tbuckley/cabot-search huggingface dataset:
The trinity of COVID-19: immunity, inflammation and intervention
Authors: Matthew Zirui Tay, Chek Meng Poh, Laurent Rénia, Paul A. MacAry, Lisa F. P. Ng
Journal: Nature reviews. Immunology (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.
Covid-19: Trust withdraws guidance that doctors need not put “covid-19” on death certificates
Authors: Clare Dyer
Journal: BMJ (2020)

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EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors
Authors: Marie Kostine, Axel Finckh, Clifton O Bingham, Karen Visser, Jan Leipe, Hendrik Schulze-Koops, Ernest H Choy, Karolina Benesova, Timothy R D J Radstake, Andrew P Cope, Olivier Lambotte, Jacques-Eric Gottenberg, Yves Allenbach, Marianne Visser, Cindy Rusthoven, Lone Thomasen, Shahin Jamal, Aurélien Marabelle, James Larkin, John B A G Haanen, Leonard H Calabrese, Xavier Mariette, Thierry Schaeverbeke
Journal: Annals of the Rheumatic Diseases (2020)

Rheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management.First, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed.The overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies.These statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.
Covid-19: Two thirds of healthcare workers who have died were from ethnic minorities
Authors: Abi Rimmer
Journal: BMJ (2020)

Two thirds of healthcare workers who have died from covid-19 were from an ethnic minority background, and at least half were not born in the UK, researchers have found.

Tim Cook, professor of anaesthesia at the Royal United Hospital Bath and the University of Bristol, and colleagues looked at the deaths of 106 healthcare workers, 63% of whom were from an ethnic minority background, and they reported their findings in the Health Service Journal .1

