tbuckley/cabot-search huggingface dataset:
Abstract 16569: Melatonin Inhibits NO-Induced Activation of BKCa Channels and Relaxation of Coronary Arteries by Increasing PKG1-Dependent Phosphorylation of PDE5
Authors: Praveen Shukla, Chengwen Sun, Stephen T ORourke
Journal: Circulation (2012)

Alterations in melatonin (MEL) blood levels are associated with several cardiovascular disorders, including hypertension, ischemic heart disease, and heart failure. We recently demonstrated that MEL, acting via MT2-receptors, impairs nitric oxide (NO)-induced relaxation in coronary arteries by inhibiting NO-induced increases in intracellular cGMP levels (JPET 336: 127, 2011). In vascular smooth muscle, PKG1 limits the physiological actions of NO/cGMP signaling by phosphorylating PDE5, thereby increasing PDE5 activity. Hypothesis: We hypothesized that MEL impairs NO-induced relaxation of coronary arteries by stimulating PKG1-dependent phosphorylation of PDE5, resulting in attenuation of NO-activated BKCa function in coronary smooth muscle cells. Methods and Results: MEL (10-9 - 10-7 M) inhibited relaxation to the NO-donors (10-10 - 10-4 M), diethylamine-NONOate and sodium nitroprusside (SNP) in isolated porcine coronary arteries (p<0.05; n=5-8), but had no effect on relaxation induced by 8-Br-cGMP, a cell ...
Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation
Authors: Vanessa M. Ferreira, Jeanette Schulz-Menger, Godtfred Holmvang, Christopher M. Kramer, Iacopo Carbone, Udo Sechtem, Ingrid Kindermann, Matthias Gutberlet, Leslie T. Cooper, Peter Liu, Matthias G. Friedrich
Journal: Journal of the American College of Cardiology (2018)
Abstract 18923: Trends in Long-term Survival After In-hospital Cardiac Arrest: Insights From Get With the Guidelines-Resuscitation®
Authors: Lauren E Thompson, Paul S Chan, Fengmeng Tang, Brahmajee K Nallamothu, Saket Girotra, Stacie L Daugherty, Steven M Bradley
Journal: Circulation (2015)

Background: Although survival to hospital discharge after in-hospital cardiac arrest (IHCA) has improved over the last decade, it is unknown if these survival gains are sustained after hospital discharge. Accordingly, we evaluated temporal trends in 1-year survival after IHCA. Methods: We linked data from Get With The Guidelines-Resuscitation (a national IHCA registry) with Medicare files and evaluated temporal trends in 1-year survival after IHCA between 2000 and 2011, using multivariable Poisson regression models to account for patient factors, clinical factors, cardiac arrest characteristics (e.g. initial rhythm, location of arrest), and hospital site. We examined 1-year survival trends overall, and separately for shockable (ventricular fibrillation [VF] and pulseless ventricular tachycardia [VT]) and non-shockable rhythms (asystole and pulseless electrical activity [PEA]). Results: Of 45,567 patients with IHCA, the majority had a presenting rhythm of PEA (43.5%) or asystole (42.2%), and half (53.6%) occurred in an ICU. Overall 1-year survival was 9.4%, with higher survival each successive year (FIGURE). Risk-adjusted 1-year survival increased over time for all IHCA (adjusted rate ratio [RR] per year, 1.05; 95% confidence interval [CI], 1.04 to 1.06; P&lt;0.001 for trend) and separately for VT/VF and PEA/asystole arrests (all p for trend &lt;0.001). Compared with 2000-01, 1-year survival after IHCA in 2011 increased by 62% (adjusted RR, 1.62 [95% CI: 1.44-1.81]) (TABLE). Conclusions: Over the past decade, 1-year survival after IHCA has significantly improved each year.
Risk Factors for Severe Dry Eye Disease: Crowdsourced Research Using DryEyeRhythm
Authors: Takenori Inomata, Masahiro Nakamura, Masao Iwagami, Tina Shiang, Yusuke Yoshimura, Keiichi Fujimoto, Yuichi Okumura, Atsuko Eguchi, Nanami Iwata, Maria Miura, Satoshi Hori, Yoshimune Hiratsuka, Miki Uchino, Kazuo Tsubota, Reza Dana, Akira Murakami
Journal: Ophthalmology (2018)
Abstract 15786: Long-Term Statin Persistence is Poor Among High-Risk Patients in a Real-World Administrative Claims Analysis
Authors: Peter Toth, Craig Granowitz, Michael Hull, Djibril Liassou, Amy Anderson, Sephy Philip
Journal: Circulation (2017)

Introduction: A decade ago, statin persistence was <50% after 1 year, and recent short-term analyses have revealed very little progress in improving statin persistence, even in patients with a prio...
Getting back to football after having a total hip replacement (twice)
Authors: Martin Sinclair
Journal: British Journal of Sports Medicine (2018)

When I was a young boy watching my Dad play football, I remember wanting to be just like him. I was delighted when I joined my first team but for one reason or another I got kicked out of the team. This might have been because of my disability—I have cerebral palsy so I’m not sure if it was because of that. I moved onto another team and never looked back from there as football is my life!

