen S. Rich, Paul W. Franks
Journal: Diabetes Care (2020)

The convergence of advances in medical science, human biology, data science, and technology has enabled the generation of new insights into the phenotype known as “diabetes.” Increased knowledge of this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence, and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions. This Consensus Report presents the American Diabetes Association (ADA) Precision Medicine in Diabetes Initiative in partnership with the European Association for the Study of Diabetes (EASD), including its mission, the current state of the field, and prospects for the future. Expert opinions are presented on areas of precision diagnostics and precision therapeutics (including prevention and treatment), and key barriers to and opportunities for implementation of precision diabetes medicine, with better care and outcomes around the globe, are highlighted. Cases where precision diagnosis is already feasible and effective (i.e., monogenic forms of diabetes) are presented, while the major hurdles to the global implementation of precision diagnosis of complex forms of diabetes are discussed. The situation is similar for precision therapeutics, in which the appropriate therapy will often change over time owing to the manner in which diabetes evolves within individual patients. This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realize its potential. This, combined with a subsequent, detailed evidence-based review (due 2022), will provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes.
David Oliver: Preventing more deaths in care homes in a second pandemic surge
Authors: David Oliver
Journal: BMJ (2020)

I hope my column last week showed that all of us had a part to play in the high number of deaths from covid-19 in care homes.1

In due course I expect there will be a public inquiry into our handling of the covid-19 pandemic, and endless research and analyses. For now, though, my main concern is what we should do differently if we have a second peak of covid-19 or a pandemic caused by another novel virus.

There are some ways in which we would be better prepared. We now have greater testing capacity in care homes, although it’s a shame it took so long, and some care homes are still …
Emerging Technologies for Pulmonary Vein Isolation
Authors: F. Daniel Ramirez, Vivek Y. Reddy, Raju Viswanathan, Mélèze Hocini, Pierre Jaïs
Journal: Circulation Research (2020)

Atrial fibrillation is the most common sustained cardiac arrhythmia and is associated with considerable morbidity and mortality. Electrically isolating the pulmonary veins from the left atrium by catheter ablation is superior to antiarrhythmic drug therapy for maintaining sinus rhythm, but its success varies depending on multiple factors, including arrhythmic burden. Although procedural outcomes have improved over the years, further gains are limited by a seemingly zero-sum relationship between effectiveness and safety, which is largely a product of the available technologies. Current energies used to create contiguous, transmural, and durable atrial lesions can result in serious complications if they reach the esophagus or phrenic nerve, for instance—structures that can be adjacent to the atrial myocardium, often within millimeters of the energy source. Consequently, high rates of pulmonary vein-left atrium reconnections are consistently seen in clinical studies and in clinical practice as operators appropriately forgo ablation effectiveness to protect patients from harm. However, as ablative technologies evolve to circumvent this stalemate, safer, and more effective pulmonary vein isolation seems increasingly realistic. Furthermore, the innovative nature of these technologies raises the prospect of markedly improved procedural efficiency, which could increase patient comfort, reduce operator occupational injuries, and enhance the use of health resources—all of which are increasingly important considerations particularly as the demand for catheter ablation for atrial fibrillation continues to rise. We herein review 3 promising candidate ablation technologies with the potential to revolutionize the management of patients with atrial fibrillation: electroporation (pulsed-field ablation), expandable lattice-tip radiofrequency ablation/electroporation, and ultra-low temperature cryoablation.
Effects of dehydroepiandrosterone supplementation on coronary reserve in men with coronary artery disease
Authors: Jerzy Krzysztof Wranicz, Iwona Cygankiewicz, Marcin Rosiak, Jolanta Słowikowska-Hilczer, Piotr Dejak, Marek Maciejewski, Włodzimierz Koniarek, Marek Lipiński, Marek Wrona, Piotr Kula, Irena Poprawska, Jan Henryk Goch, Krzysztof Kula, Wojciech Zaręba
Journal: Journal of the American College of Cardiology (2005)
Reply by Gattinoni <i>et al.</i> to Hedenstierna <i>et al.</i>, to Maley <i>et al.</i>, to Fowler <i>et al.</i>, to Bhatia and Mohammed, to Bos, to Koumbourlis and Motoyama, and to Haouzi <i>et al.</i>
Authors: Luciano Gattinoni, Silvia Coppola, Massimo Cressoni, Mattia Busana, Sandra Rossi, Davide Chiumello
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Response to: ‘The role of antimalarials in COVID-19: observational data from a cohort of rheumatic patients’ by Favalli <i>et al</i>
Authors: Vasco C Romão, Ana Rita Cruz-Machado, João Eurico Fonseca
Journal: Annals of the Rheumatic Diseases (2020)

We thank Favalli et al for their comment on our letter1 regarding the effect of antimalarials for the prevention of coronavirus disease 2019 (COVID-19).2 The authors provide updated information on a cohort of 914 patients with rheumatic and musculoskeletal diseases (RMDs), 112 of whom were treated with hydroxychloroquine (HCQ). The prevalence of confirmed or suspected COVID-19 cases was similar in both groups, and a patient with systemic sclerosis-associated lung disease treated with HCQ had a fatal outcome. Notably, 87% of patients reported rigorous compliance with contagion prevention measures.

