tbuckley/cabot-search huggingface dataset:
Covid-19: six million doses of hydroxychloroquine donated to US despite lack of evidence
Authors: Elisabeth Mahase
Journal: BMJ (2020)

<h3>Abstract</h3> Type I polyketide synthases (PKSs) are large multi-domain proteins converting simple acyl-CoA thioesters such as acetyl-CoA and malonyl-CoA to a large diversity of biotechnologically interesting molecules. Such multi-step reaction cascades are of particular interest for applications in engineered microbial cell factories, as the introduction of a single protein with many enzymatic activities does not require balancing of several individual enzymatic activities. However, functional introduction of type I PKSs into heterologous hosts is very challenging as the large polypeptide chains often do not fold properly. In addition, PKS usually require post-translational activation by dedicated 4’-phosphopantetheinyl transferases (PPTases). Here, we introduce an engineered <i>Corynebacterium glutamicum</i> strain as a novel microbial cell factory for type I PKS-derived products. Suitability of <i>C. glutamicum</i> for polyketide synthesis could be demonstrated by the functional introduction of the 6-methylsalicylic acid synthase ChlB1 from <i>Streptomyces antibioticus</i>. Challenges related to protein folding could be overcome by translation fusion of ChlB1<sub><i>Sa</i></sub> to the C-terminus of the maltose-binding protein MalE from <i>Escherichia coli</i>. Surprisingly, ChlB1<sub><i>Sa</i></sub> was also active in absence of a heterologous PPTase, which finally led to the discovery that the endogenous PPTase PptA<sub><i>Cg</i></sub> of <i>C. glutamicum</i> can also activate ChlB1<sub><i>Sa</i></sub>. The best strain, engineered to provide increased levels of acetyl-CoA and malonyl-CoA, accumulated up to 41 mg/L (0.27 mM) 6-methylsalicylic acid within 48 h of cultivation. Further experiments showed that PptA<sub><i>Cg</i></sub> of <i>C. glutamicum</i> can also activate nonribosomal peptide synthetases (NRPSs), rendering <i>C. glutamicum</i> a promising microbial cell factory for the production of several fine chemicals and medicinal drugs.
Abstract 229: What is the Real Incidence of Out-Of-Hospital Cardiac Arrest in Norway
Authors: Ingvild B Tjelmeland, Morten Larsen, Eirik Skogvoll, Jo Kramer-Johansen
Journal: Circulation (2019)

Purpose of the study: The Norwegian Cardiac Arrest Registry (NorCAR) is a mandatory national registry of resuscitation attempts that monitors the population incidence, care and outcome for cardiac arrest. Previously, substantial differences in the number of included patients per 100 000 inhabitants were observed in some “atypical” health trusts (HT). It was not known if this is a problem with data collection or reflected genuine population differences. The purpose of this study was to identify all patients that fill NorCAR’s inclusion criteria among these HTs, by imposing consistent methods for data collection. Materials and methods: The registry implemented consistent, standardised and rigorous data collection methods including targeted audits in four “atypical” health trusts, two with a high and two with a low reported population incidence. Registrations from January to March 2019 was compared with similar results from 2018. Results: In 2018, the observed nationwide annual incidence of out-of-hospital cardiac arrest was 64 per 100 000 inhabitants, varying from 40 to 102. At the four study sites the observed population incidence was stable among HT with high incidence (88 and 110) but apparently increased in the two HTs with previous low incidence after implementation of standardised collection method (from 48 to 56, and 46 to 54). Conclusions: The previously “atypical” low incidence probably reflected a problem with data collection. To achieve full coverage of the population, all data collectors need to collect data using the same method with a concise and thorough investigation of ambulance-, air ambulance-, dispatch-, and hospital records. Data collectors need to have a close relationship with ambulance and dispatch, and constant reminders and feedback on reported results are important. Implementing a new method for data collection takes time, and results need to be evaluated over time.
USEFULNESS OF SKELETAL MUSCLE AREA DETECTED BY COMPUTED TOMOGRAPHY TO PREDICT MORTALITY IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT: A META-ANALYSIS
Authors: Mohamad Soud, Fares Alahdab, Gavin Ho, Marco Cejudo-Tejeda, Kayode Kuku, Alexandre Hideo-Kajita, Hector Garcia Garcia
Journal: Journal of the American College of Cardiology (2019)
Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms
Authors: Vinaya Srirangam Nadhamuni, Márta Korbonits
Journal: Endocrine Reviews (2020)