Eighteen of the 19 doctors and dentists who have died from covid-19 were from ethnic minority backgrounds. The same was true of 71% of the 35 nurses and …
Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility
Authors: Maria Teresa Landi, D. Timothy Bishop, Stuart MacGregor, Mitchell J. Machiela, Alexander J. Stratigos, Paola Ghiorzo, Myriam Brossard, Donato Calista, Jiyeon Choi, Maria Concetta Fargnoli, Tongwu Zhang, Monica Rodolfo, Adam J. Trower, Chiara Menin, Jacobo Martinez, Andreas Hadjisavvas, Lei Song, Irene Stefanaki, Richard Scolyer, Rose Yang, Alisa M. Goldstein, Miriam Potrony, Katerina P. Kypreou, Lorenza Pastorino, Paola Queirolo, Cristina Pellegrini, Laura Cattaneo, Matthew Zawistowski, Pol Gimenez-Xavier, Arantxa Rodriguez, Lisa Elefanti, Siranoush Manoukian, Licia Rivoltini, Blair H. Smith, Maria A. Loizidou, Laura Del Regno, Daniela Massi, Mario Mandala, Kiarash Khosrotehrani, Lars A. Akslen, Christopher I. Amos, Per A. Andresen, Marie-Françoise Avril, Esther Azizi, H. Peter Soyer, Veronique Bataille, Bruna Dalmasso, Lisa M. Bowdler, Kathryn P. Burdon, Wei V. Chen, Veryan Codd, Jamie E. Craig, Tadeusz Dębniak, Mario Falchi, Shenying Fang, Eitan Friedman, Sarah Simi, Pilar Galan, Zaida Garcia-Casado, Elizabeth M. Gillanders, Scott Gordon, Adele Green, Nelleke A. Gruis, Johan Hansson, Mark Harland, Jessica Harris, Per Helsing, Anjali Henders, Marko Hočevar, Veronica Höiom, David Hunter, Christian Ingvar, Rajiv Kumar, Julie Lang, G. Mark Lathrop, Jeffrey E. Lee, Xin Li, Jan Lubiński, Rona M. Mackie, Maryrose Malt, Josep Malvehy, Kerrie McAloney, Hamida Mohamdi, Anders Molven, Eric K. Moses, Rachel E. Neale, Srdjan Novaković, Dale R. Nyholt, Håkan Olsson, Nicholas Orr, Lars G. Fritsche, Joan Anton Puig-Butille, Abrar A. Qureshi, Graham L. Radford-Smith, Juliette Randerson-Moor, Celia Requena, Casey Rowe, Nilesh J. Samani, Marianna Sanna, Dirk Schadendorf, Hans-Joachim Schulze, Lisa A. Simms, Mark Smithers, Fengju Song, Anthony J. Swerdlow, Nienke van der Stoep, Nicole A. Kukutsch, Alessia Visconti, Leanne Wallace, Sarah V. Ward, Lawrie Wheeler, Richard A. Sturm, Amy Hutchinson, Kristine Jones, Michael Malasky, Aurelie Vogt, Weiyin Zhou, Karen A. Pooley, David E. Elder, Jiali Han, Belynda Hicks, Nicholas K. Hayward, Peter A. Kanetsky, Chad Brummett, Grant W. Montgomery, Catherine M. Olsen, Caroline Hayward, Alison M. Dunning, Nicholas G. Martin, Evangelos Evangelou, Graham J. Mann, Georgina Long, Paul D. P. Pharoah, Douglas F. Easton, Jennifer H. Barrett, Anne E. Cust, Goncalo Abecasis, David L. Duffy, David C. Whiteman, Helen Gogas, Arcangela De Nicolo, Margaret A. Tucker, Julia A. Newton-Bishop, Ketty Peris, Stephen J. Chanock, Florence Demenais, Kevin M. Brown, Susana Puig, Eduardo Nagore, Jianxin Shi, Mark M. Iles, Matthew H. Law
Journal: Nature Genetics (2020)
Adherence to the Mediterranean Diet and Progression to Late Age-Related Macular Degeneration in the Age-Related Eye Disease Studies 1 and 2
Authors: Tiarnán D. Keenan, Elvira Agrón, Julie Mares, Traci E. Clemons, Freekje van Asten, Anand Swaroop, Emily Y. Chew
Journal: Ophthalmology (2020)
Introducing PIONEER: a project to harness big data in prostate cancer research
Authors: Muhammad Imran Omar, Monique J. Roobol, Maria J. Ribal, Thomas Abbott, Paul-Michael Agapow, Sonia Araujo, Alex Asiimwe, Charles Auffray, Irina Balaur, Katharina Beyer, Chiara Bernini, Anders Bjartell, Alberto Briganti, John-Edward Butler-Ransohoff, Riccardo Campi, Marinel Cavelaars, Bertrand De Meulder, Zsuzsanna Devecseri, Marc Dietrich Voss, Konstantinos Dimitropoulos, Susan Evans-Axelsson, Billy Franks, Louise Fullwood, Denis Horgan, Emma Jane Smith, Amit Kiran, Kati Kivinummi, Mark Lambrecht, Doron Lancet, Peter Lindgren, Sara MacLennan, Steven MacLennan, Maria Manuela Nogueira, Fredrik Moen, Maxim Moinat, Kishore Papineni, Christian Reich, Kristin Reiche, Stijn Rogiers, Claudio Sartini, Kees van Bochove, Femke van Diggelen, Mieke Van Hemelrijck, Hein Van Poppel, Jihong Zong, James N’Dow, Emelie Andersson, Heidi Arala, Anssi Auvinen, Chris Bangma, Danny Burke, Antonella Cardone, Joaquin Casariego, Guido Cuperus, Saeed Dabestani, Francesco Esperto, Nicola Fossati, Adam Fridhammar, Giorgio Gandaglia, Delila Gasi Tandefelt, Friedemann Horn, Johannes Huber, Jonas Hugosson, Henkjan Huisman, Andreas Josefsson, Olavi Kilkku, Markus Kreuz, Michael Lardas, Joe Lawson, Florence Lefresne, Stephane Lejeune, Elaine Longden-Chapman, Gordon McVie, Lisa Moris, Nicolas Mottet, Teemu Murtola, Charlie Nicholls, Karl H. Pang, Katie Pascoe, Marta Picozzi, Karin Plass, Pasi Pohjanjousi, Matthew Reaney, Sebastiaan Remmers, Paul Robinson, Jack Schalken, Max Schravendeel, Thomas Seisen, Angela Servan, Kirill Shiranov, Robert Snijder, Carl Steinbeisser, Nesrine Taibi, Kirsi Talala, Derya Tilki, Thomas Van den Broeck, Zdravko Vassilev, Olli Voima, Eleni Vradi, Reg Waldeck, Ward Weistra, Peter-Paul Willemse, Manfred Wirth, Russ Wolfinger, Nazanin Zounemat Kermani
Journal: Nature Reviews Urology (2020)
4-Substituted-piperazin-1-yl-carbonyl-pyrazol derivatives: A new class of highly potent cytotoxic compounds with inhibitory effects on tubulin polymerization
Authors: Silke Baasner, Matthias Gerlach, Gilbert Müller, Peter Schmidt, Emmanuel E. Polymeropoulos, Eckhard G. Günther
Journal: Cancer Research (2004)