I am most proud of being able to play in the Paralympics at London 2012 for the Great Britain Cerebral Palsy football team, as well as playing in several major international tournaments for the England Cerebral Palsy team. It was a great experience for me to travel around the world doing what I love. Walking out in front of 80 000 people at the opening ceremony of the London 2012 Paralympics is something that I will never forget. I always got goose bumps when the national anthems were sung!

I never thought that any of this would be possible when I first dislocated my hip at the age of 15. I was going down a slide at the local park, and felt my hip ‘pop’. I went straight to the hospital, but they said it was a pulled muscle so I was walking around on my painful hip for 2 weeks. Eventually I needed a wheelchair to move around as I wasn’t able to walk on my leg.

Luckily enough I already had an appointment scheduled with a surgeon about my hand …
Prevalence of Cannabis Use in Youths After Legalization in Washington State
Authors: Julia A. Dilley, Susan M. Richardson, Beau Kilmer, Rosalie Liccardo Pacula, Mary B. Segawa, Magdalena Cerdá
Journal: JAMA Pediatrics (2018)

In November 2012, voters in Washington legalized nonmedical (retail) cannabis for people aged 21 and older.Markets opened in July 2014.The effect of this change on cannabis use among youths is of public health concern.Cerdá et al 1 analyzed data from the nationally representative Monitoring the Future survey (MTF) and used differencein-differences methods to compare cannabis use prevalence trends among youths in Washington with use in states without legalization of recreational marijuana.Because the MTF is not designed to provide state-representative estimates, the article generated covariate-adjusted modeled prevalence estimates for each state.The article suggested complex association between legalization and cannabis use among youths: increases in prevalence among Washington 8th and 10th graders, but not among 12th graders, relative to use in states without legalization of recreational marijuana.The authors noted that, "the sample design may lead to discrepancies between MTF results and those found in other large-scale surveillance efforts." 1(p148) The purpose of the present study was to assess whether trends in cannabis use prevalence among youths from Washington's state-based youth survey are consistent with findings from the MTF.
The Major Causes of Death in Children and Adolescents in the United States
Authors: Rebecca M. Cunningham, Maureen A. Walton, Patrick M. Carter
Journal: New England Journal of Medicine (2018)

The Causes of Death in Children and Adolescents This report details the 10 leading causes for the 20,360 deaths of children and adolescents in the United States in 2016. The analysis also includes ...
Immunosuppressive mechanisms in acute myeloid leukemia with mutated nucleophosmin
Authors: K. Kuželová, B. Brodská, P. Otevřelová, C. Šálek
Journal: Annals of Oncology (2018)

Background: The curative potential of hematopoietic cell transplantation in the treatment of acute myeloid leukemia (AML) suggests that the immune system is involved in the disease outcome. One of the major obstacles in the development of immunotherapeutic protocols is the lack of specific antigens. Mutations in NPM1 gene are characteristic for AML, they are found in about a third of AML patients and are relatively stable during the disease course. Patients with these mutations form a specific group with better prognosis which might be associated with an immune response against the mutated protein or against its interaction partners. Methods: We evaluated a set of known markers of immune suppression in a cohort of 30 AML patients at diagnosis, with special focus on possible differences between patients with wild-type and mutated NPM1 (NPMwt versus NPMmut). Positive cell fraction and the mean expression levels were determined for each marker using flow cytometry. NPM1 mutations were detected by PCR and by immunofluorescence (cytoplasmic signal). Results: We found decreased HLA class I expression in a subgroup of NPMmut, but not in NPMwt group. Independently of NPM1 mutations, a part of patients had increased expression of PD-L1, CLIP or Tim-3. These markers were partly mutually correlated. We have also detected increased expression of CD47 and decreased expression of HLA-DR on leukemia blasts in NPMmut group compared to NPMwt. Furthermore, NPMmut patients had higher percentage of CD27-positive B-cells. On the other hand, no difference between NPMmut and NPMwt were found on T-lymphocytes. Conclusions: Our results confirm that patients with mutated NPM1 form an immunologically specific AML subgroup with increased markers of immune suppression at diagnosis. Legal entity responsible for the study: Institute of Hematology and Blood Transfusion. Funding: Ministry of Health of the Czech Republic (grant No 16-30268A). Disclosure: All authors have declared no conflicts of interest.
BMA repeats its call for second Brexit referendum
Authors: Abi Rimmer
Journal: BMJ (2018)

The BMA has restated its warning that all parts of the health service will be adversely affected by Brexit, calling again for a second referendum.

