tbuckley/cabot-search huggingface dataset:
Cloning and characterization of the sympathetic nervous system mutant, Sym3, in zebrafish
Authors: R. George, J. Lee, R. Stewart, T. Bayul, N. Campisi, F. Olale, A. Schier, J. Kanki, A. T. Look
Journal: Journal of Clinical Oncology (2007)

9541 Background: Neuroblastoma (NB) is a neural crest tumor manifesting in the adrenal gland and the sympathetic ganglia. The goal of this project was to use the zebrafish model to identify genes involved in the development of the peripheral sympathetic nervous system (PSNS). We used the expression of tyrosine hydroxylase (TH) in the cervical sympathetic ganglion (cervical complex, CC), as a marker for PSNS development. TH expression can be observed by whole-mount RNA in situ hybridization in 2–3-day zebrafish embryos in the CC. Methods: In an ethyl nitrosourea mutagenesis screen for mutations that affect PSNS development, we identified a putative mutant, Sym3, showing a change in modeling of the TH staining cells in the region of the CC. Results and Conclusion: The TH-positive cells were scattered rather than conglomerated together as is typical of cells in the normal CC. The mutant was also characterized by a “curly-tail” phenotype. After the mutation was recovered from the F3 generation, heterozygous pairs harboring the mutation were identified. Using genome wide scanning PCR assay, linkage of the Sym3 mutation to microsatellite markers z9704 and z1351, located on Linkage Group 1, was established. Complementation assays were performed with other known “curly tail” mutants in the genetic interval, which revealed that Sym3 and a previously described vic mutant were in the same complementation group. The vic mutant is characterized by curved body axis, left to right asymmetry and kidney cysts and results from a mutation in the ARL13b gene, a protein of the Ras superfamily involved in intracellular trafficking and cilial motility. The vic mutation is a C to A transition at position 104 in the second exon of the open reading frame (T35L). The ARL13b gene in Sym3 has a four aa insertion at the 5’ end of the 4th exon of the coding region.The mutant Sym3 phenotype can be rescued by overexpression of the normal ARL13b gene. The vic mutant showed defective cilia formation in the kidney. However, immunocytochemistry showed normal cilia in the Sym3 mutant, suggesting that the Sym3 allele of ARL13b affects the development of alternative tissues during development, such as the aggregation of sympathetic neurons into discrete ganglia. Further functional characterization of the Sym3 mutation is ongoing. No significant financial relationships to disclose.
TCTAP C-222 Successful Limb Salvage Case of Critical Limb Ischemia Patient with Systemic Sclerosis Treated by Endovascular Therapy in Combination with Lumbar Sympathetic Nerve Blockade
Authors: Takumi Inoue, Susumu Odajima, Kentaro Yamashita, Taro Kamada, Shun Yokota, Daisuke Tsuda, Masamichi Iwasaki, Hiroshi Okamoto, Takatoshi Hayashi
Journal: Journal of the American College of Cardiology (2017)
Myeloperoxidase Mediates Postischemic Arrhythmogenic Ventricular Remodeling
Authors: Martin Mollenhauer, Kai Friedrichs, Max Lange, Jan Gesenberg, Lisa Remane, Christina Kerkenpaß, Jenny Krause, Johanna Schneider, Thorben Ravekes, Martina Maass, Marcel Halbach, Gabriel Peinkofer, Tomo Saric, Dennis Mehrkens, Matti Adam, Florian G. Deuschl, Denise Lau, Birgit Geertz, Kashish Manchanda, Thomas Eschenhagen, Lukas Kubala, Tanja K. Rudolph, Yuping Wu, W.H. Wilson Tang, Stanley L. Hazen, Stephan Baldus, Anna Klinke, Volker Rudolph
Journal: Circulation Research (2017)