These data are in accordance with accumulating evidence published over the last 2 months, indicating the occurrence of mild and severe cases of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with RMDs treated with antimalarials (table 1).1–16 Out of 869 reported patients with RMDs with confirmed COVID-19, 190 (22%) were taking long-term antimalarials prior to the infection.1–16 Of those, 99 out of 181 (55%) with available data developed severe …
Abstract IA14: Liquid biopsies for tracking molecular resistance in cancer
Authors: Sarah-Jane Dawson
Journal: Clinical Cancer Research (2020)

Abstract Cell-free circulating tumor DNA (ctDNA) can be found in the bloodstream of cancer patients and is increasingly being explored as an important biomarker to monitor adaptive changes to cancer therapies. Cell-free DNA fragments from multiple lesions mix together in the peripheral blood; hence, ctDNA contains a wide representation of the genomes from multiple metastatic sites. For this reason, genome-wide analysis of ctDNA has the potential to provide an unprecedented insight into changes in the genomic landscape that occur during the development of disease and in response to cancer therapies. To date, the use of ctDNA to monitor the tumor landscape has been limited to tracking genomic evolution. However, it is now clear that cancers can also adapt to therapeutic pressure by significantly altering their transcriptome. Currently we have a limited understanding of how “nongenomic” transcriptional adaptation leads to clonal dominance or the evasion of cancer therapies. Here I will provide an overview of the use of ctDNA-based approaches to track both genomic evolution and transcriptional changes in real time to improve our understanding of the mechanisms leading to molecular resistance in cancer. Citation Format: Sarah-Jane Dawson. Liquid biopsies for tracking molecular resistance in cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA14.
Response to the conjugate pneumococcal vaccine (PCV13) in patients with chronic lymphocytic leukemia (CLL)
Authors: Francesca Romana Mauro, Diana Giannarelli, Clementina Maria Galluzzo, Candida Vitale, Andrea Visentin, Costantino Riemma, Serena Rosati, Marika Porrazzo, Sara Pepe, Marta Coscia, Livio Trentin, Massimo Gentile, Sara Raponi, Alessandra Micozzi, Giuseppe Gentile, Silvia Baroncelli
Journal: Leukemia (2020)
Braking the cell’s cycle and invigorating T-cell immunity against pancreatic cancer
Authors: Gregory B Lesinski
Journal: Gut (2020)

Pancreatic cancer has been an elusive target for immunotherapy. Redundant mechanisms of immune suppression have plagued efforts to elicit vigorous T-cell responses to this disease. Similar frustrations are evident in pancreatic cancer when considering efforts at targeting prominent oncogenic pathways. For example, cyclin-dependent kinase inhibitor 2A is very frequently mutated, suggesting that inhibition of cyclin-dependent kinase 4/6 (CDK4/6) may be a viable strategy against these aggressive tumours.1 Unfortunately, resistance to targeting single oncogenic pathways typically prevails, necessitating a need for combination therapy. The choice of optimal combination approaches, however, is not a simple one. Of course, decisions must be carefully metered by preclinical efficacy data, on-target and off-target toxicities, patient selection and insight into mechanisms of action. These considerations may be even more relevant when combining tumour-directed, small molecule inhibitors with immunotherapy.

