tbuckley/cabot-search huggingface dataset:
Extracellular histones are a target in myocardial ischaemia–reperfusion injury
Authors: Mohammed Shah, Zhenhe He, Ali Rauf, Siavash Beikoghli Kalkhoran, Christina Mathisen Heiestad, Kåre-Olav Stensløkken, Christopher R Parish, Oliver Soehnlein, Sapna Arjun, Sean M Davidson, Derek Yellon
Journal: Cardiovascular Research (2021)

Abstract Aims Acute myocardial infarction causes lethal cardiomyocyte injury during ischaemia and reperfusion (I/R). Histones have been described as important Danger Associated Molecular Proteins (DAMPs) in sepsis. The objective of this study was to establish whether extracellular histone release contributes to myocardial infarction. Methods and results Isolated, perfused rat hearts were subject to I/R. Nucleosomes and histone-H4 release was detected early during reperfusion. Sodium-β-O-Methyl cellobioside sulfate (mCBS), a newly developed histone-neutralizing compound, significantly reduced infarct size whilst also reducing the detectable levels of histones. Histones were directly toxic to primary adult rat cardiomyocytes in vitro. This was prevented by mCBS or HIPe, a recently described, histone-H4 neutralizing peptide, but not by an inhibitor of TLR4, a receptor previously reported to be involved in DAMP-mediated cytotoxicity. Furthermore, TLR4-reporter HEK293 cells revealed that cytotoxicity of histone H4 was independent of TLR4 and NF-κB. In an in vivo rat model of I/R, HIPe significantly reduced infarct size. Conclusion Histones released from the myocardium are cytotoxic to cardiomyocytes, via a TLR4-independent mechanism. The targeting of extracellular histones provides a novel opportunity to limit cardiomyocyte death during I/R injury of the myocardium.
PREDICTORS OF LIKELIHOOD OF TAKING SACUBITRIL-VALSARTAN AND A HYPOTHETICAL MEDICATION FOR COVID-19
Authors: Mary Catherine Thomson, Larry Allen, Scott D. Halpern, Yi-An Ko, Daniel Matlock, Miranda A. Moore, Alanna Morris, Birju Rao, Laura D. Scherer, Candace Speight, Peter A. Ubel, Neal Dickert
Journal: Journal of the American College of Cardiology (2021)
Patterned, organoid-based cartilaginous implants exhibit zone specific functionality forming osteochondral-like tissues in vivo
Authors: Gabriella Nilsson Hall, Wai Long Tam, Konstantinos S. Andrikopoulos, Leire Casas-Fraile, George A. Voyiatzis, Liesbet Geris, Frank P. Luyten, Ioannis Papantoniou
Journal: Biomaterials (2021)
Blunt Splenic Injury and Prophylactic Splenic Artery Embolization—Reply
Authors: Catherine Arvieux, Julien Ghelfi, Alison Foote
Journal: JAMA Surgery (2021)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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 Surgery journal
Re: Sophie Knipper, Luigi Ascalone, Benjamin Ziegler, et al. Salvage Surgery in Patients with Local Recurrence After Radical Prostatectomy. Eur Urol 2021;79:537–44
Authors: Francesco Montorsi, Nicola Fossati, Carlo A. Bravi, Giorgio Gandaglia, Nazareno Suardi, Alberto Briganti
Journal: European Urology (2021)
Implant Surface Texture and Breast Cancer Recurrence
Authors: Cícero de Andrade Urban, Francisco Pimentel Cavalcante, Mahmoud B. El-Tamer
Journal: JAMA Surgery (2021)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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 Surgery journal
Group Medical Visit and Microfinance Intervention for Patients With Diabetes or Hypertension in Kenya
Authors: Rajesh Vedanthan, Jemima H. Kamano, Stavroula A. Chrysanthopoulou, Richard Mugo, Benjamin Andama, Gerald S. Bloomfield, Cleophas W. Chesoli, Allison K. DeLong, David Edelman, Eric A. Finkelstein, Carol R. Horowitz, Simon Manyara, Diana Menya, Violet Naanyu, Vitalis Orango, Sonak D. Pastakia, Thomas W. Valente, Joseph W. Hogan, Valentin Fuster
Journal: Journal of the American College of Cardiology (2021)
In Isolation but Not Alone
Authors: Elizabeth Merkle Hankollari
Journal: Annals of Internal Medicine (2021)