Rationale: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase, a heme enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. Objective: To reveal the role of myeloperoxidase for the development of ventricular arrhythmias. Methods and Results: In different murine models of myocardial ischemia, myeloperoxidase deficiency profoundly decreased vulnerability for ventricular tachycardia on programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry after isoproterenol injection. Experiments using CD11b/CD18 integrin–deficient (CD11b −/− ) mice and intravenous myeloperoxidase infusion revealed that neutrophil infiltration is a prerequisite for myocardial myeloperoxidase accumulation. Ventricles from myeloperoxidase-deficient (Mpo −/− ) mice showed less pronounced slowing and decreased heterogeneity of electric conduction in the peri-infarct zone than wild-type mice. Expression of the redox-sensitive gap junctional protein Cx43 (Connexin 43) was reduced in the peri-infarct area of wild-type compared with Mpo −/− mice. In isolated wild-type cardiomyocytes, Cx43 protein content decreased on myeloperoxidase/H 2 O 2 incubation. Mapping of induced pluripotent stem cell–derived cardiomyocyte networks and in vivo investigations linked Cx43 breakdown to myeloperoxidase-dependent activation of matrix metalloproteinase 7. Moreover, Mpo −/− mice showed decreased ventricular postischemic fibrosis reflecting reduced accumulation of myofibroblasts. Ex vivo, myeloperoxidase was demonstrated to induce fibroblast-to-myofibroblast transdifferentiation by activation of p38 mitogen-activated protein kinases resulting in upregulated collagen generation. In support of our experimental findings, baseline myeloperoxidase plasma levels were independently associated with a history of ventricular arrhythmias, sudden cardiac death, or implantable cardioverter–defibrillator implantation in a cohort of 2622 stable patients with an ejection fraction &gt;35% undergoing elective diagnostic cardiac evaluation. Conclusions: Myeloperoxidase emerges as a crucial mediator of postischemic myocardial remodeling and may evolve as a novel pharmacological target for secondary disease prevention after myocardial ischemia.
Erratum: Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death
Authors: Connie R Bezzina, Julien Barc, Yuka Mizusawa, Carol Ann Remme, Jean-Baptiste Gourraud, Floriane Simonet, Arie O Verkerk, Peter J Schwartz, Lia Crotti, Federica Dagradi, Pascale Guicheney, Véronique Fressart, Antoine Leenhardt, Charles Antzelevitch, Susan Bartkowiak, Eric Schulze-Bahr, Sven Zumhagen, Elijah R Behr, Rachel Bastiaenen, Jacob Tfelt-Hansen, Morten Salling Olesen, Stefan Kääb, Britt M Beckmann, Peter Weeke, Hiroshi Watanabe, Naoto Endo, Tohru Minamino, Minoru Horie, Seiko Ohno, Kanae Hasegawa, Naomasa Makita, Akihiko Nogami, Wataru Shimizu, Takeshi Aiba, Philippe Froguel, Beverley Balkau, Olivier Lantieri, Margherita Torchio, Cornelia Wiese, David Weber, Rianne Wolswinkel, Ruben Coronel, Bas J Boukens, Stéphane Bézieau, Eric Charpentier, Stéphanie Chatel, Aurore Despres, Françoise Gros, Florence Kyndt, Simon Lecointe, Pierre Lindenbaum, Vincent Portero, Jade Violleau, Manfred Gessler, Hanno L Tan, Dan M Roden, Vincent M Christoffels, Hervé Le Marec, Arthur A Wilde, Vincent Probst, Jean-Jacques Schott, Christian Dina, Richard Redon
Journal: Nature Genetics (2013)
Long-term safety and tolerability of apremilast in patients with psoriasis: Pooled safety analysis for ≥156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2)
Authors: Jeffrey Crowley, Diamant Thaçi, Pascal Joly, Ketty Peris, Kim A. Papp, Joana Goncalves, Robert M. Day, Rongdean Chen, Kamal Shah, Carlos Ferrándiz, Jennifer C. Cather
Journal: Journal of the American Academy of Dermatology (2017)

BackgroundRandomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis.ObjectiveAssess long-term safety of oral apremilast in psoriasis patients.MethodsSafety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2.ResultsThe 0 to ≥156–week apremilast-exposure period included 1184 patients treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156–week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52–week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported.LimitationsThis study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns.ConclusionsApremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.
State of the art thoracic ultrasound: intervention and therapeutics
Authors: John P Corcoran, Rachid Tazi-Mezalek, Fabien Maldonado, Lonny B Yarmus, Jouke T Annema, Coenraad F N Koegelenberg, Victoria St Noble, Najib M Rahman
Journal: Thorax (2017)