The article by Knudsen et al 2 addresses these issues by employing a data-driven approach to identify novel combinatorial therapies for pancreatic cancer. Their strategy was to systematically define other agents that cooperate with CDK4/6 inhibitors using a live cell imaging-based in …
Red cell–bound antibodies and transfusion requirements in hospitalized patients with COVID-19
Authors: Alessandra Berzuini, Cristiana Bianco, Cinzia Paccapelo, Francesco Bertolini, Giuliana Gregato, Alessandra Cattaneo, Elisa Erba, Alessandra Bandera, Andrea Gori, Giuseppe Lamorte, Maria Manunta, Laura Porretti, Nicoletta Revelli, Francesca Truglio, Giacomo Grasselli, Alberto Zanella, Stefania Villa, Luca Valenti, Daniele Prati
Journal: Blood (2020)
Combination of tumour-infarction therapy and chemotherapy via the co-delivery of doxorubicin and thrombin encapsulated in tumour-targeted nanoparticles
Authors: Suping Li, Yinlong Zhang, Shih-Hsin Ho, Bozhao Li, Meifang Wang, Xiongwei Deng, Na Yang, Guangna Liu, Zefang Lu, Junchao Xu, Quanwei Shi, Jing-Yan Han, Lirong Zhang, Yan Wu, Yuliang Zhao, Guangjun Nie
Journal: Nature Biomedical Engineering (2020)
Should Flow Cytometry Be Considered a First Line of Study in the Diagnosis of Breast Implant–Associated Anaplastic Large-Cell Lymphoma?
Authors: Martha Romero, Andrés Melo, Nelson Bedoya, José de la Hoz, Marcela Mejía-Arango, Karen Galvis, Luz Hernandez, Gina Cuellar, Liliana Martin, Sandra Quijano, Carlos Saavedra
Journal: Journal of Clinical Oncology (2020)
Abstract A35: Cell-free tumor DNA profiling of colon cancer patients: Searching for mechanisms of chemoresistance
Authors: Veronika Vymetalkova, Barbara Pardini, Marketa Urbanova, Klara Cervena, Pavel Vodicka, Alessio Naccarati
Journal: Clinical Cancer Research (2020)

Abstract Colorectal cancer (CRC) is a worldwide health burden, with nearly 1.2 million new cases expected each year. Significant efforts are currently being employed to find patients who will benefit from chemotherapy. In fact, drug resistance is a limiting factor for the efficacy of chemotherapy in CRC treatment. In the present work, we aimed at identifying molecular markers in plasma cell-free DNA that could be associated with good/poor response and chemoresistance, comparing good responders (i.e., benefitting from chemotherapy, not having side effects like toxicity, no relapses, and having a complete response with no residual cancer) from non-/poor responders (patients with chemoresistance and lacking any response, or developing toxicity). Paired plasma samples from 10 colon cancer patients collected before and after adjuvant 5-fluorouracil (5-FU)-based therapy were profiled by a whole-exome sequencing (WES) approach in order to identify mutations associated with therapy response. In concomitance, DNA from tumor tissue from the same patients was also profiled by WES for mutation burden concordance. Analyses were performed on colon cancer patients treated with the same 5-FU-based therapy. The first sampling was performed at the time of the diagnosis (i.e., active disease), and the second after 6-9 months depending on patients’ conditions (i.e., covering the tumor resection, administration of adjuvant chemotherapy, etc.). After follow-up, 3 patients were clinically classified as “good responders” and 7 as “non-/poor responders.” All prepared libraries passed the quality control checkpoints and were sequenced. The number of total reads exceeds 2,57 × 109. Mean read length is about 100 nt. Alignment to human reference genome (hg38) is &amp;gt; 99.8%. The bioinformatics analyses are currently ongoing to profile the two different groups over time. Detailed results of the study will be presented during the meeting. The significance of the project lies in the improvement of the diagnosis and therapy efficacy in colon cancer patients. Supported by grant AZV MZ 17-30920A. Citation Format: Veronika Vymetalkova, Barbara Pardini, Marketa Urbanova, Klara Cervena, Pavel Vodicka, Alessio Naccarati. Cell-free tumor DNA profiling of colon cancer patients: Searching for mechanisms of chemoresistance [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A35.
Abstract 14961: Convergent Ablation for the Treatment of Long Standing Persistent Atrial Fibrillation - A Single Center Experience
Authors: Syed Rafay Ali Sabzwari, Lohit Garg, Nikhil Mehta, James Kimber, Hiwot Ayele, James K Wu, Babak Bozorgnia
Journal: Circulation (2019)

Introduction: The treatment of long standing persistent atrial fibrillation (AF) is very challenging and conventional catheter ablation strategies have provided only modest success. They often requ...
UK launches subscription style model for antibiotics to encourage new development
Authors: Elisabeth Mahase
Journal: BMJ (2020)

The UK has launched its subscription style payment model for antibiotics, with the first two drugs to be selected and evaluated next year.

The scheme hopes to incentivise companies to invest in researching and developing new antibiotics in the face of growing antibiotic resistance. It will see pharmaceutical companies paid upfront for their products, based on the value it provides to the NHS rather than how much is used.