On Being a DoctorApril 2021In Isolation but Not AloneElizabeth Merkle Hankollari, MDElizabeth Merkle Hankollari, MDDuke University Medical Center, Durham, North CarolinaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-4047 Audio Reading - “In Isolation but Not Alone” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “In Isolation but Not Alone” by Elizabeth Merkle Hankollari, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail His daughter wants to see him. We've arranged a tablet in his room so she can call on a secure video chat platform. She calls in; the connection sputters. After 2 exasperating hours with tech support, we abandon our efforts. I'm worried. He is well into his 70s, with several underlying medical conditions. Today, he looks more receptive, perceptive; I had hoped her voice could tug him free from the quicksand of his delirium. With each passing day in isolation, the hope of resurfacing fades. However, the secure chat app isn't working and new visitation restrictions mean that she can't ... Author, Article, and Disclosure InformationAffiliations: Duke University Medical Center, Durham, North CarolinaCorresponding Author: Elizabeth Merkle Hankollari, MD, Duke University Medical Center, DUMC Box 100800, Durham, NC 27710; e-mail, Elizabeth.[email protected]edu; Twitter: @LizHankollariMD. PreviousarticleNextarticle Advertisement Audio Reading - “In Isolation but Not Alone” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “In Isolation but Not Alone” by Elizabeth Merkle Hankollari, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics April 2021Volume 174, Issue 4Page: 560-561 ePublished: 20 April 2021 Issue Published: April 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cardiovascular RNA markers and artificial intelligence may improve COVID-19 outcome: a position paper from the EU-CardioRNA COST Action CA17129
Authors: Lina Badimon, Emma L Robinson, Amela Jusic, Irina Carpusca, Leon J deWindt, Costanza Emanueli, Péter Ferdinandy, Wei Gu, Mariann Gyöngyösi, Matthias Hackl, Kanita Karaduzovic-Hadziabdic, Mitja Lustrek, Fabio Martelli, Eric Nham, Ines Potočnjak, Venkata Satagopam, Reinhard Schneider, Thomas Thum, Yvan Devaux
Journal: Cardiovascular Research (2021)

Abstract The coronavirus disease 2019 (COVID-19) pandemic has been as unprecedented as unexpected, affecting more than 105 million people worldwide as of 8 February 2020 and causing more than 2.3 million deaths according to the World Health Organization (WHO). Not only affecting the lungs but also provoking acute respiratory distress, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to infect multiple cell types including cardiac and vascular cells. Hence a significant proportion of infected patients develop cardiac events, such as arrhythmias and heart failure. Patients with cardiovascular comorbidities are at highest risk of cardiac death. To face the pandemic and limit its burden, health authorities have launched several fast-track calls for research projects aiming to develop rapid strategies to combat the disease, as well as longer-term projects to prepare for the future. Biomarkers have the possibility to aid in clinical decision-making and tailoring healthcare in order to improve patient quality of life. The biomarker potential of circulating RNAs has been recognized in several disease conditions, including cardiovascular disease. RNA biomarkers may be useful in the current COVID-19 situation. The discovery, validation, and marketing of novel biomarkers, including RNA biomarkers, require multi-centre studies by large and interdisciplinary collaborative networks, involving both the academia and the industry. Here, members of the EU-CardioRNA COST Action CA17129 summarize the current knowledge about the strain that COVID-19 places on the cardiovascular system and discuss how RNA biomarkers can aid to limit this burden. They present the benefits and challenges of the discovery of novel RNA biomarkers, the need for networking efforts, and the added value of artificial intelligence to achieve reliable advances.
Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas
Authors: Tuyu Zheng, David R. Ghasemi, Konstantin Okonechnikov, Andrey Korshunov, Martin Sill, Kendra K. Maass, Patricia Benites Goncalves da Silva, Marina Ryzhova, Johannes Gojo, Damian Stichel, Amir Arabzade, Robert Kupp, Julia Benzel, Shinichiro Taya, Toma Adachi, Ryo Shiraishi, Nicolas U. Gerber, Dominik Sturm, Jonas Ecker, Philipp Sievers, Florian Selt, Rebecca Chapman, Christine Haberler, Dominique Figarella-Branger, Guido Reifenberger, Gudrun Fleischhack, Stefan Rutkowski, Andrew M. Donson, Vijay Ramaswamy, David Capper, David W. Ellison, Christel C. Herold-Mende, Ulrich Schüller, Sebastian Brandner, Pablo Hernáiz Driever, Johan M. Kros, Matija Snuderl, Till Milde, Richard G. Grundy, Mikio Hoshino, Stephen C. Mack, Richard J. Gilbertson, David T.W. Jones, Marcel Kool, Andreas von Deimling, Stefan M. Pfister, Felix Sahm, Daisuke Kawauchi, Kristian W. Pajtler
Journal: Cancer Discovery (2021)

Abstract Molecular groups of supratentorial ependymomas comprise tumors with ZFTA–RELA or YAP1-involving fusions and fusion-negative subependymoma. However, occasionally supratentorial ependymomas cannot be readily assigned to any of these groups due to lack of detection of a typical fusion and/or ambiguous DNA methylation–based classification. An unbiased approach with a cohort of unprecedented size revealed distinct methylation clusters composed of tumors with ependymal but also various other histologic features containing alternative translocations that shared ZFTA as a partner gene. Somatic overexpression of ZFTA-associated fusion genes in the developing cerebral cortex is capable of inducing tumor formation in vivo, and cross-species comparative analyses identified GLI2 as a key downstream regulator of tumorigenesis in all tumors. Targeting GLI2 with arsenic trioxide caused extended survival of tumor-bearing animals, indicating a potential therapeutic vulnerability in ZFTA fusion–positive tumors. Significance: ZFTA–RELA fusions are a hallmark feature of supratentorial ependymoma. We find that ZFTA acts as a partner for alternative transcriptional activators in oncogenic fusions of supratentorial tumors with various histologic characteristics. Establishing representative mouse models, we identify potential therapeutic targets shared by ZFTA fusion–positive tumors, such as GLI2. This article is highlighted in the In This Issue feature, p. 2113
Iron and platelets: A subtle, under‐recognized relationship
Authors: Eolia Brissot, Marie‐Bérengère Troadec, Olivier Loréal, Pierre Brissot
Journal: American Journal of Hematology (2021)

Abstract The role of iron in the formation and functioning of erythrocytes, and to a lesser degree of white blood cells, is well established, but the relationship between iron and platelets is less documented. Physiologically, iron plays an important role in hematopoiesis, including thrombopoiesis; iron levels direct, together with genetic factors, the lineage commitment of megakaryocytic/erythroid progenitors toward either megakaryocyte or erythroid progenitors. Megakaryocytic iron contributes to cellular machinery, especially energy production in platelet mitochondria. Thrombocytosis, possibly favoring vascular thrombosis, is a classical feature observed with abnormally low total body iron stores (mainly due to blood losses or decreased duodenal iron intake), but thrombocytopenia can also occur in severe iron deficiency anemia. Iron sequestration, as seen in inflammatory conditions, can be associated with early thrombocytopenia due to platelet consumption and followed by reactive replenishment of the platelet pool with possibility of thrombocytosis. Iron overload of genetic origin (hemochromatosis), despite expected mitochondrial damage related to ferroptosis, has not been reported to cause thrombocytopenia (except in case of high degree of hepatic fibrosis), and iron‐related alteration of platelet function is still a matter of debate. In acquired iron overload (of transfusional and/or dyserythropoiesis origin), quantitative or qualitative platelet changes are difficult to attribute to iron alone due to the interference of the underlying hematological conditions; likewise, hematological improvement, including increased blood platelet counts, observed under iron oral chelation is likely to reflect mechanisms other than the sole beneficial impact of iron depletion.