The use of thoracic ultrasound outside the radiology department and in everyday clinical practice is becoming increasingly common, having been incorporated into standards of care for many specialties. For the majority of practitioners, their experience of, and exposure to, thoracic ultrasound will be in its use as an adjunct to pleural and thoracic interventions, owing to the widely recognised benefits for patient safety and risk reduction. However, as clinicians become increasingly familiar with the capabilities of thoracic ultrasound, new directions for its use are being sought which might enhance practice and patient care. This article reviews the ways in which the advent of thoracic ultrasound is changing the approach to the investigation and treatment of respiratory disease from an interventional perspective. This will include the impact of thoracic ultrasound on areas including patient safety, diagnostic and therapeutic procedures, and outcome prediction; and will also consider potential future research and clinical directions.
NHS trusts continue to think they are over-regulated, survey finds
Authors: Gareth Iacobucci
Journal: BMJ (2017)

NHS trusts continue to believe they are overburdened by demands from regulators which remain too frequent and provide poor value for money, a new survey has found.

The poll1 of senior trust leaders by NHS Providers, the body representing NHS trusts in England, found that two thirds (68%) thought that demand from regulators including NHS Improvement and the Care Quality Commission had increased in the past 12 months.

While this was lower than the 87% who said that demand from regulators had increased when the organisation last surveyed trusts …
Implementing shared decision making in the NHS: lessons from the MAGIC programme
Authors: Natalie Joseph-Williams, Amy Lloyd, Adrian Edwards, Lynne Stobbart, David Tomson, Sheila Macphail, Carole Dodd, Kate Brain, Glyn Elwyn, Richard Thomson
Journal: BMJ (2017)

Shared decision making requires a shift in attitudes at all levels but can become part of routine practice with the right support, say Natalie Joseph-Williams and colleagues Adoption of shared decision making into routine practice has been remarkably slow, despite 40 years of research and considerable policy support.12345678 In 2010, the Health Foundation in the UK commissioned the MAGIC (Making Good Decisions in Collaboration) programme to design, test, and identify the best ways to embed shared decision making into routine primary and secondary care using quality improvement methods (box 1).910 #### Box 1: Summary of MAGIC programme ##### Phase 1 (August 2010–February 2012): Designing and testing the best ways to implement shared decision making in routine clinical settings Clinical areas ##### Phase 2 (February 2012–October 2013): Demonstrate that shared decision making can become part of routine clinical care (wider dissemination, implementation and sustainability) and build practical and transferable knowledge about the conditions for success Cardiff Newcastle
MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1
Authors: Takashi Shichita, Minako Ito, Rimpei Morita, Kyoko Komai, Yoshiko Noguchi, Hiroaki Ooboshi, Ryusuke Koshida, Satoru Takahashi, Tatsuhiko Kodama, Akihiko Yoshimura
Journal: Nature Medicine (2017)
SOURCE 3 Registry
Authors: Olaf Wendler, Gerhard Schymik, Hendrik Treede, Helmut Baumgartner, Nicolas Dumonteil, Leo Ihlberg, Franz-Josef Neumann, Giuseppe Tarantini, José Luis Zamarano, Alec Vahanian
Journal: Circulation (2017)

Background: The SOURCE 3 Registry (SAPIEN Aortic Bioprosthesis European Outcome) is a European multicenter, observational registry of the latest generation of transcatheter heart valve, the SAPIEN 3 (Edwards Lifesciences, Irvine, CA). Its purpose is to document outcomes of clinical safety and performance after European approval was given. Methods: Here, we present the 30-day outcome of the SOURCE 3 Registry. All data are self-reported, and all participating centers have committed to support their consecutive experience with the SAPIEN 3 transcatheter heart valve, dependent on patient consent, before the start of the study. Adverse events are defined with Valve Academic Research Consortium 2 criteria and adjudicated by an independent clinical events committee. Results: A total of 1950 patients from 80 centers in 10 countries were enrolled between July 2014 and October 2015. Of those, 1947 patients underwent transcatheter aortic valve implantation (TAVI) with the SAPIEN 3 (mean age, 81.6±6.6 years; 48.1% female). Main comorbidities included coronary artery disease (51.5%), renal insufficiency (27.4%), diabetes mellitus (29.5%), chronic obstructive pulmonary disease (16.0%), and a mean logistic EuroSCORE of 18.3±13.2. Transfemoral access was used in 87.1% (n=1695); nontransfemoral, in 252 patients. Conscious sedation was used in 59.9% of transfemoral procedures, and in 50% of patients, TAVI was performed without aortic balloon valvuloplasty. Implantation success (1 valve in the intended location) was 98.3%. Conversion to conventional surgery (0.6%) and use of cardiopulmonary bypass (0.7%) were rare. Adverse events were low, with site-reported 30-day all-cause mortality of 2.2%, cardiovascular mortality of 1.1%, stroke of 1.4%, major vascular complications of 4.1%, life-threatening bleeding of 5%, and post-TAVI pacemaker implantation of 12%. Moderate or greater paravalvular regurgitation was observed in 3.1% of reporting patients. Conclusions: Results from the SOURCE 3 Registry demonstrate contemporary European trends and good outcomes of TAVI in daily practice when this third-generation TAVI device is used.
포스터전시 : 페그인터페론과 리바비린 치료에 실패한 만성 C형간염 환장에서 페그인터페론과 리바비린 재치료의 효과
Authors: 강현구, 문성수, 서정아, 이상헌, 김지현, 박성재, 박은택, 이연재, 이상혁, 설상영
Journal: Clinical and Molecular Hepatology (2008)
Evidence for Very Recent Positive Selection in Mongolians
Authors: Kazuhiro Nakayama, Jun Ohashi, Kazuhisa Watanabe, Lkagvasuren Munkhtulga, Sadahiko Iwamoto
Journal: Molecular Biology and Evolution (2017)