In an editorial, published in The BMJ in November, the BMA along with The BMJ and the Royal College of Nursing, said that the British people must be allowed to make a fully informed decision on Britain leaving the European Union in a …
Medicare’s Approach to Paying for Services That Promote Coordinated Care
Authors: Joshua M. Liao, Amol S. Navathe, Matthew J. Press
Journal: JAMA (2018)

This Viewpoint discusses new fee-for-service billing codes introduced by CMS for reimbursement of virtual care including e-consults, remote physiologic monitoring, and video and image review, and proposes strategies to incentivize the activities to promote coordinated care.
Realizing Effectiveness across Continents with Hydroxyurea (REACH): A Prospective Multi-National Trial of Hydroxyurea for Sickle Cell Anemia in Sub-Saharan Africa
Authors: Leon Tshilolo, George Tomlinson, Thomas N. Williams, Brigida Santos, Peter Olupot-Olupot, Adam Lane, Banu Aygun, Susan Stuber, Teresa Latham, Patrick T. McGann, Russell E. Ware
Journal: Blood (2018)
Outcome of Patients with Myelofibrosis after Ruxolitinib Failure: Role of Disease Status and Treatment Strategies in 214 Patients
Authors: Francesca Palandri, Elena Maria Elli, Nicola Polverelli, Massimiliano Bonifacio, Giulia Benevolo, Elisabetta Abruzzese, Micaela Bergamaschi, Alessia Tieghi, Alessandra Iurlo, Monica Crugnola, Francesco Cavazzini, Gianni Binotto, Alessandro Isidori, Nicola Sgherza, Costanza Bosi, Roberto Latagliata, Giuseppe Auteri, Luigi Scaffidi, Daniele Cattaneo, Lucia Catani, Mauro Krampera, Umberto Vitolo, Franco Aversa, Roberto Massimo Lemoli, Antonio Cuneo, Gianpietro Semenzato, Robin Foà, Francesco Di Raimondo, Michele Cavo, Daniela Bartoletti, Nicola Vianelli, Massimo Breccia, Giuseppe A. Palumbo
Journal: Blood (2018)
Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect
Authors: Artur V. Cideciyan, Samuel G. Jacobson, Arlene V. Drack, Allen C. Ho, Jason Charng, Alexandra V. Garafalo, Alejandro J. Roman, Alexander Sumaroka, Ian C. Han, Maria D. Hochstedler, Wanda L. Pfeifer, Elliott H. Sohn, Magali Taiel, Michael R. Schwartz, Patricia Biasutto, Wilma de Wit, Michael E. Cheetham, Peter Adamson, David M. Rodman, Gerard Platenburg, Maria D. Tome, Irina Balikova, Fanny Nerinckx, Julie De Zaeytijd, Caroline Van Cauwenbergh, Bart P. Leroy, Stephen R. Russell
Journal: Nature Medicine (2018)
Trastuzumab Therapy for 9 Weeks vs 1 Year for Human Epidermal Growth Factor 2-Positive Breast Cancer—Reply
Authors: Val Gebski, Teppo Huttunen, Heikki Joensuu
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Guidelines Do Not Proscribe Surgeons Performing Genetic Testing—Reply
Authors: Steven J. Katz, Monica Morrow, Allison W. Kurian
Journal: JAMA Surgery (2018)

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
Precision Medicine and Advancing Clinical Care
Authors: David O. Arnar, Runolfur Palsson
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
The importance of patient perspectives in pulmonary hypertension
Authors: Michael D. McGoon, Pisana Ferrari, Iain Armstrong, Migdalia Denis, Luke S. Howard, Gabi Lowe, Sanjay Mehta, Noriko Murakami, Brad A. Wong
Journal: European Respiratory Journal (2018)

The assessment of objective measurement of cardiopulmonary status has helped us achieve better clinical outcomes for patients and develop new therapies through to the point of market access; however, patient surveys indicate that more can be done to improve holistic care and patient engagement. In this multidisciplinary review, we examine how clinical teams can acknowledge and embrace the individual patient's perspective, and thus improve the care for individual patients suffering from pulmonary hypertension by cultivating the importance and relevance of health-related quality of life in direct clinical care. At the individual level, patients should be provided with access to accredited specialist centres which provide a multidisciplinary approach where there is a culture focused on narrative medicine, quality of life, shared decision making and timely access to palliative care, and where there is participation in education. On a larger scale, we call for the development, expansion and promotion of patient associations to support patients and carers, lobby for access to best care and treatments, and provide input into the development of clinical trials and registries, focusing on the patients’ perspective.
Abstract 11237: A Novel Endothelin Receptor Antagonist, Macitentan Markedly Improved Severe Pulmonary Arterial Hypertension in Rats by a Nearly Complete Blockade of Endothelin Receptors
Authors: Mutsumi Kunita
Journal: Circulation (2013)