Abstract P383: Walking Speed is a Significant Indicator of Vascular Health in Late Midlife Women: The Study of Women’s Health Across the Nation
Authors: Samar R El Khoudary, Hsiang-Yu Chen, Emma Barinas-Mitchell, Candace McClure, Barbara Sternfeld, Naila Khalil, Elizabeth Jackson, Carrie Karvonen-Gulierrez, Kelly Ylitalo, Kim Sutton-Tyrrell
Journal: Circulation (2013)

Objective: Wider adventitial diameter (AD) is correlated with adverse cardiovascular risk factors and a higher risk of CVD. A dilated artery cannot adapt as well to adverse conditions, which may make it more vulnerable to damage. Slower walking speed, a physical functioning (PF) performance measure, is associated with subclinical measures of atherosclerosis and increased mortality in the elderly. The relationship between PF performance measures and AD, an informative measure of vascular health, has not been evaluated. We assessed whether walking speed and time needed for sit-to stand assessment are associated with carotid AD in a large sample of multi-ethnic, late midlife women. The associations with carotid intima-media thickness (IMT) and presence of carotid plaque were also evaluated. Design: Participants from the Study of Women’s Health Across the Nation who were free of CVD and had carotid AD, IMT or presence of carotid plaque assessed at the 12th annual visit were evaluated. Average 40-foot walking speed (calculated as 12.192 meters/time in seconds) (2 repetitions) and average time in seconds needed for sit-to-stand assessment (5 repetitions) were measured at the same time. Linear and logistic regression models were used as appropriate. Results: A total of 1224 women (96.9% Postmenopausal; 52.0% Caucasian, 27.9% African American, 14.3% Chinese, 5.8% Hispanic) from 6 sites across the USA, aged 59.6±2.7 years old at visit 12, were included. In models adjusted for site, race, current age, menopausal status and systolic blood pressure, slower walking speed and longer time needed for sit-to-stand (log-transformed) were significantly associated with a wider AD (β(SE):0.43(0.08) mm, P&lt;0.0001; 0.20(0.05) mm, P=0.0002, respectively), a thicker IMT (β(SE):0.05(0.01) mm, P=0.001; β(SE):0.03(0.01) mm, P=0.008, respectively) and a higher probability of presence of carotid plaque (OR (95% confidence interval [CI]) :1.82(1.09,3.04), only with walking speed). Associations between PF performance measures and IMT as well as the association between walking speed and presence of carotid plaque became non-significant after further adjustment for current body mass index. Associations between slower walking speed and wider AD (β(SE):0.18(0.08) mm, P=0.03 ) remained significant even after additional adjustment for current body mass index, lipids, insulin resistance (HOMA index), smoking, ever use of antihypertensive/lipid lowering/heart medications, ever use of hormone therapy and ever reported presence of diabetes. Conclusions: Simple objective PF performance measures such as 40-foot walking speed could be a useful tool to assess vascular health. Women with slower walking speed may be at a greater risk of vascular-related diseases.
SAT0680 EDUCATIONAL NEEDS OF A LARGE COHORT OF PATIENTS WITH DIFFERENT RHEUMATIC AND MUSCULOSKELETAL DISEASES ATTENDING A HEALTH FACILITY IN AUSTRIA
Authors: Martin Offenbächer, Loren Toussaint, Niko Kohls, Christian Hanshans, Miguel Vallejo, Javier Rivera, Fuschia Sirois, Jameson Hirsch, Johannes Untner, Bertram Hölzl, Martin Gaisberger, Mwidimi Ndosi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Patient education is an important part of the management of rheumatic and other diseases. Since patients do not have the same needs, it is crucial to assess needs of a targeted group to be able to tailor educational interventions. <h3>Objectives:</h3> To assess educational needs of a large cohort of patients with different rheumatic and musculoskeletal diseases attending a health facility in Austria. <h3>Methods:</h3> We conducted an online survey with patients attending the Gastein Healing Galleries in Bad Gastein, Austria. Approximately 12,000 patients with a variety of diseases are treated in the centre every year. Of those, 6,465 patients were invited by email to fill out an anonymous online survey. Socio-demographics and health outcomes were collected from all respondents. In addition, the Educational Needs Assessment Tool (Austrian version - OENAT) was administered to a subset of respondents. The OENAT (39 items) assesses 7 domains of educational needs: Managing Pain, Movement, Managing Feelings, Arthritis/Disease process, Treatments, Self Help Measures, Support Systems. <h3>Results:</h3> In total 2017 (31%) patients responded of which 516 had data on educational needs: AS (63%), RA (14%), and FM (24%). Their mean (SD) age was 56 (11), and 54% were male. Level of education was: Elementary School (32%), Junior High School (22%), High School (21%), College (12%), and University (14%). Table 1 presents differences in educational needs across disease groups. Across the groups, there were significant differences in following OENAT domains: Managing Pain, Feelings, Treatments, and Support Systems. There were no differences in the level of educational needs in Movements, Disease Process, and Self-Help Measures. Patients with FM had significantly lower needs for managing and higher needs for feeling education, compared to those with AS and RA (p&lt;.05). The RA group had significantly higher needs than the AS (p&lt;.05) and FM (p&lt;.05) groups for treatments education - the AS group had significantly higher needs than the FM group (p&lt;.05) in the same domain. AS patients had significantly higher needs for support system education than FM (p&lt;.05) and RA patients (p&lt;.05). <h3>Conclusion:</h3> Educational needs vary by disease groups and depend on the domain under consideration. <h3> Disclosure of Interests:</h3> None declared
Reply to Alexander Andreev-Drakhlin, Jianjun Gao, Arlene Siefker-Radtke. Levelling the Evidence: A Comparison of Neoadjuvant and Adjuvant Treatment for Upper Tract Urothelial Carcinoma. Eur Urol 2021;79:655–6
Authors: Jeffrey J. Leow, Yew Lam Chong, Steven L. Chang, Begoña P. Valderrama, Thomas Powles, Joaquim Bellmunt
Journal: European Urology (2020)
Tumor-derived IL-6 and trans-signaling among tumor, fat, and muscle mediate pancreatic cancer cachexia
Authors: Joseph E. Rupert, Ashok Narasimhan, Daenique H.A. Jengelley, Yanlin Jiang, Jianguo Liu, Ernie Au, Libbie M. Silverman, George Sandusky, Andrea Bonetto, Sha Cao, Xiaoyu Lu, Thomas M. O’Connell, Yunlong Liu, Leonidas G. Koniaris, Teresa A. Zimmers
Journal: The Journal of Experimental Medicine (2021)

Most patients with pancreatic adenocarcinoma (PDAC) suffer cachexia; some do not. To model heterogeneity, we used patient-derived orthotopic xenografts. These phenocopied donor weight loss. Furthermore, muscle wasting correlated with mortality and murine IL-6, and human IL-6 associated with the greatest murine cachexia. In cell culture and mice, PDAC cells elicited adipocyte IL-6 expression and IL-6 plus IL-6 receptor (IL6R) in myocytes and blood. PDAC induced adipocyte lipolysis and muscle steatosis, dysmetabolism, and wasting. Depletion of IL-6 from malignant cells halved adipose wasting and abolished myosteatosis, dysmetabolism, and atrophy. In culture, adipocyte lipolysis required soluble (s)IL6R, while IL-6, sIL6R, or palmitate induced myotube atrophy. PDAC cells activated adipocytes to induce myotube wasting and activated myotubes to induce adipocyte lipolysis. Thus, PDAC cachexia results from tissue crosstalk via a feed-forward, IL-6 trans-signaling loop. Malignant cells signal via IL-6 to muscle and fat, muscle to fat via sIL6R, and fat to muscle via lipids and IL-6, all targetable mechanisms for treatment of cachexia.
Molecular diagnosis of childhood immune dysregulation, polyendocrinopathy, and enteropathy, and implications for clinical management
Authors: Sarah K Baxter, Tom Walsh, Silvia Casadei, Mary M Eckert, Eric J Allenspach, David Hagin, Gesmar Segundo, Ming K Lee, Suleyman Gulsuner, Brian H Shirts, Kathleen E Sullivan, Michael D Keller, Troy R Torgerson, Mary-Claire King
Journal: Journal of Allergy and Clinical Immunology (2021)
The melanocortin-3 receptor is a pharmacological target for the regulation of anorexia
Authors: Patrick Sweeney, Michelle N. Bedenbaugh, Jose Maldonado, Pauline Pan, Katelyn Fowler, Savannah Y. Williams, Luis E. Gimenez, Masoud Ghamari-Langroudi, Griffin Downing, Yijun Gui, Colleen K. Hadley, Stephen T. Joy, Anna K. Mapp, Richard B. Simerly, Roger D. Cone
Journal: Science Translational Medicine (2021)

Pharmacological manipulation of the melanocortin-3 receptor bidirectionally controls feeding, providing a therapeutic target for eating disorders.