5424   4-Phenyl-1-piperazinyl-carbonyl substituted, nitrogen containing heterocycles have been discovered at Zentaris as a new class of potent, synthetic, small molecule tubulin binders with strong antiproliferative activity. The lead structure of this class, D-82318, proved to be a potent inhibitor of in vivo tumor growth in different xenograft models including mammary and renal cancers. As part of our efforts to expand structural diversity as well as to optimize bioavailability parameters such as solubility and metabolic stability for this compound class, we synthesized a small focused compound library. D-87264, the best representative of this series so far, has been identified by a cell based XTT assay on human tumor cell lines, namely SKOV3 (ovarian carcinoma), SF268 (CNS cancer, glioma), KB/HeLa (cervix carcinoma), and NCI-H460 (non-small cell lung cancer), and has shown good cytotoxic activity against these cell lines with IC50 values ranking from 14nM to 34nM. For further characterization the in vitro antiproliferative activity against a panel of more than 30 established human tumor cell lines including multidrug resistant (MDR1) phenotypes was tested with an average IC50 value of 40nM. Mode-of-action studies revealed that D-87264 effectively inhibits tubulin polymerization (IC50 1270nM). Dividing KB/Hela cells were arrested in the G2/M phase of the cell cycle with an IC50 value of 34nM and subsequently underwent apoptosis. Different apoptotic parameters were detected such as increase of caspase activity, cell membrane alterations or DNA fragmentation. Results of competing experiments with [3H] colchicine and [3H] paclitaxel suggest that the compound interacts with the colchicine binding site of β-tubulin (IC50 760nM for colchicine and no competition with paclitaxel). These evaluations were supported by docking experiments. For testing of in vivo activity, a maximal tolerated dose of 75mg/kg/d for p.o. (Q3dx6) administration was found in nude mice. First experiments with tumor bearing nude mice have been performed, and showed promising antitumoral effects in a renal cancer xenograft model after oral administration.
Exposure to a Surrogate Measure of Contamination From Simulated Patients by Emergency Department Personnel Wearing Personal Protective Equipment
Authors: Oren Feldman, Michal Meir, Danielle Shavit, Ravit Idelman, Itai Shavit
Journal: JAMA (2020)

This study uses an atomizer and fluorescent markers to simulate contamination of uncovered skin and hair of health care workers wearing personal protective equipment after intubating patient manikins under emergency conditions.
Disease-associated astrocytes in Alzheimer’s disease and aging
Authors: Naomi Habib, Cristin McCabe, Sedi Medina, Miriam Varshavsky, Daniel Kitsberg, Raz Dvir-Szternfeld, Gilad Green, Danielle Dionne, Lan Nguyen, Jamie L. Marshall, Fei Chen, Feng Zhang, Tommy Kaplan, Aviv Regev, Michal Schwartz
Journal: Nature Neuroscience (2020)
Administration of end-of-life drugs by family caregivers during covid-19 pandemic
Authors: Ben Bowers, Kristian Pollock, Stephen Barclay
Journal: BMJ (2020)