Introduction: Endothelin receptor antagonists (ERAs) have been used for the treatment of pulmonary arterial hypertension (PAH). However, the efficacy of ERAs in severe PAH remains limited, partly b...
Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial
Authors: Robert W Yeh, Linda R Valsdottir, Michael W Yeh, Changyu Shen, Daniel B Kramer, Jordan B Strom, Eric A Secemsky, Joanne L Healy, Robert M Domeier, Dhruv S Kazi, Brahmajee K Nallamothu
Journal: BMJ (2018)

To determine if using a parachute prevents death or major traumatic injury when jumping from an aircraft.Randomized controlled trial.Private or commercial aircraft between September 2017 and August 2018.92 aircraft passengers aged 18 and over were screened for participation. 23 agreed to be enrolled and were randomized.Jumping from an aircraft (airplane or helicopter) with a parachute versus an empty backpack (unblinded).Composite of death or major traumatic injury (defined by an Injury Severity Score over 15) upon impact with the ground measured immediately after landing.Parachute use did not significantly reduce death or major injury (0% for parachute v 0% for control; P>0.9). This finding was consistent across multiple subgroups. Compared with individuals screened but not enrolled, participants included in the study were on aircraft at significantly lower altitude (mean of 0.6 m for participants v mean of 9146 m for non-participants; P<0.001) and lower velocity (mean of 0 km/h v mean of 800 km/h; P<0.001).Parachute use did not reduce death or major traumatic injury when jumping from aircraft in the first randomized evaluation of this intervention. However, the trial was only able to enroll participants on small stationary aircraft on the ground, suggesting cautious extrapolation to high altitude jumps. When beliefs regarding the effectiveness of an intervention exist in the community, randomized trials might selectively enroll individuals with a lower perceived likelihood of benefit, thus diminishing the applicability of the results to clinical practice.
Improving mRNA-Based Therapeutic Gene Delivery by Expression-Augmenting 3′ UTRs Identified by Cellular Library Screening
Authors: Alexandra G. Orlandini von Niessen, Marco A. Poleganov, Corina Rechner, Arianne Plaschke, Lena M. Kranz, Stephanie Fesser, Mustafa Diken, Martin Löwer, Britta Vallazza, Tim Beissert, Valesca Bukur, Andreas N. Kuhn, Özlem Türeci, Ugur Sahin
Journal: Molecular Therapy (2018)

Synthetic mRNA has emerged as a powerful tool for the transfer of genetic information, and it is being explored for a variety of therapeutic applications. Many of these applications require prolonged intracellular persistence of mRNA to improve bioavailability of the encoded protein. mRNA molecules are intrinsically unstable and their intracellular kinetics depend on the UTRs embracing the coding sequence, in particular the 3′ UTR elements. We describe here a novel and generally applicable cell-based selection process for the identification of 3′ UTRs that augment the expression of proteins encoded by synthetic mRNA. Moreover, we show, for two applications of mRNA therapeutics, namely, (1) the delivery of vaccine antigens in order to mount T cell immune responses and (2) the introduction of reprogramming factors into differentiated cells in order to induce pluripotency, that mRNAs tagged with the 3′ UTR elements discovered in this study outperform those with commonly used 3′ UTRs. This approach further leverages the utility of mRNA as a gene therapy drug format. Synthetic mRNA has emerged as a powerful tool for the transfer of genetic information, and it is being explored for a variety of therapeutic applications. Many of these applications require prolonged intracellular persistence of mRNA to improve bioavailability of the encoded protein. mRNA molecules are intrinsically unstable and their intracellular kinetics depend on the UTRs embracing the coding sequence, in particular the 3′ UTR elements. We describe here a novel and generally applicable cell-based selection process for the identification of 3′ UTRs that augment the expression of proteins encoded by synthetic mRNA. Moreover, we show, for two applications of mRNA therapeutics, namely, (1) the delivery of vaccine antigens in order to mount T cell immune responses and (2) the introduction of reprogramming factors into differentiated cells in order to induce pluripotency, that mRNAs tagged with the 3′ UTR elements discovered in this study outperform those with commonly used 3′ UTRs. This approach further leverages the utility of mRNA as a gene therapy drug format.