tbuckley/cabot-search huggingface dataset:
Genetic Dissection of a Super Enhancer Controlling the <i>Nppa-Nppb</i> Cluster in the Heart
Authors: Joyce C.K. Man, Karel van Duijvenboden, Peter H.L. Krijger, Ingeborg B. Hooijkaas, Ingeborg van der Made, Corrie de Gier-de Vries, Vincent Wakker, Esther E. Creemers, Wouter de Laat, Bastiaan J. Boukens, Vincent M. Christoffels
Journal: Circulation Research (2020)

Rationale: ANP (atrial natriuretic peptide) and BNP (B-type natriuretic peptide), encoded by the clustered genes Nppa and Nppb , are important prognostic, diagnostic, and therapeutic proteins in cardiac disease. The spatiotemporal expression pattern and stress-induction of the Nppa and Nppb are tightly regulated, possibly involving their coregulation by an evolutionary conserved enhancer cluster. Objective: To explore the physiological functions of the enhancer cluster and elucidate the genomic mechanism underlying Nppa-Nppb coregulation in vivo. Methods and Results: By analyzing epigenetic data we uncovered an enhancer cluster with super enhancer characteristics upstream of Nppb . Using CRISPR/Cas9 genome editing, the enhancer cluster or parts thereof, Nppb and flanking regions or the entire genomic block spanning Nppa-Nppb , respectively, were deleted from the mouse genome. The impact on gene regulation and phenotype of the respective mouse lines was investigated by transcriptomic, epigenomic, and phenotypic analyses. The enhancer cluster was essential for prenatal and postnatal ventricular expression of Nppa and Nppb but not of any other gene. Enhancer cluster–deficient mice showed enlarged hearts before and after birth, similar to Nppa-Nppb compound knockout mice we generated. Analysis of the other deletion alleles indicated the enhancer cluster engages the promoters of Nppa and Nppb in a competitive rather than a cooperative mode, resulting in increased Nppa expression when Nppb and flanking sequences were deleted. The enhancer cluster maintained its active epigenetic state and selectivity when its target genes are absent. In enhancer cluster–deficient animals, Nppa was induced but remained low in the postmyocardial infarction border zone and in the hypertrophic ventricle, involving regulatory sequences proximal to Nppa . Conclusions: Coordinated ventricular expression of Nppa and Nppb is controlled in a competitive manner by a shared super enhancer, which is also required to augment stress-induced expression and to prevent premature hypertrophy.
Part 2: Evidence Evaluation and Guidelines Development: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Authors: David J. Magid, Khalid Aziz, Adam Cheng, Mary Fran Hazinski, Amber V. Hoover, Melissa Mahgoub, Ashish R. Panchal, Comilla Sasson, Alexis A. Topjian, Amber J. Rodriguez, Aaron Donoghue, Katherine M. Berg, Henry C. Lee, Tia T. Raymond, Eric J. Lavonas
Journal: Circulation (2020)

The 2020 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care is based on the extensive evidence evaluation performed in conjunction with the International Liaison Committee on Resuscitation. The Adult Basic and Advanced Life Support, Pediatric Basic and Advanced Life Support, Neonatal Life Support, Resuscitation Education Science, and Systems of Care Writing Groups drafted, reviewed, and approved recommendations, assigning to each recommendation a Class of Recommendation (ie, strength) and Level of Evidence (ie, quality). The 2020 Guidelines are organized in knowledge chunks that are grouped into discrete modules of information on specific topics or management issues. The 2020 Guidelines underwent blinded peer review by subject matter experts and were also reviewed and approved for publication by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. The AHA has rigorous conflict-of-interest policies and procedures to minimize the risk of bias or improper influence during development of the guidelines. Anyone involved in any part of the guideline development process disclosed all commercial relationships and other potential conflicts of interest.
Junior doctor who accessed patient records improperly and failed to engage with regulator is struck off
Authors: Clare Dyer
Journal: BMJ (2020)

A junior doctor who improperly accessed the medical records of three hospital patients without a legitimate reason and who then lied about it to a trust investigation has been struck off the UK medical register after failing to engage with the regulatory process.

