tbuckley/cabot-search huggingface dataset:
Gene therapy for inherited arrhythmias
Authors: Vassilios J Bezzerides, Maksymilian Prondzynski, Lucie Carrier, William T Pu
Journal: Cardiovascular Research (2020)

Abstract Inherited arrhythmias are disorders caused by one or more genetic mutations that increase the risk of arrhythmia, which result in life-long risk of sudden death. These mutations either primarily perturb electrophysiological homeostasis (e.g. long QT syndrome and catecholaminergic polymorphic ventricular tachycardia), cause structural disease that is closely associated with severe arrhythmias (e.g. hypertrophic cardiomyopathy), or cause a high propensity for arrhythmia in combination with altered myocardial structure and function (e.g. arrhythmogenic cardiomyopathy). Currently available therapies offer incomplete protection from arrhythmia and fail to alter disease progression. Recent studies suggest that gene therapies may provide potent, molecularly targeted options for at least a subset of inherited arrhythmias. Here, we provide an overview of gene therapy strategies, and review recent studies on gene therapies for catecholaminergic polymorphic ventricular tachycardia and hypertrophic cardiomyopathy caused by MYBPC3 mutations.
Short-term and long-term effect of a high-intensity pulmonary rehabilitation programme in obese patients with asthma: a randomised controlled trial
Authors: Yasemin Türk, Willy Theel, Astrid van Huisstede, Gert-Jan M. van de Geijn, Erwin Birnie, Pieter S. Hiemstra, Jacob K. Sont, Christian Taube, Gert-Jan Braunstahl
Journal: European Respiratory Journal (2020)

Objective To determine the short-term and long-term effects of a high intensity pulmonary rehabilitation programme on asthma control, body composition, lung function and exercise capacity in obese asthma patients. Methods Patients with obesity (body mass index (BMI)≥30 kg·m −2 ) and suboptimal controlled asthma (Asthma Control Questionnaire (ACQ)≥0.75) were randomly assigned to a 3-month pulmonary rehabilitation programme (PR only), pulmonary rehabilitation programme with the use of an internet based self-management support programme (PR+SMS) or usual care. The pulmonary rehabilitation programme included high-intensity interval training, nutritional intervention and psychological group sessions. Patients in the usual care group were advised to lose weight and to exercise. The primary outcome was the difference of change of ACQ between PR only and PR+SMS after 3 months. Total follow-up was 12 months. Results 34 patients were included in the study (14 PR only, nine PR+SMS, 11 control). Compared with patients in usual care, patients in the PR only group had a significant reduction in BMI and significant improvements in asthma control, exercise capacity and aerobic capacity after 3 months. These improvements persisted during 12 months of follow-up. No difference in ACQ between PR+SMS and PR only groups was observed. However, users of the SMS programme had a significantly lower BMI after 12 months compared with subjects in the PR only group. Conclusion A high-intensity pulmonary rehabilitation programme provides sustained improvements in asthma control, body composition and exercise capacity in obese asthmatics that are not optimally controlled and, therefore, should be considered in the treatment of these patients.
COVID-19 and immunomodulation in IBD
Authors: Markus F Neurath
Journal: Gut (2020)

The current coronavirus pandemic is an ongoing global health crisis due to COVID-19, caused by severe acute respiratory syndrome coronavirus 2. Although COVID-19 leads to little or mild flu-like symptoms in the majority of affected patients, the disease may cause severe, frequently lethal complications such as progressive pneumonia, acute respiratory distress syndrome and organ failure driven by hyperinflammation and a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In the context of IBD, several key questions arise. For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to COVID-19 and the cytokine release syndrome associated with lung injury and fatal outcomes. Another highly relevant question is how to deal with immunosuppression and immunomodulation during the current pandemic in patients with IBD and whether immunosuppression affects the progress of COVID-19. Here, the current understanding of the pathophysiology of COVID-19 is reviewed with special reference to immune cell activation. Moreover, the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed.