Abstract Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over the last few years we have recognized the role of germline and somatic mutations in a number of syndromic or nonsyndromic conditions with pituitary tumor predisposition. These include the identification of novel germline variants in patients with familial or simplex pituitary tumors and establishment of novel somatic variants identified through next generation sequencing. Advanced techniques have allowed the exploration of epigenetic mechanisms mediated through DNA methylation, histone modifications and noncoding RNAs, such as microRNA, long noncoding RNAs and circular RNAs. These mechanisms can influence tumor formation, growth, and invasion. While genetic and epigenetic mechanisms often disrupt similar pathways, such as cell cycle regulation, in pituitary tumors there is little overlap between genes altered by germline, somatic, and epigenetic mechanisms. The interplay between these complex mechanisms driving tumorigenesis are best studied in the emerging multiomics studies. Here, we summarize insights from the recent developments in the regulation of pituitary tumorigenesis.
RENAL FUNCTION AS PREDICTOR OF MORTALITY IN PATIENTS AFTER PERCUTANEOUS TRANSCATHETER AORTIC VALVE IMPLANTATION
Authors: Jan-Malte Sinning, Alexander Ghanem, Hannah Steinhäuser, Viktoria Adenauer, Christoph Hammerstingl, Georg Nickenig, Nikos Werner, Medizinische Klinik II
Journal: Journal of the American College of Cardiology (2011)
Identification of eight-protein biosignature for diagnosis of tuberculosis
Authors: Qianting Yang, Qi Chen, Mingxia Zhang, Yi Cai, Fan Yang, Jieyun Zhang, Guofang Deng, Taosheng Ye, Qunyi Deng, Guobao Li, Huihua Zhang, Yuhua Yi, Ruo-Pan Huang, Xinchun Chen
Journal: Thorax (2020)

Background Biomarker-based tests for diagnosing TB currently rely on detecting Mycobacterium tuberculosis (Mtb) antigen-specific cellular responses. While this approach can detect Mtb infection, it is not efficient in diagnosing TB, especially for patients who lack aetiological evidence of the disease. Methods We prospectively enrolled three cohorts for our study for a total of 630 subjects, including 160 individuals to screen protein biomarkers of TB, 368 individuals to establish and test the predictive model and 102 individuals for biomarker validation. Whole blood cultures were stimulated with pooled Mtb-peptides or mitogen, and 640 proteins within the culture supernatant were analysed simultaneously using an antibody-based array. Sixteen candidate biomarkers of TB identified during screening were then developed into a custom multiplexed antibody array for biomarker validation. Results A two-round screening strategy identified eight-protein biomarkers of TB: I-TAC, I-309, MIG, Granulysin, FAP, MEP1B, Furin and LYVE-1. The sensitivity and specificity of the eight-protein biosignature in diagnosing TB were determined for the training (n=276), test (n=92) and prediction (n=102) cohorts. The training cohort had a 100% specificity (95% CI 98% to 100%) and 100% sensitivity (95% CI 96% to 100%) using a random forest algorithm approach by cross-validation. In the test cohort, the specificity and sensitivity were 83% (95% CI 71% to 91%) and 76% (95% CI 56% to 90%), respectively. In the prediction cohort, the specificity was 84% (95% CI 74% to 92%) and the sensitivity was 75% (95% CI 57% to 89%). Conclusions An eight-protein biosignature to diagnose TB in a high-burden TB clinical setting was identified.
Ethical Advocacy Across the Autism Spectrum: Beyond Partial Representation
Authors: Matthew S. McCoy, Emily Y. Liu, Amy S. F. Lutz, Dominic Sisti
Journal: The American Journal of Bioethics (2020)

Recent debates within the autism advocacy community have raised difficult questions about who can credibly act as a representative of a particular population and what responsibilities that role entails. We attempt to answer these questions by defending a set of evaluative criteria that can be used to assess the legitimacy of advocacy organizations and other nonelectoral representatives. With these criteria in hand, we identify a form of misrepresentation common but not unique to autism advocacy, which we refer to as partial representation. Partial representation occurs when an actor claims to represent a particular group of people but appropriately engages with only a subset of that group. After highlighting symbolic and substantive harms associated with partial representation, we propose several strategies for overcoming it.
Covid-19: weathering the storm
Authors: Fiona Godlee
Journal: BMJ (2020)

The UK is at last in near lockdown. While further measures may be needed, the government’s announcement on Monday 23 March has brought the country nearly into step with its European neighbours. If we are indeed only two weeks behind Italy, the peak of the covid-19 pandemic is on its way. There is an eerie calm, as when the sea recedes before the tsunami. Few of us can imagine what lies ahead.