Neha Muralidharan was suspended for 10 months in July 2019, after she used her smart card at Warrington and Halton NHS Foundation Trust to access the medical records of a woman and two children. The woman complained, telling trust authorities that Muralidharan had specifically accessed her records. The trust found that Muralidharan’s card had been used to obtain the records and asked her to explain. She claimed …
Mitochondrial pyruvate carrier abundance mediates pathological cardiac hypertrophy
Authors: Mariana Fernandez-Caggiano, Alisa Kamynina, Asvi A. Francois, Oleksandra Prysyazhna, Thomas R. Eykyn, Susanne Krasemann, Maria G. Crespo-Leiro, Maria Garcia Vieites, Katiuscia Bianchi, Valle Morales, Nieves Domenech, Philip Eaton
Journal: Nature Metabolism (2020)
TCT-474 FANTOM II Long Lesion Study: Initial Safety and Performance Study of the Fantom Sirolimus-Eluting Bioresorbable Coronary Scaffold in Long Lesions—First Report: 2-Year Outcomes
Authors: Matthias Lutz, Bernard Chevalier, Didier Carrie, Jeffrey Anderson, Alexandre Abizaid
Journal: Journal of the American College of Cardiology (2021)
Epigallocatechin gallate mediated sandwich-like coating for mimicking endothelium with sustained therapeutic nitric oxide generation and heparin release
Authors: Bo Zhang, Ruijuan Yao, Cheng Hu, Manfred F. Maitz, Haoshuang Wu, Kunpeng Liu, Li Yang, Rifang Luo, Yunbing Wang
Journal: Biomaterials (2020)
α-Synuclein modulates tau spreading in mouse brains
Authors: Fares Bassil, Emily S. Meymand, Hannah J. Brown, Hong Xu, Timothy O. Cox, Shankar Pattabhiraman, Chantal M. Maghames, Qihui Wu, Bin Zhang, John Q. Trojanowski, Virginia M.-Y. Lee
Journal: The Journal of Experimental Medicine (2020)

α-Synuclein (α-syn) and tau aggregates are the neuropathological hallmarks of Parkinson's disease (PD) and Alzheimer's disease (AD), respectively, although both pathologies co-occur in patients with these diseases, suggesting possible crosstalk between them. To elucidate the interactions of pathological α-syn and tau, we sought to model these interactions. We show that increased accumulation of tau aggregates occur following simultaneous introduction of α-syn mousepreformed fibrils (mpffs) and AD lysate-derived tau seeds (AD-tau) both in vitro and in vivo. Interestingly, the absence of endogenous mouse α-syn in mice reduces the accumulation and spreading of tau, while the absence of tau did not affect the seeding or spreading capacity of α-syn. These in vivo results are consistent with our in vitro data wherein the presence of tau has no synergistic effects on α-syn. Our results point to the important role of α-syn as a modulator of tau pathology burden and spreading in the brains of AD, PDD, and DLB patients.
QT Interval in Patients With COVID-19
Authors: Matteo Bianco, Carlo Alberto Biolè, Enrico Cerrato
Journal: JAMA Cardiology (2020)