Mongols, the founders of the largest continental empire in history, successfully adapted to the harsh environments of Inner Asia through nomadic pastoralism. Considerable interest exists in ascertaining whether genetic adaptation also contributed to the Mongols' success, and dissecting the genome diversity of present-day populations in Mongolia can help address this question. To this end, we determined the genotypes of nearly 2.4 million single nucleotide polymorphisms (SNPs) of 96 unrelated Mongolian individuals in Ulaanbaatar city, and performed genome-wide scans for population-specific positive selection. We discovered signatures of Mongolian-specific positive selection at the chromosomal region 3p12.1, in which hits in genome-wide association studies were reported for medical and biological traits related to energy metabolism and reproduction. The top SNP, rs117799927, showed a distinctive geographic distribution: the frequency of the derived allele, rs117799927 G, was extremely low among worldwide populations (0.005) but exceptionally high in Mongolians (0.247). Approximate Bayesian computation-based age estimation showed that the rs117799927 G allele emerged or positive selection began to operate 50 generations before the present, near the age of the climate anomaly named Late Antique Little Ice Age. Furthermore, rs117799927 showed significant associations with multiple adiposity-related traits in Mongolians and allelic difference in enhancer activity in cells of adipocyte lineage, suggesting that positive selection at 3p12.1 might be related to adaptation in the energy metabolism system. These findings provide novel evidence for a very recent positive-selection event in Homo sapiens and offer insights into the roles of genes in 3p12.1 in the adaptive evolution of our species.
Infectious diseases in China in the post-SARS era
Authors: Katherine B Gibney, Robert Hall
Journal: The Lancet Infectious Diseases (2017)

The regional committees aim to provide technical assistance to national tuberculosis control programmes. 9 The main efforts of experts from such committees and national tuberculosis programmes should be aimed at using rapid diagnostic methods for drugresistant tuberculosis, providing access to diagnostic tests for all patients, providing appropriate treatment for patients with MDR tuberculosis, and introducing rational approaches in the use of new antituberculosis drugs. 10The most important measure that might help to prevent the spread of drug-resistant tuberculosis is the implementation of short-course regimens of chemotherapy for patients with MDR tuberculosis.Introduction of 9-12 month courses of MDR therapy will increase the effectiveness of treatment and reduce the total number of antituberculosis drugs during the course of treatment and save funds that can be used to treat more patients. 11The use of new drugs that correspond with WHO recommendations will improve the quality of treatment for adults and children with drug-resistant tuberculosis and will help to eliminate tuberculosis globally. 12,13
TCTAP A-015 “Off-hours” Versus “On-hours” Presentation in STEMI in Singapore and Its Impact on Door-to-balloon Time and Clinical Outcome
Authors: Wee Kiat Ang, Kah Hua Peck, Violet Hoon, Jason Kwok Kong Loh, Fahim Haider Jafary, David Foo, Timothy James Watson, Paul JL. Ong, Hee Hwa Ho
Journal: Journal of the American College of Cardiology (2017)
Automated Ambulatory Blood Pressure Devices and Self-Measured Blood Pressure Monitoring Devices: Their Role in the Diagnosis and Management of Hypertension
Authors: American College of Physicians.
Journal: Annals of Internal Medicine (1993)