Doctors, nurses, and family caregivers worldwide are facing tough decisions concerning the supply and administration of medications to manage symptoms when patients are dying from covid-19 or other conditions in the community or care homes.Proposed changes in practice aimed at ensuring adequate end-of-life symptom control need careful consideration alongside appropriate training and support.][3] Family caregivers willing to take on this role should be adequately trained and responsively supported with access to 24 hour phone advice.
Premature Menopause and Risk for Cardiovascular Disease
Authors: Pierre Yves Scarabin
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effect of the COVID-19 pandemic on cancer treatment and research
Authors: Kamal S Saini, Begoña de las Heras, Javier de Castro, Ramachandran Venkitaraman, Martine Poelman, Gopalakrishnan Srinivasan, Monika Lamba Saini, Sanjeev Verma, Manuela Leone, Philippe Aftimos, Giuseppe Curigliano
Journal: The Lancet Haematology (2020)

in the epidemiology and clinical association of sickle cell disease with malaria, and bacterial and viral infections (including SARS-CoV-2), suggests that sickle cell disease should be included in the Integrated Management of Childhood Illness programme to improve outcomes.Provision for sickle cell disease diagnosis and treatment should be incorporated into national health systems programming, with an emphasis on delivering sickle cell disease services in the primary care setting.COVID-19 is expected to herald a global economic recession that might result in a contraction of international funding for health systems development in Africa.The COVID-19 pandemic is currently overwhelming health systems in high-income countries and so could have an increased effect in low-resource settings in Africa where health services are already overstretched.The effect of COVID-19 on the global economy could cause recession both in Africa and around the world, posing a substantial threat to the delivery of health care in Africa.Every effort should be made to invest in primary health care, and integrate and align sickle cell disease diagnosis and treatment into existing health systems, rather than building new vertical programmes focusing only on sickle cell disease with interventions delivered separately from other health services.African governments should leverage further funding resources to accomplish this aim.The preparation and mitigation stages of the pandemic also represent important opportunities to focus international efforts at rapidly scaling up sickle cell disease-related health-care infrastructure.AZ, FN, RK, DS, and NK are members of the Pan-African Network on Emerging and Re-Emerging Infections
Log Transformation Improves Dating of Phylogenies
Authors: Uyen Mai, Siavash Mirarab
Journal: Molecular Biology and Evolution (2020)

Abstract Phylogenetic trees inferred from sequence data often have branch lengths measured in the expected number of substitutions and therefore, do not have divergence times estimated. These trees give an incomplete view of evolutionary histories since many applications of phylogenies require time trees. Many methods have been developed to convert the inferred branch lengths from substitution unit to time unit using calibration points, but none is universally accepted as they are challenged in both scalability and accuracy under complex models. Here, we introduce a new method that formulates dating as a nonconvex optimization problem where the variance of log-transformed rate multipliers is minimized across the tree. On simulated and real data, we show that our method, wLogDate, is often more accurate than alternatives and is more robust to various model assumptions.
Haem oxygenases play a pivotal role in placental physiology and pathology
Authors: Katell Peoc’h, Vincent Puy, Thierry Fournier
Journal: Human Reproduction Update (2020)