MCUb Induction Protects the Heart From Postischemic Remodeling
Authors: Jiuzhou Huo, Shan Lu, Jennifer Q. Kwong, Michael J. Bround, Kelly M. Grimes, Michelle A. Sargent, Milton E. Brown, Michael E. Davis, Donald M. Bers, Jeffery D. Molkentin
Journal: Circulation Research (2020)

Rationale: Mitochondrial Ca 2+ loading augments oxidative metabolism to match functional demands during times of increased work or injury. However, mitochondrial Ca 2+ overload also directly causes mitochondrial rupture and cardiomyocyte death during ischemia-reperfusion injury by inducing mitochondrial permeability transition pore opening. The MCU (mitochondrial Ca 2+ uniporter) mediates mitochondrial Ca 2+ influx, and its activity is modulated by partner proteins in its molecular complex, including the MCUb subunit. Objective: Here, we sought to examine the function of the MCUb subunit of the MCU-complex in regulating mitochondria Ca 2+ influx dynamics, acute cardiac injury, and long-term adaptation after ischemic injury. Methods and Results: Cardiomyocyte-specific MCUb overexpressing transgenic mice and Mcub gene-deleted ( Mcub − /− ) mice were generated to dissect the molecular function of this protein in the heart. We observed that MCUb protein is undetectable in the adult mouse heart at baseline, but mRNA and protein are induced after ischemia-reperfusion injury. MCUb overexpressing mice demonstrated inhibited mitochondrial Ca 2+ uptake in cardiomyocytes and partial protection from ischemia-reperfusion injury by reducing mitochondrial permeability transition pore opening. Antithetically, deletion of the Mcub gene exacerbated pathological cardiac remodeling and infarct expansion after ischemic injury in association with greater mitochondrial Ca 2+ uptake. Furthermore, hindlimb remote ischemic preconditioning induced MCUb expression in the heart, which was associated with decreased mitochondrial Ca 2+ uptake, collectively suggesting that induction of MCUb protein in the heart is protective. Similarly, mouse embryonic fibroblasts from Mcub −/− mice were more sensitive to Ca 2+ overload. Conclusions: Our studies suggest that Mcub is a protective cardiac inducible gene that reduces mitochondrial Ca 2+ influx and permeability transition pore opening after ischemic injury to reduce ongoing pathological remodeling.
Ultrabright fluorescent nanoscale labels for the femtomolar detection of analytes with standard bioassays
Authors: Jingyi Luan, Anushree Seth, Rohit Gupta, Zheyu Wang, Priya Rathi, Sisi Cao, Hamed Gholami Derami, Rui Tang, Baogang Xu, Samuel Achilefu, Jeremiah J. Morrissey, Srikanth Singamaneni
Journal: Nature Biomedical Engineering (2020)
PNOCARC Neurons Promote Hyperphagia and Obesity upon High-Fat-Diet Feeding
Authors: Alexander Jais, Lars Paeger, Tamara Sotelo-Hitschfeld, Stephan Bremser, Melanie Prinzensteiner, Paul Klemm, Vasyl Mykytiuk, Pia J.M. Widdershooven, Anna Juliane Vesting, Katarzyna Grzelka, Marielle Minère, Anna Lena Cremer, Jie Xu, Tatiana Korotkova, Bradford B. Lowell, Hanns Ulrich Zeilhofer, Heiko Backes, Henning Fenselau, F. Thomas Wunderlich, Peter Kloppenburg, Jens C. Brüning
Journal: Neuron (2020)

Calorie-rich diets induce hyperphagia and promote obesity, although the underlying mechanisms remain poorly defined. We find that short-term high-fat-diet (HFD) feeding of mice activates prepronociceptin (PNOC)-expressing neurons in the arcuate nucleus of the hypothalamus (ARC). PNOCARC neurons represent a previously unrecognized GABAergic population of ARC neurons distinct from well-defined feeding regulatory AgRP or POMC neurons. PNOCARC neurons arborize densely in the ARC and provide inhibitory synaptic input to nearby anorexigenic POMC neurons. Optogenetic activation of PNOCARC neurons in the ARC and their projections to the bed nucleus of the stria terminalis promotes feeding. Selective ablation of these cells promotes the activation of POMC neurons upon HFD exposure, reduces feeding, and protects from obesity, but it does not affect food intake or body weight under normal chow consumption. We characterize PNOCARC neurons as a novel ARC neuron population activated upon palatable food consumption to promote hyperphagia.