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TCT CONNECT-497 Incidence and Predictors of Cardiogenic Shock Following Tricuspid Valve Repair or Replacement
Authors: Matthew Lawlor, Polydoros Kampaktsis, Victoria Wang, Yuming Ning, Elizabeth Placheril, Michael Brener, Vivian Ng, Amisha Patel, Tamim Nazif, Torsten Vahl, Omar Khalique, Rebecca Hahn, Martin Leon, Paul Kurlansky, Nadira Hamid, Susheel Kodali, Isaac George
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-240 CTO PCI for In-Stent Restenosis: Insights From a Pooled Analysis of Four Multicenter Registries
Authors: Evangelia Vemmou, Alexandre Quadros, Joseph Dens, Pierfrancesco Agostoni, Khaldoon Alaswad, Karlyse Belli, Mauro Carlino, Dimitri Karmpaliotis, Dmitrii Khelimskii, Paul Knaapen, Oleg Krestyaninov, Soledad Ojeda, Lucio Padilla, Manuel Pan, Pedro Piccaro de Oliveira, Stéphane Rinfret, James Spratt, Simon Walsh, Judit Karacsonyi, Ilias Nikolakopoulos, Bavana Rangan, Emmanouil Brilakis, Lorenzo Azzalini
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-373 Optical Ultrasound: A New Imaging Paradigm Allowing Real-Time Visualization of In Situ Fenestration of Aortic Endovascular Grafts During Aneurysm Repair
Authors: Callum Little, Efthymios Maneas, Richard Colchester, Sacha Noimark, Jo Coote, Sunish Mathews, Debra Chong, George Hamilton, Tara Mastracci, Janice Tsui, Roby Rakhit, Adrien Desjardins
Journal: Journal of the American College of Cardiology (2020)
Transmission of Oscillatory Volumes into the Preterm Lung during Noninvasive High-Frequency Ventilation
Authors: Vincent D. Gaertner, Andreas D. Waldmann, Peter G. Davis, Dirk Bassler, Laila Springer, Jessica Thomson, David G. Tingay, Christoph M. Rüegger
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: There is increasing evidence for a clinical benefit of noninvasive high-frequency oscillatory ventilation (nHFOV) in preterm infants. However, it is still unknown whether the generated oscillations are effectively transmitted to the alveoli.Objectives: To assess magnitude and regional distribution of oscillatory volumes (VOsc) at the lung level.Methods: In 30 prone preterm infants enrolled in a randomized crossover trial comparing nHFOV with nasal continuous positive airway pressure, electrical impedance tomography recordings were performed. During nHFOV, the smallest amplitude to achieve visible chest wall vibration was used, and the frequency was set at 8 hertz.Measurements and Main Results: Thirty consecutive breaths during artifact-free tidal ventilation were extracted for each of the 228 electrical impedance tomography recordings. After application of corresponding frequency filters, Vt and VOsc were calculated. There was a signal at 8 and 16 Hz during nHFOV, which was not detectable during nasal continuous positive airway pressure, corresponding to the set oscillatory frequency and its second harmonic. During nHFOV, the mean (SD) VOsc/Vt ratio was 0.20 (0.13). Oscillations were more likely to be transmitted to the non-gravity-dependent (mean difference [95% confidence interval], 0.041 [0.025-0.058]; P < 0.001) and right-sided lung (mean difference [95% confidence interval], 0.040 [0.019-0.061]; P < 0.001) when compared with spontaneous Vt.Conclusions: In preterm infants, VOsc during nHFOV are transmitted to the lung. Compared with the regional distribution of tidal breaths, oscillations preferentially reach the right and non-gravity-dependent lung. These data increase our understanding of the physiological processes underpinning nHFOV and may lead to further refinement of this novel technique.
Understanding planetary health
Authors: Anthony Capon
Journal: The Lancet (2020)