Haem oxygenases (HO) catabolise haem, which is the prosthetic group of numerous haemoproteins. Thus, multiple primary cellular pathways and functions rely on haem availability. HO exists in two isoforms, both expressed in the placenta, namely HO-1 and HO-2, the first being inducible. Haem oxygenases, particularly HO-1, have garnered specific interest in the field of physiological and pathological placental function. These enzymes mediate haem degradation by cleaving the alpha methene bridge to produce biliverdin, which is subsequently converted to bilirubin, carbon monoxide and iron. HO-1 has anti-inflammatory and antioxidant activities.An initial literature analysis was performed using PubMed on 3 October 2018 using key terms such as 'haem oxygenase and pregnancy', 'haem oxygenase and placenta', 'HO-1 and pregnancy', 'HO-1 and placenta', 'HO and placenta', 'HO and pregnancy', 'genetic variant and HO', 'CO and pregnancy', 'CO and placenta', 'Bilirubin and pregnancy', 'Iron and pregnancy' and 'PPAR and Haem', selecting consensus conferences, recommendations, meta-analyses, practical recommendations and reviews. A second literature analysis was performed, including notable miscarriages, foetal loss and diabetes mellitus, on 20 December 2019. The three authors studied the publications independently to decipher whether they should be included in the manuscript.This review aimed to summarise current pieces of knowledge of haem oxygenase location, function and regulation in the placenta, either in healthy pregnancies or those associated with miscarriages and foetal loss, pre-eclampsia, foetal growth restriction and diabetes mellitus.HO-1 exerts some protective effects on the placentation, probably by a combination of factors, including its interrelation with the PGC-1α/PPAR pathway and the sFlt1/PlGF balance, and through its primary metabolites, notably carbon monoxide and bilirubin. Its protective role has been highlighted in numerous pregnancy conditions, including pre-eclampsia, foetal growth restriction, gestational diabetes mellitus and miscarriages.HO-1 is a crucial enzyme in physiological and pathological placentation. This protective enzyme is currently considered a potential therapeutic target in various pregnancy diseases.
Abstract 18478: Balloon Angioplasty of Branch Pulmonary Arteries in Children: A Long Term Outlook
Authors: Yinn Khurn Ooi, Sung In Kim, Scott E Gillespie, Zhi Geng, Dennis W Kim, Robert N Vincent, Petit J Christopher
Journal: Circulation (2015)

Introduction: Balloon angioplasty (BA) is widely employed for branch pulmonary artery stenosis (BPAS) in children. Vessel recoil, and hence need for repeat intervention, is common. Hypothesis: BA of BPAS has poor long term outcomes. Methods: We reviewed our cath database over an 11-year period ending in 2013 and collected data for all pts undergoing BA for BPAS. Primary endpoint was repeat intervention (RI), with other endpoints including acute results, and need for stent or surgical PA plasty (S/S). Central branch pulmonary artery (cPA) was defined as pre-hilum, while peripheral BPA (pPA) was define as post-hilum. Results: 175 pts underwent 371 BA procedures for BPAS. Primary diagnosis included major aorto-pulmonary collateral arteries (MAPCAs) in 18% (n=32) pts, and single ventricle in 11% (n=20) pts. Median age and weight were 23.6 (9.9 - 65.8) months and 10.7 kg (7.8 - 18.2 kg). Pt follow up was 4.1 (1.1 - 6.5) years. 69% (n=256) of BA was performed on cPA and 31% (n=115) on pPA. Acutely, there was a 14.9% (7.6 - 26.7%) improvement in stenosis in cPA, and 18.5% (9.8 - 28.6%) in pPA (p=0.053). Improvement of pressure gradient was 34.3% (10.4 - 63.4%) in cPA, and 31.6% (0 - 60.7%) in pPA (p=0.324). Higher rates of RI was seen in pPA (55% RI, p=0.035). For cPA, freedom from RI was 69% at 1 year and 44% at 5 years. Freedom from S/S was 81% at 1 year and 62% at 5 years. Factors associated with higher rate of RI include MAPCAs (65% RI, p=0.039), younger pt age (p=0.042), and lower pt weight (p=0.047). Lower rates of RI were seen in pts with discrete (p=0.007) and severe stenosis (p&lt;0.001). For pPA, freedom from RI was 59% at 1 year and 38% at 5 years. Freedom from S/S was 98% at 1 year and 92% at 5 years. Conclusions: Long term outcomes of BA for BPAS are disappointing. BA for BPAS is associated with a high rate of RI with rates exceeding 50% by 5 years. Patients with pre-hilar BPAS and with discrete, severe stenosis appear to respond more favorably. Peripheral BPAS and MAPCAs in particular have a high rate of recurrence.