Delayed Antibiotic Prescriptions in Ambulatory Care
Authors: Theresa A. Rowe, Jeffrey A. Linder
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Pseudomonas aeruginosa and lung function decline in patients with bronchiectasis
Authors: M.A. Martinez-García, G. Oscullo, T. Posadas, E. Zaldivar, C. Villa, Y. Dobarganes, R. Girón, C. Olveira, L. Maíz, M. García-Clemente, O. Sibila, R. Golpe, J. Rodríguez, E. Barreiro, J.L. Rodriguez, L. Feced-Olmos, C. Prados, A. Muriel, D. de la Rosa
Journal: Clinical Microbiology and Infection (2020)
Transvalvular Flow, Sex, and Survival After Valve Replacement Surgery in Patients With Severe Aortic Stenosis
Authors: Ezequiel Guzzetti, Anthony Poulin, Mohamed-Salah Annabi, Bin Zhang, Dimitri Kalavrouziotis, Christian Couture, François Dagenais, Philippe Pibarot, Marie-Annick Clavel
Journal: Journal of the American College of Cardiology (2020)
<scp>MiRNA</scp>‐181a is a novel regulator of aldosterone–mineralocorticoid receptor‐mediated cardiac remodelling
Authors: Ankita Garg, Ariana Foinquinos, Mira Jung, Heike Janssen‐Peters, Sinje Biss, Johann Bauersachs, Shashi Kumar Gupta, Thomas Thum
Journal: European Journal of Heart Failure (2020)
Platelet Tissue Factor: Expression of Pro-Coagulant Activity depends on Gpibα Activation and Signaling through Lyn-Mediated Phosphorylation. A Platelet-Based Model of Hemostasis
Authors: Olga Panes, Paula Ibarra, Valeria Matus, Claudia G. Sáez, Jaime Pereira, Diego Mezzano
Journal: Blood (2008)
Socio demographic correlates of pregnancy in cancer survivors using data from NHANES 1999–2002
Authors: C. Hammond, R. Moser, D. Jeffery, D. Harkins
Journal: Journal of Clinical Oncology (2006)

18542 Background: Many cancer therapies can cause infertility and impaired fecundity. These are important long term outcomes of concern for survivors, which can affect their quality of life. Little is known about the socio-demographic correlates of impaired fecundity (inability to get pregnant or carry child to term) in cancer survivors. The purpose of this study is to assess socio demographic correlates of “ever pregnant” in the general American population of cancer survivors. Methods: Using data from adult (&gt;20 years old) female cancer survivor participants of the 1999–2002 iterations of the population based cross sectional survey, National Health and Nutrition Examination Study (NHANES), we used logistic regression to examine the relationship between “ever” being pregnant and socio-demographic variables. Results: Complete data were available for 7558 females. Cancer survivors represented 8.2 % of that population. On univariate analysis, being married and having ≤ high school education were associated with a greater likelihood of “ever” pregnant compared to those unmarried and those with greater than high school education (p &lt; .05). In cancer survivors of reproductive age (between the ages of 20 and 50) being Black or Hispanic was associated with a greater likelihood of “ever” pregnant compared to whites (p &lt; .05). Interestingly, differences in race, income, health insurance status, and marital status were not significantly associated with “ever” pregnant on multivariate analysis of all female survivors older than 20. Conclusions: These results suggest there are differences in impaired fecundity between different groups of cancer survivors. However, questions in NHANES were not designed to explicitly examine fertility related outcomes. Additional studies that specifically examine measures of fertility in survivors are needed to understand the burden of this undesirable outcome in survivors. No significant financial relationships to disclose.