This guideline represents the American College of Physician's policy concerning the use of automated ambulatory blood pressure monitoring devices and self-measured blood pressure monitors in the diagnosis and management of hypertension. It is a technology assessment; a science-based evaluation of two blood pressure measuring devices to supplement or replace traditional office-based physician blood pressure measurements. The available evidence does not warrant widespread dissemination or routine use of automated ambulatory blood pressure measurement. On the other hand, we support a more circumspect use of such devices for research and for the care of subgroups of hypertensive patients with specific clinical problems. Self-measure blood pressure devices are increasingly being used by patients, and this practice should be encouraged. There has not been sufficient formal evaluation of this method to warrant managing patients solely using blood pressure readings obtained with self-measured blood pressure monitoring devices. We recommend that self-measured blood pressures be used as adjunct to physicians and nonphysicians office-based measurements, and that patients and physicians electing to use these devices be knowledgeable about their optimal use.
CONCUSSION KNOWLEDGE, ATTITUDES, AND BELIEFS AMONGST SPORTS MEDICINE PERSONNEL AT THE 2015 CEREBRAL PALSY FOOTBALL WORLD CHAMPIONSHIPS
Authors: Steffan Griffin, Liam Richard West, Osman Hassan Ahmed, Richard Weiler
Journal: British Journal of Sports Medicine (2017)

Background Concussion poses a challenge to sports medicine personnel, especially those working in contact sports such as football. In disability sport, the correct assessment and management of this injury is paramount. Objective To determine knowledge, attitudes, and beliefs regarding concussion amongst team physicians/physiotherapists working at the 2015 Cerebral Palsy Football World Championships (CPFWC). Design A 22-item questionnaire was provided to the ‘head of medicine’ of all teams participating at the 2015 CPFWC (n=15). Qualitative assessment of knowledge, attitudes and beliefs of participants in regard to concussion; both generally, and specifically to cerebral palsy football. Setting 2015 CPFWC, St George's Park, Burton-upon-Trent, United Kingdom. Patients (or Participants) Each nation's head of medical services (n=15; either a medical doctor or physiotherapist) were invited to complete the questionnaire during the pre-competition medical meeting. Interventions (or Assessment of Risk Factors) NA. Main Outcome Measurements Knowledge, attitudes, and beliefs related to concussion amongst sports medicine professionals at a World Championship. Results The majority of participants (8 physiotherapists and 6 doctors: or 93%) completed the questionnaire. Only one practitioner did not score 100% on identifying the signs and symptoms of concussion. 36% (n=5) believed headgear had protective effects against concussion. The use of a concussion assessment tool following suspected concussion was reported by 29% (n=4) clinicians, whilst 50% (n=7) stated that performing cognitive assessments were difficult in this population. 86% participants (n=12) reported that a disability sport concussion consensus statement would be useful. Conclusions Participants' overall knowledge around concussion was sound, but their methods for recognition and management were highly variable. Inherent difficulties were identified in the assessment and management of concussion in disabled athletes and the majority recognised an urgent need for expert clinical guidance for this population.
<i>Notes from the Field:</i> Varicella Fatality on a Cargo Vessel — Puerto Rico, 2015
Authors: Misty Ellis, Carolina Luna-Pinto, Thomas George, Joanna J. Regan, Mona Marin, Adriana Lopez, Brenda Rivera-Garcia, Kara Tardivel
Journal: MMWR Morbidity and Mortality Weekly Report (2017)
Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis
Authors: Carlos E. Ruiz, Rebecca T. Hahn, Alain Berrebi, Jeffrey S. Borer, Donald E. Cutlip, Greg Fontana, Gino Gerosa, Reda Ibrahim, Vladimir Jelnin, Hasan Jilaihawi, E. Marc Jolicoeur, Chad Kliger, Itzhak Kronzon, Jonathon Leipsic, Francesco Maisano, Xavier Millan, Patrick Nataf, Patrick T. O'Gara, Philippe Pibarot, Stephen R. Ramee, Charanjit S. Rihal, Josep Rodes-Cabau, Paul Sorajja, Rakesh Suri, Julie A. Swain, Zoltan G. Turi, E. Murat Tuzcu, Neil J. Weissman, Jose L. Zamorano, Patrick W. Serruys, Martin B. Leon
Journal: Journal of the American College of Cardiology (2017)