The scheme was first announced in July 2019,1 but officially launched 17 June 2020 after nearly a year of set up, in which the Department of Health and Social Care worked closely with the …
Usefulness of Adding Echocardiography of the Right Heart to Risk-Assessment Scores in Prostanoid-Treated Pulmonary Arterial Hypertension
Authors: Roberto Badagliacca, Silvia Papa, Giovanna Manzi, Cristiano Miotti, Federico Luongo, Susanna Sciomer, Nadia Cedrone, Francesco Fedele, Robert Naeije, Carmine Dario Vizza
Journal: JACC. Cardiovascular imaging (2020)
What Is Anosmia?
Authors: Pauline P. Huynh, Lisa E. Ishii, Masaru Ishii
Journal: JAMA (2020)

Giacomo Spinato, MD; Cristoforo Fabbris, MD; Jerry Polesel, MD; Diego Cazzador, MD; Daniele Borsetto, MD; Claire Hopkins, MA(Oxon), DM; Paolo Boscolo-Rizzo, MD
Modulation of Mammalian Cardiomyocyte Cytokinesis by the Extracellular Matrix
Authors: Chi-Chung Wu, Sylvia Jeratsch, Johannes Graumann, Didier Y.R. Stainier
Journal: Circulation Research (2020)

After birth, cycling mammalian CMs (cardiomyocytes) progressively lose the ability to undergo cytokinesis and hence they become binucleated, which leads to cell cycle exit and loss of regenerative capacity. During late embryonic and early postnatal heart growth, CM development is accompanied by an expansion of the cardiac fibroblast (cFb) population and compositional changes in the ECM (extracellular matrix). Whether and how these changes influence cardiomyocyte cytokinesis is currently unknown.To elucidate the role of postnatal cFbs and the ECM in cardiomyocyte cytokinesis and identify ECM proteins that promote cardiomyocyte cytokinesis.Using primary rat cardiomyocyte cultures, we found that a proportion of postnatal, but not embryonic, cycling cardiomyocytes fail to progress through cytokinesis and subsequently binucleate, consistent with published reports of in vitro and in vivo observations. Direct coculture with postnatal cFbs increased cardiomyocyte binucleation, which could be inhibited by RGD peptide treatment. In contrast, cFb-conditioned medium or transwell coculture did not significantly increase cardiomyocyte binucleation, suggesting that cFbs inhibit cardiomyocyte cytokinesis through ECM modulation rather than by secreting diffusible factors. Furthermore, we found that both embryonic and postnatal CMs binucleate at a significantly higher rate when cultured on postnatal cFb-derived ECM compared with embryonic cFb-derived ECM. These cytokinetic defects correlate with cardiomyocyte inefficiency in mitotic rounding, a process which is key to successful cytokinesis. To identify ECM proteins that modulate cardiomyocyte cytokinesis, we compared the composition of embryonic and postnatal cFb-derived ECM by mass spectrometry followed by functional assessment. We found that 2 embryonically enriched ECM proteins, SLIT2 and NPNT (nephronectin), promote cytokinesis of postnatal CMs in vitro and in vivo.We identified the postnatal cardiac ECM as a nonpermissive environment for cardiomyocyte cytokinesis and uncovered novel functions for the embryonic ECM proteins SLIT2 and NPNT (nephronectin) in promoting postnatal cardiomyocyte cytokinesis. Graphic Abstract: A graphic abstract is available for this article.
Racism and Health in the United States: A Policy Statement From the American College of Physicians
Authors: Josh Serchen, Robert Doherty, Omar Atiq, David Hilden
Journal: Annals of Internal Medicine (2020)

Racial minorities in the United States have reported experiencing widespread racism throughout all aspects of life, from housing to education to employment. Existing research has examined the role of racism, discrimination, and violence in one's interaction with the health care system and their association with poorer mental and physical health. Systemic racism that underlies the fabric of society often manifests itself in prominent institutions, such as law enforcement agencies, regardless of individual intent. Overt and covert racist laws and policies, personal implicit biases, and other factors result in Black individuals and other people of color being the subject of law enforcement violence and criminal justice system interactions at disproportionately high rates. The demonstrated association between discriminatory law enforcement practices and violence and personal and community health necessitates treating these issues as public health issues worthy of a public policy intervention. Addressing some of the sources of institutional racism and harm through transparency and accountability measures is the first of many steps required to begin correcting historical racial injustices.
Abstract 11895: Physician Preferences for Oral Anti-coagulation for Obese & Non-obese Patients With Non-valvular Atrial Fibrillation
Authors: Jigar Rajpura, Amol Dhamane, Deborah Goldschmidt, Elyse Swallow, Cristina Russ, Mauricio Ferri
Journal: Circulation (2019)

Introduction: This study assessed physicians’ anticoagulation preferences for obese & non-obese NVAF patients in a real-world setting. Methods: A survey of cardiologists & primary care physicians (...
Targeting DGAT1 Ameliorates Glioblastoma by Increasing Fat Catabolism and Oxidative Stress
Authors: Xiang Cheng, Feng Geng, Meixia Pan, Xiaoning Wu, Yaogang Zhong, Chunyan Wang, Zhihua Tian, Chunming Cheng, Rui Zhang, Vinay Puduvalli, Craig Horbinski, Xiaokui Mo, Xianlin Han, Arnab Chakravarti, Deliang Guo
Journal: Cell Metabolism (2020)