Long-Term Cytogenetic Follow-up of MDS Patients with 5q- Treated within the MDS-003 (CC-5013-MDS-003) Study: Evolution to Complex Clones and Progression to AML.
Authors: Gudrun Göhring, Aristoteles Giagounidis, Carlo Aul, Guntram Büsche, Hans Kreipe, Eva Hellström-Lindberg, Robert D. Knight, Brigitte Schlegelberger
Journal: Blood (2008)
A Randomized Trial of a 1-Hour Troponin T Protocol in Suspected Acute Coronary Syndromes
Authors: Derek P. Chew, Kristina Lambrakis, Andrew Blyth, Anil Seshadri, Michael J.R. Edmonds, Tom Briffa, Louise A. Cullen, Stephen Quinn, Jonathan Karnon, Anthony Chuang, Adam J. Nelson, Deborah Wright, Matthew Horsfall, Erin Morton, John K. French, Cynthia Papendick
Journal: Circulation (2019)

High-sensitivity troponin assays promise earlier discrimination of myocardial infarction. Yet, the benefits and harms of this improved discriminatory performance when incorporated within rapid testing protocols, with respect to subsequent testing and clinical events, has not been evaluated in an in-practice patient-level randomized study. This multicenter study evaluated the noninferiority of a 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol in comparison with a 0/3-hour masked hs-cTnT protocol in patients with suspected acute coronary syndrome presenting to the emergency department (ED).Patients were randomly assigned to either a 0/1-hour hs-cTnT protocol (reported to the limit of detection [<5 ng/L]) or masked hs-cTnT reported to ≤29 ng/L evaluated at 0/3-hours (standard arm). The 30-day primary end point was all-cause death and myocardial infarction. Noninferiority was defined as an absolute margin of 0.5% determined by Poisson regression.In total, 3378 participants with an emergency presentation were randomly assigned between August 2015 and April 2019. Ninety participants were deemed ineligible or withdrew consent. The remaining participants received care guided either by the 0/1-hour hs-cTnT protocol (n=1646) or the 0/3-hour standard masked hs-cTnT protocol (n=1642) and were followed for 30 days. Median age was 59 (49-70) years, and 47% were female. Participants in the 0/1-hour arm were more likely to be discharged from the ED (0/1-hour arm: 45.1% versus standard arm: 32.3%, P<0.001) and median ED length of stay was shorter (0/1-hour arm: 4.6 [interquartile range, 3.4-6.4] hours versus standard arm: 5.6 (interquartile range, 4.0-7.1) hours, P<0.001). Those randomly assigned to the 0/1-hour protocol were less likely to undergo functional cardiac testing (0/1-hour arm: 7.5% versus standard arm: 11.0%, P<0.001). The 0/1-hour hs-cTnT protocol was not inferior to standard care (0/1-hour arm: 17/1646 [1.0%] versus 16/1642 [1.0%]; incidence rate ratio, 1.06 [ 0.53-2.11], noninferiority P value=0.006, superiority P value=0.867), although an increase in myocardial injury was observed. Among patients discharged from ED, the 0/1-hour protocol had a negative predictive value of 99.6% (95% CI, 99.0-99.9%) for 30-day death or myocardial infarction.This in-practice evaluation of a 0/1-hour hs-cTnT protocol embedded in ED care enabled more rapid discharge of patients with suspected acute coronary syndrome. Improving short-term outcomes among patients with newly recognized troponin T elevation will require an evolution in management strategies for these patients.URL: https://www.anzctr.org.au. Unique identifier: ACTRN12615001379505.
Ileocecal valve opening with double clip and rubber band for countertraction facilitates R0 en bloc resection of laterally spreading tumors
Authors: Timothée Wallenhorst, Mathieu Pioche, Guillaume Bouguen, Sylvain Mottais, David Cocaign, Jérémie Jacques, Charlène Brochard
Journal: Endoscopy (2020)

Laterally spreading tumors (LSTs) of the ileocecal valve with an extension of the adenoma in the ileum remain challenging for the endoscopist despite the development of colonic endoscopic submucosal dissection (ESD). The ileocecal valve is considered to be one of the most difficult locations for ESD because of poor maneuverability of the scope. Surgery remains common [1]. Here we present a new technique developed to better expose the ileocecal valve and facilitate R0 en bloc resection of ileocecal LSTs ([Video 1]). Two cases are presented here.
Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins
Authors: Andrew J. Thompson, Liwei Cao, Yuanhui Ma, Xiaoning Wang, Jolene K. Diedrich, Chika Kikuchi, Shelby Willis, Charli Worth, Ryan McBride, John R. Yates, James C. Paulson
Journal: Cell Host & Microbe (2020)
A Randomized, Controlled Trial of Graft-Versus-Host Disease (GVHD) Prophylaxis Comparing Tacrolimus and Mycophenolate Mofetil to Tacrolimus and Methotrexate: Analysis of GVHD, Relapse and Survival.
Authors: Janelle Perkins, Melissa Alsina, Claudio Anasetti, Ernesto Ayala, Hugo F. Fernandez, Mohamed Kharfan-Dabaja, Jose Leonel Ochoa-Bayona, Lia Perez, Jyotishankar Raychaudhuri, Dan Sullivan, Jongphil Kim, Michael Schell, Teresa Field
Journal: Blood (2008)
Functional and mechanistic advantage of the use of a bifunctional anti-PD-L1/IL-15 superagonist
Authors: Karin M Knudson, Kristin C Hicks, Yohei Ozawa, Jeffrey Schlom, Sofia R Gameiro
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Anti(α)-programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy fails to provide durable clinical benefit for most patients with carcinoma. Recent studies suggested that strategies to reduce immunosuppressive cells, promote systemic T-cell responses and lymphocyte trafficking to the tumor microenvironment (TME) may improve efficacy. N-809 is a first-in-class bifunctional agent comprising the interleukin (IL)-15 superagonist N-803 fused to two αPD-L1 domains. Thus, N-809 can potentially stimulate effector immune cells through IL-15 and block immunosuppressive PD-L1. Here, we examined the antitumor efficacy and immunomodulatory effects of N-809 versus N-803+αPD-L1 combination. Methods The ability of N-809 to block PD-L1 and induce IL-15-dependent immune effects was examined in vitro and in vivo. Antitumor efficacy of N-809 or N-803+αPD-L1 was evaluated in two murine carcinoma models and an extensive analysis of immune correlates was performed in the tumor and tumor-draining lymph node (dLN). Results We demonstrate that N-809 blocks PD-L1 and induces IL-15-dependent immune effects. N-809 was well-tolerated and reduced 4T1 lung metastasis, decreased MC38 tumor burden and increased survival versus N-803+αPD-L1. Compared with N-803+αPD-L1, N-809 enhanced natural killer (NK) and CD8 + T-cell activation and function in the dLN and TME, relating to increased gene expression associated with interferon and cytokine signaling, lymphoid compartment, costimulation and cytotoxicity. The higher number of TME CD8 + T cells was attributed to enhanced infiltration, not in situ expansion. Increased TME NK and CD8 + T-cell numbers correlated with augmented chemokine ligands and receptors. Moreover, in contrast to N-803+αPD-L1, N-809 reduced immunosuppressive regulatory T cells (T reg ), monocytic myeloid-derived suppressor cells (M-MDSC) and M2-like macrophages in the TME. Conclusions Our results suggest that N-809 functions by a novel immune mechanism to promote antitumor efficacy. Foremost, N-809 enhances intratumoral lymphocyte numbers by increasing trafficking via altered chemokine levels in the TME and chemokine receptor expression on CD8 + T cells and NK cells. In addition, N-809 reduces immunosuppressive and pro-tumorigenic immune cells in the TME, including T reg , M2-like macrophages and M-MDSC. Overall, these novel effects of N-809 promote an inflamed TME, leading to lower tumor burden and increased survival. These results provide mechanistic insight and rationale supporting the potential clinical study of N-809 in patients with carcinoma.