For some, especially in London, the wave has already hit. Intensive care units are full, and hard decisions are becoming harder. On BMJ …
TCT-23 Detection by Near-infrared Spectroscopy of Large Lipid Core Plaques at Culprit Sites in Patients with Acute ST-Segment Elevation Myocardial Infarction
Authors: Ryan Madder, Sean Madden, Rishi Puri, Michael Hendricks, Stacie Vanoosterhout, Steve Sum, Annapoorna Kini, Samin Sharma, David Rizik, Emmanouil Brilakis, Kendrick Shunk, James Goldstein, Giora Weisz, Renu Virmani, Stephen Nicholls, Akiko Maehara, Gary Mintz, Gregg Stone, James Muller
Journal: Journal of the American College of Cardiology (2012)
Inaccuracies Regarding the Joint Commission Newborn Identification Standard
Authors: David W. Baker, Mark R. Chassin
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Airway Occlusion Pressure Revisited
Authors: Catherine S. Sassoon, Magdy Younes
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

samples, and with a high prevalence of bronchiectasis-the latter proving to be a major predictor of CBI.These factors may limit the generalizability of the results and call for them to be validated.Lastly, the definition of CBI was not based on a single baseline assessment but on repeated sampling over time, which complicates its clinical utility as a risk prediction tool and may have confounded the observed relationship between CBI and pneumonia.The results of this study are biologically plausible and logically appealing.The presence of low blood eosinophil counts and/or CBI appear to be risk factors that increase pneumonia risk and, therefore, influence the benefit-risk calculation for the use of ICS in COPD.That said, large-scale, routine, and repeated sputum collection and analysis poses logistic and implementation challenges, particularly in primary care.Unless this practical hurdle is overcome, it seems likely that decisions about ICS use will remain part science, part art.
Noncoding RNAs in gastric cancer: implications for drug resistance
Authors: Ling Wei, Jujie Sun, Nasha Zhang, Yan Zheng, Xingwu Wang, Liyan Lv, Jiandong Liu, Yeyang Xu, Yue Shen, Ming Yang
Journal: Molecular Cancer (2020)

Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. Advanced gastric cancer patients can notably benefit from chemotherapy including adriamycin, platinum drugs, 5-fluorouracil, vincristine, and paclitaxel as well as targeted therapy drugs. Nevertheless, primary drug resistance or acquisition drug resistance eventually lead to treatment failure and poor outcomes of the gastric cancer patients. The detailed mechanisms involved in gastric cancer drug resistance have been revealed. Interestingly, different noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are critically involved in gastric cancer development. Multiple lines of evidences demonstrated that ncRNAs play a vital role in gastric cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically summarized the emerging role and detailed molecular mechanisms of ncRNAs impact drug resistance of gastric cancer. Additionally, we propose the potential clinical implications of ncRNAs as novel therapeutic targets and prognostic biomarkers for gastric cancer.
Integrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection
Authors: Samuel W. Kazer, Toby P. Aicher, Daniel M. Muema, Shaina L. Carroll, Jose Ordovas-Montanes, Vincent N. Miao, Ang A. Tu, Carly G. K. Ziegler, Sarah K. Nyquist, Emily B. Wong, Nasreen Ismail, Mary Dong, Amber Moodley, Bonnie Berger, J. Christopher Love, Krista L. Dong, Alasdair Leslie, Zaza M. Ndhlovu, Thumbi Ndung’u, Bruce D. Walker, Alex K. Shalek
Journal: Nature Medicine (2020)

Abstract Cellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell–cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease 1,2 and nominating testable therapeutic targets 3 . Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability 4 . Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection 5 , we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination.
TCT-731 TRANSCATHETER AORTIC VALVE IMPLANTATION (TAVI) REDUCES SYMPATHETIC ACTIVITY AND NORMALIZES ARTERIAL SPONTANEOUS BAROREFLEX IN PATIENTS WITH AORTIC STENOSIS
Authors: Nicolas Dumonteil, Angelica Vaccaro, Fabien Despas, Marc Labrunee, Bertrand Marcheix, Elysabeth Lambert, Murray D. Esler, Didier Carrié, Jean Michel Senard, Michel Galinier, Atul Pathak
Journal: Journal of the American College of Cardiology (2013)
Audio Interview: Practical Measures to Help Prevent Covid-19
Authors: Eric J. Rubin, Lindsey R. Baden, Stephen Morrissey
Journal: New England Journal of Medicine (2020)

Practical Measures to Help Prevent Covid-19 In this audio interview conducted on March 25, 2020, the editors discuss transmission of SARS-CoV-2 and how to prevent it, particularly in at-risk health...
“Superdonor” Fecal Microbiota Transplant Effective for IBS
Authors: Anita Slomski
Journal: JAMA (2020)