Planetary Health: Protecting Nature to Protect Ourselves is a milestone—the first textbook for the emerging field of planetary health. I read the book under lockdown at home in Australia, a requirement of the public health response to the COVID-19 pandemic in Melbourne. At the same time, wildfires were raging in the USA that made me recall the devastating 2019–20 Australian wildfire season. Those fires were unprecedented. They killed more than 30 people, burned more than 11 million hectares of land, and resulted in prolonged smoke pollution that has since been linked to more than 400 premature deaths.
TCT CONNECT-130 Short-Term Outcomes of Aortic Valve Replacement in Patients Under the Age of 60 Years
Authors: Mohamed Gad, Islam Elgendy, Anas Saad, Ahmed Mahmoud, Toshiaki Isogai, Johnny Chahine, Amer N. Kadri, Ernesto Jimenez, Samir Kapadia, Hani Jneid
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-405 Use of Intravascular Imaging in Patients With ST-Segment Elevation Acute Myocardial Infarction
Authors: Michael Megaly, Ashish Pershad, Matthew Glogoza, Ayman Elbadawi, Marwan Saad, Amgad Mentias, Islam Elgendy, M. Nicholas Burke, Davide Capodanno, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2020)
SAT0642 PROTEIN BIOMARKERS TO DIFFERENTIATE PSORIATIC ARTHRITIS FROM PSORIASIS
Authors: Conor Magee, Yitong Pu, Anna Kwasnik, Angela MC Ardle, Belinda Hernandez, Flora Farkas, Natsumi Ikumi, Agnes Szentpetery, Loai Shakerdi, Phil Gallagher, Brian Kirby, Stephen Pennington, Oliver Fitzgerald
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The BIOmarkers of COMorbidities (BIOCOM) in Psoriasis (Pso) study is a longitudinal study in which we aim to identify clinical, genetic and protein biomarker features associated with the development of co-morbidities, notably psoriatic arthritis (PsA), in patients with psoriasis (Pso). Pso usually precedes the development of PsA with an average interval of 10 years. Thus, patients with Pso are an ideal group in which to study the early events in the evolution to PsA. <h3>Objectives</h3> To use a targeted proteomics approach to identify a serum protein, or panel of proteins, which can predict the development of PsA in patients with Pso. As a first step, we initially sought to identify serum proteins capable of discriminating between patients with Pso only and patients with established PsA. <h3>Methods</h3> 30 patients with Pso and 30 patients with established PsA were selected from the BIOCOM-Pso database. Serum samples from these patients, taken at their initial assessment, were digested using an established in-house standard operating protocol (SOP). Once digested, a targeted proteomics approach using liquid chromatography – mass spectrometry (LC-MS) and a multiple reaction monitoring (MRM) assay called PAPRICA was used to measure candidate biomarker proteins. These 206 proteins (423 peptides) were previously identified as being potential biomarkers in a number of different inflammatory rheumatological conditions. <h3>Results</h3> The demographics of the 2 patient groups are shown in Table 1. Targeted proteomics data from the PsA and Pso patients was subjected to univariate and multivariate analysis using a leave one out cross validation approach. The initial results revealed that the application of the PAPRICA method to the BIOCOM-Pso samples resulted in a dataset in which 88 of the 206 PAPRICA proteins could be reliably measured (CV Area &lt; 20%; Signal to Noise ratio &gt; 5; Library Dot Product &gt; 0.8). This subset of the PAPRICA proteins was not able to discriminate between PsA and Pso and none of the associated peptides were significantly different between the two groups (p value &lt; 0.05). <h3>Conclusion</h3> Analysis of a subset of 88 of the 206 biomarker proteins in the PAPRICA method, in patients with PsA and Pso, did not reveal peptides (proteins) that were statistically different between these two groups. Multivariate analysis generated a model that was unable to discriminate between patients with PsA and Pso. The possibility that the full PAPRICA assay may be able to discriminate between PsA and Pso will be explored, as will supplementing the PAPRICA method with additional biomarkers including proteins that may be identified in an unbiased proteome wide screen of PsA vs Pso serum samples. <h3>Disclosure of Interests</h3> None declared
Influence of probiotic supplementation on the developing microbiota in human preterm neonates
Authors: Niels van Best, Sonja Trepels-Kottek, Paul Savelkoul, Thorsten Orlikowsky, Mathias W. Hornef, John Penders
Journal: Gut Microbes (2020)

Background Oral administration of probiotic bacteria to preterm neonates has been recommended to prevent the development of necrotizing enterocolitis (NEC). The influence of probiotics on the endogenous microbiome, however, has remained incompletely understood.Study design & methods Here, we performed an observational study including 80 preterm neonates born at a gestational age <32-weeks to characterize the persistence of probiotic bacteria after no treatment or oral administration of two different probiotic formula and their influence on the microbial ecosystem during and after the intervention and their association with the development of NEC. Weekly fecal samples were profiled by 16S rRNA sequencing and monitored for the presence of the probiotic bacteria by quantitative PCR.Results Microbiota profiles differed significantly between the control group and both probiotic groups. Probiotic supplementation was associated with lower temporal variation as well as higher relative abundance of Bifidobacterium and Enterobacter combined with reduced abundance of Escherichia, Enterococcus, and Klebsiella. Colonization by probiotic bifidobacteria was observed in approximately 50% of infants although it remained transient in the majority of cases. A significantly reduced monthly incidence of NEC was observed in neonates supplemented with probiotics.Conclusion Our results demonstrate successful transient colonization by probiotic bacteria and a significant influence on the endogenous microbiota with a reduced abundance of bacterial taxa associated with the development of NEC. These results emphasize that probiotic supplementation may allow targeted manipulation of the enteric microbiota and confer a clinical benefit. (Clinical Trial Registry accession number: DRKS/GCTR 00021034)
経口耐性の誘導における形質細胞様樹状細胞の重要な役割【JST・京大機械翻訳】
Authors: Uto Tomofumi, Takagi Hideaki, Fukaya Tomohiro, Nasu Junta, Fukui Takehito, Miyanaga Noriaki, Arimura Keiichi, Nakamura Takeshi, Choijookhuu Narantsog, Hishikawa Yoshitaka, Sato Katsuaki
Journal: Journal of Allergy and Clinical Immunology (2018)
Detection of Chemotherapy-resistant Pancreatic Cancer Using a Glycan Biomarker, sTRA
Authors: ChongFeng Gao, Luke Wisniewski, Ying Liu, Ben Staal, Ian Beddows, Dennis Plenker, Mohammed Aldakkak, Johnathan Hall, Daniel Barnett, Mirna Kheir Gouda, Peter Allen, Richard Drake, Amer Zureikat, Ying Huang, Douglas Evans, Aatur Singhi, Randall E. Brand, David A. Tuveson, Susan Tsai, Brian B. Haab
Journal: Clinical Cancer Research (2020)

Abstract Purpose: A subset of pancreatic ductal adenocarcinomas (PDACs) is highly resistant to systemic chemotherapy, but no markers are available in clinical settings to identify this subset. We hypothesized that a glycan biomarker for PDACs called sialylated tumor-related antigen (sTRA) could be used for this purpose. Experimental Design: We tested for differences between PDACs classified by glycan expression in multiple systems: sets of cell lines, organoids, and isogenic cell lines; primary tumors; and blood plasma from human subjects. Results: The sTRA-expressing models tended to have stem-like gene expression and the capacity for mesenchymal differentiation, in contrast to the nonexpressing models. The sTRA cell lines also had significantly increased resistance to seven different chemotherapeutics commonly used against pancreatic cancer. Patients with primary tumors that were positive for a gene expression classifier for sTRA received no statistically significant benefit from adjuvant chemotherapy, in contrast to those negative for the signature. In another cohort, based on direct measurements of sTRA in tissue microarrays, the patients who were high in sTRA again had no statistically significant benefit from adjuvant chemotherapy. Furthermore, a blood plasma test for the sTRA glycan identified the PDACs that showed rapid relapse following neoadjuvant chemotherapy. Conclusions: This research demonstrates that a glycan biomarker could have value to detect chemotherapy-resistant PDAC in clinical settings. This capability could aid in the development of stratified treatment plans and facilitate biomarker-guided trials targeting resistant PDAC.
SAT0037 Myocardial involvement in patients with ankylosing spondylitis
Authors: N Tas, S Alpaslan, M Alpaslan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Ankylosing spondylitis (AS) is a chronic systemic disease that may involve aorta and the heart. Aortitis, aortic valve insufficiency, pericarditis, cardiac conduction abnormalities and cardiomegaly have been reported in patients with AS. It is not clear whether cardiac muscle changes are due to primary involvement of the cardiac muscle or secondary to aortic and valvular involvement in this disease. <h3>Objectives</h3> To evaluate the presence of ongoing myocyte necrosis in patients with active AS. <h3>Methods</h3> 8 patients with active AS (2 women and 6 men, mean age 36 years) were included in this study. AS was diagnosed according to the New-York criteria. Disease activity was assessed by erythrocyte sedimentation rate (ESR) and serum levels of C-reactive protein (CRP). None of the patients had macrovascular complications such as hypertension or clinical evidence of cardiac valvular insufficiency. Sex- and age-matched 8 healthy adults formed the control group. Myocardial involvement was evaluated by serum levels of cardiac specific troponin-I, an intracellular cardiac protein that is not detected in blood unless myocyte necrosis occurs. <h3>Results</h3> Mean duration of disease activity was 8 years. Electrocardiograms were normal in all subjects. The ESR and CRP levels were elevated in all patients with AS (mean values were 39 mm/h and 34 mg/l respectively) while they were normal in controls (mean values were 11 mm/h and 2 mg/l respectively). Cardiac specific troponin-I was not detected in the serum of any subject. <h3>Conclusion</h3> The absence of cardiac specific troponin-I in the serum of patients with active AS suggest that there is no ongoing primary myocyte necrosis in the active stage of this disease. Previously reported cardiac abnormalities in this disease can be the result of aortic involvement including aortic vave insufficiency. <h3>References</h3> Van Der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New-York criteria. Arthritis Rheum. 1984;27:361–8 Bergfeldt L, Insulander P, Lindblom D, <i>et al</i>. HLA-B27: an important genetic risk factor for lone aortic regurgitation and severe conduction system abnormalities. Am J Med. 1988;85:12–18 Graham DC, Smythe HA. The carditis and aortitis of ankylosing spondylitis. Bull Rheum Dis. 1958;9:171–4