Fecal microbiota transplant (FMT) using a single “superdonor” produced high rates of clinical response in patients with irritable bowel syndrome (IBS) in a trial published in Gut. Two previous randomized clinical trials of FMT for IBS had conflicting results.
Effect of Baseline Anemia on Outcomes After Left Main Coronary Revascularization
Authors: Prakriti Gaba, Patrick W. Serruys, Joseph F. Sabik, Arie Pieter Kappetein, Shmuel Chen, Marie-Claude Morice, David E. Kandzari, Aaron Crowley, Roxana Mehran, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2020)
Regenerating zebrafish fin epigenome is characterized by stable lineage-specific DNA methylation and dynamic chromatin accessibility
Authors: Hyung Joo Lee, Yiran Hou, Yujie Chen, Zea Z. Dailey, Aiyana Riddihough, Hyo Sik Jang, Ting Wang, Stephen L. Johnson
Journal: Genome biology (2020)

Abstract Background Zebrafish can faithfully regenerate injured fins through the formation of a blastema, a mass of proliferative cells that can grow and develop into the lost body part. After amputation, various cell types contribute to blastema formation, where each cell type retains fate restriction and exclusively contributes to regeneration of its own lineage. Epigenetic changes that are associated with lineage restriction during regeneration remain underexplored. Results We produce epigenome maps, including DNA methylation and chromatin accessibility, as well as transcriptomes, of osteoblasts and other cells in uninjured and regenerating fins. This effort reveals regeneration as a process of highly dynamic and orchestrated transcriptomic and chromatin accessibility changes, coupled with stably maintained lineage-specific DNA methylation. The epigenetic signatures also reveal many novel regeneration-specific enhancers, which are experimentally validated. Regulatory networks important for regeneration are constructed through integrative analysis of the epigenome map, and a knockout of a predicted upstream regulator disrupts normal regeneration, validating our prediction. Conclusion Our study shows that lineage-specific DNA methylation signatures are stably maintained during regeneration, and regeneration enhancers are preset as hypomethylated before injury. In contrast, chromatin accessibility is dynamically changed during regeneration. Many enhancers driving regeneration gene expression as well as upstream regulators of regeneration are identified and validated through integrative epigenome analysis.
TCT-650 Incidence and Clinical Impact of Stent Fracture after the PROMUS Element Platinum Chromium Everolimus-Eluting Stent Implantation
Authors: Shoichi Kuramitsu, Takashi Hiromasa, Soichiro Enomoto, Takenori Domei, Shinichi Shirai, Kenji Ando
Journal: Journal of the American College of Cardiology (2014)
A BALANCING ACT: THE IMPACT OF REDUCING MITRAL REGURGITATION AT THE EXPENSE OF INCREASED MITRAL GRADIENTS USING PERCUTANEOUS MITRAL VALVE REPAIR
Authors: Giorgio Medranda, Kunal Brahmbhatt, Kevin Marzo, William Kokotos, Daniel Donohue, Srihari Naidu, Ramesh Daggubati
Journal: Journal of the American College of Cardiology (2019)
5-YEAR FINAL RESULTS OF THE SISR (SIROLIMUS-ELUTING STENTS VERSUS VASCULAR BRACHYTHERAPY FOR IN-STENT RESTENOSIS) TRIAL
Authors: David R. Holmes, Paul S. Teirstein, Lowell Satler, Michael H. Sketch, Jeffrey J. Popma, Laura Mauri, Hong P. Wang, Patricia A. Schleckser
Journal: Journal of the American College of Cardiology (2011)
Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study
Authors: Michael S Hofman, Nathan Lawrentschuk, Roslyn J Francis, Colin Tang, Ian Vela, Paul Thomas, Natalie Rutherford, Jarad M Martin, Mark Frydenberg, Ramdave Shakher, Lih-Ming Wong, Kim Taubman, Sze Ting Lee, Edward Hsiao, Paul Roach, Michelle Nottage, Ian Kirkwood, Dickon Hayne, Emma Link, Petra Marusic, Anetta Matera, Alan Herschtal, Amir Iravani, Rodney J Hicks, Scott Williams, Declan G Murphy
Journal: The Lancet (2020)
RELATIONSHIP BETWEEN FRACTIONAL FLOW RESERVE AND ANGIOGRAPHIC AND INTRAVASCULAR ULTRASOUND PARAMETERS IN OSTIAL LESIONS: MAJOR EPICARDIAL VESSEL VS. SIDE BRANCH OSTIAL LESIONS
Authors: Jin-Sin Koh, Bon Kwon Koo, Ji-Hyun Kim, Kyung Woo Park, Hyun-Jae Kang, Han-Mo Yang, Hyo-Soo Kim, Byung-Hee Oh, Young-Bae Park
Journal: Journal of the American College of Cardiology (2012)